tbuckley/cabot-search huggingface dataset:
Risk of death and readmission of hospital-admitted COPD exacerbations: European COPD Audit
Authors: Sylvia Hartl, Jose Luis Lopez-Campos, Francisco Pozo-Rodriguez, Ady Castro-Acosta, Michael Studnicka, Bernhard Kaiser, C. Michael Roberts
Journal: European Respiratory Journal (2015)

Studies report high in-hospital and post-discharge mortality of chronic obstructive pulmonary disease (COPD) exacerbations varying depending upon patient characteristics, hospital resources and treatment standards. This study aimed to investigate the patient, resource and organisational factors associated with in-hospital and 90-day post-discharge mortality and readmission of COPD exacerbations within the European COPD Audit. The audit collected data of COPD exacerbation admissions from 13 European countries.On admission, only 49.7% of COPD patients had spirometry results available and only 81.6% had blood gases taken. Using logistic regression analysis, the risk associated with in-hospital and post-discharge mortality was higher age, presence of acidotic respiratory failure, subsequent need for ventilatory support and presence of comorbidity. In addition, the 90-day risk of COPD readmission was associated with previous admissions. Only the number of respiratory specialists per 1000 beds, a variable related to hospital resources, decreased the risk of post-discharge mortality.The European COPD Audit identifies risk factors associated with in-hospital and post-discharge mortality and COPD readmission. Addressing the deficiencies in acute COPD care such as making spirometry available and measuring blood gases and providing noninvasive ventilation more regularly would provide opportunities to improve COPD outcomes.
ENDOXY - Gas transfer of endothelialized oxygenator membranes
Authors: Christian G. Cornelissen, Sonja Engwicht, Nicole Finocchiaro, Stefan Jockenhoevel
Journal: European Respiratory Journal (2014)

Introduction: 

Extracorporeal membrane oxygenation (ECMO) can replace the lungs' gas exchange capacity. Its limited hemocompatibility, the activation of coagulation and inflammation and protein deposition hamper long-term use. In a Tissue Engineering approach, lining the blood contact surfaces of the ECMO device with endothelial cells might overcome these limitations. In this study gas transfer properties of endothelialized oxygenator membranes was investigated as a further step towards a biohybrid lung assist device (ENDOXY).

Methods: 

Poly-Methyl-Pentene (PMP) is widely used in oxygenators applied for ECMO. Subsequent to the immobilisation of GRGDS peptides on their surface, PMP membranes were coated with ovine endothelial cells. Cell coated membranes were shear stress conditioned in a custom designed oxygenator test system. Gas transfer was measured in a standard oxygenator test procedure.

Results: 

Cells seeded on gas permeable membranes grew to confluence, showed characteristic endothelial morphology and aligned with shear stress without observable cell detachment.

Gas transfer through uncoated oxygenator membranes was within the expected range. Endothelial cell coating significantly lowered gas transfer by 22%

![Figure][1] 



.

Conclusion: 

For the first time, this study demonstrates the influence of endothelial cell coating on gas transfer of oxygenator membranes, which is crucial for the successful development of a biohybrid lung assist device.

 [1]: pending:yes
The pharmacodynamic effect of TKI258 on plasma biomarkers of angiogenesis in patients with AML and advanced melanoma
Authors: M. M. Shi, M. Motwani, J. Wang, M. Steed, K. Dohoney, J. Saro, R. Wasserman, J. C. Barrett
Journal: Journal of Clinical Oncology (2008)

14680 Background: TKI258 (dovitinib lactate), is a multi-tyrosine kinase inhibitor of VEGF receptors-1,2,3, FGF receptors-1, 2, 3, PDGFR-β, c-KIT and FLT3. To evaluate the pharmacodynamic effect of TKI258 in patients, a panel of plasma angiogenesis biomarkers were evaluated in two Phase I clinical trials - acute myeloid leukemia (AML) and locally advanced or metastatic melanoma. Methods: Plasma samples were analyzed from selected dosing groups of patients during the dose escalation stages of the two Phase I trials. 19 AML patients received TKI258 at doses ranging 200 - 600 mg/day, with an initial 14 day cycle (7 days on/7 days off), followed by a continuous daily dosing schedule (28 day cycle). 16 melanoma patients received 200 - 500 mg/day on once daily dosing (28 day cycle). Plasma VEGF, placental growth factor (PLGF), basic FGF (bFGF), and soluble VEGFR1 and VEGFR2 (sVEGFR1 and 2) were measured by multiplex assays using Meso-Scale Discovery platform. Plasma levels of each marker were frequently monitored during the course of treatment. Results: Average baseline VEGF levels were higher in the melanoma patients (234 pg/ml, n=16) than in the AML patients (68 pg/ml, n=19). In AML patients, dose- dependent inductions of VEGF (3–11 fold) and PLGF (3–8 fold) at 400 and 600 mg dosing were observed at Cycle 1 Days 3 and 7, and returned to near-baseline levels at the end of Cycle 1 at Day 14 after 1 week off drug treatment 1. In melanoma patients, inductions of VEGF (∼3 fold) and PLGF (2–9 fold) as well as decrease of sVEGFR2 (30–50%) in patients treated with 400 and 500 mg TKI258 were observed at the end of Cycle 1. Significant induction of bFGF (6-fold) was observed at 500 mg TKI258 treatment group in melanoma patients at the end of Cycle 1, but not at other doses or in the AML patients. Conclusions: PlasmaVEGF and PLGF induction and sVEGFR2 decrease could serve as pharmacodynamic biomarkers of VEGFR inhibition by TKI258. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Hemostatic abnormalities in untreated cancer: incidence and correlation with thrombotic and hemorrhagic complications.
Authors: S Nand, S G Fisher, R Salgia, R I Fisher
Journal: Journal of Clinical Oncology (1987)

Over a 2-month period, 40 patients with untreated malignancy were studied for protein-C (PRC), antithrombin-III (AT-III), fibrinopeptide A (FPA), routine hemostatic screens, and presence of liver metastases to determine pretreatment changes of hemostasis and relate them to subsequent development of thrombotic or hemorrhagic complications. These patients were observed for a mean period of 18 months. There were 23 males and 17 females with a median age of 64 years. Nine patients had lung carcinoma, 8 colon carcinoma, 7 lymphoma, 5 breast carcinoma, 5 head and neck carcinoma, 2 acute leukemia, 2 prostate carcinoma, 1 adenocarcinoma of unknown primary, and 1 sarcoma. Eight patients had liver metastases. PRC was measured by ELISA, AT-III by radial immunodiffusion, and FPA by RIA. Four patients had decreased AT-III, 28 had decreased levels of PRC, and 39 had elevated levels of FPA. All patients with liver metastases had low PRC. Albumin levels were lower in patients with low PRC (mean 3.3 g/dL v 4.0 g/dL for others). Eight patients, five with liver metastases, developed thrombotic (4), hemorrhagic (3), or both (1) complications. Statistically significant associations were found between (1) presence of liver metastases and development of thrombotic and hemorrhagic complications (P less than .001), (2) presence of liver metastases and decreased PRC (P = .001), and (3) lower albumin levels and decreased PRC (P = .0001). Our study documents early changes of hemostasis in untreated malignancy. We extend previous observations that decreased PRC levels in malignancy may be due to poor synthetic functions of liver. Presence of liver metastases was the only factor associated with subsequent development of thrombotic and hemorrhagic complications. Biochemical markers of hemostatic abnormalities, even though encountered frequently at the time of presentation, are of little predictive value for development of thrombotic and hemorrhagic complications.
Placebos and sham treatments
Authors: Philip Sedgwick, Carwyn Hooper
Journal: BMJ (2015)

The effectiveness of topical chloramphenicol in preventing wound infection after minor dermatological surgery was evaluated. A randomised placebo controlled superiority trial was performed.1 Participants were patients with high risk sutured wounds who had undergone minor surgery. The intervention was a single application of topical chloramphenicol ointment to the sutured wound immediately after suturing. Chloramphenicol ointment is an antibiotic indicated for the treatment of bacterial conjunctivitis, but it is often used as prophylaxis for, or treatment of, wound infection, although little evidence exists for its effectiveness. The control treatment was placebo ointment, which consisted of a mixture of soft white and liquid paraffin with no known anti-infective properties. In total, 972 patients were recruited and randomised to topical chloramphenicol ointment (n=488) or placebo (n=484). All participants were instructed to follow standard management, keeping their wound dry and covered for 24 hours after surgery.

The primary outcome was infection on the agreed day of removal of sutures or sooner if the patient re-presented with a perceived infection. The percentage of participants with an infection in the topical chloramphenicol group was significantly lower than in the placebo group (6.6% v 11.0%; difference −4.4%, 95% confidence interval −7.9% to −0.8%; P=0.010). Although the application of a single dose of topical chloramphenicol to high risk sutured wounds after minor surgery produced a statistically significant reduction in the infection rate, the researchers concluded that the reduction …
Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production
Authors: Yanhong Guo, Yanbo Fan, Jifeng Zhang, Gwen A. Lomberk, Zhou Zhou, Lijie Sun, Angela J. Mathison, Minerva T. Garcia-Barrio, Ji Zhang, Lixia Zeng, Lei Li, Subramaniam Pennathur, Cristen J. Willer, Daniel J. Rader, Raul Urrutia, Y. Eugene Chen
Journal: Journal of Clinical Investigation (2015)

Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E-deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis.
Comparative Safety of Testosterone Dosage Forms
Authors: J. Bradley Layton, Christoph R. Meier, Julie L. Sharpless, Til Stürmer, Susan S. Jick, M. Alan Brookhart
Journal: JAMA Internal Medicine (2015)

Increases in testosterone use and mixed reports of adverse events have raised concerns about the cardiovascular safety of testosterone. Testosterone is available in several delivery mechanisms with varying pharmacokinetics; injections cause spikes in testosterone levels, and transdermal patches and gels cause more subtle but sustained increases. The comparative cardiovascular safety of gels, injections, and patches has not been studied.
Abstract 6225: Cost of Improvement of Angina-Related Health Status by Health Care System: A Secondary Analysis from the COURAGE Trial
Authors: Zugui Zhang, Paul Kolm, Ron Goeree, Claudine Jurkovitz, Koon Teo, John Spertus, David Maron, Robert O’Rourke, Pamela Hartigan, Paul Barnett, William Boden, William Weintraub
Journal: Circulation (2008)

Background: COURAGE compared percutaneous coronary intervention (PCI) plus intensive pharmacologic and lifestyle intervention (optimal medical therapy, OMT) to OMT alone in reducing the risk of cardiovascular events in patients with stable coronary disease. In this post hoc study, we assessed the cost of treating angina across the three health care systems from which patients were enrolled: Canada, US non-Veterans Affairs (VA) and U.S. VA. Methods: A total of 2,287 patients were enrolled and followed for a median of 4.6 years. Angina-related health status was assessed with the Seattle Angina Questionnaire (SAQ) and RAND-36. The cost of resource use was evaluated by DRG for hospitalizations and CPT for outpatient visits and tests. Analyses were conducted using the U.S. non-VA costing system in 2004 U.S. dollars. Clinically significant differences in the Physical Limitation, Angina Frequency, and Quality of Life domains of the SAQ were defined as scores ≥8, ≥20, and ≥16 respectively. Absolute net benefit, number of patients needed to treat (NNT) to achieve one patient with clinically significant angina improvement, and the cost of improvement in angina-related health status were estimated. Results: Added cost of PCI per patient and results for Angina Frequency are presented in the table . Results for Quality of Life were similar. Physical Limitation results varied more widely among health care systems with net benefit ranging from &lt;1% (U.S. non-VA) to 18% (Canada), and cost per patient in angina improvement from $55,700 (Canada) to over $1,000,000 (U.S. non-VA). Conclusions: The improvement of angina-related health status and corresponding costs were relatively similar across health care systems and among SAQ Angina Frequency and Quality of Life domains, but varied widely for the Physical Limitation Domain. Adding PCI to OMT improved angina-related health status, but at a cost generally considered to be prohibitive as a routine initial management strategy. Cost of Improvement of Angina-Related Health Status by Health Care System
ADP ribosylation factor like protein 2 (Arl2) regulates microtubule composition and dynamics in breast cancer cells
Authors: Anne Beghin, Celine Messana, Christelle Lamblot, Evalaure Matera, Stephane Honore, Diane Braguer, Carlos Galmarini, Charles Dumontet
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4901 

ADP-rybosilation factor like protein 2 (Arl2) has been show to interact with tubulin binding cofactor D (TBCD), a key protein involved in the production of polymerization-competent αβ tubulin heterodimers, the basic building block of microtubules. In order to study Arl2 impacts in microtubules properties, we have developed three variants of the human breast adenocarcinoma MCF7 line using stable transfection of pcDNA3 vectors containing the entire coding sequence of Arl2 (MA+ cells), or an antisens construct of Arl2 (MA- cells) or the empty vector (MP cells). MA+ cells had an Arl2 protein level 35 % higher than MP cells and MA- had a decrease of 40% of Arl2 protein level compared to MP cells. Western blot analysis processed after separation of the different fractions of tubulins (solubles heterodimers, microtubules and unfolded tubulins) showed that the content in polymerizable tubulin heterodimers was significantly increased in MA+ cells and reduced in MA- cells in comparison to the MP cells. Conversely, the fraction of unfolded tubulin which could not be induced to polymerize was larger in MA- cells and decreased in MA+ cells compared to MP cells. Time lapse analysis of microtubules dynamics was performed by microinjection of rhodamine tubulin in live cells. Microtubules dynamicity was significantly enhanced in MA+ cells and reduced in MA- cells compared to MP cells. Particularly, these alterations involved modifications of the microtubule plus end rates of growth and shortening, duration of attenuation phases, percentage of time spent in each phase (growth, shortening and attenuation) and catastrophe frequency. We also observed some modifications in expression level of protein phosphatase 2Ac, which has been shown to form a complex with Arl2 and to trigger some proteins involved in microtubules dynamic regulation. Breast cancer cells with Arl2 modified expression level have also important modifications in class III β tubulin content, which is involved in resistance mechanisms to tubulin binding agents (TBA). Finally, the cell cycle distribution was modified in these cells in response to TBA treatment such as vinorelbine and paclitaxel, which can be explained by microtubule dynamicity modifications. Consequently, Arl2 protein levels have an impact on microtubule dynamicity by the regulation of polymerization-competent αβ tubulin heterodimer levels. These observations are the first evidence of important roles of Arl2 in microtubule dynamicity and in sensitivity to TBA.
Pulmonary gas exchange in severe obesity: The effects of bariatric surgery
Authors: Eva Rivas, Ebymar Arismendi, Alvar Agusti, Marcelo Sanchez, Salvadora Delgado, Concepcion Gistau, Peter D. Wagner, Roberto Rodriguez-Roisin
Journal: European Respiratory Journal (2014)

Severe obesity (SO) is a growing health problem associated with chronic systemic inflammation. Bariatric surgery (BS) is the most efficacious weight loss therapy. Its potential effects on ventilation-perfusion (V A /Q) distributions have not been explored before.  We investigated V A /Q distributions and thoracic CT in SO subjects before and one year after BS.  We enrolled 21 SO (49±[SE]2 yrs, 19 females, body mass index [BMI] 45±2 kg/m 2 , 19 never smokers) and 9 normal weight, sex- and age-matched (BMI 25±1 kg/m 2 , never smokers) control subjects, in whom we assessed respiratory and inert gases, systemic and pulmonary hemodynamics and thoracic CT, breathing ambient air and 100% O 2 , and serum biomarkers.  Before BS, SO subjects had:  (1)  abnormal AaPO 2  (27±2, mmHg) and mild arterial hypoxemia (76±2, mmHg) caused by mild shunt (4.0±1.0, %Q T ) and broadly unimodal distributions of V A /Q ratios (Log SDQ [normal  (2)  a two-fold increase in shunt during 100% O 2  breathing (9.6±1.1, %Q T ; p (3)  mild atelectasis that increased while breathing 100% O 2  (from 2.1±0.2 to 2.6±0.3%; p A /Q distributions, and atelectasis improvements. Pre-BS BMI (p 2  improvement (overall adjusted r 2 , 0.56).  SO is associated with shunt and V A /Q disturbances, lung atelectasis and systemic inflammation. BS improves these abnormalities supporting a cause-effect relationship.  Supported by FIS  (080311),CIBERES  and Almirall.
Analysis of the cost-effectiveness of paclitaxel as alternative combination therapy for advanced ovarian cancer.
Authors: W McGuire, A I Neugut, S Arikian, J Doyle, C M Dezii
Journal: Journal of Clinical Oncology (1997)

PURPOSE A phase III trial by the Gynecologic Oncology Group (GOG) provides strong evidence that a new alternative therapy--paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) in combination with cisplatin (Platinol; Bristol-Myers Squibb Co)--is clinically more effective than the standard therapy using cyclophosphamide (Cytoxan; Bristol-Myers Squibb Co) in combination with cisplatin in the treatment of advanced ovarian cancer. We conducted a pharmacoeconomic analysis to determine whether the alternative paclitaxel-cisplatin (TP) therapy is cost-effective (CE) in comparison to standard cyclophosphamide-cisplatin (CP) therapy. METHODS Using an economic model, we applied cost data figures to resource utilization data derived from the two arms of the GOG trial. We examined paclitaxel benefits in terms of increased mean survival time, as well as median survival time. Estimates of the cumulative proportion surviving in the trial were based on Kaplan-Meier procedures. RESULTS Per year of life gained (YLG), TP therapy costs more ($19,820 more for inpatient treatment; $21,222 outpatient) than CP treatment. CONCLUSION The TP regimen's increased mean survival cost per YLG (inpatient and outpatient settings) adds a substantial benefit at an acceptable cost compared with CP therapy.
Cut-off value of D-dimer in diagnosis of pulmonary embolism in patients with chronic obstructive lung disease
Authors: Eylem Akpinar, Derya Hosgün, Beyza Doganay, Meral Gülhan
Journal: European Respiratory Journal (2013)

Introduction:  The measurement of D-dimer in patients suspected from pulmonary embolism (PE) prevents further diagnostic procedures. D-dimer may increase in patients with COPD without PE as a result of systemic inflammation. The prevalence of PE increases in patients with COPD. Aim was to determine cut-off value of D-dimer in diagnosis of PE in patients with COPD.   Method:  COPD patients who had thrombus on CT angiography were retrospectively enrolled. D-dimer levels which were measured on admission to emergency department were noted. COPD patients who were in stable period were included as control subjects. Their D-dimer measurements were done on admission to outpatient clinic. D-dimer levels of patients and control subjects were compared. Receiver operating curve analysis was done to define cut-off value of D-dimer in diagnosis of PE in COPD patients.   Results:  Thirty-five patients, 25 control subjects were included. D-dimer levels of COPD patients with PE were significantly higher than control subjects (p=0.001). The cut-off level of D-dimer for diagnosis of PE in COPD patients was found 0.552 pg/ml (sensitivity:100%, spesificity: 66.7%).   Conclusion:  The study showed that cut-off value of D-dimer in diagnosis of PE may be higher than normal in patients with COPD. Larger studies are necessary to determine exact cut-off value to prevent unnecessary further diagnostic procedures in these patients.
Identification of aspirin-induced asthma (AIA) subphenotypes using a clustering approach
Authors: Grazyna Bochenek, Joanna Kuschill-Dziurda, Hanna Plutecka, Krystyna Szafraniec, Ewa Nizankowska-Mogilnicka, Andrzej Szczeklik
Journal: European Respiratory Journal (2012)

Background: AIA is a distinct asthma phenotype which symptoms are exacerbated by aspirin and other NSAIDs. It is generally recognized as a severe difficult to treat asthma accompanied by chronic rhinosinusitis, nasal polyps, blood eosinophilia, elevated levels of urinary LTE4 (uLTE4). It seems, however, that AIA phenotype is not homogenous.  Aims: To identify distinct subphenotypes in a cohort of AIA patients by applying latent class analysis.  Methods: Clinical data from 201 AIA patients (134 women, mean age 49,4 yrs) were collected using unified questionnaire. Asthma severity and control were assessed using NAEPP EPR3 guideline. Spirometry, skin tests, blood eosinophilia, uLTE4 were evaluated.  Results: Four clusters of AIA were identified. Cluster 1: severe uncontrolled atopic asthma with non-reversible or reversible airway dysfunction, high rates of health care use (HCU) for asthma. Cluster 2: moderate uncontrolled/partially controlled non-atopic asthma with non-reversible or reversible airway dysfunction, high rates of HCU. Cluster 3: mild partially controlled atopic asthma with normal airway function, lower rates of HCU. Cluster 4: intermittent well controlled atopic/non-atopic asthma with normal airway function, lower rates of HCU. Upper airway symptoms were very common in all clusters. The groups did not differ with respect to blood eosinophilia and uLTE4.  Conclusions: From clinical point of view AIA patients are not a homogenous population. Only part of them have severe uncontrolled asthma. Despite of the presence of upper airway symptoms, some subjects have mild, better controlled disease. Atopy but not blood eosinophilia and uLTE4 may discriminate patients assigned to different clusters.