tbuckley/cabot-search huggingface dataset:
Low-dose bevacizumab plus weekly irinotecan in recurrent glioblastoma multiforme, after failure of temozolamide: A phase II study.
Authors: H. El Ghazaly
Journal: Journal of Clinical Oncology (2010)

e12543 Background: The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of low-dose bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan after failure of temozolamide. Methods: This phase II trial included one cohort of patients, comprising 60 patients, received bevacizumab at 5 mg/kg every two weeks plus irinotecan 75 mg/m2 weekly for 3 weeks and one week rest. Every 2 cycles patients were evaluated clinically and radiologically using magnetic resonance imaging. Patients continued treatment till disease progression. Patients experienced toxicity from one drug, continued on the other drug till toxicity or disease progression. The primary end point of this study was the median overall survival and the secondary end points were the assessment of response rate and evaluation of treatment toxicity. Results: The median overall survival in these patients was 9 months. The overall response rate was 38.33% (23 patients). Toxicity profile was tolerable with hypertension occurred in 8.3% (5 patients), diarrhea 3.3%, neutropenia in 10% of patient, and intracranial hemorrhage in only one patient. Conclusions: Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme after failure of temozolamide and has moderate toxicity. No significant financial relationships to disclose.
Cancer therapy and the “broken heart”: Decision making during treatment of cancer in patients with left ventricular systolic dysfunction (LVSD)
Authors: G. Curigliano, M. Locatelli, M. Lazzeroni, R. Ghisini, G. Spitaleri, D. Cardinale, C. Cipolla, A. Goldhirsch
Journal: Journal of Clinical Oncology (2008)

9619 Background: Reduced left cardiac ejection fraction (LVEF), though asymptomatic, affects cancer patients’ outcome and limits their therapeutic opportunities. We assessed treatment choice and occurrence of cardiotoxicity defined as an absolute decrease >20 percent units in rest LVEF in a selected population of cancer patients with LVSD at study entry. Methods: From January 1999 to October 2006, 548 consecutive patients with cancer were referred for a LFSD to the Cardiology Unit of the European Institute of Oncology (IEO). 282 patients (131 female, 151 male) with an abnormal EF at diagnosis were grouped as: LFSD (n=10), asymptomatic resting EF <60- 50% (G1, n=51); asymptomatic resting EF <50–40% (G2, n=100); symptomatic cardiac heart failure (CHF) EF <40–20% (G3, n=101) and severe CHF EF <20% (G4, n=3). 156 patients received no previous cancer treatment. 69 patients had a previous anthracycline treatment (55%) and 35 (12%) received previous chest radiotherapy. All patient underwent a baseline and subsequent serial LVEF measurement by ultrasound. Results: Median age of patients was 64 years (range 21–89). 85 patients (30%) had breast cancer, 60 (21%) lung, 36 (13%) gastrointestinal, 34 (12%) haemathological, 18 (6%) urogenital and 49 (18%) other cancers. Out of 100 patients with asymptomatic resting EF <50–40%, 41 pts (41%) received a tailored “cardiac function adapted” chemotherapy. In the group of patients with CHF and EF <40–20%, 29 (29%) received chemotherapy. Only 1 out of 3 patients with severe CHF was treated with chemotherapy. After a first line chemotherapy the mean LVEF decreased from EF <50–40% (G2) to symptomatic CHF in 14/41 patients (34%), even if treatment choice excluded agents with known cardiotoxicity. Conclusions: Patients with LFSD at cancer diagnosis receive an adapted, suboptimal treatment for cancer. A symptomatic impairment of LVEF was observed in patients with asymptomatic LVSD treated with chemotherapy. Reluctance to prescribe systemic treatments is due to complexity of cost-benefit evaluation in such patients. Trials including supportive therapy with angiotensin-converting enzyme inhibitors should be activated to attempt an improved cancer treatment choice for patients with LVSD. No significant financial relationships to disclose.
Twice-daily aclidinium bromide in COPD patients: A pooled analysis of lung function in the ACCORD-COPD I and ATTAIN trials
Authors: Edward Kerwin, Paul Jones, Anthony D'Urzo, Ludmyla Rekeda, Esther Garcia Gil, Cynthia Caracta
Journal: European Respiratory Journal (2012)

INTRODUCTION:  Aclidinium is a novel, long-acting muscarinic antagonist being investigated for maintenance treatment of COPD. Pooled analyses of lung function data from the ACCORD and ATTAIN trials are presented here.  METHODS:  Patients (N=1389) were randomized to aclidinium 200 μg, 400 μg, or pbo BID for 12- and 24-weeks for ACCORD and ATTAIN, respectively. Endpoints included change from baseline in FEV 1  over 3h postdose on Day 1 as well as trough and peak FEV 1  at Week 12.  RESULTS:  Mean (SD) baseline and % predicted FEV 1  were 1.45 (0.52)L and 50.3 (14.3)L, respectively. Significant improvements in lung function were seen following the first dose, as measured by change from baseline in FEV 1  at 0.5h postdose (first time point assessed) on Day 1 (200 μg, 99 mL; 400 μg, 128 mL; both p 1 ; a greater improvement and a clinically significant effect in trough FEV 1  was seen with the higher dose (200 μg, 80 mL; 400 μg, 112 mL; both p 1  was 167 mL and 191 mL for 200 μg and 400 μg, respectively (both p  CONCLUSIONS:  Both doses of aclidinium produced significant improvements in lung function in COPD patients, with the 400 µg dose being consistently more effective. Maximal improvements in lung function were seen at Day 1 and were maintained over 12 weeks.
Relationships between glutaredoxin 1 and cytokine levels in a murine model of allergic airway inflammation
Authors: Kanako Maki, Katsura Nagai, Masaru Suzuki, Takashi Inomata, Takayuki Yoshida, Masaharu Nishimura
Journal: European Respiratory Journal (2013)

Background:  Glutaredoxin 1 (Glrx1) catalyzes a reduction of S-glutathionylated protein (PrSSG) and its expression increases in the murine lungs of allergic airway inflammation and in sputum of patients with asthma. Glrx1 also regulates a production of inflammatory mediators. We hypothesized that Glrx1 would synergistically induce an inflammatory response along with Th2 and NF-κB related cytokines in a murine model of allergic airway inflammation.   Aims:  To show relationships between Glrx1, and Th2 or NF-κB related cytokine levels as well as the number of inflammatory cells in bronchoalveolar lavage fluid (BALF).   Methods:  BALB/c mice received three aerosol challenges with ovalbumin (OVA) or PBS following sensitization to OVA, then were sacrificed at 6, 24, 48, or 72 h, or 8 days. Th2 or NF-κB related cytokine levels in BALF were assessed using a Procarta Immnoassay kit.   Results:  Th2-related eotaxin at 6 and 48 h, IL-4 at 6 h, IL-5 at 6 and 24 h, and TGF-β at 6 h to 8 days after final challenge were significantly increased compared to controls in BALF (p   Conclusions:  Our data identified a sequential production of Th2 and NF-κB related cytokines followed by TGF-β in a murine model of allergic airway inflammation, which was differentially associated with Glrx1 levels in BALF and the lung tissue.
A Military Specialist Registrar in Your Department: Free Blessing or Cuckoo in the Nest?
Authors: Jason Smith, Gary Matthews
Journal: Journal of the Royal Society of Medicine (2001)

The Defence Medical Services, of which the Defence Secondary Care Agency (DSCA) is a part, has a total of 140 specialist registrars in training across all hospital specialties, of whom several are training in hospitals with no formal military connection. Most of these posts are funded by the DSCA and therefore the civilian department has, effectively, a free registrar. However, little is known outside of the Defence Medical Services about who these doctors are, where they have come from, and what can be expected of them. Indeed, is the presence of one of these registrars a blessing or an encumbrance?
Longitudinal Structural Determinants of Atherosclerotic Plaque Vulnerability
Authors: Koji Imoto, Takafumi Hiro, Takashi Fujii, Akihiro Murashige, Yusaku Fukumoto, Genta Hashimoto, Takayuki Okamura, Jutaro Yamada, Koji Mori, Masunori Matsuzaki
Journal: Journal of the American College of Cardiology (2005)
Abstract 10386: Is New Onset Atrial Fibrillation a Surrogate Marker for Heart Failure Progression?
Authors: Ryan Aleong, Gordon Davis, William Sauer, Alastair D Robertson, Michael R Bristow
Journal: Circulation (2011)

Framingham data indicate that the onsets of atrial fibrillation (AF) and chronic heart failure (HF) are often related, and in the presence of one the onset of the other increases mortality risk. These data contribute to the evidence that AF and HF have interrelated pathophysiologies, and conjoined natural histories. To test the hypothesis that new onset AF is a surrogate marker for HF progression, in the BEST trial (low LVEF advanced HF, beta-blocker bucindolol vs. placebo) we measured the all-cause mortality (ACM) and total HF hospitalization (HFH days/pt) before and after the development of new onset AF, in patients who did not have AF at randomization. [TABLE 1] In addition, we performed a within treatment group multivariate stepwise analysis (MVA) for 16 variables potentially affecting time to HFH: (Cox model p values in order of acceptance into the model, all univariate predictors are p<0.001) [TABLE 2] Summary: 1) In BEST new onset AF was associated with a 2.1 fold increase in ACM, and a 1.8 fold in...
Abstract 2284: Long-Term Outcomes of Percutaneous Mitral Balloon Valvuloplasty Versus Open Heart Surgery
Authors: Jae-Kwan Song, Mi-Jeong Kim, Sung-Cheol Yun, Suk Jung Choo, Jong-Min Song, Hyun Song, Duk-Hyun Kang, Cheol Hyun Chung, Duk Woo Park, Seung Whan Lee, Young-Hak Kim, Cheol Whan Lee, Myeong-Ki Hong, Jae-Joong Kim, Jae Won Lee, Seong-Wook Park, Seung-Jung Park
Journal: Circulation (2008)

Late functional deterioration after percutaneous mitral valvuloplasty (PMV) has raised the issue of comparing long-term outcomes between PMV and open-heart surgery (OHS). The study evaluated 402 patients who underwent PMV and 159 patients who underwent OHS between January 1, 1995, and December 31, 2000. The rates of cardiovascular death or repeated intervention (redo-PMV or OHS) were determined over a median follow-up of 109 months (mean±SD 106±27). The therapeutic effects on adverse outcomes were estimated using Cox’s proportional hazards model adjusting differences in the severity of illness before intervention, and the effects of the cardiac rhythm and echocardiographic score were also tested. The observed (unadjusted) event-free survival rate was similar for both groups, and the hazard ratio for the clinical events after PMV as compared with after OHS was 1.510 (95% confidence interval [CI], 0.914 –2.496, p=0.1079). However, the adjusted hazard ratio was 3.729 (95% CI, 1.963–7.082, p&lt;0.0001), showing a higher event-free survival rate in the OHS group. The adjusted hazard ratios after PMV as compared with after OHS in patients with echocardiographic scores ≥8 and atrial fibrillation were 5.348 (95% CI, 2.504 –11.422, p&lt;0.001) and 3.440 (95% CI, 1.805– 6.555, p=0.0002), respectively, whereas the hazard ratios in patients with echocardiographic scores &lt;8 and normal sinus rhythm did not show differences. OHS was associated with a higher adjusted rate of long-term event-free survival than PMV. Patients with high echocardiographic scores or atrial fibrillation showed better outcomes after OHS.
Abstract 35: Unprocessed and Processed Meat Consumption and Blood Pressure: The INTERMAP Study
Authors: Linda M Oude Griep, Paraskevi Seferidi, Jeremiah Stamler, Queenie Chan, Linda Van Horn, Lyn M Steffen, Katsuyuki Miura, Hirotsugu Ueshima, Nagako Okuda, Liancheng Zhao, Sabita S Soedamah-Muthu, Martha L Daviglus, Paul Elliott
Journal: Circulation (2015)

Background: Evidence from prospective cohort studies indicates that consumption of processed meats is associated with higher incidence of CHD. Processed meats are high in saturated fatty acids, cholesterol, and preservatives including sodium that may unfavorably influence blood pressure (BP), but evidence is limited. We therefore investigated associations with BP of unprocessed and processed meat consumption, including types of processed meats. Methods: We used cross-sectional data from the INTERMAP Study on 4,680 men and women aged 40-59 years from Japan, China, UK, and US. During four visits, eight BPs and four 24-hr dietary recalls were collected. Processed meats included preserved meats; fresh processed meats (ready-made, salted, and/or spiced, no curing), bacon, ham (cured and cooked), cold cuts and sausages, and canned meat products. Country-specific linear regression coefficients were estimated and pooled, weighted by inverse of their variance. Adjustments were made for demographic (age, gender, sample), lifestyle (total energy, alcohol, smoking, education, supplement use, adherence to special diet, low-fat dairy, fruit, vegetables, fiber-rich grain products, fish and shellfish), and clinical confounders (history of cardiovascular diseases or diabetes, family history of hypertension, use of anti-hypertensive, cardiovascular, or diabetes medication, BMI). The influence of adjustment for urinary sodium, total cholesterol, and total saturated fatty acids was additionally investigated. Results: Average daily unprocessed/processed meat consumption (g/1000 kcal) was 41/10 in Asian participants and 82/47 in Western participants. In Western participants, processed meats comprised fresh processed meat (36%), cold cuts and sausages (34%), ham (16%), and bacon (7%). Meat consumption was not associated with BP in Asian participants. After adjustment for demographic and lifestyle factors, significant associations with systolic BP were observed per each 50 g/1000 kcal higher intake of unprocessed (+1.19 mm Hg, P=0.02) and processed (+2.00 mm Hg, P=0.01) meat consumption in Western participants. However, these associations attenuated and did not remain significant after adjustment for BMI. We further examined types of processed meat in Western participants. Consumption of cold cuts and sausages higher by 12,5 g/1000 kcal was associated with a systolic BP difference of +0.72 mm Hg (P=0.02). Consumption of ham higher by 12,5 g/1000 kcal was associated with a systolic BP difference of -0.92 mm Hg (P=0.03). These associations prevailed after adjustment for urinary sodium excretion, intakes of saturated fatty acids, and total cholesterol. Conclusion: Unprocessed and processed meat consumption was not associated with BP, however, some types of processed meat may influence BP in opposite directions.
The Delayed Arrival: From Davy (1800) to Morton (1846)
Authors: Aileen K Adams
Journal: Journal of the Royal Society of Medicine (1996)

Dr Adams was previously consultant anaesthetist to Addenbrooke's Hospital, Cambridge, with a special interest in ophthalmic and neuroanaesthesia, and Associate Lecturer in Cambridge University. She was Dean of the Faculty of Anaesthetists of the Royal College of Surgeons of England in 1985, now the Royal College of Anaesthetists, of which she is currently Honorary Archivist/Curator. She was Hunterian Professor in the Royal College of Surgeons in 1993, and is a past president of the History of Anaesthesia Society. Within the RSM she was president of the Section of Anaesthetics in 1985-1986 and of the Section of the History of Medicine in 1994-1995, having served as Honorary Secretary of each. She is now an Honorary Treasurer of the Society.
Lung cancer cases in clean-up workers of Chernobyl NPP accident
Authors: Liudmyla Shvaiko, Victor Sushko, Kostiantyn Bazyka
Journal: European Respiratory Journal (2013)

The purpose of the study was to analyze Lung Cancer (LC) cases in cohort of clean-up workers of Chernobyl Nuclear Power Plant (ChNPP) accident (1986).  Methods: The Analysis of database which includes 7156 clean-up workers (6257 (87,4 %) men and 899 (12,6 %) women) of ChNPP accident in comparing with Cancer Registry of Ukraine was provided. The total found of 50 (0.70%) lung cancer (LC) cases in a cohort were analyzed. The probable risk factors of LC were analyzed in the named cohort of clean-up workers: age at the diagnosis of LC, age at the time of participation in the accident, anamnesis of bronchopulmonary diseases, dose of ionizing radiation, smoking.  Results: Age of patients at time of LC diagnosis ranged from 44 to 80 years and averaged 59.56 + 1.22 years. There was a clear relationship between the age of patients at LC diagnosis and the age at the time of the Chernobyl accident (r = 0,88; p = 0,0001). The average age at the time of the accident was significantly higher in those who emerged LC (43.0 + 1.12 years, p = 0.001). Among clean-up workers suffered with LC significantly more often different bronchopulmonary diseases especially COPD were found (72% and 47.01%, respectively, p = 0.001). Only 6 of 50 patients with LC never smoked, compared with 1439 (34.04%), without LC (p = 0.001). The risk of LC for smokers was 3.785 (95% CI 1.609 - 8.903). Doses of radiation exposure were higher in clean-up workers with LC, then in those without LC (36,87 + 9,08 sSv and 20,42 + 0,56 sSv, accordingly).  Conclusion: Risk factors for LC in clean-up workers of ChNPP accident were radiation exposure more than 50 sSv, chronic diseases of bronphopulmonary system, smoking and interaction of these factors.
Nasal high flow: Is it a wash - out - effect?
Authors: Jens Bräunlich, Marcus Köhler, Hans-Jürgen Seyfarth, Hubert Wirtz
Journal: European Respiratory Journal (2013)

Introduction: The treatment with nHF reduces symptoms of chronic respiratory insufficiency. In addition, a reduction of the hypercapnia was observed. Method: Patients with COPD were measured with a flow of 20 and 30 l/min. For the measurement of the breath volumes and the respiratory rates impedance measuring belts were used. These were placed 10 cm below the Xiphoids and 10 cm below the jugulum. A polysomnografy device served for the registration. The airway pressures were measured by using a water-filled tube in the hypopharyx. The BGA was taken from the hyperemic earlobe before and under nHF– use (2h). Results: Significant differences of the mean pressure and pCO2 appeared between the flows 20 and 30 l/min. The respiratory volumes and respiratory rates did not show changes between both flows. The minute volumes dropped in comparison to spontaneous breathing.  Discussion: The effects causes nHF are unclear up to now. It could be shown in an animal experiment that the pCO2 decreases in a flow-dependent size independent of pressure. In our investigations the mean pressure and the minute volume decreased in comparison to spontaneous breathing. The increase of mean pressure by rising the flow was not enough to generate significant differences in minute volume. Therefore we believe that the wash out-effect is the primary mechanism to the decrease in pCO2.
A decision tree to predict four or more positive axillary lymph nodes in breast cancer patients with positive sentinel node biopsy: Determining necessity for regional nodal irradiation in the absence of axillary dissection
Authors: R. A. Macrorie-Fairweather, K. Albuquerque, K. Yao, J. Sinacore
Journal: Journal of Clinical Oncology (2009)

e11540 Background: Regional nodal irradiation (RNI) is indicated for breast cancer patients with ≥ 4 positive axillary lymph nodes (ALN). The need for RNI is unclear for women with T1–2 tumors and 1–3 positive sentinel lymph nodes (SLN) who don’t undergo axillary lymph node dissection (ALND). In an effort to guide clinician decision-making and potentially spare patients combined toxicities of ALND and radiation, the purpose of this study was to create a decision tree of clinicopathologic variables to predict patients with ≥ 4 positive ALN. Methods: We reviewed the records of 197 women with T1–2 tumors and 1–3 positive SLN. All patients underwent a complete ALND to determine the number of positive ALN. The patients were divided into 2 groups: &lt; 4 or ≥ 4 positive ALN. Ten clinicopathologic predictive variables were identified for analysis: patient age, size of tumor, histological type, tumor grade, number of metastatic SLN, largest SLN metastasis size, detection method, estrogen receptor, Ki67 and lymphovascular invasion (LVI). The analysis used Chi-Square Automatic Interaction Detection (CHAID SPSS), a non-parametric, stepwise “regression tree” analysis, with Bonferroni adjusted p-values to create a decision tree. Results: 141 (72%) patients had &lt; 4 and 56 (28%) had ≥ 4 positive ALN. Three variables were selected into the CHAID tree based upon maximum predictability: LVI, the number of metastatic SLNs, and largest SLN metastasis size. 100% of patients (N=42) had &lt; 4 positive ALN if negative for LVI and had only 1 positive SLN with a metastasis size &lt; 0.2cm (p-value &lt; 0.0432). For patients with LVI (N=77), 13 of 14 (93%) had &lt; 4 positive ALN if the SLN metastasis size was ≤ 0.2cm (p &lt; .0014). The highest prevalence of ≥ 4 positive ALN were patients with LVI and a SLN metastasis size &gt; 0.2cm. Conclusions: The CHAID analysis more accurately predicted patients with &lt; 4 positive ALN compared to those with ≥4. The decision tree provides a new tool for the clinician to determine the necessity for RNI without ALND. No significant financial relationships to disclose.
Inspiratory muscles resistance to fatigue during simulated airway obstruction: EMG-study
Authors: Marina Segizbaeva, Nina Aleksandrova
Journal: European Respiratory Journal (2014)

Respiratory muscle fatigue can develop during simulated airway obstruction. The aim of this study was to characterize the pattern of inspiratory muscle fatigue and to assess the resistance to fatigue of diaphragm (D), parasternal (PS), sternocleidomastoid (SM) and scalene (SC). 7 healthy untrained subjects participated in this study. To identify signs of inspiratory muscles fatigue development electromyographic activity of D, PS, SCM and SC was recorded during 5-min exercise with loaded breathing (40 cm H 2 O/l  .  s -1 ). The before-to-after exercise measurements of maximal inspiratory pressure (MIP) and EMG power spectrum changes were performed. MIP declined about 12 % after exercise test compared with control, whereas the peak magnitude of integrated electrical activity of D, PS, SCM and SC during post-exercise Muller9s maneuver was significantly greater than in pre-exercise test in all subjects. The extent of inspiratory muscles fatigue was evaluated by analysis of shift in centroid frequency (f c ) of EMG power spectrum. All subjects demonstrated a significant reduction in f c  of PS, SCM and SC. f c  of D was not changed.Diaphragm is more resistant to fatigue during obstructive breathing compared with PS, SCM and SC. The data suggest that the reduction of maximum inspiratory pressure in chronic obstructive pulmonary disease also caused primarily by the weakening of the accessory muscles, while the weakness of the diaphragm may occur in the later stages of the disease. The functional failure of accessory muscles is an additional factor, which, along with the additional breathing resistance increases the load on the diaphragm, promoting its fatigue and reduced respiratory reserve.
Calcineurin Links Mitochondrial Elongation with Energy Metabolism
Authors: Paul T. Pfluger, Dhiraj G. Kabra, Michaela Aichler, Sonja C. Schriever, Katrin Pfuhlmann, Verónica Casquero García, Maarit Lehti, Jon Weber, Maria Kutschke, Jan Rozman, John W. Elrod, Andrea L. Hevener, Annette Feuchtinger, Martin Hrabě de Angelis, Axel Walch, Stephanie M. Rollmann, Bruce J. Aronow, Timo D. Müller, Diego Perez-Tilve, Martin Jastroch, Maria De Luca, Jeffery D. Molkentin, Matthias H. Tschöp
Journal: Cell Metabolism (2015)