tbuckley/cabot-search huggingface dataset:
β-Blockers, heart disease and COPD: current controversies and uncertainties
Authors: Jillian G Baker, Robert G Wilcox
Journal: Thorax (2016)

Treating people with cardiovascular disease and COPD causes significant clinician anxiety. β-Blockers save lives in people with heart disease, specifically postinfarction and heart failure. COPD and heart disease frequently coexist and people with both disorders have particularly high cardiovascular mortality. There are concerns about giving β-blockers to people with concomitant COPD that include reduced basal lung function, diminished effectiveness of emergency β-agonist treatments, reduced benefit of long-acting β-agonist treatment and difficulty in discriminating between asthma and COPD. β-Blockers appear to reduce lung function in both the general population and those with COPD because they are poorly selective for cardiac β1-adrenoceptors over respiratory β2-adrenoceptors, and studies have shown that higher β-agonist doses are required to overcome the β-blockade. COPD and cardiovascular disease share similar environmental risks and both disease states have high adrenergic and inflammatory activation. β-Blockers may therefore be particularly helpful in reducing cardiovascular events in this high-risk group. They may reduce the background inflammatory state, and inhibit the tachycardia and hypertension associated with both the endogenous adrenaline and high-dose β-agonist treatment associated with acute exacerbations of COPD. Some studies have suggested no increased and, at times, reduced mortality in patients with COPD taking β-blockers for heart disease. However, these are all observational studies and there are no randomised controlled trials. Potential ways to improve this dilemma include the development of highly β1-selective β-blockers or the use of non-β-blocking heart rate reducing agents, such as ivabridine, if these are proven to be beneficial in randomised controlled trials.
Risk of death from prostate cancer after radical prostatectomy or brachytherapy in men with low- or intermediate-risk disease.
Authors: N. D. Arvold, M. Chen, J. W. Moul, B. J. Moran, D. E. Dosoretz, L. L. Banez, M. J. Katin, M. H. Braccioforte, A. V. D'Amico
Journal: Journal of Clinical Oncology (2011)

198 Background: Radical prostatectomy (RP) and brachytherapy (BT) are widely utilized treatments for favorable-risk prostate cancer (PC). We estimated the risk of PC-specific mortality (PCSM) following RP or BT in men with low- or intermediate-risk PC using prospectively collected data. Methods: The study cohort comprised 5,760 men with low-risk PC (prostate-specific antigen [PSA] level ≤ 10 ng/mL, clinical category T1c or 2a, and Gleason score ≤ 6), and 3,079 men with intermediate-risk PC (PSA level 10-20 ng/mL, clinical T2b or T2c, or Gleason score 7). Competing risks multivariable regression was performed to assess risk of PCSM after RP or BT, adjusting for age, treatment year, cardiovascular comorbidity, and known PC prognostic factors. Results: There was no significant difference in the risk of PCSM among men with low-risk PC (11 vs. 6 deaths: adjusted hazard ratio [AHR], 1.62; 95% CI, 0.59–4.45; P = 0.35) who received BT compared to RP. However among men with intermediate-risk PC, despite significantly shorter median follow-up for men undergoing BT as compared to RP (4.1 vs. 7.2 years, P &lt; 0.001), there was a trend toward an increased risk of PCSM (18 vs. 9 deaths: AHR, 2.30; 95% CI, 0.95–5.58; P = 0.07) for men treated with BT. Conclusions: The risk of PCSM among men with low-risk PC was not significantly different following RP or BT, however there may be a reduced risk of PCSM after RP as compared to BT in men with intermediate-risk PC. [Table: see text] No significant financial relationships to disclose.
Dermatofibrosarcoma protuberans-derived fibrosarcoma: Response to escalated-dose imatinib mesylate (IM) and second-generation kinase inhibitor nilotinib.
Authors: T. N. Elrafei, G. Chrysofakis, N. Simmons, L. J. Reed
Journal: Journal of Clinical Oncology (2011)

e20529 Background: Dermatofibrosarcoma protuberans (DFSP) is a dermal sarcoma typically carrying a translocation between chromosomes 17 and 22 that generates functional platelet-derived growth factor B (PDGFB). Imatinib is active in locally advanced and metastatic DFSP harboring t(17;22) with objective response rates of 50% in pooled clinical trial results. Less is known of imatinib, or second generation kinase inhibitor nilotinib, efficacy in fibrosarcomatous-DFSP having the PDGF rearrangement. Methods: From January 2007, 2 patients with locally advanced high grade Fibrosarcoma (FS) arising in DFSP were treated with 400 mg IM. We also identified 4 DFSP and 2 FS patients without DFSP from 2003. Results: Both patients were male age 60/51 with ECOG PS=0. Patient A weighed 142 kg and had a subjective response, RECIST SD and continued PET scan activity. Dose was eventually escalated to 1600 mg. Imatinib trough level = 3710 ng/ml. The shoulder mass was resected with 1mm margin at 29 months. 54% of the cells contained PDGFB rearrangement by FISH. The patient died at 32 months of brain metastsasis. Patient B had RECIST SD and continued PET activity after 4 months of treatment and had 1 month of IM escalation to 800mg. He underwent resection of his abdominal mass but relapsed in the inguinal node and lungs. After three cycles of MAID and two cycles of gemcitabine/docetaxel he was treated with compassionate use nilotinib (Tasigna). He died of disease progression 4 weeks after initiation of nilotinib (OS from presentation 20 months). 49% of the cells contained PDGFB rearrangement at presentation and 63% at resection. Conclusions: resistance to imatinib was not related to PDGFRB expression and was not overcome by dose escalation of imatinib or nilotinib.
Antiestrogenic effects of the natural fetal estrogen estetrol (E<sub>4</sub>) in women with estrogen-receptor-positive early breast cancer.
Authors: C. F. Singer, C. Natter, S. Steurer, F. Moinfar, M. Visser, N. Appels, E. Kubista, H. Coelingh Bennink
Journal: Journal of Clinical Oncology (2011)

280 Background: Estetrol (E4) is a fetal estrogen which exerts estrogenic effects on vaginal epithelium, hot flushes and bone, but has estrogen-antagonistic effects on breast cancer cell lines in vitro and in the rat DMBA model. Therefore E4 may be suitable for Hormone Replacement Therapy (HRT) in women with breast cancer including women treated with aromatase inhibitors. Methods: We have investigated the effect of 14 days pre-operative treatment with 20 mg E4 per day on proliferation, apoptosis, ER-receptors and sex steroid levels in a prospective, randomised, double-blind, placebo-controlled, neo-adjuvant study in 15 pre- and 15 postmenopausal women with estrogen-receptor positive early breast cancer. Results: Estetrol induced a significant increase of SHBG, a significant decrease of FSH in postmenopausal women and no increase of gonadotrophins in premenopausal women. Estetrol had no effect on Ki67 expression and on apoptosis-related Bax and Bcl-2, but the apoptosis index in tumor tissue increased significantly. Systemic IGF-1 levels decreased significantly. Surprisingly the intratumoral epithelial ER-alpha expression decreased significantly, whereas the ER-beta expression showed a trend to increase. Conclusions: This data show that E4 has estrogenic endocrine effects. The data support the hypothesis that E4, may be suitable and safe for HRT in women with spontaneous or induced menopausal symptoms, since apoptosis increases, IGF-1 decreases and no unfavourable effects are observed on Ki67, Bax and Bcl-2. The decrease of ER-alpha and the increase of ER-beta suggest a mechanism of action, explaining why the natural fetal estrogen E4 has estrogen-antagonistic effects on breast cancer tissue.
Moderate/ Severe Pleural Effusion As a Side Effect in Very Old Chronic Myeloid Leukemia (CML) Patients Undergoing Imatinib Treatment
Authors: Dario Ferrero, Roberto Latagliata, Malgorzata Monika Trawinska, Francesco Cavazzini, Gabriele Gugliotta, Massimo Breccia, Mario Annunziata, Paolo Vigneri, Mario Tiribelli, Gianni Binotto, Carmen Fava, Elena Crisà, Giovanna Mansueto, Antonella Gozzini, Laura Cavalli, Raffaele Porrini, Alessandra Iurlo, Sabina Russo, Barbara Anaclerico, Antonella Russo Rossi, Patrizia Pregno, Giuseppe Visani, Isabella Capodanno, Mauro Endri, Antonio Spadea, Gianfranco Giglio, Francesca Celesti, Federica Sorà, Sergio Storti, Ada M D’Addosio, Giovanna Rege Cambrin, Elisabetta Abruzzese, Gianantonio Rosti, Luigiana Luciano, Giuliana Alimena
Journal: Blood (2011)
Prognostic factors for localized, resectable liposarcomas (LPS) of the extremities or trunk wall.
Authors: W. Dziewirski, S. Trepka, T. Morysinski, K. Ptaszynski, A. Pienkowski, M. Salamacha, I. A. Lugowska, M. Zdzienicki, P. Rutkowski
Journal: Journal of Clinical Oncology (2011)

e20515 Background: Liposarcomas are one of the most common and well-defined type of soft tissue sarcomas. The aim of the study was to analyze prognostic factors having influence on the outcomes of localized, resectable LPS of extremities/trunk wall. Methods: Between 1996 and 2008 in tertiary cancer center 187 consecutive patients, aged (18-89 years) with localized LPS (106 primary LPS, 61 clinically recurrent tumor and 20 scar after non radical resection) were treated with surgery and radiotherapy (158 cases) or surgery alone (29 cases including 6 amputations). Median follow-up: 48 months. Results: 5-year overall survival (OS), disease-free survival (DFS) and local relapse-free survival (LRFS) rates were: 80%, 57% and 75%, respectively. We identified factors having negative influence on LRFS: tumor grade 2 or 3 (p=0.04), clinically recurrent tumor (p=0.01; 5-year LRFS rates for primary versus clinically recurrent tumor versus scar after primary non radical resection were 86.5%, 52.1%, 73.3%, respectively), resection margins R1 (p=0.01) and pathological subtype (p=0.03). In multivariate analyses we have found following independent negative prognostic factors for OS (AJCC stage ≥ IIb; HR 5.8, 95% CI 2.1-16.1, p=0.001), DFS (grade 3: HR 3.9, 95% CI 1.9-7.5, p=0.0001; clinical recurrence HR 2.2, 95% CI 1.3-3.7, p=0.003 and skin infiltration, HR 2.8, 95% CI 1.4-5.7, p=0.004) and LRFS (clinically recurrent tumor HR 2.8, 95% CI 1.4-5.8, p=0.004; R1 resection margins HR 2.1, 95% CI 1.01-4.3, p=0.04). Conclusions: We have confirmed the value of AJCC staging for predicting OS in extremity/trunk wall LPS. Radical re-resection of scar after non-radical primary tumor resection (+ radiotherapy) seems to improve DFS and LRFS in this type of soft tissue sarcomas.
Closure of an Established Potts Anastomosis
Journal: JAMA (1963)

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Prevalence of testicular microlithiasis association with testicular and extragonadal germ cell tumors in a Latin American population.
Authors: Silvia P. Neciosup, Jose Quesada, David Callacondo, Ivan Aguilar
Journal: Journal of Clinical Oncology (2012)

331 Background: Testicular microlithiasis (TM) is a entity characterized by multiple areas of increased echogenicity on scrotal ultrasonography (U.S.). Studies have reported association between TM and testicular germ cell tumors (TGCT). However, a study assessing the association of TM and extragonadal germ cell tumors (EGCT) has not been performed. Methods: Scrotal U.S. were reviewed in 441 men randomly selected from our computerized database during the period 1998 and 2010 at our tertiary-care cancer hospital. The association of U.S. findings with medical records and a history of germ cell tumors (GCT) were evaluated. The type of tumor was confirmed at histology after surgery or biopsy. Exclusion criteria included age &lt;15 years and history of orchidectomy. Results: The median age was 32 years (range 15 – 88). TM was present in 95 patients (22%) and GCT were found in 130 patients (29%). 105 of these had TGCT (seminoma, n=56 and no seminoma, n=49) and 25 had EGCT (mediastinal, n=16, retroperitoneal, n=6 and CNS, n=3). Concurrent diagnosis of a TGCT was more prevalent in TM patients than in patients without TM (36/95 [38%] versus 69/346[20%] OR 2.45 95% CI 1.49–4.0; p&lt;0.0001) while a diagnosis of an EGCT was present in 13 patients with TM and 12 patient without TM (13/95 [14%] versus 12/346 [3%] OR 4.41 95% CI 1.94–10.03; p&lt;0.0001). No statistical differences were found for histology type. Conclusions: The prevalence in Latin American of TM is higher than previous reports and strongly associated with TCGT and EGCT. The clinical impact of the relationship between EGCT and TM is yet unknown and further studies are needed to clarify its role in the management. We suggest that young high-risk referral patients with TM should undergo scrotal U.S. annually; when a testicular tumor is not evident by U.S., investigations to rule out an EGCT, as thoracic or abdominal CT scans, should be considered individually in each case.
Chemoimmunotherapy with Chlorambucil and the Type II CD20-Antibody GA101 In Patients with Chronic Lymphocytic Leukemia and Comorbidity: Results of the Run-In Phase of the CLL11 (BO21004) Trial
Authors: Valentin Goede, Kirsten Fischer, Busch Raymonde, Jaeger Ulrich, Marie-Sarah Dilhuydy, Nicholas Wickham, Sophie De Guibert, Anna Maria Fink, Susanne Hagist, Natali Pflug, Jasmin Bahlo, Gabriele Kranz, Gabriel Bieska, Kathryn Humphrey, Helen Bishop, Michael Wenger, Michael Hallek
Journal: Blood (2010)
Pre-B-Cell Colony Enhancing Factor (PBEF) Is a New Cytokine Regulating Myeloid Differentiation in Healthy Individuals and Patients with Severe Congenital Neutropenia (CN).
Authors: Julia Skokowa, Lan Dan, Gunnar Cario, Axel Schambach, Cornelia Zeidler, Christopher Baum, Martin Stanulla, Karl Welte
Journal: Blood (2005)
A Genomic Predictive Signature for Rigosertib in Lower Risk MDS Derived By Integrating Clinical Response, Mechanism of Action Data and Simulation
Authors: Steven M. Fruchtman, Abdullah Mahmood Ali, Michael E. Petrone, Patrick Simon Zbyszewski, Benjamin Hoffman, Shireen Vali, Neeraj Kumar Singh, Shahabuddin Usmani, Himanshu Grover, Taher Abbasi, Azra Raza
Journal: Blood (2016)
Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases
Authors: Katherine A. Hoadley, Marni B. Siegel, Krishna L. Kanchi, Christopher A. Miller, Li Ding, Wei Zhao, Xiaping He, Joel S. Parker, Michael C. Wendl, Robert S. Fulton, Ryan T. Demeter, Richard K. Wilson, Lisa A. Carey, Charles M. Perou, Elaine R. Mardis
Journal: PLoS Medicine (2016)

Background Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual. Methods and Findings We performed DNA whole genome and mRNA sequencing on two primary tumors, each with either four or five distinct tissue site-specific metastases, from two individuals with triple-negative/basal-like breast cancers. As evidenced by their case histories, each patient had an aggressive disease course with abbreviated survival. In each patient, the overall gene expression signatures, DNA copy number patterns, and somatic mutation patterns were highly similar across each primary tumor and its associated metastases. Almost every mutation found in the primary was found in a metastasis (for the two patients, 52/54 and 75/75). Many of these mutations were found in every tumor (11/54 and 65/75, respectively). In addition, each metastasis had fewer metastatic-specific events and shared at least 50% of its somatic mutation repertoire with the primary tumor, and all samples from each patient grouped together by gene expression clustering analysis. TP53 was the only mutated gene in common between both patients and was present in every tumor in this study. Strikingly, each metastasis resulted from multiclonal seeding instead of from a single cell of origin, and few of the new mutations, present only in the metastases, were expressed in mRNAs. Because of the clinical differences between these two patients and the small sample size of our study, the generalizability of these findings will need to be further examined in larger cohorts of patients. Conclusions Our findings suggest that multiclonal seeding may be common amongst basal-like breast cancers. In these two patients, mutations and DNA copy number changes in the primary tumors appear to have had a biologic impact on metastatic potential, whereas mutations arising in the metastases were much more likely to be passengers.
Accelerated MVAC as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder.
Authors: C. Blick, P. Hall, T. Pwint, N. Munro, J. Crew, T. Powles, V. M. Macaulay, F. Al-Terkait, A. Protheroe, J. D. Chester
Journal: Journal of Clinical Oncology (2011)

235 Background: Meta-analysis data demonstrate a 5% absolute survival benefit for the use of neoadjuvant chemotherapy (NAC) using cisplatin-based combination regimens in the radical treatment of muscle-invasive bladder cancer (MIBC). However, there is currently no randomized controlled trial data on the optimum regimen for this setting. Accelerated MVAC (AMVAC) is effective in advanced disease, and has the potential advantage over other NAC regimens of minimising delays to definitive, potentially curative therapy. We present data regarding its use as NAC in MIBC patients. Methods: Retrospective analysis was performed on all 80 consecutive patients with muscle-invasive transitional cell carcinoma of the bladder, treated during a 50-month period at 2 U.K. centers. Patients received either 3 or 4 cycles of methotrexate 30mg/m 2 , vinblastine 3mg/m 2 , doxorubicin 30mg/m 2 and 4-hour infusion of cisplatin 70mg/m 2 at 2-week intervals, with G-CSF support, prior to definitive therapy with either radical surgery (RS) or radical radiotherapy (RT). Results: All planned cycles of chemotherapy were completed in 84% of patients. All 80 patients received their planned definitive therapy. Pathological complete response (pCR) was seen in 43% of 60 patients treated with surgery following chemotherapy. There were no chemotherapy-related deaths and grade 3 or 4 toxicities were seen in 11% of patients. Median duration of chemotherapy was 34 days. Dose reduction or delay was required in 7% and 9% of patients, respectively. Objective radiological local response was seen in 75% of patients. At a median follow-up of 27.5 months, 25 (32%) patients have relapsed and 11 (14%) died. Two-year disease-free survival was 65% overall, and was statistically significantly superior in patients who were radiologically node-negative prior to chemotherapy. Conclusions: AMVAC is a safe, well-tolerated, and easily deliverable regimen with excellent treatment outcomes and minimizes delays to definitive treatment. It is an appropriate comparator for future randomized trials. No significant financial relationships to disclose.
18F-Fluorodeoxyglucose Uptake in Anti-N-Methyl-D-Aspartate-Receptor Encephalitis Associated With an Immature Teratoma
Authors: Ryusuke Nakamoto, Yuji Nakamoto, Takayoshi Ishimori, Yasutaka Fushimi, Kaori Togashi
Journal: Clinical Nuclear Medicine (2016)

We report a case of anti-N-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis associated with an immature teratoma developed in a 38-year-old woman. Positron emission tomography (PET) revealed focal intense uptake of F-fluorodeoxyglucose in an area of the brain corresponding to the right medial temporal lobe as well as an intrapelvic tumor. After the PET examination, the patient complained of disorientation and short-term memory loss. The ovarian tumor was resected and diagnosed as an immature teratoma. The cerebrospinal fluid analysis was positive for anti-NMDAR antibody. After surgery, the patient's neurologic symptoms improved. The PET finding of encephalitis associated with an immature teratoma was unexpected.
The Impact of ATG/Alg in Preconditioning On the Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia
Authors: Koji Kato, Yoshiko Atsuta, Kazuteru Ohashi, Takahiro Fukuda, Shuichi Taniguchi, Heiwa Kanamori, Hisashi Sakamaki, Hiromasa Yabe, Makoto Murata
Journal: Blood (2012)
Diffuse Large B-Cell Lymphoma in the Elderly: Outcome of Patients From a Single Center
Authors: Jean-Marc Schiano de Colella, Diane Coso, Benjamin Esterni, Anne-Marie Stoppa, Vadim Ivanov, Thérèse Aurran, Florence Broussais, Jerome Rey, Frederique Rousseau, Maud Cecile, Didier Blaise, Reda Bouabdallah
Journal: Blood (2011)
Pre-Emptive Rituximab for the Prevention of EBV-Related PTLD in Umbilical Cord Blood Transplantion Patients
Authors: Sheila Mitsuma, Jose Licona, Robert Lynch, Amy Sievers, Corey Cutler, John Koreth, Vincent T Ho, Philippe Armand, Edwin P Alyea, Joseph H. Antin, Robert J. Soiffer, Francisco M Marty
Journal: Blood (2011)
Prevalence and Eradication of Colonizing Staphylococcus Aureus in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation
Authors: C. Matthias Wilk, Isabel Weber, Carole Rachmühl, Kati Seidl, Anne Holzmann Bürgel, Antonia MS Müller, Urs Schanz, Annelies S. Zinkernagel
Journal: Blood (2016)
Unmanipulated Graft Transplantation From Family Haploidentical Donors: A Survey On 183 Adult Patients with Acute Leukemias On Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)
Authors: Fabio Ciceri, Myriam Labopin, Paolo Di Bartolomeo, William Arcese, Stella Santarone, Gottardo De Angelis, Jacopo Peccatori, Mohamad Mohty
Journal: Blood (2012)