tbuckley/cabot-search huggingface dataset:
Improved preservation of larynx with the addition of cetuximab to radiation for cancers of the larynx and hypopharynx
Authors: J. A. Bonner, P. M. Harari, J. Giralt, J. Baselga, D. Shin, R. Cohen, J. Jassem, N. Azarnia, P. Molloy, K. K. Ang
Journal: Journal of Clinical Oncology (2005)

5533 Background: Recently a large phase III randomized trial compared the non-surgical treatments of radiation (R) with or without weekly cetuximab (C) for patients with locoregionally advanced head and neck cancers of the oropharynx, hypopharynx and larynx. Patients who received the combination treatment (R+C) demonstrated a statistically significant advantage with respect to locoregional control and survival compared to patients treated with radiation alone (ASCO Abstract #5507, 2004). A subgroup analysis of the patients with hypopharyngeal and laryngeal carcinoma was undertaken to assess the rates of organ preservation for the two treatments. Methods: Rates of larynx preservation (LP) were estimated by Kaplan-Meier method. Patients who underwent no or lesser surgeries were censored at death or date of last contact. Hazard ratio was calculated by Cox regression. Results: The overall trial included 424 patients and 171 patients had hypopharyngeal and laryngeal carcinoma (R=78, R+C=93). The characteristics and results of treatment are shown below: * ELND = Elective Lymph Node Dissection The hazard ratio for LP was 0.62, favoring the combination treatment (R+C), but the study was not powered for organ preservation, and the confidence interval included 1.0. Conclusions: This subset analysis was hindered by sample size. However, the results were intriguing regarding a possible cetuximab-related benefit in LP for patients with hypopharyngeal and laryngeal cancer. This potential benefit is consistent with the fact that the addition of cetuximab to radiation resulted in a locoregional control and survival benefit for the overall group of patients (n=424). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems Bristol-Myers Squibb, ImClone Systems, Merck KGA ImClone Systems Bristol-Myers Squibb, ImClone Systems, Merck KGA
Phase I clinical study of cabazitaxel plus prednisolone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in a Japanese population.
Authors: Shunji Takahashi, Hirofumi Mukai, Hirotsugu Uemura, Hiroji Uemura, Takeo Kosaka, Hiroyuki Nishiyama, Kazuhiro Suzuki, Yoshiyuki Kakehi, Koji Okihara, Shunichi Namiki, Osamu Ogawa, Masashi Kato, Yasutomo Nakai, Keiji Ohno
Journal: Journal of Clinical Oncology (2014)

237 Background: Cabazitaxel (CBZ), a novel taxoid agent, promotes tubulin assembly and stabilizes microtubules, as docetaxel (DTX). CBZ had antitumor activity in DTX-resistant tumor models in vitro. We assessed dose-limiting toxicities (DLTs), safety and efficacy of CBZ in patients (pts) with mCRPC with prior DTX treatment. Methods: This was an open-label, dose escalation study of CBZ every 3 weeks, with daily prednisolone. Two CBZ dose levels (20 or 25 mg/m 2 ) were set in the dose escalation cohort to determine the maximum tolerated dose (MTD). Pts in the expansion cohort received the MTD. DLTs were evaluated at cycle 1 and were defined as follows: Grade (Gr) 4 neutropenia &gt; 7 days, Gr 4 thrombocytopenia, Gr 4 febrile neutropenia (FN), or Gr 3/4 non-hematological toxicities. Gr 3/4 neutropenia was prospectively studied based on occurrence of Gr 3/4 neutropenia during prior DTX treatment. Results: A total of 48 pts received CBZ (median age 66.1 years; ECOG PS: 0, 34 pts; 1, 14 pts; median cumulative DTX dose 753 mg/m 2 ). None of the evaluable pts in the dose escalation cohort experienced a DLT. All pts had at least one Gr 3/4 adverse event (AE). Frequent Gr 3/4 AEs at 25 mg/m 2 were neutropenia (44 pts, 100%) and FN (24 pts, 54.5%). G-CSF prophylaxis was not allowed at cycle 1 and was only used in 10% of cycles from cycle 2 onward. Neutropenia occurrence during prior DTX treatment did not affect neutropenia or FN incidence during CBZ treatment. No pt discontinued CBZ due to neutropenia or FN and no toxic death was reported. In total, 12/41 pts (29.3%) had a PSA response, and 2/12 evaluable pts had a partial response as the best overall response. Conclusions: The safety profile of CBZ in Japanese pts was generally consistent with that reported in previous studies. The cumulative dose of prior DTX was higher and use of G-CSF prophylaxis less frequent than in previous studies, which may have contributed to the increased incidence of neutropenia and FN in Japanese pts. The majority of neutropenia and FN events were manageable and did not lead to treatment discontinuation. In terms of safety and efficacy, CBZ has a favourable risk–benefit profile in Japanese pts with mCRPC following prior DTX therapy. Clinical trial information: NCT01324583.
Effect of Diabetes on Progression of Coronary Atherosclerosis and Arterial Remodeling
Authors: Stephen J. Nicholls, E. Murat Tuzcu, Srinivasa Kalidindi, Kathy Wolski, Keon-W. Moon, Ilke Sipahi, Paul Schoenhagen, Steven E. Nissen
Journal: Journal of the American College of Cardiology (2008)
Intercontinental spread from Israel to Colombia of a KPC-3-producing Klebsiella pneumoniae strain
Authors: J.A. Lopez, A. Correa, S. Navon-Venezia, A.L. Correa, J.A. Torres, D.F. Briceño, M.C. Montealegre, J.P. Quinn, Y. Carmeli, M.V. Villegasz
Journal: Clinical Microbiology and Infection (2010)
Randomised Controlled Trial of Cognitive Behaviour Therapy Delivered in Groups of Patients with Chronic Fatigue Syndrome
Authors: Jan F. Wiborg, Jose van Bussel, Agaat van Dijk, Gijs Bleijenberg, Hans Knoop
Journal: Psychotherapy and Psychosomatics (2015)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Meta-analyses have been inconclusive about the efficacy of cognitive behaviour therapies (CBTs) delivered in groups of patients with chronic fatigue syndrome (CFS) due to a lack of adequate studies. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We conducted a pragmatic randomised controlled trial with 204 adult CFS patients from our routine clinical practice who were willing to receive group therapy. Patients were equally allocated to therapy groups of 8 patients and 2 therapists, 4 patients and 1 therapist or a waiting list control condition. Primary analysis was based on the intention-to-treat principle and compared the intervention group (n = 136) with the waiting list condition (n = 68). The study was open label. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Thirty-four (17%) patients were lost to follow-up during the course of the trial. Missing data were imputed using mean proportions of improvement based on the outcome scores of similar patients with a second assessment. Large and significant improvement in favour of the intervention group was found on fatigue severity (effect size = 1.1) and overall impairment (effect size = 0.9) at the second assessment. Physical functioning and psychological distress improved moderately (effect size = 0.5). Treatment effects remained significant in sensitivity and per-protocol analyses. Subgroup analysis revealed that the effects of the intervention also remained significant when both group sizes (i.e. 4 and 8 patients) were compared separately with the waiting list condition. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; CBT can be effectively delivered in groups of CFS patients. Group size does not seem to affect the general efficacy of the intervention which is of importance for settings in which large treatment groups are not feasible due to limited referral.
Survival of mesothelioma patients after radical extrapleural pneumonectomy in the Nancy Biobank's database
Authors: Fotis Vlastos, Georgios Kaltsakas, Jean-Michel Vignaud, Nadine Martinet Martinet, Nickolaos G. Koulouris
Journal: European Respiratory Journal (2013)

Radical extrapleural pneumonectomy (EPP) entails the complete removal of the ipsilateral lung along with the parietal pleura, pericardium and the majority of the hemidiaphragm. The Nancy “Centre of Biologic Resources” (“Centre des Ressources Biologiques”) is an ISO 9001–2000 certified biobank with biologic material and follow-up data from French lung cancer and mesothelioma patients, collected for the last 20 years. This allows for a survey of mesothelioma survival rates and impact of EPP. Therefore, we set out to investigate whether EPP can increase the survival in mesothelioma patients comparing to chemotherapy.  Clinical and occupational data from 190 consecutive mesothelioma patients who underwent EPP, only chemotherapy, and palliative care were collected from the Nancy Database. Twenty seven of the patients underwent EPP (n=9 only EPP, Group A; n=16 EPP and chemotherapy, Group B; n=1 EPP and radiotherapy; n=1 EPP, chemotherapy, and radiotherapy). One hundred four patients had chemotherapy (Group C). Fifty nine patients had palliative care (Group D).  The patients underwent EPP had mean survival time (SD±SE, months) 20.0±3.3. Group A had mean survival time 16.8±3.9. Group B had mean survival time 19.3±3.9. Group C had mean survival time 25.9±2.8. Group D had mean survival time 10.8±1.4. The survival curves of Group B and Group D were significant different (p=0.029). The survival curves of Group C and Group D were significant different (p  EPP does not appear to increase the survival of mesothelioma patients compared to chemotherapy.
No association between exhaled nitric oxide and the outcome of the eucapnic voluntary hyperpnoea provocation test in patients suspected of exercised-induced bronchoconstriction
Authors: A.-M. Vints, H. Cuypers, G. De Schutter, S. Moustie, L. Vervliet, W. De Backer, E. Oostveen
Journal: European Respiratory Journal (2014)

Introduction: Recently, Berkman et al. (Thorax 905) suggested that exhaled nitric oxide (eNO) can be used as a rapid test for the diagnosis of asthma in patients with non-specific respiratory symptoms and normal baseline spirometry. Furthermore, they concluded that eNO is as good as bronchial provocation tests.  Aim and Methods: We studied the relationship between eNO and the level of bronchial responsiveness in subjects who were referred to the pulmonary department of the Antwerp University Hospital for diagnostic evaluation. Only subjects in whom the consulting respiratory physician had a strong suspicion of exercised-induced-bronchoconstriction (EIB) but without other clinical symptoms of asthma were included. All subjects were involved in sports at the competition level. eNO was measured prior to eucapnic voluntary hyperpnoea provocation testing (EVH).  Results: In the total group of subjects (18 M:13 F, age: 19 (5 (SD) yrs, baseline FEV1= 108 (12) %pred), 12 patients exhibited a fall in FEV1> 10% baseline, i.e. positive for EIB. There was no significant correlation between eNO and the change in FEV1 after EVH challenge (see figure).  Conclusion: eNO cannot substitute the eucapnic voluntary hyperpnoea provocation test in the diagnosis of asthma, at least not in the subgroup of athletes suspected of exercised-induced bronchoconstriction.
Monocytoid B Cells Are Distinct From Splenic Marginal Zone Cells and Commonly Derive From Unmutated Naive B Cells and Less Frequently From Postgerminal Center B Cells by Polyclonal Transformation
Authors: Karoline Stein, Michael Hummel, Petra Korbjuhn, Hans-Dieter Foss, Ioannis Anagnostopoulos, Theresa Marafioti, Harald Stein
Journal: Blood (1999)
When Is a “Prognostic Factor” Really Prognostic?
Authors: Stephen A. Cannistra
Journal: Journal of Clinical Oncology (2000)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.22.3745 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11078486 When Is a "Prognostic Factor" Really Prognostic? Stephen A. Cannistra, MDxStephen A. CannistraSearch for articles by this author Show More Beth Israel Deaconess Medical Center Boston, MA https://doi.org/10.1200/JCO.2000.18.22.3745 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
ER+ PR- breast cancer defines a unique subtype of breast cancer that is driven by growth factor signaling and may be more likely to respond to EGFR targeted therapies
Authors: R. S. Finn, J. Dering, C. Ginther, M. Press, J. Forbes, J. Mackey, T. French, M. South, M. Rupin, D. J. Slamon
Journal: Journal of Clinical Oncology (2006)

514 Background: Hormonal based therapy has long been the mainstay for treatment of ER+ breast cancer. ER+ PR- disease is now known to exhibit different clinical behavior compared to ER+PR+ disease. Recent data indicate that ER+PR- disease is characterized by a lower response rate to estrogen deprivation, has a worse prognosis compared to ER+ PR+ disease, and may be dependent on other signaling pathways. To evaluate the role of the EGFR tyrosine kinase inhibitor gefitnib in the treatment of breast cancer, we conducted a pre-surgical study in women with operable disease. Methods: Frozen core biopsies were obtained at baseline. Patients then received a short-term exposure to gefitinib (at least 2 weeks) prior to definitive surgery when a frozen tumor specimen was obtained. Tissue integrity and composition was verified by H and E and RNA was isolated for microarray analysis. 59 women were enrolled in the study of which 43 were evaluable for molecular analysis. Baseline microarrays were performed on the initial biopsies to classify the ‘subtype‘ of breast cancer (e.g. basal, luminal, HER2 amplified). To analyze the genetic changes that occur in breast cancer tissue with exposure to gefitinib, a direct comparison of the baseline sample and post-treatment tumor was performed. In addition, ER and PR status were determined by immunohistochemistry and compared to the microarray findings. Changes in Ki67 and a set of cell cycle genes were used to define ‘molecular response” to gefitinib. Of the 43 samples evaluated by microarray, 11 patients were categorized as exhibiting molecular growth inhibition, 10 patients as molecular growth proliferation, and 22 did not have a significant change in Ki67 and the cell cycle gene set to assign a response. When grouped by subtype, ER+PR- and HER2 amplified tumors define a subgroup more likely to show molecular growth inhibition with gefitinib. Conversely, ER+PR+ tumors were more likely to show molecular growth proliferation. Conclusions: These results support the hypothesis that ER+PR- breast cancer is growth factor dependent and constitutes a unique subgroup of ER+ patients which may be more likely to benefit from EGFR inhibition. [Table: see text]
Routine measurement of the LCI in CF with an ultrasonic device for multiple breath nitrogen washout
Authors: Susanne Fuchs, Edmund Petri, Georg Hülskamp, Monika. Gappa
Journal: European Respiratory Journal (2012)

During the last decade multiple breath washout technique (MBW) for calculating the Lung Clearance Index (LCI) has become very popular for assessing ventilation inhomogeneity (VI) as an early manifestation of Cystic Fibrosis (CF) lung disease. However, routine use has been difficult not only due to limited availability of licensed equipment. Inert tracer gases (e.g. SF 6,  He) certified for medical purposes are not universally available. Switch to nitrogen washout (MBW N2 ) using 100% oxygen may overcome this problem.  The aim of this cross sectional study was to assess whether LCI derived from MBW N2  discriminates as well as MBW SF6  between patients with CF and healthy controls.  19 controls (7-51years) and 11 unselected patients with CF (7-25 years) performed 2-3 single MBW N2  using the EasyOne Pro LAB™ (ndd Switzerland) with 100% oxygen.  Mean (SD) LCI was 6.5 (0.64) in controls and 9.3 (1.93) in CF with a mean difference (95% ci, p-value) of -2.83 (-4.14;-1.51, 0.001) between the groups. Within-test repeatability (CV%) was 5.3% in controls and 7.7% in CF.  Assessment of LCI using licensed equipment for MBW N2  was feasible and well tolerated in both, children and adults and patients and controls. LCI based on MBW N2  differed significantly between patients with CF and controls and results were comparable to published data obtained with different equipment and with using SF 6  as tracer gas. We conclude that MBW N2  reflects VI similar to MBW SF6  and may thus be used for clinical application of MBW in patients with CF.
Abstract 1505: Sunitinib-Induced Cardiotoxicity is Mediated in Part via Direct Effects on Cardiac Myocytes and Smooth Muscle Cells
Authors: Susan M Dallabrida, Nesreen Ismail, Elke A Pravda, Flavia Cassiola, Sendia Kim, Emily M Parodi, Risto Kerkela, Thomas Force, Mark Puder, Maria A Rupnick
Journal: Circulation (2007)

Tyrosine kinase inhibitors (TKI) have revolutionized cancer therapy, spawning over 500 clinical trials, yet cardiotoxicities are emerging. Sunitinib, a multi-targeted TKI, prolongs life in renal cell and gastrointestinal cancer patients, but hypertension and heart failure have required treatment adjustments. Objective: Sunitinib cardiotoxicity may be due, in part, to direct effects on smooth muscle and cardiac myocytes. Methods: We used C57Bl/6J mice, rat neonatal cardiomyocytes (NCM), and human coronary artery smooth muscle cells (SMC) treated with Sunitinib to measure drug-induced cardiovascular toxicity. Structural (transmission electron microscopy, immunohistochemistry (IHC)/confocal microscopy) and functional [apoptosis/survival, nitric oxide synthesis (intracellular and extracellular), signaling] effects were assessed [real-time PCR, Western blotting, receptor phosphorylation (immunoprecipitation/Western blotting)]. Results: We show mitochondrial injury in hearts from Sunitinib treated mice which persisted off of the drug. In vitro , Sunitinib accumulated in myocytes, caused myofibrillar disorganization, mitochondrial injury, and localized to the lysosomes. Sunitinib caused reductions in akt, MAPK, and AMPK signaling, and activated pro-apoptotic caspase-9 in NCM and SMC with similar effects in large and small vessel endothelial cells. In hearts of Sunitinib-treated mice, we found similar changes in signaling pathways. Conclusion: Sunitinib causes direct cardiac myocyte and smooth muscle cell toxicities, which may contribute to the cardiovascular side effects seen in patients. Further understanding of these mechanisms will guide monitoring, intervention and future rational drug design.
The Imaging Probe Development Center at NIH: A central core facility for the production and dissemination of molecular imaging probes
Authors: Gary L. Griffiths
Journal: Clinical Cancer Research (2010)

Abstract The Imaging Probe Development Center (IPDC, Rockville, MD), founded as part of the 2003 trans-NIH Roadmap for Medical Research initiative, provides synthetic chemistry support needed by interdisciplinary researchers for the supply of molecular imaging probes. Such research projects run from basic through translational to clinical in nature. The IPDC has state-of-the-art equipment and is staffed by scientists drawn from diverse backgrounds encompassing expertise in synthetic, inorganic, radiochemical, and conjugation chemistries. The IPDC has worked with principal investigators from over a dozen different NIH Institutes, along with some extramural collaborators, with a preponderance of projects related to cancer imaging, and has supplied literature-reported and novel agents used in all types of imaging modalities, including MRI, optical fluorescence and PET/SPECT. Examples of probes used for cancer imaging studies will be discussed including several radiolabeled low molecular weight drugs synthesized from first principles and radiolabeled monoclonal antibodies and other proteins. Several agents are undergoing further studies in clinical and process development. Recently made probes will be used to illustrate the scope and capabilities of the Center. The Center is able to work with other interested parties in order to develop useful imaging agents, particularly those that also have therapeutic implications. For more information, or to make enquiries about probe availability or potential collaborations you may visit our website at: http://www.ipdc.nih.gov.
Recurrence patterns for venous thromboembolism - who is most at risk?
Authors: Emma Crawford, Harmesh Moudgil, Thirumalairengarajan Naicker, Nawaid Ahmad, Koottalai Srinivasan
Journal: European Respiratory Journal (2014)

National guidance regarding the treatment of venous thromboembolism (VTE) advocates anticoagulating newly diagnosed patients for three months, followed by consideration of indefinite anticoagulation to reduce the risk of recurrent VTE in certain clinical situations. (NICE Clinical Guideline CG144, issued June 2012.) There is recent evidence that although deep vein thromboses (DVT) and pulmonary emboli (PE) are manifestations of the same disease, their patterns of recurrence and hence future morbidity and mortality risk are different. (Baglin, T. et al. Journal of Thrombosis and Haemostasis 2010; 8(11):2436-2442.)  We undertook a retrospective case-note review of 416 patients diagnosed with a VTE event within our institution between January 2010 and January 2011 to assess risk and pattern of VTE recurrence.  35 patients (8.4%) had a recurrent VTE event in the 3 years following diagnosis. Median time to recurrence was 12 months (mean 16.5, SD 10.5). None of the patients were anticoagulated at the time of recurrence and no patients died as a result of their thromboembolic event.  The majority of patients with recurrent VTE in our study presented as a further DVT and as such, could be considered at lower risk of associated morbidity and mortality compared to those presenting with PE. Clinicians should consider the likely presentation of any further VTE recurrence as part of their assessment before advocating indefinite anticoagulation in these patients, particularly as the introduction of new oral anticoagulant drugs is likely to make the logistics of prescribing lifelong anticoagulation less complex.
Flow, leakage or pressure – Who determines the clinical consequences of the nasal high– Flow (nHF)?
Authors: Jens Bräunlich, Friederike Goldner, Hans-Jürgen Seyfarth, Hubert Wirtz
Journal: European Respiratory Journal (2014)

Introduction:  The nasal high flow (nHF) becomes more and more acceptance in particular in breathing support of children and neonates. However, also with adults there is already a number of interesting knowledge. nHF is able to reduce hypercapnia in patients with COPD and IPF. Nevertheless, the active mechanism is not exactly understood yet.   Method:  Patients with COPD were applied nasal high-flow 1 hour under BGA control. Besides, the following combinations were measured:  a. 20 l/min, 2 prongs, both prongs open  b. 40 l/min, 2 prongs, both prongs open  c. 40 l/min, 2 prongs, both prongs open, 1 prong in nose, 1 prong outside  d. 40 l/min, 2 prongs, 1 prong open, open prong in nose, the closed prong outside  The pressure ratios were measured, in addition, in the hypopharynx.   Results:  Differences appeared between the different seetings. A) led to the slightest decrease in pCO2. B) reached the highest airway pressure. C) led to the strongest decrease in pCO2.   Discussion:  From the investigations it arises that the increase of the airway pressure is not the dominating size in nHF. Enlargement of the leakage (wash-out) and increases of the flow speed maximizes the effects. This can be read in clearly better dropping pCO2.
Endemic psychosis in western Ireland
Authors: E F Torrey, M McGuire, A O'Hare, D Walsh, M P Spellman
Journal: American Journal of Psychiatry (1984)

For over 200 years parts of Ireland have been thought to have a high prevalence of psychosis, and recent hospital and community studies have confirmed this impression. In an intensive study of a rural area, the authors found that 4% of the population over age 40 was actively psychotic, with diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder. Psychosis seems to be endemic in some rural, lower socioeconomic areas in Ireland. Possible etiological explanations are discussed.