tbuckley/cabot-search huggingface dataset:
Reply: “Procedural Considerations on the Use of Polyurethane and/or Conical Cuffs”; “Estimating the Risk of Ventilator-associated Pneumonia as a Function of Time”; “Is Tracheobronchial Colonization a Good Marker for Microaspiration in Intubated Critically Ill Patients?”; and “Translating <i>In Vitro</i> Research: Improving Endotracheal Tube Bench Test Methodology”
Authors: François Philippart, Laurent Quinquis, Stéphane Gaudry, Islem Ouanes, Xavier Forceville, Jean-Damien Ricard, Sophie Grabar, Benoît Misset
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Targeting the MDM2/MDM4 Interaction Interface as a Promising Approach for p53 Reactivation Therapy
Authors: Marsha Pellegrino, Francesca Mancini, Rossella Lucà, Alice Coletti, Nicola Giacchè, Isabella Manni, Ivan Arisi, Fulvio Florenzano, Emanuela Teveroni, Marianna Buttarelli, Laura Fici, Rossella Brandi, Tiziana Bruno, Maurizio Fanciulli, Mara D'Onofrio, Giulia Piaggio, Roberto Pellicciari, Alfredo Pontecorvi, Jean Christophe Marine, Antonio Macchiarulo, Fabiola Moretti
Journal: Cancer Research (2015)

Restoration of wild-type p53 tumor suppressor function has emerged as an attractive anticancer strategy. Therapeutics targeting the two p53-negative regulators, MDM2 and MDM4, have been developed, but most agents selectively target the ability of only one of these molecules to interact with p53, leaving the other free to operate. Therefore, we developed a method that targets the activity of MDM2 and MDM4 simultaneously based on recent studies indicating that formation of MDM2/MDM4 heterodimer complexes are required for efficient inactivation of p53 function. Using computational and mutagenesis analyses of the heterodimer binding interface, we identified a peptide that mimics the MDM4 C-terminus, competes with endogenous MDM4 for MDM2 binding, and activates p53 function. This peptide induces p53-dependent apoptosis in vitro and reduces tumor growth in vivo. Interestingly, interfering with the MDM2/MDM4 heterodimer specifically activates a p53-dependent oxidative stress response. Consistently, distinct subcellular pools of MDM2/MDM4 complexes were differentially sensitive to the peptide; nuclear MDM2/MDM4 complexes were particularly highly susceptible to the peptide-displacement activity. Taken together, these data identify the MDM2/MDM4 interaction interface as a valuable molecular target for therapeutic reactivation of p53 oncosuppressive function.
The expression of central cell cycle regulators in non-small cell lung cancer has therapy-dependent prognostic impact
Authors: Judith Cortis, Arne Warth, Thomas Muley, Felix J.F. Herth, Hendrik Dienemann, Peter Schirmacher, Philipp A. Schnabel, Wilko Weichert
Journal: European Respiratory Journal (2012)

Aims: Cell cycle regulation in cancer is tightly linked to proliferation, metastasis, and response to chemotherapy and thus an important factor for patients' prognosis. The relevance of function and expression of central cell cycle regulators in NSCLC has been discussed with controversial and non-conclusive results. In order to shed more light on the prognostic and predictive value of cell cycle regulation in NSCLC, we evaluated expression of key regulators and correlated the data with clinico-pathologic characteristics.

Methods: Expression of CDK4, cyclin D1 and p16 were analysed immunhistochemically in 1082 completely resected NSCLC by means of tissue microarrays. The data were correlated with clinico-pathologic data including patients' surival with respect to adjuvant therapy.

Results In general, high expression of all cell cycle regulators was associated with better clinical outcome in a slightly variable way, depending on protein and prognostic parameters investigated. Interestingly, after stratification for therapy, the positive association of protein overexpression with survival was only seen in adenocarcinomas without adjuvant radio- and chemotherapy. In tumors with adjuvant irradiation and/or chemotherapy, the association was switched in the opposite direction.

Conclusions: The expression of CDK4, cyclin D1 and p16 in NSCLC has prognostic impact depending on adjuvant therapy. As an overexpression of all three proteins was associated with improved clinical outcome in completely resected pulmonary adenocarcinomas without adjuvant therapy, these markers could be used to predict the clinical outcome of patients without adjuvant radio- and chemotherapy.
Features of pulmonary involvement in patients with diffuse connective tissue diseases
Authors: Dina Petrova, Yakov Shoikhet, Sergei Berestov, Andrei Dorokhov
Journal: European Respiratory Journal (2011)

The objective is to study features of pulmonary involvement in patients with diffuse connective tissue diseases   Materials and methods:  Retrospective cohort study of 1363 patients. Inclusion criteria: patients at the age of 17-70 with diffuse connective tissue diseases. Exclusion criteria: malignant neoplasms of any localization, concomitant bronchopulmonary pathology. Standard clinical examination, electrocardiography, echocardiogram, spirometry, X-ray study, high resolution computed tomography, ultrasonic scanning of pleura were made.   Results:  The involvement of respiratory system was found in 56 (4,11%) of 1363 examined patients. The patients with systemic lupus erythematosus - 25 (44,6%) and rheumatoid arthritis– 19 (33,9%) prevailed. Fewer cases of pulmonary involvement were met in patients with system scleroderma - 9 (16,1%), overlapsyndromes– 2 (3,6%) and idiopathic dermatomyositis- 1 (1,8%). The most common manifestations of pulmonary involvement are bronchoobstructive syndrome - 39,3%, pulmonary fibrosis – 23,2%, pleuritis – 16,1% and pneumonitis – 12,5%. In 3,6% cases vasculitis and in 1,8% - combinations of pleuritis-pneumonitis, pleuritis-bronchoobstructive syndrome and pneumonitis- pleuritis- pulmonary fibrosis were diagnosed.   Conclusion:  In 4,11% cases, diffuse connective tissue disorders are accompanied with the involvement of respiratory system that is commonly manifested by bronchoobstructive syndrome, pulmonary fibrosis and pleuritis.
Till death do us part
Authors: Claudia Sellers, David Harrington, Vivian Sathianathan, Reema Patel, David Howell
Journal: BMJ (2015)

Recently our intensive care unit was asked to organise two “emergency marriages” in the space of a week, reminding us that the most important wish of dying patients may be one we are ill prepared to ask about. Discussions about the wishes of patients and families regarding care at the end of life are commonplace in critical care, but the desire for marriage in a couple dealing with terminal illness is more common than we expect. Marriage may have the power to help meet some of the spiritual and emotional needs of dying patients and …
Can 40 Seconds of Compassion Reduce Patient Anxiety?
Authors: Linda A. Fogarty, Barbara A. Curbow, John R. Wingard, Karen McDonnell, Mark R. Somerfield
Journal: Journal of Clinical Oncology (1999)

To use a standardized videotape stimulus to assess the effect of physician compassion on viewers' anxiety, information recall, treatment decisions, and assessment of physician characteristics.One hundred twenty-three healthy female breast cancer survivors and 87 women without cancer were recruited for this study. A randomized pretest/posttest control group design with a standardized videotape intervention was used. Participants completed the State-Trait Anxiety Inventory (STAI), an information recall test, a compassion rating, and physician attribute rating scales.Women who saw an "enhanced compassion" videotape rated the physician as warmer and more caring, sensitive, and compassionate than did women who watched the "standard" videotape. Women who saw the enhanced compassion videotape were significantly less anxious after watching it than the women in the other group. Nevertheless, information recall was relatively low for both groups, and enhanced compassion did not influence patient decisions. Those who saw the enhanced compassion videotape rated the doctor significantly higher on other positive attributes, such as wanting what was best for the patient and encouraging the patient's questions and involvement in decisions.The enhanced compassion segment was short, simple, and effective in decreasing viewers' anxiety. Further research is needed to translate these findings to the clinical setting, where reducing patient anxiety is a therapeutic goal.
The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus
Authors: Zong-ming Zhang, Eric C.H. Lai, Chong Zhang, Hong-wei Yu, Zhuo Liu, Bo-jiang Wan, Li-min Liu, Zu-hao Tian, Hai Deng, Qiu-hong Sun, Xiao-ping Chen
Journal: International Journal of Surgery (2015)
Physiological changes in scalp, facial and body hair after the menopause: a cross-sectional population-based study of subjective changes
Authors: I. Ali, F. Wojnarowska
Journal: British Journal of Dermatology (2010)

Significant changes in scalp, facial and body hair occur after the menopause. These can have a significant negative impact on self-esteem and are also potential markers of endocrine or metabolic diseases. Knowledge of postmenopausal hair changes is important for clinicians to distinguish between normal physiological change and those that require further medical investigation.To assess the subjective experience of scalp, facial and body hair change in a large cohort of normal postmenopausal females.Postmenopausal females aged 45 years or over of northern European origin completed a questionnaire detailing scalp, facial and body hair changes following the menopause. Women with a history of thyroid disease, oophorectomy or premature menopause were excluded from the study. The Mann-Whitney U-test and the χ(2) test were used to assess the correlation between scalp, facial and body hair changes with age.Diffuse generalized hair loss was the most common form of scalp hair loss, reported by 26% of women. Frontal hair loss was reported by 9% of women. Facial hair gain was cited by 39% of females with the chin being the most frequent site for new growth (32% of women). Body hair loss was significantly correlated with older age (P < 0·001) and was most frequent at androgen-sensitive sites. We noted two patterns: (i) diffuse hair loss in which diffuse generalized scalp hair loss was significantly correlated with body hair loss and increasing age (P < 0·05); and (ii) frontal hair loss which was associated with higher facial hair scores and relatively younger age (P < 0·05) compared with women with diffuse hair loss.This is the first comprehensive study of the subjective hair changes in postmenopausal women. This study demonstrates two distinct patterns of hair change relating to age, which may reflect different underlying pathophysiological mechanisms and are of relevance to the medical management of these women as well as being possible predictors of health outcomes.
A phase II study of sequential capecitabine plus oxaliplatin (XELOX) followed by docetaxel plus capecitabine (TX) in patients with unresectable gastric adenocarcinoma: The TCOG T3211 trial.
Authors: Ming-Huang Chen, June-Seng Lin, Chin-Fu Hsiao, Yan-Shen Shan, Yeu-Chin Chen, Li-Tzong Chen, Tsang-Wu Liu, Chung-Pin Li, Yee Chao
Journal: Journal of Clinical Oncology (2015)

4024 Background: Fluorouracil and platinum can be considered a standard option for advanced gastric cancer (AGC). Docetaxel is also an effective agent with no cross-resistance with fluorouracil and platinum. Concomitant combination of docetxel with fluorouracil and platinum had been explored, but demonstrated intolerable toxicities. A different way to include all active agents in first-line treatment of gastric adenocarcinoma may be to use them sequentially. We aimed to evaluate the activity and the safety profile of sequential chemotherapy with capecitabine plus oxaliplatin followed by docetaxel plus capecitabine in the first-line treatment of AGC. Methods: We conducted a phase II study of first-line sequential chemotherapy in AGC. Treatment consisted of 6 cycles of capecitabine plus oxaliplatin (XELOX, Capecitabine 1000 mg/m2 bid on day 1-10 and Oxaliplatin 85 mg/m2 on day 1, Q2W) followed by 4 cycles of docetaxel plus capecitabine (TX, Docetaxel 30 mg/m2 on D1 and D8, Capecitabine 825 mg/m2 bid on day 1-14, Q3W). Primary end-point was the objective response rate. Results: Fifty-one patients were enrolled: median age 63 years; Male/Female: 37/14. Main grade 3-4 toxicities were ANC decreased (25.5%), diarrhea (11.8%), hand-foot syndrome (15.7%) and anemia (11.8%). The objective response rate was 56.9%. Median PFS and OS were 8.6 and 10.8 months, respectively. Five patients (9.8%) received surgery after chemotherapy and four were still on disease-free status. Conclusions: This sequential treatment demonstrated feasibility with a favorable safety profile and produced encouraging results in terms of activity and efficacy. Clinical trial information: NCT01558011.
The DCIS score: Potential for health care savings?
Authors: Rebekah Young, Shalom Kalnicki, Jana Lauren Fox
Journal: Journal of Clinical Oncology (2014)

35 Background: The Oncotype Dx Recurrence Score for DCIS (DCIS Score) is a 12-gene assay derived from the original Oncotype DX test. The DCIS Score provides a local recurrence risk estimate at 10 years after lumpectomy for DCIS. Results can guide decisions regarding adjuvant radiation (RT). Foregoing RT can be a source of significant healthcare savings. We investigated the actual healthcare dollar savings to-date in our patients. Methods: We evaluated patients in whom the DCIS Score was ordered (x) and calculated total cost of testing. Potential cost of RT was that of IMRT as reimbursed by Medicare for a 16 fraction course, multiplied by x. Many of our patients with large breasts require IMRT for dose homogeneity and normal tissue parameters. We also calculated potential cost with 3D conformal (3D-CRT). Total potential cost was the sum of testing and treatment costs, determined for each modality. The number of patients ultimately treated (y) was also multiplied by these costs. Total actual cost was the sum of test expenses and actual treatment costs. Savings was the difference between total actual and total potential cost. Results: From 2/2012 to 5/ 2014 the DCIS Score was performed in 38 patients (x = 38). Median age was 66 (40 to 85). Grade was low in 39%, intermediate in 45%, and high in 16%. Fifty percent had necrosis and median size was 0.5 cm (0.1 to 3.1cm). The total cost of testing was $4125 * 38 = $156,750. IMRT reimburses at $23, 000 and 3D-CRT at $11,000. Potential total cost of RT ranged from $418,000 to $874, 000; testing brought total potential costs to $574, 750 to $1,030, 750. Upon receipt of test results, 12 (y) patients ultimately underwent therapy. IMRT was given in 11 patients and 3D-CRT in 1, for a total treatment cost of $264, 000. Therefore, total actual expenditures were $420, 750. Savings amounted to (574, 750 – 420, 750) = $154, 000 to (1,030, 750 – 420, 750) = $610, 000. Conclusions: In the era of rising healthcare costs, it is imperative to examine instances of possible overtreatment. The DCIS Score has the potential to save not only healthcare dollars, but to spare patients radiation side effects, time lost from work, and transportation expenses. While there are costs associated with the assay, if ordered judiciously, these can be offset by the subsequent savings from eliminating treatment.
Postoperative radiation therapy for high-risk colon carcinoma.
Authors: C G Willett, C Y Fung, D S Kaufman, J Efird, P C Shellito
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study examines the experience of patients treated with postoperative radiation therapy after resection of high-risk colon carcinoma in an effort to assess the potential role of this modality in combination with current systemic therapies. PATIENTS AND METHODS From 1976 to 1989, 203 patients received postoperative radiation therapy with and without concurrent fluorouracil (5-FU) chemotherapy following resection of modified Astler-Coller B2, B3, C2, and C3 colon tumors. Of the 203 patients, 30 (15%) were identified as having residual local tumor after subtotal resection, whereas 173 (85%) had no known residual disease. The 173 patients treated with adjuvant radiation therapy were compared with a historical control group of 395 patients undergoing surgery only. RESULTS Three groups of patients who appeared to benefit from postoperative radiation were identified. Improved local control and recurrence-free survival rates were seen for patients with stage B3 and C3 colon carcinoma treated with postoperative radiation therapy compared with a similarly staged group of patients undergoing surgery only. Irradiated patients whose tumors had an associated abscess or fistula formation had improved local control and recurrence-free survival rates compared with a similar group of patients undergoing surgery only. There appears to be a subset of patients with residual local disease after subtotal resection that may be salvaged by high-dose postoperative radiation therapy. CONCLUSION Selected groups of patients with colon carcinoma may benefit from postoperative radiation in addition to current systemic therapies. Integration of 5-FU and levamisole with postoperative radiation therapy should be considered for patients with (1) stage B3 and C3 lesions, (2) tumors associated with abscess or fistula formation, and (3) residual local disease after subtotal resection.
Rhinovirus infection induces secondary bacterial infection in COPD
Authors: Patrick Mallia, Joseph Footitt, Rosa Sotero, Annette Jepson, Gregory Oleszkiewicz, Julia Aniscenko, Onn Min Kon, Papi Alberto, Sebastian Johnston, Girolamo Pelaia
Journal: European Respiratory Journal (2011)

Aim: To investigate the relationship between rhinovirus infection and secondary bacterial infection.

Methods: We performed experimental rhinovirus (RV) infection in COPD subjects (GOLD stage II, N=20), smokers with normal lung function (SMK, N=21) and non-smokers (NS, N=11). Sputum was collected at baseline and following inoculation. RV infection was confirmed with PCR and semi-quantitative bacterial culture performed. SLPI, elafin and neutrophil elastase (NE) were measured in sputum by ELISA.

Results: 1 subject with bacteria in baseline sputum was excluded. Following RV infection bacteria were detected in 65% of COPD, 19% of SMK and 30% of NS (P=0.0086). 92% of bacteria in the COPD group were pathogenic bacteria, compared with 50% in SMK and 33% in NS (P=0.045). Peak sputum virus load was on day 5 and peak bacterial load on day 15. Following RV infection sputum SLPI and elafin fell from baseline in the bacteria+ve subjects and increased in the bacteria-ve subjects.

![Figure][1] 

Figure 1





Peak virus load (8.4±0.72 vs 6.5±0.6 copies/mL,P=0.049) and sputum NE on day 9 (0.65±0.14 vs 0.31±0.07μg/mL, P=0.026) were higher in subjects with bacterial infection compared to those without.

Conclusions: Secondary bacterial infection is common following rhinovirus infection in COPD and is associated with higher virus loads and NE, but lower levels of SLPI and elafin in sputum. Degradation of SLPI and elafin by NE may be a mechanism of increased susceptibility to bacterial infection.

 [1]: pending:yes
Abediterol: Efficacy, safety and tolerability of the novel LABA in patients with persistent asthma
Authors: Jutta Beier, Beatriz Seoane, Eric Massana, Gonzalo De Miquel, Helena Pujol, Sandrine Ruiz
Journal: European Respiratory Journal (2014)

Background:  Abediterol (LAS100977) is a novel, once-daily, LABA in development for treatment of asthma and COPD. Previously, abediterol (2.5-10 μg) showed no dose-response relationship in male patients with persistent, stable asthma. We assessed lower doses in a similar population to establish a dose-response relationship.   Methods:  Patients were randomised to once-daily abediterol (0.625, 1.25 or 5 μg) and placebovia Cyclohaler ®  in a Phase II, 4-period crossover study. Endpoints included: change from baseline in trough and peak FEV 1 , normalised FEV 1  area under the curve (AUC; 0-12 and 0-24 hours), and safety and tolerability.   Results:  N=26/28 patients completed the study. Abediterol (all doses) achieved clinically significant dose-related improvements in bronchodilation vs placebo (Table). Bronchodilation was rapid: 5 minutes post-dose (5 μg) and 15 minutes post-dose (0.625 and 1.25 μg). Median time to peak FEV 1  was 3 hours (all doses), with significant bronchodilation vs placebo maintained over time. Treatment-emergent adverse events (22-27% abediterol; 11% placebo) were mostly mild-to-moderate.   Conclusions:  Single dose abediterol (0.625, 1.25 and 5 μg) was safe and well tolerated and showed rapid, clinically significant improvements in bronchodilation vs placebo in patients with persistent asthma (dose-response relationship).   Funding:  This study was supported by Almirall S.A., Barcelona, Spain.
Everolimus for Patients with Metastatic Renal Cell Carcinoma (Mrcc) Refractory to Anti-Vegf Therapy: Updated Results of a Pooled Analysis of Noninterventional Studies
Authors: L. Albiges Sauvin, U. Kube, J. Eymard, M. Schmidinger, A. Bamias, N. Kelkouli, B. Mraz, S. Florini, C. Rose, A. Cattaneo, L. Bergmann
Journal: Annals of Oncology (2014)
Influence of short-term passive smoking on symptoms, lung mechanics and airway responsiveness in asthmatic subjects and healthy controls
Authors: R Jorres, H Magnussen
Journal: European Respiratory Journal (1992)

We studied the acute effect of passive smoking on symptoms, lung mechanics and airway responsiveness. Twenty four patients with mild to moderate bronchial asthma (11 male and 13 female; mean(SD) age 34(15) yrs; forced expiratory volume in one second (FEV1) 91(17) % pred) were investigated. Sixteen of them had a history of passive smoke-induced respiratory symptoms. For comparison we studied 16 controls (7 male and 9 female; mean(SD) age 31(9) yrs; FEV1 106(13) % pred). On two different days, the subjects were exposed in an exposure chamber for one hour to either ambient air (Sham) or environmental tobacco smoke (ETS). During exposure to ETS, the mean concentrations of particles and CO were 3,095 micrograms.m-3 and 20.3 ppm, respectively. Before and immediately after exposure, symptoms and lung mechanics were assessed, followed by an inhalation challenge to determine the provocative concentrations of methacholine necessary to increase specific airway resistance (sRaw) by 100%, (PC100sRaw), and to decrease FEV1 by 20% (PC20FEV1). In the asthmatic subjects, during Sham exposure, mean (SEM) decrease of sRaw and FEV1 was 0.23(0.22) cmH2O.s and 0.04(0.03) l, respectively, (NS). During ETS, mean(SEM) decrease of sRaw and FEV1 was 0.55(0.46) cmH2O.s and 0.13(0.06) l, respectively. The significance of this decrease, however, disappeared when taking into account the individual variability of FEV1. Geometric mean(SEM) PC100sRaw and PC20FEV1 were 0.35(1.32) and 0.23(1.34) mg.ml-1 after Sham, and 0.34(1.37) and 0.28(1.36) mg.ml-1 after ETS, respectively, with no difference between the two study days. In the controls, the two exposure conditions did not exert any significant effects on sRaw, FEV1 and airway responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)