tbuckley/cabot-search huggingface dataset:
Benign Breast Disease and Consumption of Beverages Containing Methylxanthines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C La Vecchia, S Franceschi, F Parazzini, M Regallo, A Decarli, G Gallus, S Di Pietro, G Tognoni
Journal: JNCI Journal of the National Cancer Institute (1985)

The relationship between methylxanthine (Mx) consumption and benign breast disease was evaluated in a case-control study of 288 women with histologically confirmed benign breast lumps (203 dysplastic lesions and 85 benign tumors) and 2 groups of control women—285 patients in the hospital for acute conditions apparently unrelated to the consumption of Mx-containing beverages and 291 outpatients. The relative risk estimates of dysplastic breast lesions (fibrocystic disease), with allowance for all identified potential distorting factors, for women who drank 1–2 or 3 or more cups of coffee per day were 4.1 and 6.4, respectively, when the hospital controls were the comparison group and 2.0 and 3.7, respectively, when the outpatient controls were the comparison group. The relationship was even stronger when the total consumption of Mx-containing beverages (coffee plus tea) was considered and increased with increasing duration of use. The association was not explained by any of the major risk factors for fibrocystic breast diseases or by differences in general characteristics or other lifestyle habits between cases and controls. Mx consumption was not related to the risk of benign breast tumors (fibroadenomas). These findings support the hypothesis that Mx consumption is related to the risk of dysplastic lesions of the breast.
Exposure-response (E-R) relationship of ramucirumab (RAM) from two global, randomized, double-blind, phase 3 studies of patients (Pts) with advanced second-line gastric cancer.
Authors: Josep Tabernero, Atsushi Ohtsu, Kei Muro, Eric Van Cutsem, Sang Cheul Oh, Gyorgy Bodoky, Yasuhiro Shimada, Shuichi Hironaka, Jaffer A. Ajani, Jiri Tomasek, Howard Safran, Kumari Chandrawansa, Yanzhi Hsu, Michael Heathman, Azhar Z Khan, Lan Ni, Allen S. Melemed, Ling Gao, David Ferry, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2015)

121 Background: We evaluated the E-R relationship of RAM in pts with advanced gastric cancer from the REGARD and RAINBOW trials. Methods: Pts received RAM (8 mg/kg) or placebo (PL) q2w in REGARD; or RAM (8 mg/kg) or PL q2w + paclitaxel (PAC) 80 mg/m 2 on days 1, 8, and 15 (28-day cycle) in RAINBOW. Sparse pharmacokinetic (PK) samples were collected; a population PK analysis was conducted. A model-predicted minimum concentration after first RAM dose (C min,1 ) was used for correlation with efficacy and safety variables. Kaplan-Meier, Cox regression, and logistic regression analyses evaluated E-R relationships. Results: Analyses included 72 RAM and 35 PL pts from REGARD and 321 RAM+PAC and 335 PL+PAC pts from RAINBOW. Conclusions: Ram was safe and effective at 8 mg/kg q2w. Population PK suggests higher RAM exposures were associated with longer PFS and OS, better hazard ratios, and increased toxicity. Further studies to validate the PK model and evaluate RAM dosing are warranted. [Table: see text]
Use of a pharmacist/nurse model for the delivery of supportive care in adult oncology clinics at the University of North Carolina Hospital.
Authors: S. A. Bernard, J. Valgus, S. Jarr, M. Rice, R. Schwartz
Journal: Journal of Clinical Oncology (2010)

9166 Background: Since February 2008, we have begun a Supportive Care Consult Service that uses a pharmacist/nurse model of care delivery. Requests are called in from all adult oncology clinics—Hem/Onc; Gyn Onc, Surg Onc, or Rad Onc to the nurse. The team then goes to the individual clinic where the consult is done by either the pharmacist or nurse, with physician backup. A separate half-day clinic was begun in April 2008 to address patients needing ongoing follow-up or complex patients that could not be dealt with as consults only. Methods: We carried out an analysis of the practice with an IRB-approved database using standard descriptive statistical methods. Results: In the first 18 months of the service, 89 new patients were seen. Overall there were 292 encounters, reflecting both new and return visits. Details of the encounters are shown in the Table. Demographics: M/F: 47%/53%; Age: >60 y.o.-45%; 44-59-34%, <44-21%; Ethnic/Racial Group: White 70%, African Am. 21%, Hispanic 8%, Native American 1%; Referral Site: Rad Onc 48%, Med Onc 33%, Gyn Onc 11%, Surg Onc 8%. Pain was the reason for consult in 75%, constipation 11%, N/V 8%, Anxiety 4%, Spiritual 2%. Tumor types including Lung 20%, Gyn Onc 20%, H & N 15%, GU 12%, GI 8%, and Breast 7%. Substance abuse was fairly common: Ethanol, 26%, Cocaine 23%, and Heroin 9%. Results: For the first year of the service, 52/53 pts were already on opioids. Recommendations lead to: Increase in medication 57%, Decrease 4%, No Change 21%, Switch 21%, Additional meds 32%, and Stopped 6%. In a sample of 49 patients, we have demonstrated a reduction of pain score from 4 to 2.7 (scale of 5 = maximum) by the second visit; nausea from 4 to 1.4 by the second visit; and constipation from 2 to 1.6 by the second visit. These results maintained beyond the 2nd visit but patient numbers were smaller. Conclusions: Use of a roving pharmacist/nurse model for supportive care represents a novel method of care delivery that results in significant improvement in symptoms. Funded in part by University Cancer Research Fund. Encounter type Nurse Pharmacist Physician New patient 27.4% 24.7% 10.7% Returning patient 55.1% 40% 31.6% Total 82.5% 64.7% 42.3% No significant financial relationships to disclose.
Phase II study of bevacizumab in combination with S-1 plus cisplatin in patients with advanced nonsquamous non-small cell lung cancer.
Authors: Reiko Yoshino, Kyoichi Kaira, Yoshio Tomizawa, Toshifumi Kazama, Akihiro Yoshii, Yousuke Miura, Shinichi Ishihara, Naoto Fueki, Koichi Minato, Noriaki Sunaga
Journal: Journal of Clinical Oncology (2012)

e18037 Background: Cisplatin combined with S-1 is an active regimen for patients with advanced non-small cell lung cancer (NSCLC). Although the addition of bevacizumab to platinum based regimens significantly improved outcome, it remains unknown about the safety and efficacy of first-line cisplatin plus S-1 with bevacizumab. Therefore, we conducted a phase II study to evaluate the efficacy and tolerability of bevacizumab in combination with S-1 plus cisplatin regimen in patients with advanced non-squamous NSCLC. Methods: Patient with ages ranging from 20 to 74 years, non-squamous NSCLC, no prior systemic therapy, no brain metastases and ECOG PS 0-1 were enrolled. Patients received cisplatin 60mg/m2 and bevacizumab 15mg/kg on day 1 of each cycle, and S-1 80mg/m2 orally twice daily for 14 days every 21 days. After 4-6 courses, patients were continued on bevacizumab until progression disease (PD). Primary end point was response rate (RR). Secondary end points included overall survival (OS), PFS, time to treatment failure (TTF), and safety. Results: Twenty-nine patients were enrolled in this study. Median age was 67 years (range: 42 to 74); male/female=17(58%)/12(42%); ECOG PS 0/ 1 = 18 (62%) / 11(38%); stageIIIB/IV=3(10%)/26(90%); adeno / NSCLC = 26 (90%) / 3 (10%). The median courses of the induction therapy was 4 (range: 2 to 6), and that of the maintenance therapy was 3 courses (range: 1 to 15). Response rate (RR) was 65.5%, and disease control rate (DCR) was 100%. Median PFS was 5.39 months (95%CI, 125-265 days). Hematological adverse events reaching grade 3 or 4 were leukocytopenia (6.8%), neutropenia (20.9%), anemia (3.4%), thrombocytopenia (6.9%), and febrile neutropenia (3.4%). Nonhematological toxicities of grade3/4 were hypertension (17.2%), appetite loss (3.4%), mucositis oral (3.4%), alkaline phosphatase elvation (3.4%), serum amylase elevation (3.4%), and hyponatremia (3.4%). Seven patients delayed the start of next course because of adverse events. Conclusions: Bevacizumab in combination with S-1 plus cisplatin was effective in disease control and well-tolerated regimen for the treatment of patients with advanced non-squamous NSCLC.
Curative-intent resection for bronchogenic carcinoma in patients with prior spinal cord injury: The Department of Veterans Affairs experience
Authors: L. S. Brunworth, D. Dharmasena, K. S. Virgo, F. E. Johnson
Journal: Journal of Clinical Oncology (2006)

17127 Background: There are approximately 250,000 people with spinal cord injury (SCI) in the US, and they have a high prevalence of smoking. A literature search yielded no published information concerning the clinical course of SCI patients who subsequently develop bronchogenic carcinoma and undergo pulmonary resection for this condition. We hypothesized that poorer outcomes of surgery would be observed in this population, as compared to neurally-intact patients. Methods: We conducted a study of all veterans at Department of Veterans Affairs (DVA) Medical Centers during fiscal years 1993–2002 who were diagnosed with SCI, subsequently developed non-small cell lung cancer and were then surgically treated with curative intent. Inclusion criteria included American Spinal Injury Association type A injury (complete loss of neural function distal to the injury site) and traumatic etiology. Data were compiled from national DVA datasets and supplemented by operative reports, pathology reports, progress notes, and discharge summaries. Results: Of 12,634 patients who underwent surgery for bronchogenic carcinoma, 55 also had codes for prior SCI; 7 were evaluable. The mean age was 64. Five (71%) had one or more co-morbid conditions in addition to their spinal cord injuries. All 7 underwent pulmonary lobectomy. Post-operative complications occurred in 4 patients (57%). Two patients died post-operatively on days 29 and 499, yielding a 30-day mortality rate of 14% and an in-hospital mortality rate of 29%. Conclusions: We believe this isthe only report in the English language literature on this topic. SCI patients with resectable bronchogenic carcinoma have a high incidence of co-morbid conditions. Those who undergo curative-intent surgery have high morbidity and mortality rates. This evidence suggests that SCI should be considered a risk factor for adverse outcomes of surgery for primary lung cancer, strengthening the case for alternative treatments. No significant financial relationships to disclose.
IQ change within three years of radiation therapy in pediatric brain tumor patients treated with proton beam radiation therapy versus photon radiation therapy.
Authors: Lisa Kahalley, M. Fatih Okcu, M. Douglas Ris, David Grosshans, Arnold Paulino, Murali M. Chintagumpala, Bartlett Moore, Heather Stancel, Robert Wickham, Paras Mehta, Anita Mahajan
Journal: Journal of Clinical Oncology (2013)

10009 Background: Radiation therapy (RT), an essential treatment for pediatric brain tumors, increases the risk of cognitive impairment. Advanced RT techniques reduce the volume of normal tissues receiving radiation dose. Proton beam radiation therapy (PBRT) minimizes irradiation to surrounding healthy brain tissue, with the potential to preserve cognitive function better than photon radiotherapy (XRT). We examined change in IQ over time between patients treated for pediatric brain tumors with PBRT versus XRT. Methods: IQ scores obtained in the first 3 years post-RT were abstracted for pediatric brain tumor patients treated with PBRT or XRT. Results: Baseline and follow-up IQ scores were available for 53 survivors (31 PBRT, 22 CRT). A linear regression model predicted follow-up IQ scores controlling for baseline IQ, age-at-RT, time-since-RT, and craniospinal irradiation (CSI), F(7,45)=23.4, p&lt;.001. Follow-up IQ scores were significantly lower in the XRT group compared to the PBRT group (p&lt;.05). The XRT group lost 10.3 IQ points on average with each additional year post-RT (p&lt;.01), while the PBRT group remained stable, losing only 0.1 points per year on average (p&lt;.05). CSI was associated with IQ decline in both groups (p&lt;.05), while age-at-RT was not in either group (p=.154). Total RT dose was not associated with IQ with the above variables in the model. Conclusions: Findings suggest significant cognitive risk is associated with XRT, with IQ scores declining by more than half a standard deviation with each additional year post-RT. In contrast, IQ remained stable in the PBRT group. Preliminary findings suggest that PBRT may spare cognitive functioning in the first 3 years post-RT. Future research should replicate these findings with a larger sample and should study longer-term cognitive outcomes in patients treated with PBRT versus XRT. [Table: see text]
Initial DNA Damage and Heritable Permanent Change in Pepsinogen Isoenzyme Pattern in the Pyloric Mucosae of Rats After Short-Term Administration of &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;′-nitro-&lt;italic&gt;N&lt;/italic&gt;-nitrosoguanidine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Masae Tatematsu, Daizo Saito, Chie Furihata, Yukitada Miyata, Takao Nakatsuka, Nobuyuki Ito, Takashi Sugimura
Journal: JNCI Journal of the National Cancer Institute (1980)

Initial DNA breakage and heritable permanent change in the pepsinogen isoenzyme pattern in the pyloric mucosae of male inbred W rats treated with N-methyl-N′ nitro-N-nitro-soguanidine (MNNG) were studied. The life-span (turnover) of pyloric gland cells, as estimated by pulse labeling, was about 10 days and was not influenced by administration of MNNG in the drinking water for 8 days. Intragastric administration of two 12-mg doses of MNNG (interval, 6 hr) induced DNA breakage in the pyloric mucosa. This breakage was detected by alkaline sucrose density gradient centrifugation and was repaired within 12 hours after the second dose of MNNG. No decrease or disappearance of pepsinogen isoenzyme 1 (Pg 1) was observed at this time, but a decrease of Pg 1 was observed in 3 of 10 rats after 10 days. However, 167 μg MNNG/ml administered in the drinking water for 8 days did not cause any DNA change detectable by alkaline sucrose density gradient centrifugation. Decrease or disappearance of Pg 1 was scarcely noticeable 4 days after the beginning of MNNG administration in the drinking water, but high incidences of MNNG were observed 2, 10, 25, 40, and 455 days after the end of MNNG administration for 8 days. Histopathologically preneoplastic changes were found only 455 days after MNNG treatment. These results indicated that 1) changes in the pepsinogen isoenzyme pattern were a response of newly formed pyloric gland cells that were derived from germ (stem) cells modified by MNNG and that these altered germ cells produced altered pyloric gland cells continuously and irreversibly at least until day 455; and 2) doses of MNNG too low to induce DNA breakage detectable in an alkaline sucrose density gradient could induce permanent alterations, which were expressed as a phenotypic change in pepsinogen isoenzymes. A change in Pg 1 was found to be a good marker of biochemical preneoplastic changes preceding such changes detectable morphologically.
P0120 : The 3-month readmission rate remains unacceptably high in a large multi-center cohort of cirrhotic patients
Authors: J.S. Bajaj, K.R. Reddy, G. Garcia-Tsao, F. Wong, M.B. Fallon, R. Subramanian, S.W. Biggins, B. Maliakkal, P.S. Kamath, P. Thuluvath, L.R. Thacker, J.G. O’leary
Journal: Journal of Hepatology (2015)
Guilt and conscience in major depressive disorders
Authors: M Prosen, D C Clark, M Harrow, J Fawcett
Journal: American Journal of Psychiatry (1983)

The authors propose definitions of guilt as a self-critical feeling state and of conscience as a set of standards, to permit independent assessment of their prevalence in a sample of 93 depressed, 29 schizophrenic, and 43 normal subjects. Patients with feelings of guilt tended to have a more severe conscience and lower self-esteem. While guilt is prominent in a moderate percentage of depressed patients, negative self-esteem may form one of the cornerstones for depressed patients of all types. The authors propose that the operational definition of psychoanalytic concepts such as guilt and conscience permits a valid and more rigorous test of clinical generalizations.
Metro-FOLFIRI as first line chemotherapy in metastatic colorectal cancer (MCRC). Preliminary report of a phase II trial
Authors: M. Nardi, D. Azzarello, A. Avallone, M. Raffaele, R. Giannicola, R. Carboni, M. Zavettieri, P. Del Medico, A. Falzea, R. Maisano
Journal: Journal of Clinical Oncology (2005)

3722 Background: FOLFIRI regimen is standard therapy in MCRC. Angiogenesis is a critical step in the metastatic process of colorectal cancer. New agents with antiangiogenic effect showed to be active in MCRC. In preclinical studies irinotecan demonstrated to have at metronomic dose (1/6 standard dose) antiangiogenic activity. For these reasons we carried out this pilot study in order to evaluate the safety and the activity of metronomic FOLFIRI regimen as first line chemotherapy in inoperable MCRC. Methods: From 10/03 to 10/04 we treated 26 pts (14M 12F), median age 66 years (range 41–77) with this mixed FOLFIRI schedule: CPT-11 10 mg/mq days 1, 7, 10 and CPT-11 150 mg/mq day 2, Folinic Acid 100 mg/mq days 2 and 3, 5-FU 400 mg/mq bolus days 2 and 3 and 5-FU 600 mg/mq 44 hours c.i. days 2 and 3 every two weeks for a maximum of 12 cycles. Results: All pts are evaluable for toxicity and 22 for activity. The chemotherapy was well tolerated; no toxic deaths occurred, no therapy ended for toxicity. 3 pts had 25% reduction dose for diarrhea G4 after the first cycle. The main toxicities recorded on a total of 173 cycles (cy) delivered were: diarrhea G4 1.7% and G3 2.3% of the cy. Neutropenia G3 5.8% and vomiting G3 0.5% of the cy. Anemia G2 was recorded in 7 pts. All pts suffered from partial alopecia and half of the pts from mild oral mucositis. As regard activity we registered 3 CR (13.6%), 9 PR (40.9%), 7 SD (31.8%) and 3 PD (13.6%). Before start therapy and after 4th, 8th and 12th cycle we collected blood samples of the pts in order to evaluate sVEGF modifications in relation to objective response. These data will be presented. Conclusions: Metro-FOLFIRI regimen appears to be safe and active in MCRC. No significant financial relationships to disclose.
Abstract 294: Thrombolytics Improve Extracorporeal Cardiopulmonary Resuscitation After 30 Minutes of Untreated Cardiac Arrest
Authors: Elena Spinelli, Ryan P Davis, Xiaodan Ren, Amit Iyengar, Parth Sheth, Trevor Tooley, Brandon Sowell, William C Stacey, Robert H Bartlett, Alvaro Rojas-Pena, Robert W Neumar
Journal: Circulation (2014)

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) after prolonged cardiac arrest (CA) often fails to restore cardiac and cerebral function. The primary limiting factor is presumed to be ischemia duration. An alternative hypothesis is that intravascular coagulation prevents tissue reperfusion. Hypothesis: Adding thrombolytics to ECPR after prolonged untreated CA improves cardiac and cerebral recovery when compared to ECPR alone. Methods: We developed a porcine model of 30 minute untreated ventricular fibrillation followed by ECPR for 6 hours. Animals were instrumented for hemodynamic and intracranial pressure (ICP) monitoring and continuous EEG. Two groups were studied: t-ECPR (n=7) with streptokinase 1 MU added to prime circuit; c-ECPR (n=6) with no streptokinase. ECPR goals included: flow &gt;50 ml/kg/min, MAP &gt;70 mmHg, PaO2 150±50 mmHg, PaCO2 40±5 mmHg, core temperature 33±1 °C. Recovery of heart function was assessed by echocardiography and weanability from ECPR. After 6 hours, animals were euthanized and brain harvested for quantification of intracerebral hemorrhage and neuronal injury. Results: Recovery of heart function following defibrillation occurred in 1/6 c-ECPR and 7/7 t-ECPR animals (p &lt;0.05). Successful weaning from ECPR within 6 hours was achieved in 1/6 c-ECPR and 4/7 t-ECPR animals. Six-hour lactate clearance was significantly lower in c-ECPR than in t-ECPR (18±2 % vs 40±15 %, p &lt;0.05). Marked increase in post-arrest ICP occurred in c-ECPR but not in t-ECPR (19±13 mmHg vs 1±3 mmHg, p &lt;0.05). Quantitative EEG analysis revealed no recovery of brain activity in either group. Thrombolytics did not result in increased intracerebral hemorrhage (c-ECPR 0.011±0.001 % vs 0.003±0.002 % t-ECPR, p &lt;0.05). Composite histologic damage score (scale 0 to 5) was not different between groups (c-ECPR 3.2±0.9 vs. 3.2±1.1 t-ECPR, p &gt;0.05). Conclusions: Thrombolytic enhanced ECPR after prolonged untreated CA improves recovery of cardiac function and reduces brain edema without increasing bleeding. However, we detected no effect on early EEG recovery or ischemic neuronal injury. Additional studies are needed to determine if thrombolytic enhanced ECPR improves long-term survival and neurologic outcomes after prolonged CA.
Rapid spread of drug-resistant influenza A viruses in the Basque Country, northern Spain, 2000-1 to 2008-9
Authors: D Vicente, G Cilla, M Montes, J Mendiola, E Pérez-Trallero
Journal: Eurosurveillance (2009)

A worldwide increase of adamantane-resistant influenza A(H3N2) and oseltamivir-resistant influenza A(H1N1) viruses has been observed in recent years. The aim of this study was to analyse the prevalence of antiviral drug-resistant influenza A in a region of northern Spain. Resistance to adamantanes was detected in 45.3% (68/150) of influenza AH3 viruses analysed for the period from 2000-1 to 2008-9. Adamantane-resistance was absent in our region during the 2000-1 to 2002-3 influenza seasons. However, after the first adamantane-resistant virus (characterised as A/Fujian/411/2002) was detected in the 2003-4 season, a rapid increase in the proportion of resistant strains was observed (4.9% [2/41], 80% [8/10] and 100% [53/53] in the 2004-5, 2006-7 and 2008-9 seasons, respectively). Four of the first five adamantane-resistant AH3 viruses detected were isolated from adult patients, but the subsequent spread was observed mainly among children. No resistance to adamantanes was detected among the 65 influenza AH1 viruses analysed throughout the study period. Among the 172 influenza A (76 AH1 and 96 AH3) viruses analysed, five strains (AH1 with mutation H274Y) showed oseltamivir resistance, and all were detected in the last season. Amantadine use was very scarce in our region, and oseltamivir was not used at all; therefore the increase of resistance was attributed to imported drug-resistant influenza viruses.