tbuckley/cabot-search huggingface dataset:
The outcome of community-acquired pneumonia in patients with COPD, asthma and ILD - a case-control study
Authors: Frank Dusemund, Joannis Chronis, Florent Baty, Werner Albrich, Martin Brutsche
Journal: European Respiratory Journal (2014)

Background  The impact of preexisting chronic lung diseases on complications and outcome in CAP is not well described. We aimed to investigate the impact of COPD, asthma and ILD on complications and outcome in hospitalized adult CAP-patients in a matched case-control study.  Methods  We used a nation-wide database including all hospitalizations in Switzerland from 2002 to 2010. Inclusion criteria were hospitalization due to CAP and age over 17 years. Exclusion criteria were HIV-infection, cancer and chronic lung diseases except COPD, asthma and ILD. The groups were matched according to age, gender and month of hospitalization. Endpoints were the incidence of lung abscess, parapneumonic pleural effusion, empyema, ARDS, in-hospital mortality and length of stay.  Results  We found less disease-related complications of CAP in hospitalized COPD and asthma patients compared with their controls. This difference was in both groups mainly related to a lower incidence of pleural effusion (COPD: 4.3% vs. 4.9%, p=0.011; asthma: 3.4% vs. 5.2%, p  Conclusions  Our novel and provocative results should be viewed as hypothesis-generating, with different possible explanations for our findings, including possible influence of ICS therapy, a possibly higher awareness of physicians while treating patients with chronic lung diseases, the different germ spectrum or an up-regulated immune response.
Abstract 16788: Classification of Patent Foramen Ovale Tunnel Morphology; A Real Time 3-Dimentional Transesophageal Echocardiographic Study
Authors: Jun Tanaka, Kenji Harada, Masaki Izumo, Takeji Saito, Swaminatha Gurudevan, Kirsten Tolstrup, James R Siegel, Takahiro Shiota
Journal: Circulation (2012)

Background: Shape of patent foramen ovale (PFO) tunnel has been classified anatomically into 3 types by 2D-TEE. However, PFO morphology is 3-dimensional structure, which may be difficult to classif...
Avoiding re-admissions of patients presenting with c (AECOPD) by nurse led telephone call follow up
Authors: Edward Davies, Joanne Wright, Rachel Fitzsimmons, Sarah Taylor, Imran Aziz
Journal: European Respiratory Journal (2014)

Background   The Royal College of Physicians COPD audit (Buckingham RJ et al, 2008) showed that patients presenting with AECOPD have a 33% re-admission rate within 90 days of index presentation. It is not clear if the high re-admission rate is due to disease deterioration or a lack of support at home. This places high workload on busy general practitioners and hospitals.   Aims and Objectives   To observe if weekly domiciliary visits for 2 weeks and successive telephone consultations for 4 weeks following index presentation of AECOPD, is effective in reducing re-admission.   Methods   Patients who accessed our acute COPD service from 09-09-2013 to 15-11-2013 (68 days) were included. Patients were excluded if they lived out of area or had other diagnoses. The patients taken into the scheme underwent an initial assessment and optimisation of current treatment. They received 2 domiciliary visits over a fortnight followed by weekly telephone follow up consultations over 4 weeks, they were then discharged from the service 6 weeks after the initial presentation.   Results   86 patients {51 female: mean (range) age 67.2 (46-82) years} were included, 6 died during the scheme and were excluded from further analysis. 17 (21%) of the remaining 80 patients were re-admitted with AECOPD within 90 days of the index admission.   Conclusions   We have shown a 6 week domiciliary and telephone follow-up service appreciably the re-admission rate of patients with AECOPD. Thus reducing admission pressures to hospital and providing reliable support to patients in the community.  {If accepted we will present data for the full project - till 31-12-2013}.
Oncogenic Transformation Can Orchestrate Immune Evasion and Inflammation in Human Mesenchymal Stem Cells Independently of Extrinsic Immune-Selective Pressure
Authors: Alex Miranda, Juan M. Funes, Nilda Sánchez, Celia M. Limia, Mónica Mesa, Sergio A. Quezada, Rolando Pérez, Joel de León
Journal: Cancer Research (2015)

Abstract Immune escape is a hallmark of cancer, but whether it relies upon extrinsic immune-selective pressure or is inherently orchestrated by oncogenic pathways is unresolved. To address this question, we took advantage of an in vitro model of sequentially transformed human mesenchymal stem cells (hMSC). Neoplastic transformation in this model increased the natural immune-evasive properties of hMSC, both by reducing their immunogenicity and by increasing their capacity to inhibit mitogen-driven T-cell proliferation. We also found that IFNγ signaling was globally affected in transformed hMSC. As a consequence, the natural inhibitory effect of hMSC on T-cell proliferation switched from an inducible mechanism depending on IFNγ signaling and mediated by indoleamine 2,3-dioxygenase to a constitutive mechanism that relied upon IL1β involving both secreted and membrane-expressed molecules. After transformation, increased IL1β expression both sustained the immunosuppressive properties of hMSC and increased their tumorigenicity. Thus, in this model system, IL1β acted as intrinsic inflammatory mediator that exerted an autocrine influence on tumor growth by coordinately linking immune escape and tumorigenicity. Collectively, our findings show how oncogenes directly orchestrate inflammation and immune escape to drive the multistep process of cancer progression, independently of any need for immunoediting in the tumor microenvironment. Cancer Res; 75(15); 3032–42. ©2015 AACR.
A Role for miR-145 in Pulmonary Arterial Hypertension
Authors: Paola Caruso, Yvonne Dempsie, Hannah C. Stevens, Robert A. McDonald, Lu Long, Ruifang Lu, Kevin White, Kirsty M. Mair, John D. McClure, Mark Southwood, Paul Upton, Mei Xin, Eva van Rooij, Eric N. Olson, Nicholas W. Morrell, Margaret R. MacLean, Andrew H. Baker
Journal: Circulation Research (2012)

Despite improved understanding of the underlying genetics, pulmonary arterial hypertension (PAH) remains a severe disease. Extensive remodeling of small pulmonary arteries, including proliferation of pulmonary artery smooth muscle cells (PASMCs), characterizes PAH. MicroRNAs (miRNAs) are noncoding RNAs that have been shown to play a role in vascular remodeling.We assessed the role of miR-145 in PAH.We localized miR-145 in mouse lung to smooth muscle. Using quantitative PCR, we demonstrated increased expression of miR-145 in wild-type mice exposed to hypoxia. PAH was evaluated in miR-145 knockout and mice treated with anti-miRs via measurement of systolic right ventricular pressure, right ventricular hypertrophy, and percentage of remodeled pulmonary arteries. miR-145 deficiency and anti-miR-mediated reduction resulted in significant protection from the development of PAH. In contrast, miR-143 anti-miR had no effect. Furthermore, we observed upregulation of miR-145 in lung tissue of patients with idiopathic and heritable PAH compared with unaffected control subjects and demonstrated expression of miR-145 in SMC of remodeled vessels from such patients. Finally, we show elevated levels of miR-145 expression in primary PASMCs cultured from patients with BMPR2 mutations and also in the lungs of BMPR2-deficient mice.miR-145 is dysregulated in mouse models of PAH. Downregulation of miR-145 protects against the development of PAH. In patient samples of heritable PAH and idiopathic PAH, miR-145 is expressed in remodeled vessels and mutations in BMPR2 lead to upregulation of miR-145 in mice and PAH patients. Manipulation of miR-145 may represent a novel strategy in PAH treatment.
Annual prevalence and treatment estimates of nontuberculous mycobacterial pulmonary disease in Europe: A NTM-NET collaborative study
Authors: Dirk Wagner, Jakko van Ingen, Jennifer Adjemian, Christoph Lange, D. Rebecca Prevots, David Griffith, Jack Gallagher, Renu Gupta, Charles Haworth
Journal: European Respiratory Journal (2014)

Background:  The prevalence of nontuberculous mycobacterial pulmonary disease (NTMPD) has been increasing in Europe; yet, comprehensive analyses and reliable estimates on treatment practices are lacking. We developed methods to assess annual prevalence, and used chart audits to evaluate treatment practices in 5 European countries (EU5): United Kingdom (UK), France, Germany, Italy, and Spain.   Methods:  NTMPD patients diagnosed annually was estimated by a 2-round Delphi method. A representative sample of physicians extracted treatment information from records of NTMPD patients with a confirmed diagnosis of  Mycobacterium avium  complex (MAC) or  M. abscessus  pulmonary disease.   Results:  Approximately 88% of all physicians contacted and 62% (446) with qualified patients participated. Pulmonologists made up the largest group of study physicians (Italy 17%, UK 38%). In EU5 most NTMPD patients are male (73%) and have a history of smoking (75%); COPD is the most common comorbidity (33%). MAC was the predominant species reported (79%). NTMPD estimated annual prevalence in EU5 ranged from 5.9 (Spain) to 6.5/100,000 (UK). A wide regional heterogeneity within countries was noted, particularly in France (Parisian region [13.6/100,000] vs Southwest region [1.3/100,000]). Logistic regression analysis showed that the decision to treat was most dependent on country (odds ratio = 6.2, Spain vs France) and severity of presenting symptoms (odds ratio = 1.9, severe vs mild).   Conclusions:  Annual prevalence of NTMPD is uniform on a per capita basis in EU5, but heterogeneous within different regions. The percentage of patients treated varies widely by country and severity.
Reliability of apnea/hypopnea index (AHI) determined by two different auto-CPAP in patients with obstructive sleep apnea syndrome (OSAS)
Authors: Androula Marinou, Clementina Leone, Berardino Mastropasqua, Antonio Foresi
Journal: European Respiratory Journal (2011)

Current Auto-CPAP devices retain information on their use, pressure, leaks and respiratory events and can operate also as CPAP. We evaluated reliability of AHI values recorded by two devices (Auto-Set Spirit II - 22 pts and REMstar auto M series -15 pts) as compared to those recorded by the Embletta, in a group of 37 consecutive adults with OSAS (mean age: 58 yrs; 14 F; BMI range: 24-61). Each patient underwent the following procedures: a. baseline ambulatory recording by Embletta; b. 3-7 nights recordings by Auto-CPAP; c. 3-7 nights recordings by CPAP; d. ambulatory recording by Embletta while using CPAP titrated on the basis of the Auto-CPAP records. Respiratory events were assessed by manual analysis of Embletta traces or based on at least 4 nights records of Auto-CPAP devices. We selected only nights during which patients used the device at least 5 hrs and leaks were
A Phase I Trial of the Anti-KIR Antibody IPH2101 and Lenalidomide in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Don M. Benson, Adam D. Cohen, Sundar Jagannath, Nikhil C. Munshi, Gary Spitzer, Craig C. Hofmeister, Yvonne A. Efebera, Pascale Andre, Robert Zerbib, Michael A. Caligiuri
Journal: Clinical Cancer Research (2015)

Natural killer (NK) cells may play an important role in the immune response to multiple myeloma; however, multiple myeloma cells express killer immunoglobulin-like receptor (KIR) ligands to prevent NK cell cytotoxicity. Lenalidomide can expand and activate NK cells in parallel with its direct effects against multiple myeloma; however, dexamethasone may impair these favorable immunomodulatory properties. IPH2101, a first-in-class antiinhibitory KIR antibody, has acceptable safety and tolerability in multiple myeloma as a single agent. The present work sought to characterize lenalidomide and IPH2101 as a novel, steroid-sparing, dual immune therapy for multiple myeloma.A phase I trial enrolled 15 patients in three cohorts. Lenalidomide was administered per os at 10 mg on cohort 1 and 25 mg on cohorts 2 and 3 days 1 to 21 on a 28-day cycle with IPH2101 given intravenously on day 1 of each cycle at 0.2 mg/kg in cohort 1, 1 mg/kg in cohort 2, and 2 mg/kg in cohort 3. No corticosteroids were utilized. The primary endpoint was safety, and secondary endpoints included clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD).The biologic endpoint of full KIR occupancy was achieved across the IPH2101 dosing interval. PD and PK of IPH2101 with lenalidomide were similar to data from a prior single-agent IPH2101 trial. Five serious adverse events (SAE) were reported. Five objective responses occurred. No autoimmunity was seen.These findings suggest that lenalidomide in combination with antiinhibitory KIR therapy warrants further investigation in multiple myeloma as a steroid-sparing, dual immune therapy. This trial was registered at www.clinicaltrials.gov (reference: NCT01217203).
Down-regulation of SLPI by cysteinyl leukotrienes in human bronchial epithelial cells can be reverted by glucocorticoids
Authors: Siiri Altraja, Kaido Värbu, Alan Altraja
Journal: European Respiratory Journal (2011)

Secretory leukoproteinase inhibitor (SLPI) protects the lung against proteinases implicated in the pathogenesis of diseases like COPD, but has also antimicrobial and anti-inflammatory properties. A fall in SLPI contents in the airways has been detected in COPD and asthma, however, the factors involved in the regulation of SLPI gene expression in the airway epithelial cells have insufficiently studied.  To evaluate whether pro-inflammatory cysteinyl leukotrienes (CysLT) exert regulatory effects on SLPI expression in normal human bronchial epithelial cells, the cultured cells were exposed to 0-50 nM LTE 4  for 3-6 h. Expression of SLPI mRNA was analyzed by RT-qPCR. The potential of glucocorticoids (GC) to revert the CysLT-induced effect on SLPI expression was addressed by incubating the cells for additional 3 h with 10 nM fluticasone propionate (FP) and 20 nM budesonide (BUD). Montelukast at 10 -6  mol/L was used to block the possible CysLT 1 -mediated action of LTE 4 .  Exposure of the cells to 50 nM LTE 4  resulted in a significant drop in SLPI expression after 6 h (p 4 , both FP and BUD fully reverted the CysLT-induced drop in SLPI (p=0.001 and p=0.003, respectively). The presence of montelukast did not additionally influence the potency of GC.  In conclusion, by down-regulation of SLPI in bronchial epithelial cells, CysLT may augment the pathogenetic events leading to COPD providing a pathway for more rapid decline in lung function in COPD patients with a concomitant CysCT-mediated disorder like asthma. Fortunately, this can be overpowered by treatment with GC.
HAGE in Triple-Negative Breast Cancer Is a Novel Prognostic, Predictive, and Actionable Biomarker: A Transcriptomic and Protein Expression Analysis
Authors: Tarek M.A. Abdel-Fatah, Stephanie E.B. McArdle, Devika Agarwal, Paul M. Moseley, Andrew R. Green, Graham R. Ball, A. Graham Pockley, Ian O. Ellis, Robert C. Rees, Stephen Y.T. Chan
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The expression of HAGE as a novel prognostic and predictive tool was assessed in 1,079 triple-negative breast cancers (TNBC). Experimental Design: HAGE protein expression was investigated in an early primary TNBC (EP-TNBC; n = 520) cohort who received adjuvant chemotherapy (ACT) and in a locally advanced primary TNBC cohort who received anthracycline combination Neo-ACT (n = 110; AC-Neo-ACT). HAGE-mRNA expression was evaluated in the METABRIC-TNBC cohort (n = 311) who received ACT and in a cohort of patients with TNBC who received doxorubicin/cyclophosphamide Neo-ACT, followed by 1:1 randomization to ixabepilone (n = 68) or paclitaxel (n = 64) as part of a phase II clinical trial. Furthermore, a cohort of 128 tumors with integrated HAGE gene copy number changes, mRNA, and protein levels were analyzed. Results: In patients with EP-TNBC, who were chemotherapy-naïve, high HAGE protein expression (HAGE+) was associated with a higher risk of death [HR, 1.3; 95% confidence interval (CI), 1.2–1.5; P = 0.000005] when compared with HAGE− cases. Patients who received ACT and expressed mRNA-HAGE+ were at a lower risk of death than those who were mRNA–HAGE− (P = 0.004). The expression of HAGE was linked to the presence of tumor-infiltrating lymphocytes (TIL), and both features were found to be independent predictors for pathologic complete response (pCR, P &amp;lt; 0.001) and associated with prolonged survival (P &amp;lt; 0.01), following AC-Neo-ACT. In patients with residual disease, HAGE+ had a 2-fold death risk increase (P = 0.018) compared with HAGE−. Conclusions: HAGE expression is a potential prognostic marker and a predictor of response to anthracycline treatment in TNBC. A prospective clinical trial to examine the therapeutic value of HAGE for TNBC cases is warranted. Clin Cancer Res; 22(4); 905–14. ©2015 AACR.
Effects of smoking habits on annual change in FEV1: A 12-year follow-up study
Authors: Hisamitsu Omori, Ayumi Onoue, Yayoi Funakoshi, Hironori Yada, Megumi Nagano, Shuichi Mihara, Yasuhiro Ogata, Hirotsugu Kohrogi, Takahiko Katoh
Journal: European Respiratory Journal (2011)

Background: The rate of forced expiratory volume in 1 second (FEV1) decline is a marker of chronic obstructive pulmonary disease risk. To date, limited longitudinal data exist on airflow obstruction (COPD) and FEV1 decline in Japan.  Aims and objectives: The aim of this study was to investigate the rate of FEV1 decline by smoking habits over a 12-year periods in Japanese males.  Methods: The study included 913 male subjects, aged 30-76 years at baseline, who underwent lung function tests at a medical check-up in 1994 (baseline), 1999, and 2006. The study group consisted of 263 persistent never smokers, 296 early quitters (those who stopped smoking between 1994 and 2006), 117 late quitters 8those who stopped smoking between 1999 and 2006), and 237 persistent smokers without airflow obstruction at baseline. Airflow obstruction (AO) was defined as FEV1/FVC  Results: Mean annual decline in FEV1 over a 12-year periods were -35.0 ml/yr in persistent never smokers, -37.9 ml/yr in early quitters, -40.7 ml/yr in late quitters, and -44.8 ml/yr in persistent smokers. Mean annual decline in FEV1 over a 12-year periods defined using the fixed criteria and the LLN criteria were -34.6 ml/yr, -34.3ml/yr in persistent never smokers without AO, -42.3 ml/yr, -42.3 ml/yr in persistent smokers without AO, -60.3 ml/yr, and -56.7 ml/yr in persistent smokers with AO, respectively.  Conclusions: Persistent smokers with AO had a significant reduced FEV1 decline compared with those in persistent never smokers and current smokers without AO. Our study confirmed that early cessation of smoking may reduce the FEV1 decline and prevent the development of AO among smokers.
Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis
Authors: Diana G. Eng, Maria W. Sunseri, Natalya V. Kaverina, Sebastian S. Roeder, Jeffrey W. Pippin, Stuart J. Shankland
Journal: Kidney International (2015)

As adult podocytes cannot adequately proliferate following depletion in disease states, there has been interest in the potential role of progenitors in podocyte repair and regeneration. To determine whether parietal epithelial cells (PECs) can serve as adult podocyte progenitors following disease-induced podocyte depletion, PECs were permanently labeled in adult PEC-rtTA/LC1/R26 reporter mice. In normal mice, labeled PECs were confined to Bowman's capsule, whereas in disease (cytotoxic sheep anti-podocyte antibody) labeled PECs were found in the glomerular tuft in progressively higher numbers by days 7, 14, and 28. Early in disease, the majority of PECs in the tuft coexpressed CD44. By day 28, when podocyte numbers were significantly higher and disease severity was significantly lower, the majority of labeled PECs coexpressed podocyte proteins but not CD44. Neither labeled PECs on the tuft nor podocytes stained for the proliferation marker BrdU. The de novo expression of phospho-ERK colocalized to CD44 expressing PECs, but not to PECs expressing podocyte markers. Thus, in a mouse model of focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed by regeneration, PECs undergo two phenotypic changes once they migrate to the glomerular tuft. Initially these cells are predominantly activated CD44 expressing cells coinciding with glomerulosclerosis, and later they predominantly exhibit a podocyte phenotype, which is likely reparative.
Involved-field radiotherapy and intra-Ommaya methotrexate/cytarabine in patients with AIDS-related lymphomatous meningitis.
Authors: M C Chamberlain, L Dirr
Journal: Journal of Clinical Oncology (1993)

To evaluate combined limited-field radiotherapy and concentration times time (C X T) intra-CSF chemotherapy in patients with AIDS-related lymphomatous meningitis (LM).Fourteen men and one woman with AIDS had cytologically documented LM. Eleven patients had systemic non-Hodgkin's lymphoma (NHL) (all B-cell histology, including six immunoblastic, four large cell, one small cell) with leptomeningeal metastases and four patients had primary CNS lymphoma (PCNSL) (all B-cell histology, including two immunoblastic, two large cell) with CSF dissemination. Presenting neurologic examinations included cranial neuropathies (n = 7), normal (n = 4), abulia (n = 2), paraparesis (n = 2), ataxia (n = 1), hemiparesis (n = 1), and aphasia (n = 1). Standardized pretreatment evaluations included contrast cranial magnetic resonance/computed tomography (MR/CT), placement of an intraventricular reservoir, CT myelogram/contrast spine MR, ophthalmologic examination, and indium 111-pentetic acid (DTPA) CSF flow studies. Regions of bulky or symptomatic disease were treated with limited-field radiation therapy, which included whole brain in 10 patients combined with spinal cord irradiation in five patients. Concurrent systemic chemotherapy was administered in 12 patients. All patients were scheduled to receive intraventricular methotrexate (MTX) 2 mg/d for 5 consecutive days biweekly for 8 weeks (induction), followed in cytologically responding patients by MTX administered in a similar manner every 4 weeks (maintenance). In MTX-responsive and consenting patients with cytologic relapse, intraventricular cytarabine (ara-C) was administered, 25 mg/d for 3 consecutive days weekly for 4 weeks (induction), followed by ara-C administered in a similar manner every 4 weeks (maintenance). CSF cytology and neurologic examinations were performed biweekly.In 13 assessable patients (two patients refused CNS directed therapy following standardized pretreatment evaluations), median time to tumor progression was 60 days (range, 3 to 260) and median survival duration was 125 days (range, 44 to 260). Response rate, determined clinically (four of 13 patients) and cytologically (nine of 13), was 69%. Complications included reservoir infection (n = 2) and myelosuppression (n = 11); the latter was felt to be a consequence of coadministered systemic chemotherapy.There were no treatment-related deaths. We conclude that involved-field irradiation and intraventricular MTX/ara-C is effective palliative treatment of AIDS-related LM.