tbuckley/cabot-search huggingface dataset:
Abstract 17123: Correlation Between Ethnicity and Extent of Coronary Artery Disease on Coronary CT Angiography: Results From the Advanced Cardiovascular Imaging Consortium
Authors: Kavitha M Chinnaiyan, Chad Poopat, David Share, Gilbert Raff, Ella Kazerooni, Karthik Ananthasubramaniam, Tauqir Goraya, Steven Girard, Michael J Gallagher, Patricia Peyser
Journal: Circulation (2011)

Background: Although racial differences in prevalence of coronary artery disease (CAD) are well-known, race is not included in widely used risk assessment algorithms. The purpose of this study was to establish if race was an independent predictor of significant CAD (&gt;50% stenosis) on coronary CT angiography (CCTA). Methods: Patients with no known CAD undergoing CCTA at 41 institutions and enrolled in a large statewide registry, the Advanced Cardiovascular Imaging Consortium (ACIC) between July 2007 and April 2011 were included. Demographics, risk factors, Framingham Risk Scores (FRS), pre-test CAD likelihood and extent of CAD on CCTA were compared between racial groups. Multivariable models were constructed adjusting for FRS, gender, pre-test likelihood and race to predict &gt;50% stenosis. Results: Of the 19,105 patients studied, 86.8% were self-identified as Caucasian, 11.7% African and 1.5% Asian. Caucasians were older, more often asymptomatic, had history of peripheral vascular disease and atrial fibrillation while Africans were more often obese with history of diabetes, hypertension, stroke, congestive heart failure and chronic kidney disease (p&lt;0.0001). On CCTA, Caucasians more often had a stenosis &gt;50% compared to Africans and Asians (16.5% vs. 9% and 12.8%, respectively, p&lt;0.0001). On multivariate analysis, Caucasian race remained a significant and independent predictor of &gt;50% stenosis on CCTA in men and women, with incremental value over FRS and pre-test likelihood (Table). Conclusions: Risk factors and extent of CAD differ significantly among ethnicities. In this large population, race/ethnicity was an independent predictor of significant CAD on CCTA, suggesting that it should be considered in risk assessment schemes.
Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi study): a randomised controlled trial
Authors: Claire Davey, Zaid Zoumot, Simon Jordan, William H McNulty, Dennis H Carr, Matthew D Hind, David M Hansell, Michael B Rubens, Winston Banya, Michael I Polkey, Pallav L Shah, Nicholas S Hopkinson
Journal: The Lancet (2015)

Lung volume reduction surgery improves survival in selected patients with emphysema, and has generated interest in bronchoscopic approaches that might achieve the same effect with less morbidity and mortality. Previous trials with endobronchial valves have yielded modest group benefits because when collateral ventilation is present it prevents lobar atelectasis.We did a single-centre, double-blind sham-controlled trial in patients with both heterogeneous emphysema and a target lobe with intact interlobar fissures on CT of the thorax. We enrolled stable outpatients with chronic obstructive pulmonary disease who had a forced expiratory volume in 1 s (FEV1) of less than 50% predicted, significant hyperinflation (total lung capacity >100% and residual volume >150%), a restricted exercise capacity (6 min walking distance <450 m), and substantial breathlessness (MRC dyspnoea score ≥3). Participants were randomised (1:1) by computer-generated sequence to receive either valves placed to achieve unilateral lobar occlusion (bronchoscopic lung volume reduction) or a bronchoscopy with sham valve placement (control). Patients and researchers were masked to treatment allocation. The study was powered to detect a 15% improvement in the primary endpoint, the FEV1 3 months after the procedure. Analysis was on an intention-to-treat basis. The trial is registered at controlled-trials.com, ISRCTN04761234.50 patients (62% male, FEV1 [% predicted] mean 31·7% [SD 10·2]) were enrolled to receive valves (n=25) or sham valve placement (control, n=25) between March 1, 2012, and Sept 30, 2013. In the bronchoscopic lung volume reduction group, FEV1 increased by a median 8·77% (IQR 2·27-35·85) versus 2·88% (0-8·51) in the control group (Mann-Whitney p=0·0326). There were two deaths in the bronchoscopic lung volume reduction group and one control patient was unable to attend for follow-up assessment because of a prolonged pneumothorax.Unilateral lobar occlusion with endobronchial valves in patients with heterogeneous emphysema and intact interlobar fissures produces significant improvements in lung function. There is a risk of significant complications and further trials are needed that compare valve placement with lung volume reduction surgery.Efficacy and Mechanism Evaluation Programme, funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.
Microanalysis of Working Through in Psychotherapy
Authors: MARDI J. HOROWITZ
Journal: American Journal of Psychiatry (1974)

This journal has published few papers on psychodynamic psychotherapy recently—not because of prejudice but because only a few such papers have been submitted. One of the reasons for the paucity of psychodynamic papers is that they usually require lengthy case reports to illustrate theoretical assertions, and their preparation is thus very time-consuming. The author contends that selection of small segments of therapy for analysis is possible and should be encouraged because it focuses attention on low-level clinical inferences rather than on metapsychology. He presents a method of microanalysis that details the ideational structure of a conflict, views emotions as responses to incongruent ideas, describes the controlling operations motivated by these emotional responses, and indicates the sequential changes in conscious experience during a treatment episode.
Abstract 8693: Knockout of p47phox Attenuates Angiotensin II-induced Endothelial Dysfunction and Vessel Damage in Vivo
Authors: Junjie Du, Jian-Mei Li
Journal: Circulation (2011)

Increased bioavailability and activity of angiotensin II (AngII) have been found to be associated with vascular oxidative stress derived from a Nox2 enzyme. The Nox2 has several regulatory subunits i.e. p40phox, p47phox, p67phox and rac1. However, it is unclear about the role of p47phox (a key regulatory subunit of Nox2 activation) in mediating AngII-induced vessel dysfunction. In this study, we examined the effect of p47phox knockout (KO) on AngII-induced hypertension and aortic dissection using littermates of C57BL/6 wild-type (WT) and p47phox KO mice (n=7) at the age of 10~12 months. In WT mice, AngII infusion (1.15mg/kg/day delivered by osmotic mini-pump for 14 days) increased significantly the systolic blood pressure (SBP) from 127 + 13 to 172 + 11 mmHg, and this was accompanied with significant indication of cardiac hypertrophy (heart/body weight ratio increased ~17.9 + 0.1%) as compared to vehicle infused controls (P < 0.05), and 3 out of 7 AngII-infused WT mice developed aortic dissection. However...
Do kinetics of interferon-gamma responses predict TB relapse?
Authors: Cynthia Chee, Kyi-Win KhinMar, Suay-Hong Gan, Timothy Barkham, Yee-Tang Wang
Journal: European Respiratory Journal (2011)

Evidence that quantitative T-cell interferon-gamma responses to  M. tuberculosis- specific antigens may reflect mycobacterial burden has raised interest in these responses as biomarkers for treatment outcomes.  A cohort of 263 HIV-negative, culture-positive pulmonary TB patients enrolled between August 2005 and May 2007 who completed treatment and who were tested with QuantiFERON-Gold In-tube® (QFT-IT) and T-SPOT. TB®  assays pre- and post-treatment were matched with the national TB registry for any re-notification as at December 31 2010.  Four patients relapsed with culture-positive, pansensitive pulmonary TB (relapse rate 1.5%). The time to relapse was 11, 17, 35 and 44 months. All were male. At the time of the first TB episode, their mean age was 45.4 years old, two were diabetic, two were cigarette smokers; all were baseline sputum AFB smear-positive; two had cavitary disease. All received directly-observed, 6-month chemotherapy with four first-line drugs in the intensive phase, followed by thrice weekly Rifampicin and Isoniazid in the continuation phase. All had one negative sputum culture (done once only) at two months of treatment.  All four patients were IGRA positive at baseline. The QFT-IT was negative at end of treatment and 6 months post treatment-completion in three and four patients respectively. All remained T-SPOT positive at treatment completion, while two reverted their T-SPOT results 6 months thereafter. Compared to the whole treatment cohort, a lower proportion of relapsed patients tested IGRA positive at 6 months post-treatment completion (0% vs 46.3% for QFT-IT; 50% vs 79.2% for T-SPOT).  Our observations suggest that the kinetics of interferon-gamma responses are not useful for predicting disease relapse.
The value of bacterial culture in patients with suspected lung cancer evaluated by bronchoscopy: A prospective study of 155 patients
Authors: Matthew Koslow, Alona Matveychuk, Michael Kuchuk, Alexander Guber, David Shitrit
Journal: European Respiratory Journal (2014)

Background: Bronchial colonization with potentially pathogenic microorganisms (PPM) is associated with adverse outcomes in lung cancer patients undergoing resection.  Methods: A prospective study of 155 patients with suspected malignancy evaluated by bronchoscopy  .  Results: Of 155 patients, 30% demonstrated bacterial growth with PPM. Clinical infection significantly predict PPM growth, 35% and 5%, respectively (p=.000).  Conclusion: Bronchial colonization with PPM is common (30%) among patients with malignancy and clinical infection. Bacterial culture during bronchoscopy may assist with targeted antibiotic therapy prior to treatment.
Cisplatin, vinblastine, and mitoguazone chemotherapy for epidermoid and adenocarcinoma of the esophagus.
Authors: A A Forastiere, M Gennis, M B Orringer, F P Agha
Journal: Journal of Clinical Oncology (1987)

Thirty-six patients with adenocarcinoma or epidermoid carcinoma of the esophagus were entered into a phase II trial evaluating the combination of cisplatin 100 mg/m2 intravenously (IV) day 2, vinblastine 1.6 mg/m2 IV days 1 to 4, and mitoguazone (MGBG) 500 mg/m2 IV days 1 and 8. Twenty-nine patients (group A) were newly diagnosed with local-regional disease only and were candidates for transhiatal esophagectomy (THE). These patients received two courses of chemotherapy at 3-week intervals prior to surgery. Response was assessed by measuring changes in the primary tumor length and depth on serial biphasic contrast esophagrams and comparing this result with tumor measurements obtained from the surgical specimen. Complete (CR) and partial responders (PR) received three additional postoperative cycles. Seven patients had recurrent or metastatic disease (group B) and were treated every 4 weeks until disease progression. Of 34 patients evaluable for response, there was one pathologically confirmed CR and 15 PRs (47%). This consisted of 12 of 27 (44%) group A patients (seven of 11 epidermoid, five of 16 adenocarcinoma) and four of seven (57%) group B patients (two of four epidermoid, two of three adenocarcinoma). Toxicity included leukopenia in one third of treatment courses and thrombocytopenia in 21%. Nausea and vomiting occurred in 60% of patients, diarrhea in 18%, transient nephrotoxicity in 18%, peripheral neuropathy in 12%, and ototoxicity in 3%. Twenty-five group A patients underwent resection. Four chemotherapy nonresponders (NR) and one PR had known disease left at surgery; all others (80%) had gross total removal of their disease. The median survival time (MST) of the 29 group A patients was 14 months, with 21% alive at 36 months. The MST of group A chemotherapy responders was 15 months compared with 9 months for NRs (P = .032). Initial sites of recurrence in 14 patients were local-regional in six, distant only in six, both local-regional and distant in two. This regimen, administered in maximally tolerated doses, was active in epidermoid and adenocarcinoma histologies, recurrent disease and newly diagnosed patients. However, nearly all responses were PRs and the MST of resected patients was similar to a prior series of patients treated with esophagectomy alone. Observations from this pilot trial and those of others have led to a follow-up study, in progress, evaluating intensive preoperative chemotherapy and concurrent radiation therapy (RT).
Late-breaking abstract: Protein tyrosine phosphatase (PTP)α promotes profibrotic responses in fibroblasts via Smad signaling
Authors: Gregory Downey, Rachel Zemans, Yael Aschner
Journal: European Respiratory Journal (2014)

Idiopathic pulmonary fibrosis (IPF) is a fatal fibrosing lung disease for which treatment remains suboptimal. Transforming Growth Factor (TGF)-β, a pleiotropic cytokine, is critical in the pathogenesis of pulmonary fibrosis. We have reported that genetic deficiency of PTPα prevents the development of pulmonary fibrosis in murine models and that PTPα is required for TGF-β-induced myofibroblast differentiation. To determine the mechanism by which PTPα controls profibrotic responses, we compared phosphorylation of Smad 2/3 in wild type (WT) and PTPα-/- mice treated with intratracheal instillation of adenovirus expressing active TGF-β. These studies revealed that p-Smad2/3 levels were markedly attenuated in the lungs of PTPα-/- compared to WT mice as determined by immunostaining. Phosphorylation of Smad3 was markedly attenuated in PTPα-/- compared to WT fibroblasts after TGF-β stimulation. Further analysis revealed that while early (15 min) Smad3 phosphorylation was comparable between PTPα-/- and WT cells, the levels of pSmad3 diminished rapidly (by 30 min) in PTPα-/- cells whereas they persisted for 90 min in WT cells. This was also true for levels of nuclear pSmad3. Total Smad2/3 levels were unchanged, suggesting that PTPα prolongs the duration of Smad phosphorylation but not degradation. PTPα interacted with TGF-β receptor II as determined by co-immunoprecipitation. We conclude that PTP promotes profibrotic responses in fibroblasts via regulation of Smad-dependent signaling pathways, possibly by control of TGF-β receptor activation. These observations identify a key check point in profibrotic signaling controlled by PTPα that may represent a novel therapeutic target.
Epigenetic regulation of alveolar ion transport
Authors: Lukasz Wujak, Simone Becker, Werner Seeger, Rory Morty
Journal: European Respiratory Journal (2011)

The Na,K-ATPase regulates alveolar ion transport and fluid balance in the lung, generating the driving force for alveolar fluid clearance (AFC). Transforming growth factor (TGF)-β is a mediator of acute lung injury (ALI), and impacts AFC. It was hypothesised that TGF-β influences Na,K-ATPase function by controlling subunit expression and stoichiometry. The ATP1B1 subunit of the Na,K-ATPase regulates cell-surface stability of the heteromeric Na,K-ATPase complex. Quantitative RT-PCR analysis revealed downregulation of the  ATP1B1  gene both in the lungs from ALI patients (4-fold; p=0.03) and lungs from bleomycin-treated mice which developed ALI (2.1-fold; p=0.002); as well as in TGF-β-treated A549 cells (2-fold; p=0.02). Moreover, biotinylation and  86 Rb +  uptake assays revealed that TGF-β depleted Na,K-ATPase cell-surface abundance by 66%, and reduced Na,K-ATPase activity by 85%, respectively, in primary mouse alveolar type II cells (as well as in A549 cells; not shown).  In sillico  and dual-luciferase reporter analyses of the  ATP1B1  promoter identified several putative TGF-β-responsive elements. Gene ablation experiments confirmed that the downregulation of  ATP1B1  expression does not rely on conventional TGF-β transcriptional regulation. Rather, an epigenetic mechanism based on class I histone deacetylase (HDAC) action is involved in the regulation of  ATP1B1  expression by TGF-β. This was clarified using a class I HDAC inhibitor, MGCD0103. Preliminary siRNA knockdown experiments suggest that HDAC1 and HDAC11 are the leading candidates implicated in this process. Together, these data suggest that TGF-β impacts Na,K-ATPase function by epigenetic regulation of subunit stoichiometry in the alveolar epithelium.
Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis
Authors: Thibault Griseri, Isabelle C. Arnold, Claire Pearson, Thomas Krausgruber, Chris Schiering, Fanny Franchini, Julie Schulthess, Brent S. McKenzie, Paul R. Crocker, Fiona Powrie
Journal: Immunity (2015)

The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target.
Cytogenetic remissions in high-risk myelodysplastic syndrome: Results in 124 patients treated with low-dose 5-aza-2 '-deoxycytidine (Decitabine), a DNA methylation inhibitor.
Authors: M Lubbert, Augustin Ferrant, P Wijermans, R Kunzmann, G. Verhoef, André Bosly, C Ravoet, Marc André
Journal: Blood (2000)
Burnout and associated characteristics in oncology fellows
Authors: D. S. Lessen, M. K. Buss, G. Panagopoulos, R. L. Levine, J. H. von Roenn, R. M. Arnold, S. D. Block
Journal: Journal of Clinical Oncology (2005)

8168 Background: A substantial number of practicing oncologists report burnout. We sought to investigate the extent to which burnout and its three components: high emotional exhaustion (EE), high depersonalization (DP) and low personal accomplishment (PA), were present in oncology fellows, and to identify associated demographic and training program characteristics. Methods: A convenience sample of fellows attending the 2004 ASCO meeting were asked to complete a survey containing the 22-item, self-reported, validated, Maslach Burnout Inventory (MBI) and demographic questions. The MBI assesses three aspects of the burnout syndrome: EE, DP and PA. Subscale scores were categorized as low, average or high based on previous data from over 1100 medical professionals. High scores on all three subscales indicated a high degree of burnout. Descriptive statistics were calculated for continuous variables and frequencies for categorical variables. A multivariate analysis of variance was employed to detect differences in subscales based on demographic and training characteristics. Results: Data were obtained from 73 U.S. fellows: Twenty-five percent of respondents were first year fellows, 44% second year fellows, and 31% third year fellows. Mean age was 34.8 years and 48% were male. 49% scored high on at least one subscale, 21% scored high on at least two subscales and 6% scored high on all three subscales indicating a high degree of burnout. Average or higher scores on all three subscales were present in 30% indicating at least an average degree of burnout. Higher EE was associated with fewer opportunities to enroll patients on clinical trials (p<.02). Fellows who spent more time on research reported less EE (p=.03). Training in medical oncology was associated with higher DP compared to combined hematology/oncology (p=.03). No differences in EE, DP or PA were observed on the basis of gender, marital status, year of training or time spent in patient care setting. Conclusions: High levels of burnout were present in a small, but significant number of fellows and many more had average levels of burnout. Further work is needed to identify contributory and protective program-related characteristics to facilitate the development of new approaches to reduce burnout. No significant financial relationships to disclose.
U.K. guidelines for the management of cutaneous melanoma
Authors: D.L.L. Roberts, A.V. Anstey, R.J. Barlow, N.H. Cox, J.A. Newton Bishop, P.G. Corrie, J. Evans, M.E. Gore, P.N. Hall, N. Kirkham
Journal: British Journal of Dermatology (2002)

Summary These guidelines for management of cutaneous melanoma present evidence‐based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. To reflect the collaborative process for the U.K., they are subject to dual publication in the British Journal of Dermatology and the British Journal of Plastic Surgery.1
Gathering intelligence on antiplatelet drugs: the view from 30 000 feet
Authors: M. Reilly, G. A FitzGerald
Journal: BMJ (2002)

Papers p 71 Education and debate p 103 

The efficacy of aspirin in the secondary prevention of myocardial infarction and stroke is widely accepted. The evidence which supports this perception includes its identification as an inhibitor of cyclo-oxygenase and platelet aggregation; identification of the major product of platelet cyclo-oxygenase as thromboxane A2, a vasoconstrictor and platelet agonist; the discovery that aspirin irreversibly acetylates cyclo-oxygenase, permitting cumulative inhibition by low doses of thromboxane A2 formation in the presystemic circulation; the discovery that thromboxane A2 biosynthesis is increased during ischaemic episodes of unstable angina; and the demonstration in individual, controlled, prospective double blind trials that aspirin reduces both myocardial infarction and death in unstable angina by 50%, whether given at 75 mg, 324 mg, or 1300 mg/day. 1 2

Following these discoveries Collins, Peto, Baigent, and their colleagues in Oxford organised the Antithrombotic Trialists' Collaboration to share data and permit overview analyses of controlled trials of antiplatelet drugs. At the time of the initial reports, these trials mainly involved aspirin and confirmed its efficacy in syndromes of acute vascular occlusion such as unstable angina, while suggesting a net benefit in the secondary prevention of stroke.3–5 Today, Baigent and colleagues report further analyses (p 71),6 though a critic …