tbuckley/cabot-search huggingface dataset:
Abstract 14299: The Prognostic Value of Insulin-like Growth Factor-Binding Protein 7 in Patients With Heart Failure and Preserved Ejection Fraction: Results From Irbesartan in Heart Failure and Preserved Ejection Fraction (I-PRESERVE) Trial
Authors: Parul U Gandhi, Sheryl L Chow, Thomas S Rector, Henry Krum, Hanna K Gaggin, John J McMurray, Michael Zile, Michel Komajda, Robert S McKelvie, Peter E Carson, James L Januzzi, Inder S Anand
Journal: Circulation (2015)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is associated with considerable morbidity and mortality. Insulin-like growth factor-binding protein 7 (IGFBP7) is a cell cycle arrest biomarker associated with abnormal diastology and prognosis in HF with reduced EF (HFrEF). Its role in patients with HFpEF is unknown. Hypothesis: IGFBP7 will be associated with adverse outcomes in HFpEF. Methods: Baseline (BL) IGFBP7 (n=302; placebo=154, irbesartan=148) and 6 month change (Δ; n=293; placebo=147, irbesartan=146) were measured and correlated with clinical data, biomarkers, estimated glomerular filtration rate (eGFR), and the primary outcome of all-cause mortality (ACM) or cardiovascular hospitalization (CVH) in patients from the Irbesartan in HFpEF (I-PRESERVE) Trial; secondary outcomes included HF events. Results: Median BL IGFBP7 concentration was 218 ng/mL, higher than previously seen in patients with HFrEF. BL IGFBP7 was correlated with age (R 2 =0.13; P&lt;0.0001) and other prognostic variables including amino-terminal pro-B-type natriuretic peptide (NT-proBNP; R 2 =0.22; P&lt;0.0001) and eGFR (R 2 =0.14; P&lt;0.0001). BL IGFBP7 was associated with the primary outcome (hazard ratio [HR]=1.06 per 10 ng/mL; P&lt;0.001), ACM (HR=1.08 per 10 ng/mL; P&lt;0.001), and HF events (HR=1.07 per 10 ng/mL; P&lt;0.001; Figure ) and remained significant for all outcomes after adjustment for NT-proBNP and eGFR. After 6 months, IGFBP7 did not change significantly in either treatment group. ΔIGFBP7 was not independently associated with outcomes but was associated with a decrease in eGFR in patients randomized to receive irbesartan (R 2 =0.09; P&lt;0.002). Conclusions: IGFBP7 is associated with adverse outcomes in HFpEF. Further studies are needed to identify the mechanistic link between IGFBP7, renal function, and outcomes in patients with HFpEF.
TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial
Authors: Elisabeth Quoix, Hervé Lena, Gyorgy Losonczy, Frédéric Forget, Christos Chouaid, Zsolt Papai, Radj Gervais, Christian Ottensmeier, Aleksandra Szczesna, Andrzej Kazarnowicz, Joseph T Beck, Virginie Westeel, Enriqueta Felip, Didier Debieuvre, Anne Madroszyk, Julien Adam, Gisèle Lacoste, Annette Tavernaro, Bérangère Bastien, Céline Halluard, Tania Palanché, Jean-Marc Limacher
Journal: The Lancet Oncology (2015)
Levels of emotional awareness: a cognitive-developmental theory and its application to psychopathology [published erratum appears in Am J Psychiatry 1987 Apr;144(4):542]
Authors: R D Lane, G E Schwartz
Journal: American Journal of Psychiatry (1987)

The authors present a cognitive-developmental theory of emotional awareness that creates a bridge between normal and abnormal emotional states. Their primary thesis is that emotional awareness is a type of cognitive processing which undergoes five levels of structural transformation along a cognitive-developmental sequence derived from an integration of the theories of Piaget and Werner. The five levels of structural transformation are awareness of bodily sensations, the body in action, individual feelings, blends of feelings, and blends of blends of feelings. The authors suggest applications of this model to current unresolved problems in psychiatric theory, research, and practice.
Differential effects of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 on atherosclerosis and monocyte/macrophage invasion
Authors: Karina Di Gregoli, Sarah J. George, Andrew C. Newby, Jason L. Johnson
Journal: Cardiovascular Research (2015)

MMPs contribute to atherosclerotic plaque progression and instability, but the relative potency of their endogenous tissue inhibitors of metalloproteinases (TIMPs) as protective factors has not been defined. We therefore investigated the impact of TIMP-1 and TIMP-2 knockout on atherosclerotic plaque burden and composition in apolipoprotein E-knockout (Apoe−/−) mice and studied the underlying effects on monocyte/macrophage behaviour. Analysis of brachiocephalic artery plaques revealed comparable atherosclerotic lesion areas between TIMP-1−/− Apoe−/− or TIMP-2−/− Apoe−/− double deficient mice and relevant age-matched, strain-matched Apoe−/− controls after 8 weeks of high-fat feeding. However, lesions from TIMP-2−/− Apoe−/− mice had higher levels of markers associated with plaque vulnerability, including increased macrophage: vascular smooth muscle cell ratios, larger necrotic core areas, reduced collagen contents, increased macrophage proliferation, and apoptosis frequencies, compared with TIMP-1−/−Apoe−/− and controls. In contrast, TIMP-1−/− Apoe−/− animals only had a significant reduction in vascular smooth muscle cell content compared with Apoe−/− controls. In vitro and in vivo findings implicated heightened monocyte/macrophage invasion in the detrimental effects observed on atherosclerotic plaque composition in TIMP-2−/− Apoe−/− mice. Moreover, TIMP-2 specifically decreased MMP-14-dependent monocyte/macrophage infiltration into sites of experimentally induced inflammation and established atherosclerotic lesions. Our data demonstrate that TIMP-2 plays a greater protective role than TIMP-1 during the pathogenesis of atherosclerosis, in part by suppressing MMP-14-dependent monocyte/macrophage accumulation into plaques.
Histone deacetylase activity and recurrent bacterial bronchitis in severe eosinophilic asthma
Authors: L. Zuccaro, A. Cox, C. Pray, K. Radford, K. Novakowski, M. Dorrington, M. G. Surette, D. Bowdish, P. Nair
Journal: Allergy (2015)

An increase in P13 Kinase activity and an associated reduction in histone deacetylase activity may contribute to both relative steroid insensitivity in patients with severe eosinophilic asthma and impaired macrophage scavenger function and susceptibility to recurrent infective bronchitis that may, in turn, contribute to further steroid insensitivity.
Neoadjuvant chemotherapy with epirubicin and cyclophosphamide followed by docetaxel (ECT) in locally advanced and inflammatory breast cancer (BC): Saint Louis experience
Authors: S. Giacchetti, M. Habdous, H. Hocini, C. Cuvier, A. De Roquancourt, F. Perret, M. Espié
Journal: Journal of Clinical Oncology (2006)

10729 Background: Neoadjuvant chemotherapy is increasingly used in locally advanced breast cancer ptes. We studied the histological response after neoadjuvant chemotherapy in ptes with locally advanced and inflammatory breast cancer. Methods: From 2003 to 2005, 50 ptes with locally advanced and inflammatory breast cancer received neoadjuvant chemotherapy (Epirubicin 75 mg/m 2 , Cyclophosphamide 750 mg/m 2 (d1-q21, 4 courses (c)) followed by Docetaxel 100 mg/m 2 (d1-q21, 4 c). All ptes had a surgical biopsy prior chemotherapy, initial conservative surgery was impossible. Clinical responses were evaluated by the same oncologist and the surgery slices reviewed by the same pathologist. Histological complete response is defined as no infiltrative and/or in situ tumor in the breast and negative lymph nodes. Results: Ptes characteristics: median age 50 y (30–74), 30 premenopausal ptes; T2: 5 ptes, T3: 24, T4: 21, median tumor size 60 mm; N0: 12, N1: 38, 11 ptes had inflammatory tumor. Histological features: 43 infiltrating ductal carcinoma, 7 infiltrating lobular carcinoma, SBR grade 1/2/3: 2/23/24; vascular embols (13 positive, 37 negative), RH+: 28 ptes (16 RE+/RP+; 12 RE+/RP-) and 22 RH-, C-erb2 status (43 negative and 7 positive). All the ptes received 8 courses of chemo. Clinical response at 8 c: 22 (44 %) ptes had a complete response, 14 (32%) partial response, 9 (20%) stable disease, 4 ptes (8%) had progressive disease, 1 was not evaluated. 42 ptes had breast surgery, 5 are too early, 2 progressed and received a second line chemo, 1 refuse surgery. Out of 42 operated ptes, 37 had mammectomy, 5 tumorectomy, 39 had axillary dissection. Histological response: 7 ptes had a complete pathological response (pCR) (17 %), 3 had pCR with persistant in situ carcinoma (7%), 32 ptes (76%) had persistant infiltrative carcinoma [histological response &gt;50% 14 ptes (33%), &lt;50% 18 ptes (43%)]; 11 (26%) ptes had negative lymph nodes, 28 (66 %) had positive lymph nodes [10 1–3 N+; 18 ≥ 4 N+]. Conclusion: In this population with a large amount of T3-T4 (median size 60mm) and inflammatory cancers the complete histological response rate of 17% (24% with in situ) is close to the series with smaller tumors. The rate of breast conservation is low (12%). No significant financial relationships to disclose.
O005 : Retreatment of patients who failed 8 or 12 weeks of ledipasvir/sofosbuvir-based regimens with ledipasvir/sofosbuvir for 24 weeks
Authors: E. Lawitz, S. Flamm, J.C. Yang, P.S. Pang, Y. Zhu, E. Svarovskaia, J.G. McHutchison, D. Wyles, P. Pockros
Journal: Journal of Hepatology (2015)
Activation of innate and adaptive immunity as an effective combined strategy for cancer immunotherapy
Authors: Alexander Rakhmilevich, Mildred Felder, Lauren Lever, Tyler Van De Voort, Alan J Korman, Stephen D Gillies, Paul M Sondel
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immunotherapeutic approaches can demonstrate some antitumor benefit, but their efficacy is limited when they are used as a single modality. We asked if a combinatory approach activating both innate and adaptive immunity would improve cancer immunotherapy. We have previously shown
Abstract 16201: Combined Treatment of the PI3k/mTOR Inhibitor BEZ235 With Doxorubicin Does Not Increase Cardiotoxicity While Improving Efficacy in Breast Cancer Cells
Authors: David E Durrant, Samya Dyer, Anindita Das, Rakesh C Kukreja
Journal: Circulation (2014)

Background: Cardiotoxicity is a major clinical limitation with doxorubicin (DOX). Also, the PI3K/Akt survival pathway is one of the most commonly mutated pathways in cancer. Therefore, the combination of kinase inhibitors and chemotherapy, such as DOX, are necessary for achieving cancer control. The PI3K pathway is also critical for protecting the heart from stress. Therefore, we examined the combined effect of BEZ235 (BEZ), a dual PI3k/mTOR inhibitor, with DOX on cardiac function and killing of breast cancer cells. Methods and results: c57 mice were treated with BEZ (40 mg/kg daily oral gavage) and DOX (3 IV injections of 5 mg/kg) either alone or in combination. Systolic function was assessed 12 weeks after initial treatment using echocardiography. Decreased ejection fraction was observed after DOX treatment. Interestingly, the combined treatment with BEZ and DOX did not exacerbate DOX cardiotoxicity (Fig. A). Western blot analysis showed significant increase in AKT (thr 308) and ERK phosphorylation with BEZ and DOX as compared individual treatment with BEZ or DOX in the heart (Fig. B). To address the anti-cancer effects of these drugs, MDA-MB-231 breast cancer cells were treated with BEZ and DOX either alone or in combination for 48 hours. Necrosis, measured using the trypan blue assay, showed a significant increase in dead cells compared to either drug alone (Fig. C). Conclusion: Concurrent treatment with DOX and BEZ did not exacerbate cardiac toxicity as demonstrated by similar level of deficit in ejection fraction between DOX as well as DOX plus BEZ. This could be due to enhanced survival signaling in the combination group. BEZ also sensitized breast cancer cells to DOX resulting in increased cell death. We propose that this combination strategy might lead to improved long term outcomes for patients with breast cancer without additional complications related to cardiac dysfunction.
Patient-reported outcomes (PROs) in patients (pts) with pancreatic neuroendocrine tumors (NET) receiving sunitinib (SU) in a phase III trial.
Authors: A. Vinik, Y. Bang, J. Raoul, J. W. Valle, P. Metrakos, D. Hörsch, B. Korytowsky, R. Mundayat, R. C. Chao, E. Raymond
Journal: Journal of Clinical Oncology (2010)

4003 Background: SU 37.5 mg/day continuous daily dosing vs placebo (PBO) was assessed in pts with progressive, well-differentiated pancreatic endocrine tumors in a phase III trial (NCT00428597). SU demonstrated prolonged median progression-free survival (PFS) vs PBO (11.4 vs. 5.5 months; p = 0.0001) and was well tolerated. The trial included PRO assessments, reported here. Methods: Pts completed the validated, 15-domain, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) v 3.0, on Day 1, every 4 wks (cycle) thereafter, and at end of treatment/withdrawal. Between-treatment comparison of estimated mean differences in change from baseline was carried out using repeated measures mixed-effects models. Statistical (2-sided p value; 0.05 level) and clinical (≥ 10 point difference, minimally important difference; Osoba et al. J Clin Oncol 1998;16:139-44) significance of differences were assessed. Results: QLQ-C30 data were available for 73/86 and 71/85 pts in SU and PBO arms. PRO analysis was limited to the first 10 cycles, during which each arm had ≥ 10 pts. All 15 QLQ-C30 domain scores had a ≤ 7-point mean difference between arms at baseline. Analysis based on mixed-effects model found pts in the SU arm had overall clinically and statistically significant worsening of diarrhea (diff = 21.38, p < 0.001). In this arm there was also a significant trend towards worsening of insomnia (diff = 7.753, p = 0.0372) vs PBO. However, in QoL, cognitive, emotional, physical, role, and social functioning domains and other symptoms and scales, there were no overall clinically or statistically significant differences. There was no significant difference between arms in observed mean change from baseline in global QoL nor in most other domains, when compared using the 2-sample t-test. Additional analyses are planned. Conclusions: SU resulted in significant PFS improvement vs PBO and maintained global health-related QoL in pts with pancreatic NET. The expected toxicity of diarrhea had limited impact on global QoL and functioning scales in patients treated with SU. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Ansar, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, K V Pharmaceuticals, Lilly, Merck, Novartis, Pfizer, R W Johnson Pharmaceuticals, sanofi-aventis, Takeda, Tercica Pfizer Pfizer Abbott Laboratories, American Diabetes Association, Arcion Therapeutics, GlaxoSmithKline, Lilly, Merck Research Labs, Mitsubishi/Medpace, Inc, NIH/NIA, Old Dominion Research Foundation, Pfizer, Reliant Pharmaceuticals, sanofi-aventis Pfizer
A Phase 1B Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Advanced Urothelial Tract Cancer
Authors: E.R. Plimack, S. Gupta, J. Bellmunt, R. Berger, B. Montgomery, E.J. Gonzalez, J. Pulini, M. Dolled-Filhart, K. Emancipator, K. Pathiraja, C. Gause, R. Perini, J. Cheng, P.H. O'Donnell
Journal: Annals of Oncology (2014)
Teniposide in the treatment of leukemia: a case study of conflicting priorities in the development of drugs for fatal diseases.
Authors: J L Grem, D F Hoth, B Leyland-Jones, S A King, R S Ungerleider, R E Wittes
Journal: Journal of Clinical Oncology (1988)

Teniposide, a semisynthetic epipodophyllotoxin, was found to be highly active against murine leukemias, and the combination of teniposide with cytosine arabinoside (ara-C) was curative in murine leukemia models. The antitumor activity in preclinical models prompted introduction of teniposide into the clinic in 1971. Although teniposide as a single agent rarely produced a complete remission in heavily pretreated leukemia patients, teniposide plus ara-C produced complete remissions in some patients with refractory and relapsed acute lymphoblastic leukemia (ALL). Innovative front-line and salvage regimens using teniposide have been developed that incorporate a multi-drug strategy with early intensification, rotation of drug combinations in maintenance, and regional therapy in an effort to improve the cure rate in leukemia. However, as the complexity of these regimens increases, the contribution of an individual component such as teniposide becomes less clear. Although some of these regimens for newly diagnosed and relapsed ALL are now thought to represent the best available therapy, teniposide remains an investigational agent. In this review, we outline and discuss the conflicts arising from the need to answer drug-specific issues, and, at the same time, facilitate the implementation of innovative, curative regimens.
Distribution of Opioids by Different Types of Medicare Prescribers
Authors: Jonathan H. Chen, Keith Humphreys, Nigam H. Shah, Anna Lembke
Journal: JAMA Internal Medicine (2015)

This study shows that contrary to the California Worker’s Compensation data showing a small subset of prescribers accounting for a disproportionately large percentage of opioid prescribing, Medicare opioid prescribing is distributed across many different types of prescribers and specialities.
Patients' should be able to say no
Authors: J. Menage
Journal: BMJ (1995)

EDITOR,—John N Lunn comments, “Consent for anaesthesia is different from consent for surgical or medical treatment because cooperative effort is not required. In order to be anaesthetised patients have to do very little.”1 It is precisely because anaesthetised patients are helpless and unable to defend their personal boundaries that it is important to obtain their consent …
Diabetes, Lower-Extremity Amputation, and Death
Authors: Ole Hoffstad, Nandita Mitra, Jonathan Walsh, David J. Margolis
Journal: Diabetes Care (2015)

The goal of the study was to determine whether complications of diabetes well-known to be associated with death such as cardiovascular disease and renal failure fully explain the higher rate of death in those who have undergone a lower-extremity amputation (LEA).This was a longitudinal cohort study of patients cared for in the Health Improvement Network. Our primary exposure was LEA and outcome was all-cause death. Our "risk factor variables" included a history of cardiovascular disease (a history of myocardial infarctions, cerebrovascular accident, and peripheral vascular disease/arterial insufficiency), Charlson index, and a history of chronic kidney disease. We estimated the effect of LEA on death using Cox proportional hazards models.The hazard ratio (HR) for death after an LEA was 3.02 (95% CI 2.90, 3.14). The fully adjusted (all risk factor variables) LEA HR was diminished only by ∼22% to 2.37 (2.27, 2.48). Furthermore, LEA had an area under the receiver operating curve (AUC) of 0.51, which is poorly predictive, and the fully adjusted model had an AUC of 0.77, which is better but not strongly predictive. Sensitivity analysis revealed that it is unlikely that there exists an unmeasured confounder that can fully explain the association of LEA with death.Individuals with diabetes and an LEA are more likely to die at any given point in time than those who have diabetes but no LEA. While some of this variation can be explained by known complications of diabetes, there remains a large amount of unexplained variation.
Screening potential biomarkers for idiopathic pulmonary fibrosis in bronchoalveolar lavage fluid
Authors: Inge M. Vercauteren, Stijn E. Verleden, Bart M. Vanaudenaerde, Elly Vandermeulen, David Ruttens, Hannelore Bellon, Els De Dycker, Christophe Dooms, Jonas Yserbyt, Geert M. Verleden, Wim A. Wuyts
Journal: European Respiratory Journal (2014)

IPF is the most lethal form of interstitial lung disease. Diagnosis is based on multidisciplinary consensus, but sensitive biomarkers are lacking.

In this study Vitamin D, Krebs von den Lungen-6 (KL-6), C-peptide, Immunoglobulin E (IgE) and a fragment of Cytokeratin 19 (CYFRA21-1) were screened as possible biomarkers for IPF.

Using the Lumipulse ® G1200 (Fujirebio, Ghent, Belgium) the analytes were measured in BAL samples of 83 IPF patients and 10 controls. The mean follow-up of the IPF patients was 930 days and during this timeframe 25 patients died. Lung function (FVC, FEV1, DLCO, TLC) was evaluated at the time of BAL and around 6 months after BAL sampling in the IPF patients. Survival analysis was performed for IPF patients with high concentrations of the analytes (> median concentration) and IPF patients with low concentrations (≤ median concentration).

Vitamin D was not measurable and KL-6 did not significantly differ between the IPF patients and controls. However, there was a significant increase in the levels of C-peptide (p=0.0015), IgE (p=0.0006) and CYFRA21-1 (p=0.0004) in the IPF patients compared to the controls. IPF patients with high levels (> 1.2 ng/ml) of CYFRA21-1 had a worse survival than patients with lower levels of CYFRA21-1 (p=0.045). The other analytes did not correlate with the survival of the IPF patients. None of the examined analytes were predictive for the lung function evolution in the first 6 months.

Of the tested analytes in BAL, CYFRA21-1 correlated with survival and therefore deserves more attention as a possible biomarker for IPF. But more validation and analysis is requested including serum measurement, other ILD types and multivariate analysis.
Frequency and Predictor of Coronary Thin-Cap Fibroatheroma in Patients With Acute Myocardial Infarction and Stable Angina Pectoris
Authors: Kenichi Fujii, Motomaru Masutani, Takahiro Okumura, Daizo Kawasaki, Takafumi Akagami, Akira Ezumi, Tsuyoshi Sakoda, Tohru Masuyama, Mitsumasa Ohyanagi
Journal: Journal of the American College of Cardiology (2008)
Is it GER? Different diagnostic approaches for detection of gastroesophageal reflux in patients with chronic cough
Authors: Elzbieta Magdalena Grabczak, Anna Domeracka-Kolodziej, Marta Dabrowska, Rafal Krenke, Ryszarda Chazan
Journal: European Respiratory Journal (2012)

Background: Gastroesophageal reflux (GER) is a common cause of chronic cough. Different methods can be used to detect it. The limited accessibility of some devices or difficulties in assessment of relationship between GER and cough may influence their practical usefulness.

Objectives: To assess the utility of different methods in the diagnosis of GER in patients with chronic cough.

Methods: We included 60 consequent, nonsmoking, adult patients, with history of cough longer than 8 weeks, with normal chest radiograph. We used the Carlsson questionnaire (CQ), assessment of abnormalities in larynx mucosa (Belafsky reflux finding score, RFS), upper gastrointestinal tract radiography, 24-hour-pH monitoring and multichannel impedance (MI) of esophagus.

Results: Sixty patients were included (M/F =1:1.86), mean age 48.8 yrs, mean cough duration 260 weeks (range 16-1440). Sixteen subjects were excluded from further studies due to consent withdrawal or technical problems with pH probe insertion. Positive results of CQ and RFS were observed in 13 and 50/54 cases respectively. Mean calculated RFS was 11.7 points. Esophageal hernia or reflux during radiography was shown in 6 and 7/54 pts, respectively. Increased esophagus exposure to acid reflux was diagnosed in 43/58 pts using pH monitoring alone, and in 37/44 on the basis of MI. Time-relationship between GER and cough was found in 23 and 21 cases, respectively. MI probe was slightly worse tolerated.

Conclusions: Diagnosis of GER was most frequent on the basis of RFS and MI. Combination of few methods allows to recognize GER more precisely. The time relationship between GER and cough, can be assessed not by all devices used.