tbuckley/cabot-search huggingface dataset:
Recurrent respiratory papillomatosis - rapid response to systemic bevacizumab
Authors: Christoph Schliemann, Christoph Biermann, Andreas Hilbis, Thorsten Kessler, Joachim Schmidt, Karsten Wiebe, Klaus-Michael Müller, Thomas K. Hoffmann, Claudius Werner, Andreas H. Groll, Christina Kessler, Rainer Wiewrodt, Claudia Rudack, Berdel Wolfgang, Michael Mohr
Journal: European Respiratory Journal (2013)

Recurrent respiratory papillomatosis (RRP) is a potentially devastating, non-curable disease caused by infection with human papilloma virus (HPV), mainly HPV-6 and -11. Manifestations of RRP can occur everywhere in the respiratory tract and may lead to laryngeal, tracheal or bronchial obstructions, pulmonary nodes and cystic lesions due to valve effects. Malignant transformation occurs in 3 to 5% of the cases. Long-term management of patients with recurrent respiratory papillomatosis (RRP) remains challenging. Local debulking is the current treatment of choice and antiviral therapy is a possible adjuvant approach. Here, we report an immediate and sustained therapeutic effect of systemically applied bevacizumab without further local treatment in a series of five consecutive patients (7-56y) with RRP. In all cases, a rapid response to the first infusion of bevacizumab could be documented bronchoscopically within a few days.

![Figure][1] 



Continued anti-VEGF treatment resulted in sustained (very good) partial responses of tracheal or laryngeal papilloma manifestations. Due to limited alternatives VEGF-targeted therapies represent a promising novel strategy in the treatment of RRP and should be further investigated in clinical trials.

 [1]: pending:yes
Mental Health Services for Parents Who Lost a Child to Cancer: If We Build Them, Will They Come?
Authors: Wendy G. Lichtenthal, Geoffrey W. Corner, Corinne R. Sweeney, Lori Wiener, Kailey E. Roberts, Raymond E. Baser, Yuelin Li, William Breitbart, David W. Kissane, Holly G. Prigerson
Journal: Journal of Clinical Oncology (2015)

To examine bereavement mental health service use, barriers to use, and factors associated with use in parents bereaved by cancer.A multicenter, cross-sectional study of 120 parents bereaved by cancer between 6 months and 6 years after their loss was performed. Parents completed self-report assessments of mental health service use and barriers, prolonged grief, depression, anxiety, attachment styles, and sense of meaning by phone, in person, or on their own.Forty-one percent of bereaved parents were currently using mental health services (talk therapy, psychotropic medication, and/or a support group), most commonly within the first 2 years after their loss. Talk therapy was the most frequently used service, although 36% of parents who discontinued therapy did so because it was not helpful. Forty percent of parents who wanted bereavement support reported they were not receiving services. The most common barriers to service use were that it was too painful to speak about the loss (64%) and too difficult to find help (60%). Factors associated with current mental health service use included more recent loss, prior mental health service use, subclinical/increased depression, insecure attachment styles, and a decreased sense of meaning. Minority parents were more likely to have unmet needs than nonminority parents.Parents appear to need, want, and often access bereavement mental health services, which could be offered in oncology settings. However, barriers to service use must be addressed, particularly for those with more debilitating grief symptoms and for minorities. High treatment dropout rates suggest the importance of improving retention, training providers, and developing effective grief interventions.
Diagnosis of ovarian cancer
Authors: Sudha Sundar, Richard D Neal, Sean Kehoe
Journal: BMJ (2015)

#### The bottom line

Ovarian cancer is the seventh most common cancer in women worldwide, with 239 000 new cases diagnosed in 2012.1 As with many other types of cancer, geographical variation in the incidence of and mortality from ovarian cancer is substantial, with a higher incidence in economically developed regions of the world.2 Incidence is highest in the 50-70 year old age group, with 75% of cases diagnosed in women aged more than 55 years.3 In 80% of women the disease will be advanced at presentation, with a low five year survival rate; the all stage five year survival in the United Kingdom is 46%.4 This low survival rate in the UK has been recognised in the International Cancer Benchmarking Partnership and has been attributed at least partly to less timely diagnosis.5 This review summarises the presenting features, diagnostic tests, risk factors, and groups at high risk of ovarian cancer and is aimed at primary care practitioners and hospital doctors in other specialties.

#### Sources and selection criteria

We carried out an electronic search of PubMed, Medline, Embase, the Cochrane Library, and the Cochrane database of systematic …
An Italian, observational, multicentre trial to describe treatment management in COPD patients: Preliminary results of the MISTRAL study
Authors: Francesco Tursi, Gino Scalone, Alfio Pennisi, Evren Karayel, Marta Bartezaghi, Francesco Sergio
Journal: European Respiratory Journal (2014)

Introduction   In the 2011 GOLD update 1 , important changes in the severity classification have been introduced determining a possible positive implication in the disease management. The aim of this study is to better understand and characterize patient (pts) pharmacologic treatment pathways, with a particular focus on GOLD 2011 guideline in two different cohorts defined according to the rate of exacerbations (frequent [FE] ≥2 and non-frequent [NFE] up to 1 exacerbation).   Methods   This observational, longitudinal, multicenter study includes two cohorts (FE and NFE [1:1 ratio]) of pts (aged ≥ 40 yrs) with COPD and smoking history of ≥ 10 pack-yrs followed 3 yrs period. The primary objective is to describe the therapeutic approach in the 2 cohorts of pts with COPD during 3-yrs. Secondary outcomes are to evaluate, changes in COPD treatment management, clinical outcomes (CAT questionnaire, respiratory function and exacerbations, treatment persistence).   Results   The first 217 out of 1500 pts enrolled in the first 6 months with recorded e-CRF data 39% were FE and 61% were NFE. Characteristics of the two cohorts are presented (see table)  .   Conclusion   The preliminary results showed that FE have twice COPD duration, lower FEV 1  and relatively younger as compared to NFE. The majority of pts are symptomatic, especially in the FE group in line with the expectations that exacerbations reduce quality of life.
A Lymphocytopenic Filterable Agent Derived From Tissue Cell Cultures of Murine Carcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N. Molomut, M. Padnos, L. W. Smith
Journal: JNCI Journal of the National Cancer Institute (1965)

A lymphocytopenic virus was isolated from a cell culture derived from a strain of Ehrlich ascites carcinoma and from the mouse passage strain of Ehrlich ascites carcinoma. The virus was not cytopathic in tissue culture but was infective in adult mice in the several strains tested. The major pathologic changes were in the spleen, lymph nodes, and thymus and resulted in a marked diminution of lymphocytes, accompanied by degenerative hepatitis and the development of peritoneal and pleural fluid. The infection was of short duration and was followed by morphologic and functional regeneration of tissue. In the period post infection, the Swiss and C3H mice developed a fibrous encapsulation of the visceral organs. The pathologic changes associated with this virus are different from those known to be associated with mouse hepatitis, and Reo III and murine leukemia viruses.
The treatment of a non-Largenhans-cell histiocytosis, Erdheim-Chester disease: A-case report
Authors: Dane Ediger, Asli Gorek Dilektasli, Ahmet Ursavas, Duygu Koprucuoglu, Saduman Balaban Adim, Gokhan Gokalp, Ugur Yayla, Ercument Ege
Journal: European Respiratory Journal (2012)

Erdheim-Chester disease (ECD) is a rare, non-Largerhans histiocytosis with multisystem involvement. Pulmonary involvement is uncommon. We present a 46-year-old woman who presented with chronic chough, dyspnea and yellowish plaques in the periorbital area. She was previously diagnosed as diabetes insipidus. Chest radiographs showed bilateral diffuse interstitial infiltrates.  Symmetric sclerotic bone lesions, dural nevre thickening were defined on imaging studies. Histopathologic examination of the skin lesions revealed infiltration of CD-68 positive foamy histiocytes. She was diagnosed as ECD with pulmonary, pituitary, skeletal, orbita, central nervous system and skin involvement. Following first-line treatment with corticosteroids her syptoms worsened. Treatment with interferon-alpha was started. She had an marked improvemet in symptoms, radiologic findings and skin involvement under this treatment.  Conclusion: ECD should be considered in the differential diagnosis of interstitial lung diseases. As there is no standard treatment for this disorder, interferon-alpha can be effective in the treatment of Erdheim-Chester disease.
Lower limit of normal (LLN) for lung function parameters for over 80 year-old caucasians
Authors: Simone Accordini, Alessandro Fois, Barbara Piras, Giovanni Porqueddu, Valentina Spada, Francesco Borgo, Roberto de Marco, Pietro Pirina
Journal: European Respiratory Journal (2011)

Spirometric reference values for over 80 year-old populations have not been calculated yet. The present study is aimed at estimating the LLN equations for Caucasians.  In an ongoing clinical study, 214 subjects aged 80-88 performed valid lung function tests (according to the acceptability and reproducibility criteria of the American Thoracic Society) in 2001/2011 at the University Hospital of Sassari in Sardinia (Italy). During the clinical examination, these subjects: (i) did not report a diagnosis of respiratory diseases, symptoms of dyspnoea at rest/productive cough/bronchospasm, drug use for respiratory problems, and comorbidities (associated with impaired lung function) during lifetime; (ii) reported to be non smokers or to have quit smoking for ≥20 years. Past smokers with >15 pack-years were excluded.  Among the 120 males and 94 females, the mean height was 162 and 151 cm, and the percentage of past smokers was 59.2 and 4.3%, respectively. The sex-age specific mean (standard deviation) of FEV1, FVC, and FEV1/FVC ratio is reported in the following table:  On average, the FEV1/FVC ratio did not significantly decrease according to age among males (p=0.42), whereas it slightly increased among females (p=0.054).  These preliminary results suggest that the reference equations obtained from younger populations cannot be used for the long-term survivors. Appropriate LLN equations will be computed when a greater sample size is reached.
Sensitization to individual allergens and bronchial responsiveness in the ECRHS
Authors: S. Chinn, P. Burney, J. Sunyer, D. Jarvis, C Luczynska, None on behalf of the European Community Respiratory Health Survey
Journal: European Respiratory Journal (1999)

Little is known about the relation of bronchial responsiveness (BHR) to sensitization to individual allergens, or its variation between countries. Data were obtained for BHR, specific immunoglobulin E and confounding variables from 11,215 subjects, aged 20-44 yrs at the start of the European Community Respiratory Health Survey, in 34 centres in 15 countries. The relation of BHR to sensitization to cat, house dust mite, timothy grass and Cladosporium was estimated by means of multiple regression for each centre, and combined across centres by random effects meta-analysis, controlling for baseline lung function, height, sex, season of testing, age, smoking and age/sex and age/smoking interactions. BHR was greater, on average, in those sensitized to cat (p=0.023), house dust mite (p&lt;0.001) and timothy grass (p=0.018), but not to Cladosporium (p=0.60), and increased with degree of sensitization (p&lt;0.001). All relations showed heterogeneity between centres, although to a lesser extent in the relation to sensitization to house dust mite. More variation in bronchial responsiveness was explained by sensitization and degree of sensitization to the individual allergens than by atopy defined as any positive test in each centre, but the relative importance of each allergen varied. The use of atopy as a single variable in relation to bronchial hyperresponsiveness may be misleading.
The method for diagnosis matters in sleep apnea. A systematic analysis of polygraphy and polysomnography data in the European Sleep Apnea Database (ESADA)
Authors: Pierre Escourrou, Fadia Jilwan
Journal: European Respiratory Journal (2012)

In the ESADA study, each of the 23 participating centers used its own routine clinical and diagnostic procedures for OSA detection. Alltogether, data from 8228 patients with suspected OSA (M or F, 18–80 yrs) were analysed in order to compare results obtained by polygraphy (PG) (n= 5032) or polysomnography (PSG) (n=3196). The AASM 2007 criteria have been used for visual scoring of apnoea/hypopnoea and in addition in a PSG study, an event with ≤50% flow reduction, associated with arousal was also classified as hypopnoea (Eur Respir J 2011; 38: 635–642).  AHI was higher by PSG (29.9 ± 26 hr-1) than by PG (22.3 ± 23 hr-1) (p 15 by PSG whereas only 50% of patients were above this limit by PG (p -1  by PSG and 19 ± 22 hr -1  by PG. Furthermore the difference between the AHI and ODI scores was higher by PSG (8.6 ± 15.7) than by PG (1,1 ± 10) (p  In summary, the AHI is underestimated by PG leading to a lower rate of patients suffering from significant OSA than by PSG. This discrepancy is likely to relate to the scoring of hypopnea by arousal rather than the result of the time dilution effect.  supported by enabling grants from RESMED and PHILIPS RESPIRONICS.
A Phase I Study of Gemcitabine (Gem), Cisplatin (Cddp), and S-1 Combination in Untreated Patients (Pts) with Advanced Biliary Tract Cancer (Abtc)
Authors: T. Moriwaki, H. Ishida, M. Araki, S. Endo, S. Yoshida, M. Kobayashi, Y. Hamano, A. Sugaya, M. Shimoyamada, N. Hasegawa, M. Imanishi, Y. Ito, D. Sato, K. Ishige, K. Fukuda, M. Abei, T. Yamaguchi, I. Hyodo
Journal: Annals of Oncology (2014)

ABSTRACT   Aim: GEM plus CDDP has been established as standard first-line chemotherapy based on the results of the phase III study (ABC-02) in ABTC. An oral FU derivative, S-1 showed a similar activity to GEM in a phase II study and is mainly used in GEM-refractory pts in Japan. To develop a triplet regimen, GEM + CDDP + S-1 (GPS), we assessed its safety in this phase I study.  Methods: The main eligibility criteria were; histologically or cytologically confirmed ABTC, ECOG Performance Status (PS) 0-2, no prior chemotherapy, and written informed consent. Dose limiting toxicities (DLT) were evaluated in following 2 dose levels; GEM (1000 mg/m2 at level 1 and 1200 mg/m2 at level 2 on day 1) + CDDP (fixed dose of 30 mg/m2 on day 1) + S-1 (fixed dose of 40—60 mg/day bid for 7 days), repeated every 2 weeks until progression. The relative dose intensity of GEM and CDDP at level 2 corresponded to 90% of standard GEM plus CDDP regimen. In each level, 6-10 pts were enrolled and assessed. DLTs were evaluated during the first 2 cycles.  Results: Between Oct 2011 and Oct 2013, 18 pts were enrolled and 16 pts were evaluated (median age: 71 years, ECOG PS 0/1: 10/6, intrahepatic/extrahepatic/gallbladder: 7/3/6). DLTs (grade 3 nausea to stop S-1 in cycle 1 and treatment delay due to grade 3 neutropenia in cycle 2) at level 1 were observed in 2 of the first 6 pts. Additional 4 pts enrolled at this dose level experienced no DLTs. A DLT (G3 anorexia) at level 2 was observed in 1 of 6 pts. Grade 3 or 4 treatment-related adverse events within the first 2 cycles were leukocytopenia (38%), neutropenia (50%), thrombocytopenia (0.6%), nausea (0.6%), and anorexia (0.6%). Of 14 pts with measurable lesions, 7 (50%) pts had partial response and 6 (43%) patients had stable disease. Median progression free survival was 9.2 months (95%CI 6.8-11.6, event in 63%) and overall survival did not reach the median value (event in 38%).  Conclusions: GPS of dose level 2 (GEM 1200 mg/m2 and 30 mg/m2 on day 1 plus S-1 for 1-7 days, given bi-weekly) was well tolerated, and showed preliminary anti-tumor activity. Further study is warranted. Clinical trial information: UMI06123.  Disclosure: T. Moriwaki: Research funding for other study and honoraria from Taiho Pharmaceutical; I. Hyodo: Research funding for other study from Taiho Pharmaceutical and Lilly. Honoraria from Taiho Pharmaceutical. All other authors have declared no conflicts of interest.
Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization
Authors: A.A.Y. Cheah, T. Spelman, D. Liew, T. Peel, B.P. Howden, D. Spelman, M.L. Grayson, R.L. Nation, D.D.M. Kong
Journal: Clinical Microbiology and Infection (2013)
How expert physicians would wish to be treated if they had genitourinary cancer.
Authors: M J Moore, B O'Sullivan, I F Tannock
Journal: Journal of Clinical Oncology (1988)

A questionnaire describing six clinical scenarios was mailed to urologists (in Britain, Canada, and the United States) and to radiation and medical oncologists in the United States, who practice genito-urinary (GU) oncology. In each scenario, the surgeon or physician was asked to consider himself as a patient with bladder, prostate, or kidney cancer, and to select his own treatment. Accompanying each scenario were one or two clinical trials for which the physician would be eligible. He was asked to state if he would agree to be randomized in each trial, and if he refused, to state his reasons. We found that (1) there were major differences of opinion about management for each scenario; (2) choice of treatment was influenced more by specialty training or geographic location than by the results of previous clinical trials (which are available to all); (3) British urologists tended to be less aggressive than their North American colleagues, with respect to the use of radical surgery and chemotherapy; (4) acceptance of clinical trials ranged from 3% to 60%; and (5) agreement to clinical trials was quite poor even when they were designed to compare the most popular options for management. This physician surrogate method is a valuable tool in assessment of the degree of consensus amongst expert physicians and in the determination of whether new clinical trials address important areas of controversy.
The β-Agonist Lung Injury Trial (BALTI)
Authors: Gavin D. Perkins, Daniel F. McAuley, David R. Thickett, Fang Gao
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Experimental data suggest that manipulation of alveolar fluid clearance with beta-agonists can accelerate the resolution of alveolar edema and improve survival.To determine if a sustained infusion of intravenous salbutamol (albuterol) would accelerate the resolution of alveolar edema in adult patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).This was a single-center, double-blind, randomized controlled trial. Patients with ALI/ARDS were randomized to treatment with intravenous salbutamol (15 microg kg(-1) h(-1)) or placebo for 7 d. The primary endpoint was extravascular lung water measured by thermodilution (PiCCO) at Day 7.Sixty-six patients were screened; of these, 40 met the inclusion criteria and were enrolled during 2001-2003. Patients in the salbutamol group had significantly lower lung water at Day 7 than the placebo group (9.2 +/- 6 vs. 13.2 +/- 3 ml kg(-1); 95% confidence interval difference, 0.2-8.3 ml kg(-1); p = 0.038). Plateau airway pressure was lower at Day 7 in the salbutamol group (23.9 +/- 3.8 cm H2O) versus placebo (29.5 +/- 7.2 cm H2O; p = 0.049). There was a trend toward lower Murray lung injury score at Day 7 in the salbutamol group (1.7 +/- 0.9) versus placebo (2.0 +/- 0.6; p = 0.2). Patients in the salbutamol group had a higher incidence of supraventricular arrhythmias (26 vs. 10%; p = 0.2).Although further research is required to confirm the efficacy and safety of intravenous salbutamol in ALI/ARDS, this trial provides the first proof of principle that, in humans with ALI/ARDS, sustained treatment with intravenous beta-agonists reduces extravascular lung water.
Phase II trial of imatinib mesylate and hydroxyurea for grade III malignant gliomas
Authors: A. Desjardins, D. A. Reardon, J. A. Quinn, J. N. Rich, J. J. Vredenburgh, S. Sathornsumetee, A. Salvado, H. S. Friedman
Journal: Journal of Clinical Oncology (2006)

1573 Background: We evaluated the combination of imatinib mesylate (Gleevec) and hydroxyurea in WHO grade III malignant gliomas following the encouraging response of this combination demonstrated in glioblastoma multiforme. Methods: Eligibility: adult patients with recurrent/relapsing AA or AO with measurable disease; 2 weeks since surgical resection or 4 weeks since radiotherapy or chemotherapy; Karnofsky 60% and adequate organ function. Imatinib and hydroxyurea were given orally daily. Imatinib was administered at 400 mg daily to patients not on enzyme inducing antiepileptic drugs (EIAED) while those on EIAED received 500 mg twice a day. Hydroxyurea was administered to all patients at 500 mg twice a day. Each cycle was 28 days of therapy. Results: Thirty-nine patients with recurrent AA (n= 32) or AO (n=7), following prior radiation therapy and chemotherapy, have been enrolled, including 21 (54%) not on EIAED and 18 (46%) on EIAED. Patient characteristics were comparable between both strata. Median age was 39 years (range, 21–59 years). The most frequent grade III-IV toxicities were neutropenia (n=11), leukopenia (n=8), thrombocytopenia (n=6), deep venous thrombosis (n=3), fatigue (n=2) and pulmonary edema (n=2). One patient presented grade V brain hemorrhage at the time of disease progression. Four patients achieved a partial response, for an overall response rate of 10%. Thirteen patients (33%) achieved disease stabilization. Twelve patients (67%) not on EIAED had progressive disease as their best response compared to only 4 patients (27%) on EIAED. The median time to progression for all patients, and for those not on EAIED and on EIAED was 14.1 weeks, 10.9 weeks and 26.0 weeks, respectively. Conclusions: Daily imitanib mesylate plus hydroxyurea demonstrates encouraging activity and is well tolerated among patients with recurrent AA or AO. As observed with glioblastoma multiforme patients, patients on EAIED seem to demonstrate a better response. [Table: see text]
TNFα release by monocyte-derived macrophages at stable and exacerbation states in COPD
Authors: Richa Singh, Kylie Belchamber, Alexander Mackay, Beverly Kowlessar, James Allinson, Simon Brill, Gavin Donaldson, Peter Barnes, Jadwiga Wedzicha, Louise Donnelly
Journal: European Respiratory Journal (2014)

Inflammation is a hallmark of COPD and contributes to its pathogenesis. Inflammatory cells, such as alveolar macrophages, release inflammatory mediators including TNFα. We investigated basal and bacteria stimulated TNFα release by monocyte-derived macrophages (MDMs) at stable and exacerbation states.  MDMs were cultured from 26 COPD patients at paired stable and exacerbation states. The MDMs were incubated for 4 h at 37 o C with 100μl of RPMI (controls), inert beads (4.5x10 9  microspheres/ml), or heat-killed  Haemophilus influenzae  (HI) or  Streptococcus pneumoniae  (SP) (both at 5x10 8  cfu/ml). Subsequent TNFα release was measured by ELISA.  There was no difference in basal TNFα release from MDMs at stable and exacerbation states (p=0.247). There was a significant difference in TNFα release between the inert beads, HI and SP (p 0.05). In response to SP, TNFα release significantly increased at exacerbation compared to stable state (p=0.007, Figure 1A), but not in response to HI (p=0.513, Figure 1B).  HI is more pro-inflammatory than SP at both stable and exacerbation COPD states. However, a significant increase in TNFα release from stable to exacerbation state is only seen in response to SP. Further work is needed to investigate this response and the relationship with phagocytosis.