tbuckley/cabot-search huggingface dataset:
Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence
Authors: Liesbeth Duijts, Raquel Granell, Jonathan A.C. Sterne, A. John Henderson
Journal: European Respiratory Journal (2015)

The objective of this study was to examine the associations of childhood wheezing phenotypes with asthma, lung function and exhaled nitric oxide fraction ( F eNO ) in adolescence. In a population-based, prospective cohort study of 6841 children, we used latent class analysis to identify wheezing phenotypes during the first 7 years of life. Physician-diagnosed asthma, spirometry and F eNO were assessed at 14–15 years . Compared with never/infrequent wheeze, intermediate-onset and persistent wheeze were consistently strongest associated with higher risk of asthma (risk ratio (95% CI) 10.9 (8.97–13.16) and 9.13 (7.74–10.77), respectively), lower forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ratio (mean difference in standard deviation units (SDU) (95% CI) −0.34 (−0.54– −0.14) and −0.50 (−0.62– −0.38), respectively), lower forced expiratory flow at 25–75% of FVC (FEF 25–75% ) (mean difference in SDU (95% CI) −0.30 (−0.49– −0.10) and −0.42 (−0.54– −0.30), respectively) and increased FEV 1 bronchodilator reversibility (mean difference in SDU (95% CI) 0.12 (0.02–0.22) and 0.13 (0.06–0.19), respectively). Prolonged early and persistent wheeze were associated with a decline in FEV 1 /FVC ratio and FEF 25–75% between 8–9 and 14–15 years. Intermediate-onset, late-onset and persistent wheeze were associated with higher F eNO ratios (ratio of geometric means (95% CI) 1.90 (1.59–2.29), 1.57 (1.39–1.77) and 1.37 (1.22–1.53), respectively, compared with never/infrequent wheeze). Early-onset wheezing phenotypes persisting after 18 months of age show the strongest associations with asthma, lower lung function, even worsening from mid-childhood, and higher F eNO levels in adolescence.
Gemcitabine and Cisplatin as Induction Regimen for Patients With Biopsy-Proven Stage IIIA N2 Non–Small-Cell Lung Cancer: A Phase II Study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC 08955)
Authors: N. Van Zandwijk, E.F. Smit, G.W. P. Kramer, F. Schramel, S. Gans, J. Festen, A. Termeer, N.J. J. Schlosser, C. Debruyne, D. Curran, G. Giaccone
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Our objective was to better define the activity/feasibility of gemcitabine/cisplatin (GC) as induction chemotherapy in patients with stage IIIA N2 non–small-cell lung cancer (NSCLC) followed by surgery or radiotherapy within a large, ongoing comparative study (EORTC 08941). PATIENTS AND METHODS: Forty-seven chemotherapy-naive patients with NSCLC, median age of 58 years, stage IIIA N2 disease, World Health Organization performance status of 0 or 1, and the ability to tolerate a pneumonectomy received gemcitabine 1,000 mg/m 2 on days 1, 8, and 15 and cisplatin 100 mg/m 2 on day 2, every 4 weeks. Patients received induction chemotherapy (three cycles) before re-evaluation and randomization to surgery or radiotherapy. RESULTS: Grade 3/4 thrombocytopenia, the main hematologic toxicity, occurred in 60% of patients but was not associated with bleeding. Full-dose gemcitabine was given in 48% of the courses. Severe nonhematologic toxicity was uncommon. Two patients with preexisting, autoimmune pulmonary fibrosis had deterioration of pulmonary function after radiotherapy. Thirty-three (70.2%; 95% confidence interval, 55.1% to 82.7%) of the 47 eligible patients had objective responses (three complete responses and 30 partial responses). Mediastinal nodes were tumor-free after induction therapy in 53% of cases. Resections were considered complete in 71% of the patients who underwent thoracotomy after induction therapy. Median survival for all recruited patients (N = 53) was 18.9 months, with an estimated 1-year survival rate of 69%. CONCLUSION: In patients with N2 stage IIIA NSCLC, GC is a highly active and well-tolerated induction regimen. GC should be explored in combination with surgery or radiotherapy in stage I and II patients.
Abstract 9455: Change of Heart Rate Variability and Correlation With Cardiac Function During Development Process of Chronic Heart Failure in Large Animal Model
Authors: Yuichiro Kishimoto, Kentaro Ohnuma, Mamoru Arakawa, Akihide Umeki, Yoshiaki Takewa, Motonobu Nishimura, Eisuke Tatsumi
Journal: Circulation (2012)

Introduction; Heart rate variability (HRV) is conceived to have a close relationship with prognosis of heart failure (HF). However, there is few study on HRV during diagnostic and treating process of HF in clinical settings. By investigating this process, HRV may become a more useful approach for non-invasive estimation of cardiac function. In this study, we examined the change of HRV and its correlation with cardiac function throughout the entire course of progressing HF in newly developed large animal chronic heart failure (CHF) models created by combination of micro-embolization and rapid pacing. Methods; CHF was introduced in 12 adult goats (60.9±4.1 kg) by coronary microsphere embolization (50μm, 0.201±0.014 million) to the left anterior descending artery and subsequent rapid ventricular pacing (HR[[Unable to Display Character: &amp;#8786;]]200) for 5 weeks. Electrocardiogram was recorded continuously for 24 hours under pacing off per week. HRV was analyzed by Memcalc/CHIRAM (Suwa Trust, GMS Inc.), which calculated time-domain index (SDNN etc.) and frequency domain index (LF, HF etc.), evaluated correlation with left ventricle ejection fraction (EF) and cardiac output (CO). Results; Ten goats survived and developed CHF successfully, showing decreased EF (from 90.4±4.1% to 48.3±5.6%) and CO (from 5.6±0.5L/min to 4.0±0.6 L/min). All indexes of HRV were decreased along with progress of HF (SDNN decreased from 166.1±39.1msec to 51.9±33.3msec). LF/HF which is the index of sympathetic nerve activity increased from 1.4±0.9 to 10.7±8.3. A strong correlation was observed between SDNN and cardiac function (Fig). Two cases of sudden death in course showed significant decrease of HRV as compared with the surviving cases. Conclusions; HRV was decreased along with progress of HF, strongly indicating aggravation of sympathetic nerve activity. These findings suggest that HRV analysis has a potential to become a useful and reliable approach for non-invasive estimation of cardiac function and severity of HF.
The Importance of Global Health Experiences in the Development of New Cardiologists
Authors: Marwah Abdalla, Neal Kovach, Connie Liu, Julie B. Damp, Eiman Jahangir, Anthony Hilliard, Rakesh Gopinathannair, Mazen S. Abu-Fadel, Mikhael F. El Chami, Sameer Gafoor, Rajesh Vedanthan, Monica Sanchez-Shields, Jon C. George, Tiffany Priester, Mirvat Alasnag, Colin Barker, Andrew M. Freeman
Journal: Journal of the American College of Cardiology (2016)
Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (GemOx): A randomized phase II trial in advanced pancreatic cancer
Authors: V. Heinemann, T. Hoehler, G. Seipelt, A. Wein, A. Golf, R. Mahlberg, B. Schmid, S. Boeck, S. Neugebauer, A. Hochhaus
Journal: Journal of Clinical Oncology (2005)

4030 Background: Gemcitabine, oxaliplatin, and capecitabine are active agents in pancreatic cancer. This study was performed to define an optimal regimen for combination therapy. Methods: Between July 2002 and May 2004, 190 patients were recruited from 44 centres. Patients received 3-week regimens of either capecitabine 2 x 1000mg/m2 po d1–14 plus oxaliplatin 130mg/m2 iv d1 (CapOx) or capecitabine 2 x 825mg/m2 po d1–14 plus gemcitabine 1000mg/m2 iv d1+8 (CapGem) or gemcitabine 1000 mg/m2 iv d1+8 plus oxaliplatin 130 mg/m2 d8 (GemOx). Results: Patients in the CapOx, CapGem, and GemOx-arms were well balanced according to the strata Karnofsky Performance status (KPS >70% in 89% vs 92% vs 90%) and stage of disease (metastatic disease in 74% vs 76% vs 75%). Median age was 63 years (range 37–75). Patients received a median of 4 cycles of treatment. In a per patient analysis of CapOx vs CapGem vs GemOx, hematological grade 3–4 toxicity occurred in 6%, 16%, and 19%. Grade 3–4 neurosensoric toxicity was observed in 7%, 0% and 4%, while grade 2–3 hand-foot-syndrome was noted in 9%, 6%, and 2%, respectively. In October 2004, 141 patients were evaluable for response. The analysis of CapOx vs CapGem vs GemOx did not show any complete remission, while partial responses were obtained in 22%, 16%, and 13% of patients, and stable disease was documented in 33%, 45%, and 30% for a disease control rate of 55%, 61%, and 43%, respectively. Median PFS was 127 days, 143 days, and 91 days, while median overall survival was 243 days, 229 days, and 241 days, respectively (two-sided logrank test, p=0.6). Conclusions: The current interim evaluation of this trial indicates a comparable efficacy and tolerability for the investigated regimens CapOx, CapGem, and GemOx. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo
Comprehensive Analysis of p16INK4a in Childhood Acute Lymphoblastic Leukemia Reveals Homozygous Deletion, Haploinsufficiency and Acquired Isodisomy at the 9p Locus with Intact p16INK4a.
Authors: Sarina Sulong, Julie Irving, Marian Case, Lynne Minto, Nick Bown, Simon Bailey, Christine Harrison, Andrew Hall
Journal: Blood (2006)
Sources and Functions of Extracellular Small RNAs in Human Circulation
Authors: Joëlle V. Fritz, Anna Heintz-Buschart, Anubrata Ghosal, Linda Wampach, Alton Etheridge, David Galas, Paul Wilmes
Journal: Annual Review of Nutrition (2016)

Various biotypes of endogenous small RNAs (sRNAs) have been detected in human circulation, including microRNAs, transfer RNAs, ribosomal RNA, and yRNA fragments. These extracellular sRNAs (ex-sRNAs) are packaged and secreted by many different cell types. Ex-sRNAs exhibit differences in abundance in several disease states and have, therefore, been proposed for use as effective biomarkers. Furthermore, exosome-borne ex-sRNAs have been reported to elicit physiological responses in acceptor cells. Exogenous ex-sRNAs derived from diet (most prominently from plants) and microorganisms have also been reported in human blood. Essential issues that remain to be conclusively addressed concern the (a) presence and sources of exogenous ex-sRNAs in human bodily fluids, (b) detection and measurement of ex-sRNAs in human circulation, (c) selectivity of ex-sRNA export and import, (d) sensitivity and specificity of ex-sRNA delivery to cellular targets, and (e) cell-, tissue-, organ-, and organism-wide impacts of ex-sRNA-mediated cell-to-cell communication. We survey the present state of knowledge of most of these issues in this review.
Abstract 17019: IVUS Predictors of the Improvement of Slow Flow After Intracoronary Nitroprusside in the Percutaneous Coronary Intervention
Authors: Toru Iwasaka, Tetsuro Ohta, Seiji Okada, Taku Nakamura, Toshihiko Ohoka, Shuji Ishihara, Hirotomo Sato, Rinji Murakami
Journal: Circulation (2012)

The microcirculatory flow is the key to restoring the myocardial tissue perfusion. The beneficial effects of better restoration of the epicardial coronary flow (TIMI flow grade 3 fast or 4: corrected TIMI frame count, CTFC < 23) following percutaneous coronary intervention (PCI) were reported. Previous studies have shown that intracoronary nitroprusside injection (ICNTP) is effective for slow flow after PCI. We investigated the relationship between the improvement of CTFC after ICNTP and pre-intervention intravascular ultrasound (IVUS) findings in 112 patients with slow flow following PCI. IVUS assessment included (1) plaque area, (2) arc of calcium and (3) presence of attenuated plaque (plaque with deep echo attenuation, but without calcification). The contribution of the three IVUS findings and distal protection was tested through multiple logistic regression analysis. Results: The mean CTFC after ICNTP was decreased significantly from 48.4±18.9 to 26.0±10.0 (p<0.0001). Multivariate logistic regression ...
Otitis Media
Authors: J. Owen Hendley
Journal: New England Journal of Medicine (2002)

An otherwise healthy 17-month-old boy had a cold accompanied by two days of rhinorrhea, cough, and fever (temperature of up to 38.8°C). On day 5, he became fussy and woke up crying several times during the night. The following day he was afebrile, and a physical examination was normal except for findings of a slightly red left tympanic membrane with no middle-ear fluid and a bulging right tympanic membrane with white fluid behind it, obscuring the umbo. How should he be treated?
In vivo pre-clinical evaluation of the IGF-1R-specific antibody AVE1642 as single agent and in combination with Velcade ® /Bortezomib
Authors: Friedhelm Bladt, Patricia Vrignaud, Stephane Guerif, Noelle Boussac, Thomas Chittenden, Thierry Hercend, Marielle Chiron, Marie-Christine Bissery
Journal: Cancer Research (2007)

4115   The insulin-like growth factor 1 receptor (IGF-1R) has been strongly implicated in the pathogenesis and progression of various cancers, providing a rationale for therapeutically targeting IGF-1R. To this end, we have developed a monoclonal antibody (mAb), EM164 and its humanized version AVE1642, which effectively inhibits growth of primary and secondary tumors (Poster abstract AACR 2006). Here we characterize further the therapeutic activity of AVE1642 as a single agent and evaluate the  in vivo  activity of AVE1642 in combination with bortezomib (Velcade ® ). Breast cancer frequently metastasises to the bone and to the lung. To evaluate the effect of AVE1642 on human breast cancer cells in the bone milieu, we implanted in the tibia of SCID mice, MDA-MB-231-Luc-D3H1 cells expressing the firefly luciferase gene. In recipient mice treated bi-weekly for 8 weeks with AVE1642 at 40 mg/kg/injection (day 1 - 80 post implantation), tumor growth measured by bioluminescent signal before onset of osteolysis, was significantly (p  In conclusion, AVE1642 effectively inhibited tumor growth within the bone and pulmonary microenvironment. The combination of AVE1642 with bortezomib, was found more active than the individual agents, showing the clinical potential of this antibody in patients with multiple myeloma.
Abstract 18335: Long-Term Follow-Up of Patients with Acute Myocardial Infarction with Chronic Total Occlusion in the Non-Infarct Related Artery
Authors: Masashi Fujino, Masaharu Ishihara, Satoshi Honda, Shoji Kawakami, Takafumi Yamane, Toshiyuki Nagai, Kazuhiro Nakao, Tomoaki Kanaya, Leon Kumasaka, Yasuhide Asaumi, Tetsuo Arakawa, Michio Nakanishi, Teruo Noguchi, Kengo Kusano, Toshihisa Anzai, Yoichi Goto, Satoshi Yasuda, Hisao Ogawa
Journal: Circulation (2014)

Introduction: It remains unclear whether revascularization of chronic total occlusion (CTO) of the non-infarct related artery (non-IRA) during the index episode of hospitalization will favorably alter long-term outcomes in patients with acute myocardial infarction (AMI). Methods: We studied 208 consecutive patients with AMI and CTO in non-IRA who underwent urgent coronary angiography at National Cerebral and Cardiovascular Center in Japan between 2000 and 2010. The patients were divided into 3 groups according to the treatment during the index episode of AMI: 60 patients with successful PCI for CTO, 30 patients with CABG and 118 patients with optical medical therapy (OMT). Follow-up was obtained for total death and major adverse cardiac events (MACE), including cardiac death, recurrent myocardial infarction, repeat revascularization and re-hospitalization because of heart failure. Results: During follow-up (median, 5.1 years), total death and MACE-free survival were lower in OMT group than PCI and CABG gr...
Abstract P6-02-05: Systemic statin treatment and intra-tumoral lipid metabolism - report from a window-of-opportunity breast cancer trial
Authors: Maria Feldt, Julien Menard, Mattias Belting, Signe Borgquist
Journal: Cancer Research (2015)

Abstract Background: In recent years, attention has been drawn to the plasma cholesterol lowering drugs statins (HMGCR-inhibitors) due to their exertion of pleiotropic intratumoral effects such as induction of apoptosis and inhibition of proliferation, generating a possible utility in cancer prevention and treatment. However, the molecular mechanisms are complex and remain largely undefined. The aim of this study was to assess the statin induced changes of the intra-tumoral levels of cholesterol, to gain enhanced understanding of the role of the mevalonate pathway in cancer lipid metabolism. Methods: The study was designed as a window-of-opportunity trial, where 50 patients with primary invasive breast cancer were included, and treated with 80 mg of atorvastatin/day for two weeks, between the time of diagnosis and surgery. From frozen tumor tissue samples pre- and post atorvastatin treatment, lipids have been extracted, and the cholesterol levels have been measured using a cholesterol quantification assay. In vitro experiments on MCF7-cells treated with atorvastatin was used for optimization and comparison on the cellular level. Results: 42 patients completed all study parts, and assessment of the cholesterol levels in the paired frozen tumor tissue was achievable in 14 pairs. Following atorvastatin treatment, the intra-tumoral levels of total cholesterol was significantly increased (P=0.035), with an increase in 11 of the pairs, and decrease in 3 pairs. Similar findings were observed in the in vitro experiments, demonstrating increased levels of total cholesterol and storage in lipid droplets in the cells treated with atorvastatin. Conclusions: We have earlier reported statin-induced anti-proliferative effects in breast cancer. This study shows a statin-induced increase in the intra-tumoral cholesterol levels, which may however rely on the increased cholesterol storage in lipid droplets, a phenomenon observed in the in vitro experiments with MCF7 cells treated with atorvastatin. Our results suggest that the anti-proliferative effects exerted by statins reluctantly reduce cell metabolism and consequently increase the storage of e.g. lipids. Citation Format: Maria Feldt, Julien Menard, Mattias Belting, Signe Borgquist. Systemic statin treatment and intra-tumoral lipid metabolism - report from a window-of-opportunity breast cancer trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-02-05.
Ibandronate is effective in preventing skeletal events in patients with bone metastases secondary to colorectal carcinoma
Authors: P. Heras, S. Karagiannis, K. Kritikos, A. Hatzopoulos, I. Stavrinadis, D. Mitsibounas
Journal: Journal of Clinical Oncology (2005)

3639 Background: Patients with metastatic colorectal carcinoma (CRC) often develop metastases to bone with a high risk of complications. Methods: A randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of ibandronate in patients with bone metastases from CRC. The primary efficacy endpoint was proportion of patients with skeletal related events (defined as pathologic fracture, spinal cord compression, radiation therapy to bone, change in antineoplastic therapy and surgery to bone). Secondary endpoints included time to first skeletal event, skeletal morbidity rate (events/year) and time to progression of bone lesions. Results: In 30 patients with CRC, treatment with intravenous ibandronate 6mg over a15-minute infusion significantly reduced the proportion of patients with skeletal events (39% versus 78% with placebo; p=0.019) and prolonged the time to first event by at least 6 months (median >279 versus 93 days with placebo; p=0.009). Ibandronate also significantly reduced the skeletal morbidity rate (mean 2.36 versus 3.14 with placebo; p=0.018) and prolonged time to progression of bone lesions (214 days versus 81 days with placebo; p=0.018). Ibandronate was well tolerated with very rare grade 3 or 4 toxicity. The incidence of renal adverse events was comparable to placebo and there were no clinically-relevant changes of serum creatinine. Conclusion: Ibandronate provided significant clinical benefit in patients with bone metastases secondary to CRC. This small pilot study suggests a role for ibandronate in metastatic bone disease from colorectal carcinoma. Larger confirmatory studies are required. No significant financial relationships to disclose.
Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) to characterize cachexia in newly diagnosed advanced cancer patients
Authors: A. Vigano, B. Trutschnigg, J. A. Morais, P. Chaudhury, E. Lucar, P. Metrakos, M. Hassanain, H. Molla, L. Hornby, R. D. Kilgour
Journal: Journal of Clinical Oncology (2009)

9574 Background: Our objective was to evaluate whether the scored PGSGA questionnaire in advanced cancer patients (ACP) might relate better then weight loss (WL) alone to the nutritional, functional, biological and quality of life features of cachexia (C) and to some complications related to this syndrome. Methods: 214 newly diagnosed ACP with non-small cell lung and gastrointestinal primaries were categorized according to PG-SGA triage intervals of 0–1, 2–8 and ≥9 and also according to WL ≤5% or &gt;5%. Baseline assessments included: hand-grip strenght, body composition by DXA, selective measures of symptom and quality of life (QoL), CBC and differential counts, albumin and CRP. Survival hospitalization rates and data on chemotherapy tolerability were recorded during patient follow-up. Beta coefficients (β), odds ratios (OR), and hazard ratios (HR) were estimated to compare patients with &gt;5% WL to those with ≤5% WL and to compare patients with PGSGA of 0–1 to those with 2–8 and ≥9 scores. All analyses were controlled for gender, age, diagnosis (lung/GI), treatment (radio/chemo), survival (at 8 weeks), and medications. Results: PGSGA was better than the simple recording of WL in defining a population of patients that differed for WBC 10 9 / L(&gt;5% WL β: 0.25 vs. 2–8 PGSGA β: 0.57 and ≥9 PGSGA β: 1.72), CRP mg/L (4.12 vs. 2.16 and 17.49), albumin g/L(-0.63 vs -2.60 and -4.45); weakness 0–10 (1.57 vs.1.56 and 3.32), anorexia 0–10 (2.36 vs. 2.36 and 5.17); Brief Fatigue Inventory 0–90 (17.75 vs. 9.89 and 25.15); McGill QoL 10–0 (-0.95 vs. -0.64 and -2.29); grip strength lbs.(-4.04 vs. -8.82 and -8.06); body fat kg. ( -8.74 vs. -5.94 and -11.72). PGSGA was able to better identify patients with higher rates of both hospitalization (2.6 vs. 1.62 and 9.46) and dose reduction of chemotherapy (1.2 vs. 0.58 and 1.74). Finally, PGSGA was able to better characterize patient survival as compared to WL alone (&gt;5% WL HR: 1.85; 2–8 PGSGA HR: 1.6 and ≥9 PGSGA HR 3.35). Conversely, WL alone was associated with higher probability of a sarcopenia diagnosis by DXA (&gt;5% WL OR: 1.56)Conclusions: Our data support the use of the PGSGA versus the simple recording of WL for identifying C, monitoring its clinical course and predicting possible complications of this syndrome in ACP. No significant financial relationships to disclose.