tbuckley/cabot-search huggingface dataset:
FEV1 decline in asymptomatic young adults: relationships with some tests of small airways function
Authors: L Marazzini, G Cavigioli, B Mastropasqua, A Pelucchi
Journal: European Respiratory Journal (1989)

The aim of this study is to determine whether some tests proposed as diagnostic of small airways obstruction (SAO) are useful in identifying the subjects at risk of developing chronic airflow limitation. Eighty five healthy male workers (46 nonsmokers and 39 smokers, aged 21-41 yrs), living in the same area and not exposed to occupational pollutants were re-examined after an interval of 6 yrs. At the first survey 39 had functional evidence of SAO as determined by the presence of one of: maximal mid-expiratory flow (MMEF) less than 65% of predicted value (pred); maximal expiratory flow when 25% forced vital capacity remains to be expired (Vmax25) less than 60% pred; closing capacity (CC) greater than 130% pred; 46 had all functional values in the normal range. We considered four subgroups: smokers and nonsmokers with and without SAO. The rate of decline in FEV1, the decline in %delta FEV1 and delta FEV1.height-3, have been evaluated and compared in the subgroups. Initial values of specific tests (MMEF, Vmax25, CC and slope of phase III) have been examined for a possible relationship with decline of FEV1. Statistical analysis of our data showed that only CC was related to FEV1 decline. However, there were no significant differences in FEV1 decline among the subgroups. We conclude that in young adult subjects functional characteristics of SAO have no predictive value for development of chronic airways obstruction.
Implications of identifying the pathogen in ventilator-associated pneumonia (VAP)
Authors: Margarida Dias, Paulo Marçal, Piedade Amaro
Journal: European Respiratory Journal (2013)

Background:  VAP is associated with increased mortality and costs. Lower airways secretions should be obtained from patients with suspected VAP and empirical antibiotic therapy should be started promptly.   Objectives:  To evaluate the impact of identifying the pathogen in VAP on antibiotic therapy and intubation length, length of intensive care unit (ICU) stay and mortality.   Methods:  Retrospective study of all patients diagnosed with VAP in an ICU between 1/8/2001 and 31/12/2011. Patients were divided in two groups depending on pathogen identification in the lower airways. Antibiotic therapy and intubation length, length of ICU stay and mortality were compared between groups.   Results:  Of 206 patients included, the pathogen was identified in 154. Agents identified the most were  P. aeruginosa  (48%),  S. aureus  (27%) and  Acinectobacter sp .(8%).  For patients with pathogen identification, empirical therapy was inappropriate in 29% while de-escalation was achieved in 25%.  There were no differences between groups in ICU mortality, intubation length and length of ICU stay. Pathogen identification was associated to longer antibiotic therapy in ICU (11.4 vs 8.6 days, p=0.02).  When empirical therapy was inappropriate (n=44), mortality was higher (34% vs 25%, p>0.05) and appropriate therapy was longer (12.9 vs 10.2 days, p=0.016).   Conclusions:  Pathogen identification revealed inappropriate therapy in 29% of patients with impact in mortality. Pathogen identification did not alter significantly intubation length, length of ICU stay and mortality but was associated to longer therapy. This can be explained by high prevalence of non-fermentable gram-negative bacilli. Of relevance, de-escalation was possible in 25% of patients.
Comparison of different predicted and lower limit of normal (LLN) values in ventilation disorders detection
Authors: Marina Kameneva, Artem Tishkov, Alina Bykhova, Vasiliy Trofimov
Journal: European Respiratory Journal (2012)

Aim : To estimate the agreement of Russian equations (Klement), ECCS and NhanesIII spirometry evaluating systems in determining the types of ventilation abnormalities by predicted and LLN (5th percentile) values.   Materials and methods : The study enrolled 7,779 Caucasians examined in pulmonary clinics of St.Petersburg Pavlov9s State Medical University in 2005-2011: 3,584 males (mean age 47.40±0.25, mean height 175.44±0.18) and 4,195 females (mean age 49.66±0.20, mean height 162.29±0.10). The cases that can not be classified as norm, obstruction or restriction, were accumulated in the mixed group.   Conclusion : The best agreement was obtained by ECCS and Klement systems both in predicted values and LLN. NhanesIII significantly differs from both Klement and ECCS in LLN for all groups. In predicted values these three systems agreed in obstruction but still generally disagree in norm and restriction.
Oral High-Dose Multivitamins and Minerals After Myocardial Infarction
Authors: Gervasio A. Lamas, Robin Boineau, Christine Goertz, Daniel B. Mark, Yves Rosenberg, Mario Stylianou, Theodore Rozema, Richard L. Nahin, Lauren Lindblad, Eldrin F. Lewis, Jeanne Drisko, Kerry L. Lee
Journal: Annals of Internal Medicine (2013)

Background: Whether high-dose multivitamins are effective for secondary prevention of atherosclerotic disease is unknown. Objective: To assess whether oral multivitamins reduce cardiovascular events and are safe. Design: Double-blind, placebo-controlled, 2 × 2 factorial, multicenter, randomized trial. (ClinicalTrials.gov: NCT00044213) Setting: 134 U.S. and Canadian academic and clinical sites. Patients: 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier and had serum creatinine levels of 176.8 µmol/L (2.0 mg/dL) or less. Intervention: Patients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture or placebo. Measurements: The primary end point was time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. Results: The median age was 65 years, and 18% of patients were women. The qualifying MI occurred a median of 4.6 years (interquartile range [IQR], 1.6 to 9.2 years) before enrollment. Median follow-up was 55 months (IQR, 26 to 60 months). Patients received vitamins for a median of 31 months (IQR, 13 to 59 months) in the vitamin group and 35 months (IQR, 13 to 60 months) in the placebo group (P = 0.65). Totals of 645 (76%) and 646 (76%) patients in the vitamin and placebo groups, respectively, completed at least 1 year of oral therapy (P = 0.98), and 400 (47%) and 426 (50%) patients, respectively, completed at least 3 years (P = 0.23). Totals of 394 (46%) and 390 (46%) patients in the vitamin and placebo groups, respectively, discontinued the vitamin regimen (P = 0.67), and 17% of patients withdrew from the study. The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]; P = 0.21). No evidence suggested harm from vitamin therapy in any category of adverse events. Limitation: There was considerable nonadherence and withdrawal, limiting the ability to draw firm conclusions (particularly about safety). Conclusion: High-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate. Primary Funding Source: National Institutes of Health.
Clinical failure in hospitalized patients with community acquired pneumonia (CAP): Preliminary results from the FAILCAP study
Authors: Stefano Aliberti, Letizia Morlacchi, Andrea Gramegna, Elena Parazzini, Daiana Stolz, Leonardo Ruvolo, Fabienne Karrer, Giulia Cervi, Roberto Cosentini, Annamaria Zanaboni, Almerico Marruchella, Elena Magni, Paula Peyrani, Alberto Pesci, Julio Ramirez, Francesco Blasi
Journal: European Respiratory Journal (2011)

Although clinical failure is one of the most relevant outcomes in CAP patients, there is little discussion in literature on its incidence and etiology. The aim of the study was to evaluate incidence, risk factors and outcomes of CAP patients undergoing a clinical failure during hospitalization. An international, multicenter, prospective, observational study was performed from October 2009 to December 2010 in 8 Respiratory Dpts, enrolling consecutive patients hospitalized with CAP (ClinicalTrials: NCT01143155). Clinical failure was defined as either acute pulmonary or hemodynamic deterioration or in-hospital death. Risk factors associated to the development of clinical failure were analyzed by a multivariable analysis. Among the 431 patients enrolled (56% males; mean±SD age:73±16 yrs), incidence of clinical failures was 17% (72 patients). The majority of the clinical failures were related to the pneumonia. The development of cardiovascular events was significantly higher in patients who failed in comparison to the rest of the population (36% vs. 17%, respectively, p
Tracheo-bronchial collapsibility in different clinically determined COPD phenotypes
Authors: Gianna Camiciottoli, Francesca Bigazzi, Stefano Diciotti, Simone Lombardo, Mario Mascalchi, Massimo Pistolesi
Journal: European Respiratory Journal (2011)

Tracheo-bronchial collapsibility (TBc) has been detected at computed tomography (CT) in Chronic Obstructive Pulmonary Disease (COPD). TBc is considered a local response to inflammatory agents not closely related to the obstructive functional pattern and to lung attenuation values at CT. We hypothesize however that TBc could influence symptoms and daily performance in patients with COPD. The purpose of our study was to investigate whether TBc is related to dyspnoea, exercise capacity and clinical phenotypes in patients with COPD.  Thirty-six patients (mean age 68±8, mean FEV1% 60±24) underwent clinical examination, lung function test, 6 minutes Walking Test and inspiratory-expiratory CT.TBc was measured by an automated software and correlated with MRC and Borg dyspnoea scales and with walked distance. Moreover we compared TBc in patients with predominant chronic bronchitis (CB) and predominant emphysema (E) phenotypes according to the rule available at www.clipcopd.com.  No significant relationship was found between TBc and MRC (r=-0.24, p=0.15), Borg scale (r=-0.12, p=0.48),walked distance (r=0.17, p=0.33). TBc was significantly higher in patients with CB phenotype (p=0.02, Fig. 1).  Patients with a predominant CB phenotype show a high level of TBc supporting the idea that the same inflammatory process could involve both trachea and bronchial tree. Dyspnoea and exercise capacity are global indexes of COPD that are not related to TBc.
Comparison of l and dl forms of folinic acid in Gercor C96.1 trial (A phase III trial comparing bimonthly LV5FU2 to monthly high-dose 5FU-leucovorin in patients with Dukes’ B2 and C colon cancer)
Authors: E. M. Quinaux, I. Baumgaertner, A. Khalil, C. Louvet, M. E. Buyse, A. de Gramont, T. André
Journal: Journal of Clinical Oncology (2009)

e15004 In C96.1 study (André T et al; J Clin Oncol. 2007 20;25:3732–8), patients were randomized to either monthly 5FU-LV hd (dl LV 200 mg/m 2 or l LV 100 mg/m 2 15 min iv followed by 5FU 400 mg/m 2 15 min iv, d1–5 q4 wk) or LV5FU2 (dl LV 200 mg/m 2 or l LV 100 mg/m 2 2-hour infusion followed by iv bolus 5FU 400 mg/m 2 and 22 hours continuous infusion 600 mg/m 2 , d1 and d2 q 2 wk). Form l LV was administered to 60% (n=519) of patients and dl LV to 40% (n=357) of patients. It was unknown in 29 patients. No randomization was made between form l or dl (It was the choice of each center). The aim of this analysis was to compare the 2 LV forms in term of safety and efficacy. Important prognostic characteristics were well balanced between the 2 groups. The proportion of any grade III-IV toxicity was 20% in l form and 17% in dl form. There was no difference in term of toxicity between the two groups, except a trend for more diarrhea grade 3–4 in form l (8% in l form vs 4% in dl form, p=0.07). The median follow-up time was 6.2 years in l form and 6.0 years in dl form. There were no statistically significant differences between l and dl forms in term of disease free survival (33.3% vs 32.8% of patients with at least one event in l and dl forms respectively, hazard ratio=1.03, 95% CI=[0.82–1.31], p=0.78). In term of overall survival, there was a trend without statistical significance in favor of l form (21.8% vs 25.5% of patients who died, hazard ratio=1.28, 95% CI=[0.97–1.69], p=0.078). We conclude that the toxicity profile is similar between the two forms (excepted diarrhea). The difference in overall survival should not be attributed to folinic acid form as no difference was observed on DFS. No significant financial relationships to disclose.
Abstract 137: Pharmacologically Controlled IGF-1 Release For Paracrine Support Of Engineered Heart Muscle
Authors: POH LOONG SOONG, Malte Tiburcy, Jan Christoph, Stefan Luther, Fawad Jebran, Fritz Schoendube, Wolfram H Zimmermann
Journal: Circulation Research (2014)

Tissue engineered heart repair is developing rapidly, but needs refinement before clinical translation. We tested the hypothesis that force generating human engineered heart muscle (EHM) can be enhanced by integration of insulin-like growth factor-1 (IGF-1) secreting fibroblasts. Methods: TetOn lentiviral particles encoding for IGF-1 and the Tet-transactivator (tTA) were cloned and used to stably transduce human foreskin fibroblasts (HFF). Baseline and doxycycline induced IGF-1 release from HFFTetOn+IGF1 was quantified by ELISA. HFFwt and HFFTetOn+IGF1 conditioned medium was layered over human embryonic stem cell (HES2) derived cardiomyocytes followed by an analysis of AKT-phosphorylation. EHMs were assembled from HES2-derived cardiomyocytes and HFF (HFFwt or HFFTetOn+IGF1) at 70:30 ratio. Transgene activation was induced by addition of doxycycline (10 ng/ml) for 7 days. Twitch forces and response to pharmacological stimuli were measured to assess the functional consequences of IGF-1 release. EHMs were subsequently subjected to morphological analysis or dissociated into single cells to assess cellular composition of EHMs. Results: HFFTetOn+IGF1 released IGF-1 upon doxycycline stimulation (3.3x10-6 vs 8.3x10-8 [HFFwt] ng/ml/cell/day. Secreted IGF-1 from HFFTetOn+IGF1 induced Akt phosphorylation in HES2-derived cardiomyocytes (2.4±0.6 fold increase of [HFFwt]; n=3). EHMs with HFFTetOn+IGF1 developed significantly higher twitch forces than EHMs with HFFwt (0.24±0.03 vs 0.15±0.02 mN; n=10) under baseline conditions (IGF-1 leak). Doxycycline induced IGF-1 release further enhanced (P&lt;0.05) EHM twitch force (0.26±0.03 mN; n=10). Single cell analysis from EHMs demonstrated cardiomyocyte hypertrophy in response to paracrine IGF-1 release (154±11% of [HFFwt] control; n=4). Histological analyses demonstrated that HFFTetOn+IGF1 supplemented EHMs contained thicker muscle bundles and enlarged cardiomyocytes. Conclusion: EHM can be functionally enhanced by integration of drug-controllable IGF-1 release. Drug controllable, cell based paracrine release of protective factors may not only be exploited to enhance tissue engineered myocardium in vitro but also to achieve better survival and integration of EHM grafts in vivo.
Abstract 2829: Degeneration of Ventricular Tachycardia Into Ventricular Fibrillation Following Right Ventricular Dilation
Authors: Yuxuan Hu, Viatcheslav Gurev, Jason Constantino, Natalia Trayanova
Journal: Circulation (2009)

Studies showed that hemodynamics changes during arrhythmias lead to rapid dilation of right ventricle (RV). RV dilation results in a gradient of refractoriness between left ventricle (LV) and RV through mechano-electric feedback (MEF). We hypothesize that the gradient of refractoriness between LV and RV caused by MEF in the dilated RV is responsible for the degradation of ventricular tachycardia (VT) to ventricular fibrillation (VF). We employed a 3D model of rabbit ventricular electromechanics that incorporated a non-selective cationic stretch-activated channel (SAC). To simulate isovolumic ventricular contraction during VT and VF, a heuristic model of calcium dynamics of the cardiac myofilament with accurate force-rate dependence was included. The conductivity of the SAC depended on the magnitude of the local strain. Two different reversal potentials (−60, −10mV) were tested in the model. VT was induced by S1-S2 pacing. RV was dilated to twice its initial volume over a period of 0.5s following S2. Cases without and with RV dilation were compared. S1-S2 pacing resulted in two stable spiral waves, one on the posterior wall and another on the anterior. Breakup of spiral waves occurred only in the case of RV dilation with SAC of −10mV reversal potential. The wave breakup was due to inactivation of Na channels at elevated resting potential mediated by the stretch-induced current. 2s after the onset of arrhythmia, the patterns of VF were organized into a single stable spiral wave in LV lateral wall and multiple reentrant circuits in RV free wall (Fig 1). RV dilation establishes a gradient of refractoriness between RV and LV with the recruitment of SAC, which causes degeneration of VT into VF.
Eosinophilic pneumonia - Our own experience with diagnosis and treatment
Authors: Jan Plutinsky, Ivan Marget, Stanislav Majernik, Daniel Magula, Frantisek Dvorak
Journal: European Respiratory Journal (2012)

Eosinophilic pneumonia (EP) is a rare disease. Some EP could be caused by concomitant diseases (CD), while in others the cause is unclear (idiopathic). EP is divided into acute (AEP) and chronic (CEP) forms.  The aim: The authors share their own experience with EP diagnosis and treatment.  Methods: EP was diagnosed in 23 patients (pts). Clinical examination, X-ray, CT, laboratory examinations with a peripheral blood count of eosinophils (Eo), microbiology, mycobacteriology, fiberbronchoscopy or histology were used. The pts were divided into two groups: AEP and CEP. Statistical analysis was performed.  Results: 15 F, median age 66 yrs (36-87) and 8 M, median 67 yrs (55-85) had one of the two forms: AEP in 7 pts and CEP in 16 pts. The main clinical symptoms were dyspnoe in 20 pts (95.2%), cough in 19 pts (90.5%), fever in 17 pts (80.9%), pain in 5 pts (23.8%). AEP or CEP was the result of CD in 3 pts (toxoplasmosis), in 1 pt. with sarcoidosis, rhinitis and in 2 with allergic bronchopulmonary aspergillosis. In 17 pts no CD was identified. A statistical significance was found between the age of pts with AEP (56±12.2) and CEP (67.8±12.9) (p  Conclusions: EP is a very interesting disease. Treatment with antibiotics is unsuccessful, but corticosteroid treatment leads to a dramatic improvement. Dividing EP into AEP and CEP is not so clear cut.
Abstract 3818: Notch1 Receptor Blockade Results in Dilated Cardiomyopathy in the Neonatal Mouse Heart
Authors: Konrad Urbanek, Silvia Maestroni, Regina Lee Sohn, Francesca Delucchi, Federica Del Monte, Ronglih Liao, Sabina Signoretti, Robero Rizzi, Federico Quaini, Marcello Rota, Piero Anversa, Annarosa Leri
Journal: Circulation (2008)

The objective of this study was to determine whether Notch1 receptor plays a crucial role in the commitment of c-kit-positive cardiac progenitor cells (CPCs) to the myocyte lineage. This possibility was tested in the neonatal mouse heart because of the dramatic increase in the myocyte compartment early postnatally. CPCs are located within the primitive heart and their number increases progressively with gestational age and after birth. c-kit colocalizes with transcription factors and contractile proteins specific of myocytes, pointing to a lineage relationship between CPCs and myocytes in the prenatal and postnatal heart. Notch1 intracellular domain (N1ICD) was consistently found together with Nkx2.5 suggesting that Notch1 receptor represents an early determinant of myocyte differentiation. The critical function of Notch1 in the generation of myocytes was established by interfering with this pathway through the administration of a γ-secretase inhibitor to newborn mice for 3–7 days; γ-secretase inhibition opposes the cleavage of the active fragment of Notch and initiation of transcription. Treated mice showed a dilated myopathy characterized by decreased muscle mass, wall thinning and impaired fractional shortening and ejection fraction. There was also a marked reduction in the fraction of CPCs and myocytes expressing the Notch1 active fragment N1ICD. Myocyte number decreased 28% while myocyte volume remained constant, suggesting that Notch1 blockade affects myocyte formation and conditions the development of a dilated myopathy. This hypothesis is supported further by a 57% decrease in replicating myocytes positive for Ki67. These anatomical and functional changes were accompanied by downregulation of Nkx2.5 transcripts in the pathologic heart. A perfect consensus site for the target gene of Notch, RBP-Jk, was recognized in the promoter of Nkx2.5. The formation of a functional complex between Nkx2.5 promoter and RBP-Jk protein was demonstrated by electrophoretic mobility assay, chromatin immunoprecipitation and luciferase reporter assay. In conclusion, Notch1 promotes the commitment of CPCs to the myocyte lineage and inhibition of Notch1 interferes with cardiomyogenesis leading to a dilated cardiomyopathy in the postnatal heart.
Abstract 17196: An Improved Equation for Estimation of LDL Cholesterol in European and African American Adults
Authors: Harrison Wang, Diane M Becker, Dhananjay Vaidya, Taryn F Moy, Lisa R Yanek, Brian G Kral
Journal: Circulation (2011)

Introduction: The Friedewald equation (FE) has been the US standard for estimating LDL-cholesterol (LDL-C) levels when direct measures are not available, but loses accuracy at triglyceride (TG) levels ≥400 mg/dL. A new formula (Chen et al) has been shown to more accurately estimate LDL-C across the range of TG, including values ≥400 mg/dL in a Chinese population. We tested the new Chen formula (CF) and the FE against LDL-C measured by NMR spectroscopy in European (EA) and African American (AA) adults. Methods and Results: The sample consisted of 937 apparently healthy subjects ages 31 to 75 years (51.3 ± 8.1 years; 58.3% female; 47.2 EA, 52.8 % AA). Blood was obtained in fasting subjects and total cholesterol (TC), HDL cholesterol (HDL-C), and TG were measured using standard enzymatic methods; LDL-C was estimated using both the FE, [(LDL-C)=(TC)-(HDL-C)-(TG/5)], and the CF [(LDL-C)=0.9[(TC)-(HDL-C)] - 0.1(TG)]. LDL-C was also measured directly using proton NMR spectroscopy (NMR) as the reference standard. Overall mean LDL-C was 130.2 ± 40.mg/dL 1 for FE and 128.6 ± 36.5 mg/dL for CF, p=&lt;0.0001 for correlation (r2= 0.95). The % error for each the FE and CF against NMR LDL-C is plotted against TG levels (log) in the Figure. The FE underestimates NMR LDL-C as TG increases, (beta -1.6% error per 10% higher TG), whereas the CF only slightly overestimates NMR LDL-C at higher values of TG (beta 0.5% error per 10% higher TG) and remains accurate at levels ≥400 mg/dL. Conclusion: The CF more accurately estimates LDL-C compared with the FF across all TG values and remains accurate for levels ≥400 mg/dL in both races. Thus, the Chen formula may offer improved LDL-C estimation utility in African American and European American adults, particularly for TG levels ≥400 mg/dL, when direct measurement of LDL-C is not accessible or cost prohibitive. Figure: Friedewald Equation and Chen Formula Estimates of LDL-C Across TG Levels