tbuckley/cabot-search huggingface dataset:
Prevention of chemotherapy-induced febrile neutropenia (FN) by antibiotics (AB) versus antibiotics plus granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC): A randomized phase III study
Authors: J. Timmer-Bonte, B. Biesma, J. Smit, F. Wilschut, J. Akkermans, T. De Boo, G. Bootsma, V. C. Tjan-Heijnen
Journal: Journal of Clinical Oncology (2004)

8002 Background: FN is a major complication of chemotherapy in patients (pts) with SCLC. G-CSF is used to prevent FN, but its primary use is only recommended in pts with a considerable (>40%) risk of FN (ASCO guidelines, JCO 2000). AB are also effective in preventing FN, even reduce infection-related mortality and are cost-effective (Tjan-Heijnen, Ann Oncol 2001). In this multicenter randomised phase III trial the role of combined primary prophylaxis with AB plus G-CSF in pts with SCLC at increased risk of FN was determined. Methods: Pts with SCLC-limited disease and performance status (PS) 2–3, or age over 60 years or judged not suitable for concurrent chemo/radiotherapy and pts with SCLC-extensive disease were considered at increased risk of FN. Pts were stratified for age (</≥ 60 years), PS (0–1/2), extend of disease (LD/ED) and line of therapy (1st/2nd) and randomised for primary prophylaxis with AB (ciprofloxacin 500mg + roxithromycin 150mg, bid, days 4–13) alone or in combination with G-CSF (filgrastim 5 μ g/kg/day days 4–13). Chemotherapy consisted of cyclophosphamide 1000mg/m2 day 1, doxorubicin 45mg/m2 day 1 and etoposide 100mg/m2 days 1,2,3, i.v., q 3 weeks, × 5. Primary endpoint: incidence of FN in first cycle, targeted accrual: N=156 pts (78/ arm). Results: See table;171 pts were eligible. Patient characteristics were well balanced. Conclusion: The addition of primary prophylactic G-CSF to prophylactic antibiotics significantly reduced the incidence of chemotherapy-related FN in SCLC patients at increased risk of FN, especially in the first cycle by 50%. Supported by a research grant of Dutch Healthcare Insurance Board. No significant financial relationships to disclose.
Reply to Prakoso et al.
Authors: D. Urbain, M. Aerts, H. Reynaert, F. Mana, B. Neyns
Journal: Endoscopy (2010)

We agree with the interesting remarks of Prakoso and Selby [1]. Our experience in small-bowel melanoma metastases confirms that some of them can be polypoid. We also observed in some patients that polypoid and flat lesions could coexist. This was also the case in the patient we reported [2]. In some patients, the small-bowel melanoma metastases look more like a submucosal bulging ([Fig. 1]). This appearance of lesions can also be encountered in peritoneal or mesenteric metastases growing into the small bowel. Endoscopists should indeed be aware of the variability of the melanoma metastatic lesions in the small bowel.
Cocaine Use in Pregnancy
Authors: Ira J. Chasnoff, William J. Burns, Sidney H. Schnoll, Kayreen A. Burns
Journal: New England Journal of Medicine (1985)

With the increasing use of cocaine in the United States, there has been growing concern regarding its effects on the fetuses and neonates of pregnant cocaine abusers. Twenty-three cocaine-using women enrolled in a comprehensive perinatal-addiction program were divided into two groups: those using cocaine only and those using cocaine plus narcotics. These two groups were compared with a group of women who had used narcotics in the past and were maintained on methadone during pregnancy, and with a group of drug-free women. All four groups were similar in maternal age, socioeconomic status, number of pregnancies, and cigarette, marijuana, and alcohol use. Their medical histories indicated that the cocaine-using women had a significantly higher rate of spontaneous abortion than the women in the other two groups. In the pregnancies under study, four cocaine-using women had onset of labor with abruptio placentae immediately after intravenous self-injection of cocaine. Neonatal gestational age, birth weight, length, and head circumference were not affected by cocaine use. However, the Brazelton Neonatal Behavioral Assessment Scale revealed that infants exposed to cocaine had significant depression of interactive behavior and a poor organizational response to environmental stimuli (state organization). These preliminary observations suggest that cocaine influences the outcome of pregnancy as well as the neurologic behavior of the newborn, but a full assessment will require a larger number of pregnancies and longer follow-up.
Effect of Immunization with a Common Recall Antigen on Viral Expression in Patients Infected with Human Immunodeficiency Virus Type 1
Authors: Sharilyn K. Stanley, Mario A. Ostrowski, Jesse S. Justement, Kira Gantt, Susan Hedayati, Margaret Mannix, Kim Roche, Douglas J. Schwartzentruber, Cecil H. Fox, Anthony S. Fauci
Journal: New England Journal of Medicine (1996)

Activation of the immune system is a normal response to antigenic stimulation, and such activation enhances the replication of human immunodeficiency virus type 1 (HIV-1). We studied the effect of immunization with a common recall antigen on viral expression in HIV-1-infected patients, on the ability to isolate virus, and on the susceptibility to HIV-1 infection of peripheral-blood mononuclear cells (PBMCs) from control subjects not infected with HIV-1.Thirteen HIV-1-infected patients and 10 uninfected adults were given a 0.5-ml booster dose of tetanus toxoid. Studies were performed to evaluate changes in the degree of plasma viremia, proviral burden, the ability to isolate HIV-1, and the susceptibility of PBMCs to acute infection in vitro. Two patients underwent sequential lymph-node biopsies for the assessment of viral burden in these tissues.All 13 HIV-1-infected patients had transient increase in plasma viremia after immunization, and the proviral burden increased in 11. These changes did not correlate with the base-line CD4+ T-cell counts. The lymph-node tissue also had increases in the proviral burden and viral RNA after immunization. The virus was more easily isolated from PBMCs from nine of the patients after immunization than before immunization. Despite considerable variability in the results, PBMCs from 7 of the 10 normal subjects were more easily infected in vitro with HIV-1 after immunization than before immunization.Activation of the immune system by an ongoing antigen-specific immune response to an exogenous stimulus transiently increases the expression of HIV-1 and may enhance the susceptibility of uninfected subjects to HIV-1.
Abstract 50: Abrogation of stromal TGF-β signaling induces DNA damage and genetic/epigenetic alterations in neighboring epithelia
Authors: B. Achyut, David A. Bader, Yanli Pang, Curtis C. Harris, Li Yang
Journal: Cancer Research (2012)

Abstract Inactivation of tumor suppressor genes in stromal fibroblast induces epithelial cancer development, suggesting an important role of stroma in epithelial homoeostasis. We investigated the underlying mechanisms in squamous cell carcinoma (SCC) development due to loss of TGF- signaling in FSP1+ fibroblasts (Tgfbr2fspKO). We found that stroma specific deletion of Tgfbr2 resulted a loss of p15 and p16, the cyclin dependent kinase (CDK) inhibitors in adjacent epithelia. In addition, there was an increased p21 methylation in the promoter region of the p53 binding site. These data suggest that multiple cell cycle checkpoints were compromised in the epithelia of Tgfbr2fspKO mice. Consistent with these observations, there was an increased cell proliferation in the epithelial compartment. The mechanisms mediating the cross talk between the epithelia and the stroma apparently involved inflammation that occurred only in the Tgfbr2fspKO mice but not in Tgfbr2flox/flox mice. This is characterized by an increased CD45+ leukocyte infiltration, increased cytokines expression (IL-10, IFN-γ TNF-α and GM-CSF) and elevated levels of iNOS, COX2 and NFκB. Interestingly, a significant DNA damage, featured by 8-Oxo-dG DNA adduct formation, and elevated expression of γ-H2AX, a histone protein in response to DNA double strand break, was observed in Tgfbr2fspKO mice. Inhibition of inflammation with COX2 inhibitor (Celecoxib) or germ free housing condition, significantly delayed epithelial hyperplasia/dysplasia and reduced DNA damage in Tgfbr2fspKO mice. Examination of human esophageal cancers showed a downregulation of TβR2 in the stromal fibroblast, and an increased inflammation and DNA damage similar to Tgfbr2fspKO mice. Together, our data demonstrate that attenuation of stromal TGF- signaling induces inflammation that in turn causes DNA damage, epigenetic and genetic alterations in epithelia. Therefore, therapeutic targeting of inflammation and tumor microenvironment may be useful in treating cancers with downregulation of TGF- signaling in stroma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 50. doi:1538-7445.AM2012-50
AB1011 Correlation between Hip Pain and Synovitis in Osteoarthritic Hips: Evaluation with Contrast Enhanced MR Images and Hip Arthroscopy
Authors: R. Kawakami, K. Fukuda, T. Hayama, H. Sugiyama
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The causes of hip pain in osteoarthritis remain unknown. In recent years, Femoroacetabular impingement has attracted much attention as a cause of this symptom. In cases of knees, Roemer et. al. suggested that out of several osteoarthritic MRI features, synovitis is related to knee pain<sup>1</sup>. <h3>Objectives</h3> To investigate the correlation between pain and synovitis in symptomatic hips, by using Contrast Enhanced Magnetic Resonance Images (CEMRI) and hip arthroscopy findings. <h3>Methods</h3> Approval was obtained from Institutional Review Board. Consent was obtained from 29 patients included in this study. In collecting the data, 10 exclusions were made on several grounds, including contraindication to the use of contrasts, high risk for anesthetics, and cases that had MR images taken with non-routine sequences. Hip pain was evaluated with Hip Disability and Osteoarthritis Outcome Score (HOOS) and Japanese Orthopedic Association Hip Score (JOAHS). Two board-approved orthopedic surgeons performed the hip arthroscopy, assessing the severity of synovitis on labral recess, acetabular fossa and lateral aspect of head-neck junction of femur. Two board-approved musculoskeletal radiologists evaluated the thickness of synovial membrane of the hip at the specified location in Hip Osteoarthritis MRI Scoring System (HOAMS) and the designated location assessed under the arthroscopy, on CEMRI. The correlation between clinical scores and severity of synovitis was evaluated. <h3>Results</h3> 19 subjects were included (mean age 37.57 years old, range 11-66, BMI 23.89kg/m<sup>2</sup> range 17.72-32.92kg/m<sup>2</sup>, 6 male and 13 female, 11 right hips 8 left hips). The thickness of synovial membrane on CEMRI showed association with the synovial findings of hip arthroscopy (P=0.023). Severity of synovitis showed association with clinical hip pain scores on the anterior aspects of the labral recess (P=0.009). <h3>Conclusions</h3> The thickness of synovial membrane on CEMRI associated with the findings of hip arthroscopy. CEMRI is a reliable investigation for assessing the severity and location of synovitis responsible for hip pain. Synovitis on the anterior aspect of the labral recess showed strongest association with hip pain. This is thought to be due to the large anterior range of movement of the hip. Performing CEMRI may reveal the location of synovitis responsible for hip pain. This may reduce unnecessary investigative arthroscopy and shorten the length of procedure by locating the site of synovitis pre-operatively. <h3>References</h3> F.W. Roemer et.al. Osteoarthritis and cartilage. 2011; 19: 946-962 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4907
SP0013 The 5 Year Course of Physical Work Capacity in People with Early OA: A Longitudinal Study in the Check Cohort
Authors: A. Bieleman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> The impact of osteoarthritis (OA, a common disorder with increasing prevalence) on peoples’ functional capacity is hardly known. Therefore the objective of this study was to evaluate the course of functional capacity of subjects in a prospective cohort study on early OA of hip and/or knee. <h3>Methods</h3> Functional capacity of 94 subjects from the CHECK study (Cohort Hip and Cohort Knee) was measured at baseline, using a protocolled Functional Capacity Evaluation. Subjects were invited to participate in 1-, 2- and 5-year follow-up measurements. Descriptive data will be presented for these 4 measurements; later on data will be analysed with regression analysis or multilevel analysis. <h3>Results</h3> The numbers of participants at the measurements at 0, 1, 2 and 5 year, were 93, 65, 57 and 29, respectively. Their mean age at baseline was 56 years and 61 at T5; 79-86% were females. There were no statistically significant differences between test performances at the 4 measurements. Overall means (SD’s) were: lifting low 19.9 (9.3) kg, lifting high 9.7 (5.2) kg, carry long 21.6 (11.1) kg, overhead static work 175 (79) sec, walking 337 (112) meters. <h3>Discussion</h3> The functional capacity of the subjects remains more or less stable in 5 years. However, the number of participants decreased significantly with each measurement and the results have to be controlled for selective drop-out. The relation between functional capacity and other subject characteristics will be addressed. A point of discussion is the best way to analyse these results, for example with multi-level analysis. <h3>Disclosure of Interest</h3> None Declared
Zika virus and congenital malformations in perspective
Authors: Christian Drosten
Journal: Eurosurveillance (2016)

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Abstract P1-13-07: Association Between Delayed Initiation of Adjuvant Chemotherapy and Survival in Breast Cancer: A Single-institution Study and A Systematic Review and Meta-analysis
Authors: K-D Yu, L Fan, C Yang, Z-M Shao
Journal: Cancer Research (2012)

Abstract Objective: Adjuvant chemotherapy (AC) improves survival among patients with operable breast cancer. However, the effect of delay in AC initiation on survival is unclear. We performed a single-institution data analysis and a systematic review and meta-analysis to determine the relationship between time to AC and survival outcomes. Methods: PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Web-of-Science databases (before March-20, 2012) were searched to identify relevant eligible studies. An additional retrospective analysis including 1,408 patients from the prospectively maintained database of Shanghai Cancer Center was performed and results were also included. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) from each study were converted to a regression coefficient (β) and its standard error corresponding to a continuous representation per 4-week delay of AC. Individual adjusted β were combined using a fixed-effects or random-effects model depending on heterogeneity. Results: We included 8 eligible studies with 10 independent analytical groups involving 21,221 patients, 1 prospective observational study, 2 secondary analyses in randomized trials (4 analytical groups), and 5 hospital-/population-based retrospective studies. In our single-institution study, every 4-week delay in initiation of AC significantly decreased OS (HR = 1.38; 95% confidence interval [CI], 1.03–1.87) and DFS (HR = 1.35; 95% CI, 1.08–1.69) after adjustment for other prognostic variables. The overall meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both OS (HR = 1.20; 95% CI, 1.03–1.39; random-effects model) and DFS (HR = 1.21; 95% CI, 1.08–1.36; fixed-effects model). One study caused a significant between-study heterogeneity for OS (p = 0.001; I2=74.1%); after excluding that single study, there was no heterogeneity (p = 0.345; I2=11.1%) and the HR was more significant (HR = 1.24; 95% CI, 1.14–1.35; P &amp;lt; 0.001; fixed-effects model). Our single-institution data did not fundamentally influence the positive outcomes, since the HR of OS was 1.17 (95% CI, 1.00–1.37; random-effects model) after removing our study. No evidence of publication bias was observed either in OS or in DFS. Conclusion: The present meta-analysis suggests that longer time to AC was associated with worse survival in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-07.
Leydig-Cell Agenesis
Authors: François Berthezène, Maguelone G. Forest, Jean Alexis Grimaud, Bruno Claustrat, René Mornex
Journal: New England Journal of Medicine (1976)

We studied a 35-year-old patient with female external genitalia, primary amenorrhea and XY karyotype. Plasma testosterone was 10 ng per deciliter, which did not change after administration of human chorionic gonadotropin, increased to 22 ng per deciliter after ACTH, and decreased to 0.9 ng per deciliter after dexamethasone. Plasma Δ4-androstenedione, dehydroepiandrosterone and 17-hydroxyprogesterone were in the normal range. Plasma luteinizing hormone was high, but follicle-stimulating hormone normal (7.5 mlU per milliliter). There were two testes with epididymis and vas deferens, but no Müllerian structures. Microscopical examination showed hyalinization of tubules, which were lined by normal Sertoli cells and occasional immature germ cells. No Leydig cells were seen. After castration follicle-stimulating hormone increased to 43 mlU per milliliter. We conclude that this case of male pseudohermaphroditism was probably due to a Leydig-cell agenesis, that the epididymis and vas deferens can be developed in such a condition and that follicle-stimulating hormone secretion is regulated, at least in part, by a non-androgen substance secreted by Sertoli cells. (N Engl J Med 295:969–972, 1976)
Predictive capacity of a new staging system for upper aerodigestive tract NK/T-cell lymphoma
Authors: J. Xiao, C. C. Guo, Y. Huang, L. Z. Zhai, X. Fu, J. Huang, L. Zhang, W. Li, S. Wang, T. Lin
Journal: Journal of Clinical Oncology (2008)

8601 Background: Extranodal NK/T-cell lymphoma, nasal type (NKTL) is a rare disease originated from NK or toxic T cells. NKTL arising from the upper aerodigestive tract (UNKTL) is a newly recognized but most common subtype. UNKTL has been actively studied these years but the optimal staging system is still unknown. This study is to investigate the predictive value of a new staging system which was designed on the basis of recent findings published in literatures. Methods: UNKTL patients with detailed imaging data and prognostic information in our center since 1999 to 2006 were retrospectively analyzed with the major study endpoint of overall survival (OS). Central pathological review was performed. Survival curves were estimated by Kaplan-Meier method and tested by Log Rank method. Localized disease without nodal involvement was divided into stage I and II according to the local invasiveness of tumor which was defined as: T3 in TNM system, bony invasion or skin invasion. Localized disease with regional nodal involvement was categorized as stage III and the others were stage IV. Results: 134 cases of UNKTL with a median follow-up duration of 21.4 months were included. 37 ladies and 97 gentlemen had a median age of 43. 65 patients presents B symptoms and only 12 have ECOG PS larger than 1. In the new system, 50, 32, 31 and 18 patients were grouped into stage I-IV respectively, showing a well balanced distribution. The 3-year OS is 45%(95%CI: 35%, 55%) for the whole group and 67%, 53%, 31% and 19% for stage I-IV respectively with a statistically significant difference (P<0.001). While Ann Arbor system failed to demonstrate prognostic importance in this study (P=0.051). Conclusions: The new staging system is a prospective model to predict prognosis and prompt stratified treatment for UNKTL. But it still needs further confirmation for the limited sample size of this study. New staging system Stage Description I Localized disease without local invasiveness II Localized disease with local invasiveness III Localized disease with regional nodal involvement IV Disseminated disease No significant financial relationships to disclose.
CBIO-11EFFECT OF PROSTAGLANDIN E2ON CELL MIGRATION IN U251 MG AND U87 MG HUMAN GLIOMA CELLS
Authors: Renata Nascimento Gomes, Alison Colquhoun
Journal: Neuro-Oncology (2015)

INTRODUCTION: Glioblastoma (GBM) is the most common brain cancer in adults. The high ability of migration and invasion throughout the brain tissue via the degradation of the extracellular matrix are among the biological processes that give GBM a high degree of malignancy and poor prognosis. Prostaglandin E2 (PGE2), the main catalyzed product of COX-2 from arachidonic acid, plays a key role in proliferation, migration and apoptosis. However in GBM the role of the PGE2 is poorly understood. OBJECTIVE: The aim of this study was to analyze the role and mechanisms of PGE2 upon cell migration in U251 and U87 human glioma cell lines. METHODS: The migration activity was quantified using a Transwell assay, where cells were treated with 10 µM PGE2 for 12 hours in U251 and U87 glioma cell lines. Next, the expression of the COXs, synthases, and receptors was assessed by real-time PCR and immunohistochemistry. To verify the production of these prostanoids, LC/ESI-MS/MS was used. Pharmacologic inhibitors of EP2 (Butaprost: 1 µM) and EP4 (AH6809: 1 µM) receptors were used to determine the role these receptors in mediating the effect of PGE2 on cell migration. RESULTS: PGE2 increases migration by 38% in U251 and by 42% in U87. The expression of COXs, synthases, and receptors was observed by real-time PCR and Immunofluorescence in both cell lines. LC/ESI-MS/MS confirmed the presence of the 2-series prostanoids. Antagonists selective for the EP2 and EP4 receptor significantly reduced migration. CONCLUSION: The present study, demonstrated the PGE2 plays an important role in glioma cell migration, through their EP2 and EP4 receptors, but the mechanisms by which this occurs are not known. Therefore, there is a need in continuing studying the mechanisms by which PGE2 interferes with cell migration, to determine new targets and new adjuvant therapeutic strategies in the treatment of GBM.