tbuckley/cabot-search huggingface dataset:
Occupational asthmogens and total IgE according to asthma status in the EGEA study
Authors: Orianne Dumas, Valérie Siroux, Bénédicte Jacquemin, Isabelle Pin, Jean Bousquet, Rachel Nadif, Francine Kauffmann, Nicole Le Moual
Journal: European Respiratory Journal (2011)

Introduction: The comprehension of the relationship between asthma and immunoglobulin E (IgE) remains a challenge. Several occupational asthmogens have been identified to cause or aggravate asthma, but their associations with IgE have rarely been studied.

Aim: To study the relationship between occupational exposure to asthmogens and total serum IgE in non-asthmatics, childhood-onset and adult-onset asthmatics.

Methods: Analyses were conducted in 1212 adults (aged 17-79 years, 48% men) from the Epidemiological study on the Genetics and Environment of Asthma (EGEA2, 2003-07) without missing data for work history and IgE. Lifetime exposure to asthmogens was estimated using an asthma-specific job-exposure matrix.

Results: 32%, 28% and 36% of non-asthmatics, childhood-onset and adult-onset asthmatics had respectively ever been exposed to asthmogens. In non-asthmatics, exposed subjects had a significantly lower total IgE level. In asthmatics, no association was observed. Nevertheless, among women with childhood-onset asthma, exposure to asthmogens was associated with higher IgE level (adjusted OR (95%CI) for IgE>=100 IU/ml: 2.49 (1.07-5.83)).

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Conclusion: Our results suggest a healthy worker effect among non-asthmatics. Further analyses will be conducted by distinguishing the types of asthmogens.

Founded in part: AFSSET-EST-09-15
Defining a New Prognostic Index for Stage I Nonseminomatous Germ Cell Tumors Using CXCL12 Expression and Proportion of Embryonal Carcinoma
Authors: Duncan C. Gilbert, Reem Al-Saadi, Khin Thway, Ian Chandler, Daniel Berney, Rhian Gabe, Sally P. Stenning, Joan Sweet, Robert Huddart, Janet M. Shipley
Journal: Clinical Cancer Research (2015)

Up to 50% of patients diagnosed with stage I nonseminomatous germ cell tumors (NSGCTs) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up front. Late toxicities from chemotherapy are increasingly recognized. Based on a potential biologic role in germ cells/tumors and pilot data, our aim was to evaluate tumor expression of the chemokine CXCL12 alongside previously proposed markers as clinically useful biomarkers of relapse.Immunohistochemistry for tumor expression of CXCL12 was assessed as a biomarker of relapse alongside vascular invasion, histology (percentage embryonal carcinoma), and MIB1 staining for proliferation in formalin-fixed paraffin-embedded orchidectomy samples from patients enrolled in the Medical Research Council's TE08/22 prospective trials of surveillance in stage I NSGCTs.TE08/TE22 trial patients had a 76.4% 2-year relapse-free rate, and both CXCL12 expression and percentage embryonal carcinoma provided prognostic value independently of vascular invasion (stratified log rank test P = 0.006 for both). There was no additional prognostic value for MIB1 staining. A model using CXCL12, percentage embryonal carcinoma, and VI defines three prognostic groups that were independently validated.CXCL12 and percentage embryonal carcinoma both stratify patients' relapse risk over and above vascular invasion alone. This is anticipated to improve the stratification of patients and identify high-risk cases to be considered for adjuvant therapy.
Effects noninvasive mechanical ventilation on muscle strength, ambulation, and functional performance in the intensive care
Authors: Sahveren Cakartas, Deniz Inal Ince, Sema Savci, Hulya Arikan, Arzu Topeli Iskit
Journal: European Respiratory Journal (2011)

Aim: Muscle weakness is a common complication of stay in the intensive care unit (ICU). The aim of this study was to compare the effects of noninvasive mechanical ventilation (NIMV) and standard medical care on muscle strength, ambulation level and functional performance in ICU patients with acute respiratory failure.  Methods: Fifteen patients undergoing standard medical care (53.1±15.5 years) and 15 patients undergoing NIMV (59.9±14.4 years) participated in the study. Patients9 characteristics, admission findings and length of ICU stay were recorded. An Acute Physiology and Chronic Health Evaluation (APACHE II) score was calculated. Peripheral muscle strength was assessed using the Medical Research Council Scale and handgrip dynamometry. Functional performance was evaluated using the Barthel Index. Ambulation level was recorded as six levels: (1) unsupported sitting in the bed, (2) transfer to chair, (3) sitting in the chair, (4) standing, (5) walking, (6) walking >30 m.  Results: APACHE II score was similar in both groups (p>0.05). Barthel Index score, ambulation score, and MRC sum score were significantly lower in patients with NIMV (p 0.05). Length of ICU stay was significantly longer in patients undergoing NIMV (p  Conclusion: Patients receiving NIMV had peripheral muscle weakness. These patients had more limitations in their functional performance as compared to patients undergoing standard care. Application of NIMV, similar to invasive mechanical ventilation, results in limitations in functional performance, ambulation, and muscle strength in the ICU.
Observations in Micturating Cystourethrography
Authors: D H Rose, A C Eaton
Journal: Journal of the Royal Society of Medicine (1983)

Combined studies of micturating cystourethrography (MCU), bladder pressure and urinary flow rate measurements (urodynamic studies) have been analysed in 1584 adult patients of both sexes. The combined study is called a videocystometrogram (VCM). The simple MCU is satisfactory for demonstrating vesicoureteric reflux, but in the investigation of other problems of the lower urinary tract in adults, conclusions based on the MCU alone can be misleading. It is recommended that if the MCU is performed at all in the investigation of adult incontinence and suspected urinary outflow obstruction, it should be combined with a urodynamic study. This increases the examination time by about 50% but greatly improves the diagnostic accuracy, especially in establishing whether surgery is indicated or inappropriate.
Pulmonary alveolar proteinosis: prolonged spontaneous remission in two patients
Authors: MA Martinez-Lopez, G Gomez-Cerezo, C Villasante, F Molina, S Diaz, J Cobo, C Medrano
Journal: European Respiratory Journal (1991)

Pulmonary alveolar proteinosis is a rare idiopathic diffuse airspace disease characterized by intra-alveolar accumulation of large quantities of lipoproteinaceous material, with preservation of the lung interstitium. The clinical course of pulmonary alveolar proteinosis is variable. Spontaneous resolution is known to occur in up to a quarter of the cases. We describe two patients with untreated pulmonary alveolar proteinosis who experienced complete clinical, functional and radiographic resolution. In follow-up periods of fourteen and six years, both patients have remained asymptomatic.
Higher than expected prevalence of alpha-1-antitrypsin deficiency (AATD) may not necessarily impact on airflow, gas exchange or acute exacerbation rate (AER)
Authors: Ronald Dandurand, Jean Bourbeau, David Eidelman
Journal: European Respiratory Journal (2012)

AATD is estimated to occur in 1-3% of COPD patients and is believed to accelerate disease. To determine its prevalence in a community practice and impact on disease progression, all patients with COPD, >10 pack-year smoking history and a post-bronchodilator FEV1/FVC
Air pollution exposure during pregnancy and infancy and childhood asthma
Authors: David Olsson, Lennart Bråbäck, Bertil Forsberg
Journal: European Respiratory Journal (2014)

Recent reviews support an association between exposure to air pollution from traffic and incidence of asthma in children. However, inconsistent results and the risk of awareness bias in parental-reported data motivate further analyses in large studies using objective air pollution data and registry-based outcome data.  Our aim was to study the associations between early-life exposure to traffic-related air pollution and childhood asthma in Greater Stockholm. We constructed a register-based cohort by linking data from the Swedish Medical Birth Register, the Swedish Prescribed Drug Register and the Swedish Patient Register. We included all children born between June 2000 and November 2005, n = 78,770. Asthma was defined as receiving prescribed asthma medication during the 6 th  year of life. NO x  levels at residence were estimated using a dispersion model and used as an indicator of motor vehicle exhaust.  9.7 % of the children were classified as having asthma. Asthma was more common among children who were born preterm, were small for gestational age, or had a family history of asthma. There was no association between NO x  levels during pregnancy or infancy and asthma; the tendency was even negative (ORs = 0.97 and 0.98). However, we found a tendency that moving to a residence with higher concentrations than the first was associated with an increased risk for asthma (OR = 1.04).  We observed no evidence suggesting that the vehicle exhaust level at home during gestation or infancy, using NO x  as a proxy, is associated with the risk of childhood asthma.
Cytokine pattern in blister fluid and serum of patients with bullous pemphigoid: relationships with disease intensity
Authors: None Ameglio, None D'auria, None Bonifati, None Ferraro, None Mastroianni, None Giacalone
Journal: British Journal of Dermatology (1998)

Few and contrasting data are available in the literature concerning the levels of various cytokines in blister fluid (BF) and in the serum of patients affected with bullous pemphigoid (BP). Using commercially available ELISA kits, this study reports the levels of 11 cytokines detected both in BF and sera of 15 BP patients and compares them with those of 15 control subjects' sera. Generally, no significant differences were observed in BP and control sera. In contrast, interleukin (IL) 1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, tumour necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ) showed increased BF levels as compared with BP sera. Two cytokines, IL‐11 and IL‐12 did not show significant differences between BP BF and sera, while an opposite behaviour was observed for transforming growth factor βl (TGF‐β1), whose serum levels were higher than the concentrations in BF. Using the number of lesions of the patients as a possible disease intensity marker, significant correlations were found with the BF levels of IL‐1β, IL‐8, TNF‐α and, most closely, IL‐5. These data may have pathogenetic relevance and suggest the possibility that these biological modulators may be used as a quantitative marker of disease intensity.
Comprehensive genomic profiling of biliary tract cancers to reveal tumor-specific differences and genomic alterations.
Authors: Jeffrey S. Ross, Kai Wang, Daniel Virgil Thomas Catenacci, Juliann Chmielecki, Siraj M. Ali, Julia Andrea Elvin, Roman Yelensky, Doron Lipson, Matthew J. Hawryluk, Vincent A. Miller, Philip J. Stephens, Milind M. Javle
Journal: Journal of Clinical Oncology (2015)

231 Background: Intrahepatic cholangiocarcinoma (IHCCA), extrahepatic cholangiocarcinoma (EHCCA) and gallbladder carcinomas (GBCA) typically present at an advanced stage and systemic chemotherapy provides only modest benefit in most cases. We queried whether comprehensive genomic profiling (GCP) of IHCCA, EHCCA and GBCA would reveal clinically relevant genomic alterations (CRGA) that could lead to targeted therapies. Methods: DNA was extracted from 40µ of FFPE sections from 412 IHCCA, 57 EHCCA and 85 GBCA. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of &gt;600X for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The CGP assay included base substitutions, INDELs, copy number alterations and fusions/rearrangements. CRGA were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Patient characteristics were similar for all three tumor types. IHCCA and GBCa were more common in females and EHCCA were more common males. CGP revealed the results in the Table. Multiple antitumor responses to targeted therapies in each of the 3 tumor types will be presented. Conclusions: IHCCA, EHCCA and GBCA share GA in cell cycle regulation (CDKN2B) and chromatin remodeling (ARID1A). IHCCA features FGFR fusions, IDH1/2 substitutions, BRAF substitutions and MET amplification with a low KRAS mutation frequency. EHCCA and GBCA feature ERBB2 amplifications (GBCA &gt; EHCCA) and PIK3CA/MTOR pathway alterations. EHCCA has a high KRAS mutation frequency whereas the KRAS GA in GBCA is low. The diverse landscape of CRGA in biliary tract cancers can serve as targets for therapies for patients with CCA, BDCA and GBCA and have the potential to improve outcomes for these aggressive forms of malignancy. [Table: see text]
Surgery for sternal tumors: Extent of resection, reconstruction and survival
Authors: Danail Petrov, Georgi Yankov, Elyuar Goranov, Michhail Plochev, Svilen Alexov
Journal: European Respiratory Journal (2012)

Objective. To evaluate the postoperative results after different sternal resections for malignances.  Methods. A total of 15 patients (mean age 48.9 years) were operated on during a 7 years period. There were 8 sarcomas (4 chondrosarcomas, 3 radiation-induced sarcomas, 1 osteosarcoma), 1 recurrent desmoid tumor, 3 local breast tumor recurrences, 1 plasmocytoma, and 2 metastases of other tumors. Four cm free margins on each side were achieved in all patients with total sternectomy (4), subtotal sternal resection (9), and partial resection (2). Concurrent en bloc resection included anterior ribs (4), clavicle (3), pericardium (2), brachiocephalic vein (2), and diaphragm (1). The chest was reconstructed with Marlex mesh and myocutaneous flap in 8 (53.3%) patients or omentum in 1 (6.7%) patient, only double layer Marlex mesh with breast mobilization in 4 women (26.7%), and a combination of Marlex mesh and a metal bar in 2 patients (13.3%).  Results. There was no 30-day operative mortality. Mechanical ventilation for 5 days was needed in a 78 years old female after total sternectomy. Local suppuration was found in 1 patient. The mean in-hospital stay was 11.4 days. After a median follow-up of 51 months the overall 5-year survival was 48%, with a median survival of 57 months. Local recurrence occurred in 1 patients, who underwent a repeat resection. Metastases developed in 2 patients.  Conclusion. Wide sternal resection is a safe and effective treatment of sternal malignances. The chest wall reconstruction depends on the size and site of the resection, and should be planed with plastic surgeons.
Beyond KRAS: The quest for novel genetic markers predictive for response to anti-epidermal growth factor receptor (EGFR) therapy in patients with metastatic colorectal cancer (mCRC).
Authors: A. Sood, D. McClain, R. Seetharam, M. Al-rahamneh, A. Kaubisch, L. Rajdev, K. Tanaka, J. Mariadason, S. Goel
Journal: Journal of Clinical Oncology (2010)

3567 Background: EGFR directed therapy is limited by mutations in KRAS or BRAF; however, the search for other predictive biomarkers is critical (Clin Cancer Res, 2008; 68: 1953). In our study, we evaluated hotspots in the EGFR pathway with a focus on PTEN. Methods: Patients (pt) who had received cetuximab or panitumumab and had available tissue were identified from pharmacy database. In all, 76 pt (119 tissue samples) were tested for mutations by pyrosequencing at 15 hotspots – KRAS codons 12/13/61, BRAF(V600E), PIK3CA Exon 9 (E542K, E545K) and Exon20 (R1023Q, H1047R), PIK3R1 (splice site mutation in intron 12-13), AKT (E17K), PTEN truncating mutations (R130X, Q214X, R233X, Q245X, R335X) and methylation analysis of 4 CpG islands in promoter region of PTEN gene by methylation specific polymerase chain reaction. One hundred and six tissues were tested for PTEN expression by immunohistochemistry (IHC); 44 pt had at least 4 weeks of therapy and were considered for clinical correlates. Results: Among 76 pt, mutation prevalence was KRAS12/13/61 (29, 13, 5 %), BRAF (8%), PIK3CA - E542K, E545K, R1023Q, H1047R (4, 20, 4, 2.5%), PIK3R1 (17%), PTEN - R130X, R233X, Q245X and R335X (2.5, 2.5, 1, 28%), and none in AKT, and PTEN Q214X. PTEN IHC was positive in 21/51 metastatic and 22/54 primary tissues, with a concordance rate of 47% between matched primary and metastatic pairs. We observed 4 partial responses (PR) among 44 pts (9%). All PR were PTEN positive in the primary tumor and lack of PTEN by IHC in primary predicted for lack of response (Fisher Exact test [FET] p = 0.04). KRAS and BRAF mutations predicted for clinical benefit (PFS 8.5 vs. 23.3 wk, HR 2.12, p = 0.0085 and OS 23.9 vs. 46wk, HR 2.178, p = 0.0055); while PIK3CA mutations did not. Truncating PTEN mutation R335X was associated with IHC negativity (FET 0.002), however promoter methylation was not. Conclusions: Absence of PTEN in the primary tumor (by IHC), is predictive of lack of benefit from anti EGFR therapy in pt with mCRC. PTEN truncating mutation correlates with IHC and is a potential biomarker requiring further exploration in larger studies. PIK3CA mutations are not predictive of benefit from anti-EGFR therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems
Prevalence of airflow obstruction according GOLD, ATS and ERS criteria in symptomatic ever-smokers referring to a pulmonary rehabilitation department
Authors: Elisa De Mattia, Adriano Vaghi, Ilaria Pessina, Giuseppe Pepe, Benedetto Rho, Nicola Barbarito
Journal: European Respiratory Journal (2011)

Aim:  To evaluate prevalence of airflow obstruction (AO) in ever-smokers ≥ 45 years old with both dyspnoea and chronic productive cough, using European Respiratory society (ERS) statement (FEV1/SVC    Methods:  Lung function tests were performed in each patients referred to our Pulmonary Rehabilitation department because of respiratory diagnosis or symptoms. For analysis, in patients showing AO we used post-bronchodilator lung function values.   Results:  In 184 ever-smoker patients with symptoms of chronic obstructive pulmonary disease (COPD), the prevalence rates of AO were as follows: ERS = 89.7%, ATS = 76.6%, and GOLD = 63.6%. Patients with AO according ERS criteria showing moderate to severe (M/S) obstruction (i.e., FEV1    Conclusions:  Prevalence of AO is highly dependent on which guidelines it is based. ATS and particularly GOLD statement can cause a large underdiagnosis even of moderate to severe COPD. Diagnosis of COPD may be overlooked if SVC is not performed.
Prognostic significance of neutrophil to lymphocyte ratio in chronic obstructive pulmonary disease
Authors: Nejat Altintas, Begum Kocar, Mukadder Tiryaki
Journal: European Respiratory Journal (2014)

Objectives: The blood neutrophil to lymphocyte ratio (NLR) has been identified as a potentially useful marker of clinical outcome in disease states with an inflammatory component. We have investigated the role of NLR in the prediction of long-term mortality in patients with chronic obstructive pulmonary disease (COPD).

Methods: This is a retrospective observational cohort study in which 129 patients with COPD were enrolled. Patients with cancer disease, ischemic heart disease, and systemic infections and chronic inflammatory diseases were excluded from the study. The primary end point was survival during follow-up. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal NLR cutoff level with regard to mortality.

Results: There were 107 men and 22 women, mean age 69.4±10.6 years. The mean follow-up duration was 32±5 months, during which 32 patients with COPD died. The mean NLRs were 2.3±1.2 and 4.42±3.8 in surviving and nonsurviving patients, respectively (P<0.001). Kaplan-Meier survival analysis was carried out according to the median NLR above and below 3 based on ROC analysis. Patients with NLR of at least 3 had a significantly lower survival (log rank, P<0.001). NLR was found to be an independent predictor of mortality in all Cox Regression models (hazard ratio 1.4; 95% confidence interval 1.3-1.5; P<0.001).

Conclusion: NLR, which is quick, cheap, easily measurable property with routine complete blood count analysis, is a predictor of mortality in patients with COPD.
Depression of Murine Macrophage Accumulation by Low-Molecular-Weight Factors Derived From Spontaneous Mammary Carcinomas2
Authors: George J. Cianciolo, Ronald B. Herberman, Ralph Snyderman
Journal: JNCI Journal of the National Cancer Institute (1980)

Extracts prepared from spontaneous mouse mammary adenocarcinomas, as well as plasma and urine from inbred C3H/HeN mice carrying murine mammary tumor virus and bearing such tumors, significantly inhibited the accumulation of macrophages at inflammatory sites in inbred the accumulation of macrophages at inflammatory sites in inbred C3Heb/FeJ mice. Much of the inhibitory activity from tumor cells was associated with products having a molecular weight (¿ 30,000); the inhibitory factor isolated from the plasma and urine of tumor-bearing animals had a molecular weight of 30,000 or less. Liver and spleen tissue, plasma, and urine from non-tumor-bearing animals had a molecular weight of 30,000 or less. Liver and spleen tissue, plasma, and urine from non-tumor-bearing animals had no effect on macrophage accumulation. Tumor cell extracts, plasma, and urine from tumor-bearing mice were shown to be free of infectious lactate dehydrogenase virus, a frequent contaminant of transplanted tumor and a known modifier of macrophage function. These results agreed with earlier reports of inhibitory activity for macrophage accumulation found in the tumors and sera of mice bearing multiple-passaged transplanted tumors and suggested that spontaneously arising neoplasms may subvert immune surveillance by depressing the ability of macrophages to respond to inflammatory stimuli.
Alveolar lymphocyte phenotype and respiratory distress syndrome
Authors: Karine Risso, Céline Sanfiorenzo, Gaurav Kumar, Francine de Salvador-Guillouet, Alain Bernard, Gilles Bernardin, Pierre-Marie Roger
Journal: European Respiratory Journal (2011)

Introduction:  The role played by adaptive immunity in the physiopathology of acute lung injury (ALI) and acute respiratory distress syndromes (ARDS) is largely unknown. We characterized lymphocytes phenotype in broncho-alveolar lavage (BAL) during respiratory distress syndromes.   Patients and method:  Analyses were carried out on BAL samples of three patients groups: ALI/ARDS patients (ARDS group), healthy patients (control group) and inflammatory pulmonary diseases patients (ID group). Lymphocyte and monocyte/macrophage phenotype determination used cytofluorometric technics. CD45RA+, CD45RA- and CD25FoxP3+ cells were respectively identified as naive, memory and regulatory T cells. HLADR, KI67 and annexin V were used as markers for cell activation, proliferation and apoptosis respectively. CD4, CD8, CD80, CD86, CD28, CD40/CD40L and CTLA-4 were used as costimulatory cell markers.   Results:  9 BAL were obtained from 8 ARDS patients, 8 BAL from 8 controls and 8 from ID patients. A significant increase of HLADR, KI67 and CTLA-4 on T CD4+ lymphocytes was observed in ARDS group compared to control. Concerning CTLA-4, the difference still persisted when comparing ID to ARDS group. KI67 expression was significantly increased on T CD8 T. HLA-DR and CD86 were significantly decreased on alveolar macrophages (AM) compared to others groups.   Discussion:  During ALI/ARDS activation and proliferation of T lymphocyte are noticeable, associated with alteration of the CD28/CTLA-4 costimulatory pathway and its ligand on AM.   Conclusion:  This is the first human study on adaptive immunity in ARDS/ALI identifying relevant modifications on T cell phenotype which may account for the dramatic alveolar inflammation observed in these syndromes.