tbuckley/cabot-search huggingface dataset:
Update in Cystic Fibrosis 2014
Authors: Thida Ong, Bonnie W. Ramsey
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The clinical face of cystic fibrosis (CF) has significantly changed over the 25 years since its basic genetic defect was discovered (1). Increasing numbers of patients are diagnosed at newborn screening, and soon the majority of the CF population will be adult patients (2). With the 2012 approval of the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy, ivacaftor, the CF community has been able to experience the clinical and biological impact of this therapeutic approach in a small subset of patients with the G551D mutation (3). The findings are very encouraging and push investigators and clinicians to move forward with the development of additional modulators to improve the health of the majority of patients in the future. As a result, worldwide scientific collaborations have contributed to advances in therapeutics with the eventual goal of early intervention before the onset of symptoms. At the same time, the research community continues to elucidate the fundamental mechanisms of disease. In this article, we highlight some of the important scientific developments of 2014 with a focus on CFTR function and its complex role in mucociliary clearance (MCC), microbiology, and inflammation of the airway. In addition, advances in novel therapeutics and clinical outcomes are reviewed, with discussion of how those advances are impacting the field. CFTR Function and Its Role in MCC
Biomarkers in sarcoidois follow-up: Angiotensin-converting enzyme or chitotriosidase?
Authors: Matevz Harlander, Mirjana Zupancic, Barbara Salobir, Marjeta Tercelj
Journal: European Respiratory Journal (2014)

Introduction: Chitotriosidase (CTO) and angiotensin-converting enzyme (ACE) are both markers of sarcoidosis activity and both derive from chronically activated macrophages. In this study we compared the two biomarkers in the follow-up of sarcoidosis.  Methods: The study comprised 100 patients. Five were excluded because they lacked CTO activity (homozygotes for common CHIT1 polymorphism) and 8 because they were receiving ACE inhibitors (87 included, 46 female, mean age 44±13 years). The patients were followed-up for 24-60 months. CTO and ACE measurements were done every 3-6 months and correlated to clinical symptoms, chest X-ray and lung function (FVC, DLco). In 33 patients clinical outcome status (COS) at 5 years was determined.  Results: Initially, ACE was increased above upper normal level in 35.6% and CTO in 98.9% of patients. ACE and CTO were both significantly lower in no disease groups (COS 1 and 2) versus persistent disease groups (COS 5 through 9) (p = 0.008 and p = 0.050, respectively). In the follow-up period, there was a positive correlation between ACE and CTO and changes in clinical symptoms (p  Conclusions: Both biomarkers correlated similarly with COS score and with changes in clinical symptoms and chest X-ray. Only CTO correlated with changes in lung function. The interpretation of ACE values can be difficult due to large number of patients with ACE activity in the normal range. In comparison, CTO was increased in majority of patients and had a greater range of blood concentrations.
Abstract 1278: Over-expression of GATA-4 in Bone Marrow Stem Cells Enhances Their Transdifferentiation Potential and Cardioprotection against Ischemia
Authors: Ying Dai, Muhammad Ashraf, Yigang Wang, Meifeng Xu
Journal: Circulation (2007)

We hypothesize that over-expression of GATA-4 in bone marrow stem cells (BMSCs) promotes cardiac protection and repair of ischemic myocardium. Methods: Four types of stem cells were used: niched BM...
PF-3512676 may enhance the clinical activity of taxane/platinum chemotherapy in advanced non-small cell lung cancer
Authors: A Osman
Journal: Thorax (2009)

Current first-line therapy for stage IIIB–IV non-small-cell lung cancer (NSCLC) is taxane plus platinum-based chemotherapy. With this regime the 1-year survival rate is less than 40%. Toll-like receptors (TLR) can stimulate innate and antigen-specific acquired immunity. PF-3512676 is a TLR9-activating oligodeoxynucleotide and has confirmed antitumour activity against a variety of cancers.

This randomised phase II study examined the …
Predicted impact of access to varenicline on abstinence simulating multiple quit attempts over smokers' lifetimes
Authors: Richard J. Willke, Denis Getsios, Jeno P. Marton, Nikhil Revankar, Kelly H. Zou, James Xenakis
Journal: European Respiratory Journal (2011)

Background:  Relapse to smoking is a common challenge to many quitters, thus, access to effective smoking cessation treatment (SCT) for multiple quit attempts may be important in achieving permanent abstinence.   Objective:  To evaluate the impact of access (V [+] )  vs.  no-access to varenicline (V [–] ) on predicted health benefits and costs over smokers9 lifetimes.   Methods:  A discrete event simulation of SCT allowing multiple quit attempts (QA) with choice of treatments predicting response and possible relapse, as well as estimates of lifetime health and economic outcomes in a U.S. population was developed. The simulations compare outcomes of smokers who had access to varenicline for all QA9s with those without any access to varenicline. Smokers could also use NRT, bupropion, behavioral modification, or “cold turkey” for any QA, regardless of access to varenicline.   Results:  The average predicted total abstinence time (tAT) is 113 months with V [–]  and 126 months with V [+] . The corresponding average lifetime QAs/smoker are 9.0 with V [–]  and 7.5 with V [+]  conditions. The percent of individuals achieving permanent abstinence (at least 2 years by the time of death) is 68% with V [–]  and 72% with V [+] . For each simulated comorbidity (COPD, lung cancer, coronary heart disease and stroke), the incidence of new cases is lower with V [+] . Access to varenicline is dominant,  i.e.  more effective and less costly than no-access across all comparisons.   Conclusion:  Providing access to varenicline over smokers9 lifetimes results in better health outcomes at lower costs.
Care at end of life isn't being properly managed, says ombudsman
Authors: C. Dyer
Journal: BMJ (2015)

Terminally ill people are enduring painful and distressing deaths through failure by the NHS in England to properly manage care at the end of life, says a report from the parliamentary and health service ombudsman.1

The ombudsman service said that its investigations into complaints about the care received by patients nearing death had uncovered “tragic cases where people’s suffering could have been avoided or lessened with the right care and treatment as they approached the end of their lives.”

Clinicians failed in some cases to recognise that people were dying, noted the report, Dying without Dignity , which was based on complaints that had gone to the ombudsman after they were unable to …
Comprehensive analysis of mutations in the hepatitis delta virus genome based on full-length sequencing in a nationwide cohort study and evolutionary pattern during disease progression
Authors: E. Shirvani-Dastgerdi, S. Amini-Bavil-Olyaee, S. Moayed Alavian, C. Trautwein, F. Tacke
Journal: Clinical Microbiology and Infection (2014)
Molecular test supporting early lung cancer detection project based on pilot Pomeranian lung cancer screening program
Authors: Amelia Szymanowska-Narloch, Rafal Dziadziuszko, Malgorzata Jelitto-Gorska, Witold Rzyman
Journal: European Respiratory Journal (2011)

Introduction:  Lung cancer is one of the most common malignant neoplasms worldwide. Only 10% of patients can be cured, mostly due to late diagnosis and high aggressiveness of lung cancer.   Aim:  Aim of the Molecular Test Supporting Early Detection of Lung Cancer Project is to perform genetic studies and serum protein studies in order to increase the efficacy of radiological examinations in early lung cancer screening and to define population of particularly high risk of lung cancer development. The project consists of five thematic areas.   Results:  Pomeranian Pilot Early Detection Program has been realized from the 17th November 2008. In this project 8000 healthy subjects with high risk of developing lung cancer (age 50-75, at least 20 pack-years) were screened with low-dose CT scanning of the lungs. As a co-project blood samples were taken from those patients who gave informed consent. In the first year of project realization 6836 healthy subjects were screened. In above a half of the cases (53%) at least one pathological alteration in lung tissue was found. Among 186 patients, in whom the lesion was above 1 cm in diameter, in 56 cases lung cancer was diagnosed. Almost 60% of lung cancer cases were in stage IA.   Conclusions:  Pomeranian Pilot Lung Cancer Screening Program and Molecular Test Supporting Early Lung Cancer Screening Project - Moltest 2013 are dedicated to define population of particularly high risk of lung cancer development.
Dose-intensive vinorelbine with concurrent granulocyte colony-stimulating factor support in paclitaxel-refractory metastatic breast cancer.
Authors: R B Livingston, G K Ellis, J R Gralow, M A Williams, R White, C McGuirt, B B Adamkiewicz, C A Long
Journal: Journal of Clinical Oncology (1997)

PURPOSE We evaluated weekly single-agent intravenous (IV) vinorelbine as salvage therapy for metastatic breast cancer. After the first five patients, all received elective growth factor support with granulocyte colony-stimulating factor (G-CSF; filgrastim) in an attempt to maximize delivered dose-intensity (DDI). Objective tumor response, DDI, and toxicity were assessed, as well as time to progression (TTP) and survival. PATIENTS AND METHODS This single-center nonrandomized trial enrolled 40 patients. Anthracycline exposure and subsequent progression were common to all patients, and 38 of 40 were paclitaxel-refractory. Vinorelbine was given initially at 30 mg/m2/wk, then at 35 mg/m2/wk in a phase I/II design, which involved first intermittent (6 days of 7) and then continuous (daily) administration of G-CSF at 5 micrograms/kg. RESULTS The maximum-tolerated starting dose was 35 mg/m2/wk with continuous G-CSF support. The mean DDI was 27.7 mg/m2/wk for all patients. There were two complete responses (CRs) and eight partial responses (PRs) in 40 assessable patients for an overall response rate of 25% (95% confidence interval [CI], 13% to 41%). The median TTP was 13 weeks and median survival time 33 weeks. The dose-limiting toxicity was neutropenia, with dose delay or reduction required in 14 of 27 patients entered at 35 mg/m2. Febrile neutropenia that required hospitalization was unusual (three of 40 patients, 8%). There were no treatment-related deaths. Grade 3/4 thrombocytopenia occurred in nine patients (23%) and 26 patients (65%) required RBC transfusions for anemia. Seven patients (18%) had reversible grade 3/4 nonhematologic complications, primarily related to neurotoxicity. Grade &gt; or = 3 mucositis was absent. CONCLUSION Concurrent administration of weekly vinoralbine and daily G-CSF is feasible and permits an increase in DDI for vinorelbine of 43% to 76% over that reported in series without growth factor support. The response rate, TTP, and survival data are encouraging for therapy given to heavily pretreated patients with metastatic breast cancer. Vinorelbine is not cross-resistant with paclitaxel and should be considered for further trials in the dose-intensified mode made possible by G-CSF, alone or combined with other agents.
Use of COPD assessment (CAT) test in monitoring acute exacerbations
Authors: Irfan Shafiq, Kayleigh Huggett, Luaie Idris, Banu Rudran, Timothy Shaw
Journal: European Respiratory Journal (2011)

Introduction: The COPD Assessment Test (CAT) is a new patient completed questionnaire that has recently been validated to provide a simple assessment of health status in COPD. It is known that patients with moderate to severe exacerbation score about 5 units higher on CAT [1] and hence it may be useful in diagnosing and monitoring exacerbations.

Methods: We administered the CAT at the time of presentation with exacerbation and at the time of discharge home. We also measured the FEV1 on both encounters.

Results: We have results of 102 patients (60 men and 42 women). The initial mean CAT score was 22.55 and it improved to 19.28 by the time of discharge, this is an improvement of 3.27 points in CAT score on recovery from exacerbation. Although the mean improvement in CAT was not as high as 5 points, the difference between the two Cat scores was highly significant (p 0.002). Mean FEV1 improved from 0.89 to 1L but the difference was not statistically significant (p 0.073). The full results are displayed in the table below.

View this table:

Baseline characteristics and results





Conclusions: CAT might be a useful tool in monitoring recovery from COPD exacerbation and could help to determine the optimum time for discharging patient from hospital. Larger studies are needed to validate this use of CAT.

References: 

*   1. Jones PW, Harding G, Berry P, et al . Development and first validation of the COPD Assessment Test. Eur Respir J 2009; 34: 648-54.
Exercise for breathing pattern dysfunction – Time to re-group?
Authors: Amy Olley, Sita Kansagra, Gemma Pound, James Hull, Andrew Menzies-Gow
Journal: European Respiratory Journal (2014)

Introduction   Breathing pattern dysfunction (BPD) is an important cause for exertional dyspnoea & can co-exist with chronic respiratory disorders (e.g. asthma). Physiotherapy led breathing retraining, that can include exercise, is often used to improve symptom control in BPD, yet the benefit of a structured group exercise programme for BPD has not been studied.   Methodology   BPD patients, diagnosed if two or more elements of normal breathing control were absent (flow, rate, depth & locality), referred to the physio department over a year period were evaluated.  The group (n=5) exercise programme was provided every two weeks for 4 sessions. Education & breathing re-training advice was provided & patients were encouraged to exercise at BORG level 4-6. Outcome measures included; incremental shuttle walk (ISWT), resting BORG, MRC, Dyspnoea12 (D12) & Nijmegen score (NS). If patients had co-existing asthma (n=5); asthma quality of life (AQLQ) was completed.   Results   Thirty two patients (n=6 male) were evaluated; mean (SD) age 52.3 yrs (14.5), FEV1%pred 77% (24.8) & BMI 29 (5.7).  Pre & post intervention data was available for n=13. A 28% drop out (n=9) rate was recorded & 6 patients were lost to follow up.  Statistically significant improvements were seen in ISWT, MRC & AQLQ & decreased symptom scores shown by D12 & NS.   Conclusion   Physiotherapy led structured group exercise for BPD leads to improvement in exercise capacity & perceived breathlessness. Further studies are needed to evaluate this prospectively.
A feasibility/phase II study of gemcitabine (G) and split dose cisplatin (C) in advanced or metastatic non-small cell lung cancer (NSCLC) in an outpatient setting
Authors: S. A. Hussain, D. H. Palmer, D. E. Swinson, P. Riley, C. Brown, A. Wills, A. El-Modir, D. W. Rea, A. D. Chetiyawardana, M. H. Cullen
Journal: Journal of Clinical Oncology (2006)

17048 Background: This is a feasibility/phase II trial with GC on a 21-day cycle, with G and C split between d1, 8. Split dose C allowed administration in an outpatient setting. Objectives: To document the toxicity and define the objective response rate; and determine progression free and overall survival. Methods: Pts with stage III/IV NSCLC received: G/C 1250/40mg/m 2 (G and C given on d1, 8 every 3 wks). Eligibility: ECOG PS 0–2, adequate bone marrow/liver function, calculated GFR &gt; 50 ml/min. Results: 56 pts enrolled, all evaluable for toxicity; 47 evaluable for response; 4 patients too early for response assessment and 5 patients did not complete 1 cycle of chemotherapy. Characteristics: 70% male, median age 66 yrs (41–77), 25% GFR 50- 60 ml/min, 62% Stage IV. Radiotherapy was allowed after completing chemotherapy. 165 cycles have been delivered. Cycles with hematological toxicity: Grade 3: 5 anaemia, 17 neutropenia, 6 thrombocytopenia; Grade 4: 7 neutropenia, 4 thrombocytopenia. There were 3 episodes of febrile neutropenia. Cycles with non-hematological toxicity: Grade 4: 1 myocardial infarction (MI), 1 gastrointestinal (GI) bleed, 1 pulmonary embolism, 1 stroke; Grade 3: 3 nausea, 1 deep vein thrombosis, 4 chest infection, 1 hypomagnesemia; Grade 2: 3 renal toxicity, 2 seizure, 1 hypomagnesemia. Five cycles were deferred due to grade 4 neutropenia; 2 for renal toxicity (in one patient with diabetes and hypertension renal function declined after 1 cycle necessitating discontinuation of chemotherapy). 2 deaths occurred on treatment: 1 MI (patient with a previous history of MI); 1 GI bleed (on aspirin). Overall ITT RR was 33% (17/52: 1 CR+ 16 PR) (36% [17/47] for assessable pts). Median survival is 310-days. 1- year survival rate is 38%. Conclusion: G plus C in a 21-day schedule is active and well tolerated in an outpatient setting. This modified regimen with C split between d1 and d8, and, eligibility criteria of GFR as low as 50mls/min widens the spectrum of patients receiving cisplatin-based chemotherapy. Phase III trial is warranted. [Table: see text]
Quantitative assessment of cell-associated and cell-free virus in cervicovaginal samples of HIV-1-infected women
Authors: Maurizia Debiaggi, Arsenio Spinillo, Francesca Zara, Antonella De Santolo, Roberto Brerra, Renato Maserati, Egidio Romero, Gaetano Filice
Journal: Clinical Microbiology and Infection (1999)
ST-Segment Elevation Interpretation on Electrocardiogram
Authors: Ali Pourdjabbar, Martin S. Green, Pablo B. Nery
Journal: JAMA Internal Medicine (2015)

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Evaluating the Competence of Trainees: It's Nothing Personal
Authors: ROBERT H. KLEIN, RAYMOND BABINEAU
Journal: American Journal of Psychiatry (1974)

The process of evaluating the professional competence of trainees in the mental health field is accompanied by complexities that are more extensive than in other professional fields. The authors draw on personal experiences with mental health trainees to delineate some of the rational and irrational components of the evaluation process. They describe dilemmas and conflicts for both the evaluator and the trainee and make a number of recommendations aimed at clarifying individual and institutional roles and responsibilities and minimizing personal and institutional distress.
Alveolar macrophage populations are distorted in immunocompromised patients with pneumonitis
Authors: DH Bray, SB Squire, E Bagdades, PM Mulvenna, MA Johnson, LW Poulter
Journal: European Respiratory Journal (1992)

Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from patients presenting with pneumonitis: 30 human immunodeficiency virus (HIV)-infected individuals and 12 transplant recipients. Nine normal volunteers acted as controls. The cells were washed and cytospins prepared. Monoclonal antibodies (MoAbs) and immunoperoxidase methods were used to analyse the expression of HLA-DR molecules as well as phenotypic macrophage markers. P values apply to the differences between medians using the Mann-Whitney test. Median percentages of macrophages, lymphocytes and neutrophils were similar in all three groups. No differences were found in the median percentages of macrophages expressing the monocyte phenotype (MoAb UCHM1, CD14). However, in HIV-infected patients and transplant recipients a median of only 45% of macrophages expressed the pan-macrophage phenotype identified by MoAb EBM11 (CD68) in contrast with 98% in the normal volunteers. The AM population expressing the dendritic cell marker (MoAb RFD1) was also markedly reduced in both groups of immunocompromised patients (2 vs 28% in normal volunteers). Transplant recipients had significantly more phagocytic cells identified by MoAb RFD7 than the HIV-infected patients (25 vs 2%), but the numbers were still low when compared with the volunteers (48%). HLA-DR expression on BAL cells was reduced by 90% in both immunocompromised groups. For the transplant recipients, severity of pneumonitis was correlated with expression of dendritic cell marker RFD1, (Spearman's rank correlation r = 0.538, p less than 0.05) and pan-macrophage marker EBM11 (r = 0.581, p less than 0.05), while no such correlation was found in HIV-infected patients. These results suggest that a defective macrophage population is probably a serious factor contributing to immunosuppression.
Current Recommendations for Systemic Therapy of Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer
Authors: Matthew G. Fury, David G. Pfister
Journal: Journal of the National Comprehensive Cancer Network (2011)

For palliation of patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC), the major classes of commonly used cytotoxic chemotherapeutic agents are platinum agents (cisplatin, carboplatin), taxanes (paclitaxel, docetaxel), and antimetabolic agents (methotrexate, 5-fluorouracil). Cetuximab, a monoclonal antibody directed against the extracellular domain of the epidermal growth factor receptor, also shows modest activity against R/M HNSCC. Because the overall management of patients with R/M HNSCC often involves multidisciplinary input, this review focuses on data that help guide decision-making in scenarios in which palliative chemotherapy is planned. Avenues for ongoing research are also presented.