tbuckley/cabot-search huggingface dataset:
Efficacy of gemcitabine and cisplatin (GP) as first-line combination therapy in patients with triple-negative metastatic breast cancer: Preliminary results report of a phase II trial.
Authors: Z. Wang, X. Hu, L. Chen, J. Wang, H. Wang, L. Wang, G. Liu, Z. Hu, J. Wu, S. Zhimin
Journal: Journal of Clinical Oncology (2010)

1100 Background: Triple-negative breast cancer (TNBC) contributes to the poor prognosis. Only a few studies have revealed that cisplatin-based therapy may be effective for this subtype of breast cancer. The objective of this study was to evaluate doublet with gemcitabine/cisplatin (GP) as first-line therapy in patients with metastatic TNBC. Methods: This is a single-institutional phase II trial. The primary endpoint was progression-free survival (PFS). Eligible subjects were aging from 18 to 75 years old, with no prior chemotherpay for MBC, with tumors negative for ER, PR, or HER2, with at least one measurable disease according to the RECIST criteria, with ECOG PS of 0-1, and with adequate organ function. Patients received 21-day cycles of gemcitabine (1,000mg/m2) on days 1, 8 and cisplatin (25 mg/m2) on days 1-3. Treatment was continued until disease progression or unacceptable toxicity or up to 8 cycles. Response rate was evaluated every six weeks. Results: As of Nov. 2009, 65 patients had been enrolled with a planned sample size of 80 patients. The first 45 patients had completed the treatment and were analyzed. A median age was 48 years. 42 patients had received adjuvant chemotherapy (39 patients with anthracycline and/or taxane). The median number of GP treatment cycles was six. The median PFS was 6.2 months (95% CI: 5.0-7.3). The response rate was 62.2% (28/45, 95% CI: 47.5%-77%); stable disease was 31.1% (14/45); progressive disease was 6.7% (3/45). G3/4 toxicities were neutropenia 40% (18pts); thrombocytopenia 33.3% (15pts); fatigue 17.8% (8pts); anorexia 15.6% (7pts); anemia 13.3% (6pts); nausea/vomiting 8.9% (4pts). The chemotherapy doses were reduced in 13.3% (6 pts) because of toxicity. Conclusions: This preliminary analysis demonstrated that GP regimen as first-line chemotherapy is highly effective and safe in patients with TNBC. No significant financial relationships to disclose.
Induction chemotherapy for stage III/IV oral and oropharyngeal squamous cell cancers.
Authors: M. K. Chadha, N. R. Rigual, K. Thankappan, V. Jayaprakash, M. Sullivan, M. E. Reid, T. R. Loree
Journal: Journal of Clinical Oncology (2010)

e16012 Background: There is limited data on the role of induction chemotherapy (IC) in the treatment of advanced oral and oropharyngeal squamous cell carcinoma (OSCC). We present our experience using IC followed by definitive treatment with surgery, CRT or their combination, in the management of stage III/ IV OSCC. Methods: Total of 42 OSCC patients [22 oral cavity (OC) and 20 oropharyngeal (OP)] were included in the study. Six patients had stage III and 36 had stage IV disease. Median age was 59 years with 36% females. Patients were treated with a median of 2 cycles of cisplatin based IC (range: 2 to 4) on a weekly or every 3 week basis. Response to IC was determined clinically and radiologically. Patients with no residual disease were considered to have complete response (CR), >80% response were classified as near complete response (NCR), <80% response as partial response (PR) and no change was considered as no response (NR). Results: Among the 22 OC patients, 2 had CR, 7 had NCR, 8 had PR and 5 had NR to IC. Among the 20 OP patients, 2 had CR, 7 had NCR, 10 had PR and 1 had NR. (a) Complete responders: All 4 CR patients underwent definitive surgery with pathologic CR and remain disease free (mean follow-up:24.2 months); (b) Near complete responders: Of the 14 NCR patients, 1 OP developed local recurrence in 13 months; rest remain disease-free; (c) Partial Responders: Among the 8 OC -PR patients, 2 developed local recurrence and 2 distant disease, 4 patients remained disease free (mean follow-up:19.5 months). Among the 10 OP- PR patients, 5 developed locoregional recurrence and 4 remained disease free (mean follow-up:16.7 months). One patient died of metastatic disease before definitive treatment. (d) Non responders: Among the 5 OC – NR patients, 1 had local recurrence, 2 had distant metastasis and 2 remained disease free for average of 9 months. The OP – NR patient remained disease free for 2 months after definitive therapy. There was a significant difference between disease free survival of OP and OC CR/NCR versus PR/NR (p=0.007). Overall, 43% had CR/NCR while 43% had PR and 14%NR. Conclusions: IC is effective and well-tolerated neo-adjuvant therapy for OSCC. Responders to IC had longer disease-free survival compared to non-responders. No significant financial relationships to disclose.
Pharmacodynamic separation of erlotinib and docetaxel (DOC) in advanced non-small cell lung cancer (NSCLC): Overcoming hypothesized antagonism
Authors: A. M. Davies, P. J. Hesketh, L. Beckett, D. Lau, P. C. Mack, P. N. Lara, J. Jernigan, J. LaPointe, D. R. Gandara
Journal: Journal of Clinical Oncology (2007)

7618 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) given concurrently with chemotherapy do not improve patient (pt) outcomes compared with chemotherapy alone in advanced NSCLC. Based on our preclinical data, we hypothesized that G1 cell cycle arrest from EGFR-TKI antagonizes the cytotoxicity of concurrent chemotherapy, and that pharmacodynamic separation (PDS) by intermittent delivery of EGFR-TKIs with chemotherapy would increase efficacy (Gumerlock, ASCO 2003, Davies, ASCO 2005). To test this concept, we conducted a phase I-II study of intermittent erlotinib combined with DOC. Methods: 37 previously treated IIIB (pleural effusion) or IV NSCLC pts received DOC 70–75 mg/m 2 IV on day 1 every 21 days and erlotinib orally days 2–16 (150–200 mg). Patients without progression after 6 cycles continued erlotinib alone. Primary endpoint was response rate. Results: Pt characteristics: Age: median/range 57/35–80; Sex: 14 M; KPS ≥90=13; smoker/non-smoker/unknown 20/13/4, Median cycles: 5. Adenoca: 18. Prior chemotherapy regimens: 1 - 26; &gt;1 - 11. In 34 evaluable pts: 1 CR, 11 PR (35% response rate), 16 stable disease. Median time to progression (TTP) was 5.6 months (95% CI: 3.7 - 7.9). MST: not reached. Treatment was generally well tolerated. Most common grade (Gr) 3/4 toxicities included: neutropenia (60%), diarrhea (16%), infection (11%), febrile neutropenia (8%). Gr 1/2 acneform rash: 88%. PK analysis showed that PDS was achieved in nadir levels of erlotinib in 4 pts tested. Correlative studies examining biomarkers for response with EGFR TKIs are ongoing. Conclusions: 1) DOC every 3 weeks plus intermittent dosing of erlotinib (2 weeks on, 1 week off) achieved PDS in limited PK sampling. 2) This combination resulted in a favorable response rate and TTP in previously treated NSCLC, with MST not yet reached. 3) Febrile neutropenia necessitated the prophylactic use of G-CSF. 4). Further clinical study of this concept is warranted, and trials are currently ongoing. [Table: see text]
Pulmonary Oxidative Stress, Reperfusion Injury and Lung Tissue Damage During Cardiac Surgery: The Outcome of an Experimental Trial in a Porcine Model
Authors: Ishtiaq Rahman, Laura Walker, Guillaume Chanoit, Pamela Murison, James Hillier, Joya Pawade, Kim Dora, Timea Beleznai, Gianni Angelini, Saadeh Suleiman, Raimondo Ascione
Journal: Circulation (2013)

Background and Objective: The incidence of pulmonary complications following cardiac surgery remains high and is associated with increased in-hospital mortality and costs. Established surgical prac...
Competing Influences of Genetic and Leukaemia-Specific Factors on P-Glycoprotein Expression in Blasts from 817 Patients Entered into the NCRN AML14 and 15 Trials.
Authors: Claire H. Seedhouse, Martin Grundy, Paul White, Yun Li, Janet Fisher, Darya Yakunina, Anthony Moorman, Nigel Russell, Alan Burnett, Monica Pallis
Journal: Blood (2006)
Preparations for the European football championship (EURO 2008) in Switzerland
Authors: A Dreyfus, J Marfurt, A Birrer, H. C. Matter, P-A Raeber
Journal: Eurosurveillance (2008)

The European football championship (EURO 2008) is taking place in Austria and Switzerland between 7 and 29 June 2008. From a public health point of view, such a mass gathering requires attention with regard to infectious disease prevention because of (i) a potential increased risk for disease transmission (ii) increased media attention and (iii) its potential as a target for actions of a bioterrorist nature [2,6,8,9]. This article gives an overview of the preparations for Euro 2008 on the national level in Switzerland with regards to infectious diseases.
Pharmacodynamic study of FLT-PET imaging in patients treated with sunitinib
Authors: G. Liu, R. Jeraj, S. Perlman, M. Vanderhoek, J. Kolesar, J. Eickhoff, D. Alberti, G. Wilding
Journal: Journal of Clinical Oncology (2008)

3515 Background: Sunitinib (SU) is a tyrosine kinase inhibitor (TKI) with activity against vascular endothelial growth factor receptors (VEGFR). During VEGFR TKI withdrawal, increase in pain at sites of known metastasis has been observed. We hypothesized this withdrawal flare is caused by increased tumor proliferation. [18F]-fluoro-3’-deoxy-3’-L-fluorothymidine (FLT) accumulates in cells with high thymidine kinase-1 activity, reflecting areas of cell proliferation. By correlating changes in FLT-PET, plasma VEGF levels and peripheral blood mononuclear cell (PBMC) HIF1-α expression, we assessed FLT-PET as a marker of response, and changes in blood markers as a mechanism of VEGFR TKI escape. Methods: Patients with advanced solid malignancies and no prior anti-VEGF exposure were enrolled. All patients had metastatic lesions amendable to PET/CT imaging. SU was given at the standard dose of 50 mg PO daily x 4 weeks, followed by a 2 week break (6 week cycles). FLT-PET scans were obtained at baseline, week 4 (on SU), and week 6 (off SU). Plasma samples for VEGF and nuclear extracts prepared from PBMCs for HIF1-α were obtained weekly during cycle 1, and day 1 of each subsequent cycle. Disease assessments were repeated after every 2 cycles. Results: 10 subjects have been enrolled to date, of which 5 (3 renal, 1 small cell lung, 1 thymus) complete sets of FLT-PET scans have been obtained and analyzed. Changes in total and maximum standardized uptake value (SUVtot, SUVmax) were calculated together with RECIST measurements. Change in SUVtot from baseline to week 4 ranged from -80% to +10% (on SU). All subjects had a relative increase in proliferation (off SU) from week 4 to week 6 (range +40% to +180%). Conclusions: Change in SUVtot at week 4 appeared to be associated with the degree of tumor response seen on the first disease assessment scan. Proliferative increase in the target lesions during SU withdrawal was seen in all patients to date, supporting the hypothesis that a VEGFR TKI withdrawal leads to a transient period of rapid tumor regrowth. The results of this study support the hypothesis that a continuous dosing schedule of VEGFR TKI might be preferable. Ongoing work is being performed with alternative schedules of SU, assessing pharmacodynamic change with FLT-PET. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer
Little Change in Diet After Onset of Type 2 Diabetes, Metabolic Syndrome, and Obesity in Middle-Aged Adults: 11-Year Follow-up Study
Authors: Tasnime N. Akbaraly, Adam G. Tabak, Martin J. Shipley, Thibault Mura, Archana Singh-Manoux, Jane E. Ferrie, G. David Batty, Mika Kivimaki
Journal: Diabetes Care (2016)

Randomized controlled trials have established the beneficial effect of a healthy diet in the treatment of cardiometabolic disorders. Healthy diet recommendations are based on this evidence (1). However, limited evidence is available on whether individuals with these conditions actually follow such dietary recommendations in an effective way, that is, by making long-term changes in their dietary behavior.

In this cohort study of 4,703 participants (mean age 49.5 years, 27.8% women) from the Whitehall II study (www.ucl.ac.uk/whitehallII), we screened participants for type 2 diabetes (T2D), metabolic syndrome (MetS), and obesity and then followed changes in diet with follow-up surveys. Participants were informed that they had diabetes or were obese but were not informed if they had MetS, and no dietary advice was given. Both prevalent (in 1991/1993) and new-onset cases (occurrence between 1991/1993 and 2002/2004) of T2D (according to the World Health Organization criteria [2]), MetS (the National Cholesterol Education Program Adult Treatment Panel III criteria definition), and obesity (BMI ≥30 kg/m2) were considered, as described elsewhere (3). Changes in diet were determined using repeated measures of the Alternative Healthy Eating Index (AHEI) over an 11-year follow-up (from …
Contribution of PET Imaging to the Diagnosis of Septic Embolism in Patients With Pacing Lead Endocarditis
Authors: Sana Amraoui, Ghoufrane Tlili, Manav Sohal, Benjamin Berte, Elif Hindié, Philippe Ritter, Sylvain Ploux, Arnaud Denis, Nicolas Derval, Christopher A. Rinaldi, Charles Cazanave, Pierre Jais, Michel Haissaguerre, Laurence Bordenave, Pierre Bordachar
Journal: JACC. Cardiovascular imaging (2016)
Breast cancer incidence and mortality: trends over 40 years among women in Shanghai, China
Authors: Z. Huang, W. Wen, Y. Zheng, Y.T. Gao, C. Wu, P. Bao, C. Wang, K. Gu, P. Peng, Y. Gong, M. Zhang, Y. Xiang, W. Zhong, F. Jin, Y.B. Xiang, X.O. Shu, A. Beeghly-Fadiel
Journal: Annals of Oncology (2016)
PTU-183 Advice from a dietitian regarding the low fodmap diet broadly maintains nutrient intake and does not alter fibre intake
Authors: H Staudacher, FS Ross, ZM Briscoe, PM Irving, K Whelan, MC Lomer
Journal: Gut (2015)

<h3>Introduction</h3> Dietary restriction of certain fermentable carbohydrates (low FODMAP diet, LFD) is increasingly utilised for managing symptoms of irritable bowel syndrome (IBS). Exclusion diets carry a risk of nutritional inadequacy, and lower calcium intake has been reported during a LFD. Furthermore, it is important to understand whether the positive impact of the LFD is due to FODMAP restriction or an unintended dietary change (e.g. fibre intake). This single-blind randomised controlled trial aimed to compare nutrient intake in patients with IBS following LFD advice with baseline and a sham diet. <h3>Method</h3> Adult patients with IBS referred to a secondary care dietetic service were screened for inclusion (n = 162). Suitable patients who were following their habitual diet (baseline) were randomised to blinded LFD advice or sham (placebo) dietary advice provided by a registered dietitian. The sham diet was designed to be equivalent in nutrients and FODMAP content compared with baseline intake. A 7-day diet record was completed and weight recorded at baseline and 4 weeks. Mean daily nutrient intakes were calculated from diet records (excluding supplements) entered into dietary composition software (Dietplan 6, Forestfield Software Ltd). Comparisons were made with dietary reference values (DRVs). Data was analysed using t-tests and McNemar tests. <h3>Results</h3> A total of 95 patients completed the study (63 females, 66%) with 8 withdrawals and 1 lost to follow up (LFD n = 4, sham n = 5). Mean weight change was not different between groups (LFD -0.3 kg vs sham -0.4 kg, p = 0.738). There were no differences in mean energy and nutrient intakes, including calcium, between LFD and sham at baseline or follow up except vitamin B<sub>12</sub>at follow up (LFD 6.3 µg/d vs sham 4.7 µg/d, p = 0.004). There was a significant reduction in mean iron intake in LFD from baseline (11.3 mg/d) to follow up (10.2 mg/d, p = 0.008), although proportion of LFD meeting the iron DRV did not differ (baseline 52% vs follow up 48%, p = 0.375). Proportion of LFD meeting the fibre DRV did not change (baseline 53% vs follow up 53%, p = 1.00). Proportion of LFD meeting the calcium DRV at baseline was higher (64%) than after LFD (47%, p = 0.039). Overall, mean LFD nutrient intakes were similar to data for the healthy population. <h3>Conclusion</h3> More than half of patients following LFD advice did not meet DRVs for iron and calcium, although mean nutrient intakes were comparable to the healthy population. Energy and nutrient intake after LFD advice is not different to sham dietary advice, confirming that altered fibre intake is not responsible for its impact on IBS symptoms. <h3>Disclosure of interest</h3> None Declared.
Abstract 232: Role of Transient Receptor Potential Melastatin 2 in Cardiomyocyte Apoptosis Induced by TNF-α
Authors: Shuzhuang Li, Xuan Liu, Deqin Yu, Chong Chen, Xiaolong Chen
Journal: Circulation Research (2012)

Mechanical trauma, such as that induced by motor vehicle crashes, represents a major medical and economic problem in the world. Identifying the mechanisms responsible for post-traumatic secondary myocardial injury is critical in order to reduce overall mortality and improve quality of life after trauma. We have previously demonstrated that mechanical trauma-induced overproduction of TNF-α plays a causative role in cardiomyocyte apoptosis via oxidative/nitrative stress. Transient receptor potential melastatin 2 (TRPM2) is a Ca 2+ permeable non-selective cation channel activated by oxidative stress, expressed in the cardiomyocytes. The present study attempted to identify whether TRPM2 is involved in TNF-α-induced cardiomyocyte apoptosis. Cardiomyocytes were isolated from adult male Sprague Dawley rats and cultured with TNF-α (10 ng/ml) for 12h. RT-PCR and semi-quantitative immunohistochemistry were used to quantify TRPM2 mRNA and protein levels respectively. Significant increases in TRPM2 mRNA and protein expression were observed in TNF-α-treated cardiomyocytes, suggesting that TRPM2 may contribute to TNF-α-induced cardiomyocyte apoptosis. To identify the effect of TRPM2 on TNF-α-induced cardiomyocyte apoptosis, cardiomyocytes were cultured with TNF-α or TNF-α + TRPM2 inhibitor (flufenamic acid (FFA) 100uM or clotrimazole 30uM), respectively. Exposure of cardiomyocytes to TNF-α for 12h induced significant apoptosis as determined by caspase-3 activation (1.7-fold increase vs. control, P &lt; 0.01). In contrast, TNF-α-induced caspase-3 activity increases were significantly depressed by FFA and clotrimazole, respectively (P &lt; 0.05). To further confirm the effect of TRPM2 on TNF-α-induced cardiomyocyte apoptosis, we tested the effects of TRPM2-specific small interfering RNA (siRNA). As a result, impressively, TNF-α-induced increases of caspase-3 activity and lysate nucleosomes were significantly reduced in TRPM2-specific siRNA-treated cardiomyocytes (P &lt; 0.01). These results indicate that TRPM2 plays an important role in TNF-α-induced cardiomyocyte apoptosis. We propose functional inhibition of TRPM2 channels as a new therapeutic strategy for treating mechanical trauma-induced secondary myocardial injury.
Discriminatory analysis in determination of high risk of gastric cancer
Authors: S. A. Terekhova, A. F. Lazarev, V. D. Petrova, T. V. Sinkina, I. A. Selezneva, J. N. Dimitriadi
Journal: Journal of Clinical Oncology (2007)

1540 Background: Determination of the high risk of gastric cancer and target examination of patients from high-risk groups makes early detection of gastric cancer possible and contributes to the decrease of mortality rates as the outcome of gastric cancer treatment is primarily dependant on the stage of disease. Methods: 700 patients with gastric cancer and 1069 persons without any oncopathology referred to Altay oncological center for consultation in 2002–2004 were interviewed and examined to get the data on different factors known as risk factors for gastric cancer (endogenic, environmental, lifestyle, nutritive factors, results of blood-tests and non-oncological stomach diseases, etc.). Results: By means of discriminatory analysis from 131 investigated factors there were 26 factors distinguished and corresponding coefficients of canonical function of discrimination calculated, on the basis of which the prognosis of gastric cancer development may be ascertained (p&lt;0.001): age, body mass, education, duration of stress, insomnia, extrasleep during daylight hours, family history of gastric cancer, family history of cancer, presence of clinical symptoms, lifetime history of smoking, usage of strong spirits, amount of spirits used per month, regularity of nutrition (eating patterns), time intervals between food intakes, variety of food allowance, usage of food and drinks of high temperature, animal fats, spicy food, canned and preserved food, bakery, strong black tea and coffee, fresh vegetables and fruit, sour milk products, green tea, level of haemoglobin, ESR. Multiplying the interval values of those significant factors and corresponding coefficients of canonical function of discrimination and subsequent summarizing of the results and the constant gives an &lt;&lt;integral rate&gt;&gt;, the positive value of which is the evidence of high risk of gastric cancer either to be developed or already exists. Negative integral rate is the evidence of low risk. Cross check up showed the 95.1% test-sensitivity and 95.0% test-specificity. Conclusions: Thus, the value of the integral rate can be used as a criterion for selection of concrete patients with high risk of gastric cancer to be deeply examined and to be under monitoring for detection of early gastric cancer. No significant financial relationships to disclose.
Abstract 217: Emergency Department Overcrowding Is Not Associated with Deterioration of Resuscitation Effort, Efficiency and Patient Outcomes in Out-of-Hospital Cardiac Arrest Patients
Authors: Jiwon Kang, Joonghee Kim, Yu hwan Jo, Kyuseok Kim
Journal: Circulation (2014)

Background: ED (emergency department) overcrowding is a rampant problem in US. It has been reported that it is associated with poor patient care as well as overall outcomes. Currently it is unknown whether ED overcrowding has significant influence on ED resuscitation for cardiopulmonary resuscitation (CPR) of out-of-hospital cardiac arrest (OHCA) patients. We hypothesised that it has significant impact on the amount of resuscitation effort and long-term outcomes.

Methods: This is a retrospective observational study of OHCA patients resuscitated in ED for prehospital resuscitation failure from 2008 to 2012. Demographic information, Utstein factors and information regarding patient outcomes were retrieved from an OHCA registry. Surrogate markers of ED overcrowding including total number of patients in the ED, the number of patients being cared in critical zone as well as the number of patients boarded for more that two or three days were provided from the administrative department. We also included the number of new patient visits for one hour after the beginning of resuscitation.

Results: 608 patients were included for this study. The total number of patients in ED was not associated with the surrogate markers of resuscitation effort or efficiency which include the duration of resuscitation effort for unresponsive patients and the time to intubation success and first drug administration. Similarly, it was not associated with the chance of prescribing hypothermia after successful resuscitation. Patient outcomes including the chance of achieving sustained ROSC, survival discharge and 6-month cerebral performance category also did not show any significant association.

Conclusion: In this retrospective study of OHCA patients, ED overcrowding did not lead to significant deterioration of resuscitation effort, resuscitation efficiency or long-term outcomes.

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