tbuckley/cabot-search huggingface dataset:
Phase II study of docetaxel monotherapy in elderly patients with advanced non-small-cell lung cancer (NSCLC)
Authors: N. Takigawa, Y. Segawa, D. Kishino, K. Fujiwara, T. Shinkai, Y. Watanabe, M. Tabata, K. Kiura, H. Ueoka, M. Tanimoto
Journal: Journal of Clinical Oncology (2004)

8192 Background: Treatment of elderly patients with lung cancer is of particular concern, since the incidence of lung cancer peaks at the age of more than 75 years. Methods: Chemotherapy-naïve elderly patients (age ≥ 76 years) with locally advanced or metastatic NSCLC were accrued. Docetaxel was given at a dose of 60 mg/m2 on day 1 and repeated every 3 to 4 weeks. Patients who were considered ineligible for this study were also registered. Assessment of symptom control using a questionnaire was performed during the treatment period. In addition, the pharmacokinetics of docetaxel were evaluated. Results: Between Nov. 1999 and Dec. 2001, 35 elderly patients with advanced NSCLC were accrued in this study. Of them, 15 (43%) met the study eligibility criteria. The reasons for ineligibility consisted mainly of poor PS, poor bone marrow function and hypoxemia. Six patients achieved a PR (40%; 95% CI, 15 to 65%). Median survival time was 15.6 months (95% CI, 11.4 to 19.8 months). The major toxicity was hematologic, with grade 3 or greater neutropenia and grade 3 neutropenic fever developing in 13 (87%) and five (33%) patients, respectively. However, symptoms assessed by symptom control score did not clearly decline during treatment period. The pharmacokinetic profile of docetaxel (n = 12) exhibited a considerable degree of interpatient variability. In addition, Cmax, T1/2 and AUC0→inf in the elderly patients were each somewhat lower than in the non-elderly population. Conclusions: Toxicities were more frequent than expected, however, this therapy was considered manageable from the view point of symptom control assessment. Usefulness of docetaxel monotherapy in selected elderly patients with advanced NSCLC should be examined in a phase III study. No significant financial relationships to disclose.
Coinhibitory Pathways in Immunotherapy for Cancer
Authors: Susanne H. Baumeister, Gordon J. Freeman, Glenn Dranoff, Arlene H. Sharpe
Journal: Annual Review of Immunology (2016)

The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors exploit these coinhibitory pathways to evade immune eradication. Blockade of the PD-1 and CTLA-4 checkpoints is proving to be an effective and durable cancer immunotherapy in a subset of patients with a variety of tumor types, and additional combinations are further improving response rates. In this review we discuss the immunoregulatory functions of coinhibitory pathways and their translation to effective immunotherapies for cancer.
The Janus Face of Drug-Eluting Stents⁎⁎Editorials published in the Journal of American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: James S. Forrester, Michael S. Lee, Nikhil Kapoor, Raj R. Makkar
Journal: Journal of the American College of Cardiology (2006)
Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers
Authors: Iñigo Landa, Tihana Ibrahimpasic, Laura Boucai, Rileen Sinha, Jeffrey A. Knauf, Ronak H. Shah, Snjezana Dogan, Julio C. Ricarte-Filho, Gnana P. Krishnamoorthy, Bin Xu, Nikolaus Schultz, Michael F. Berger, Chris Sander, Barry S. Taylor, Ronald Ghossein, Ian Ganly, James A. Fagin
Journal: Journal of Clinical Investigation (2016)

BACKGROUND. Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are rare and frequently lethal tumors that so far have not been subjected to comprehensive genetic characterization.
"Doom anxiety" and delirium in lidocaine toxicity
Authors: S M Saravay, J Marke, M D Steinberg, C J Rabiner
Journal: American Journal of Psychiatry (1987)

Of 15 patients with psychiatric reactions to lidocaine, 12 (80%) had mood changes, 11 (73%) had "doom anxiety," eight (53%) had overt confusional states, and six (40%) had hallucinations and delusions. The authors contend that morbid fears of impending doom or the belief that death has occurred are specific manifestations of lidocaine toxicity and may be mistakenly attributed to "understandable" fears about death during the course of recovery from a myocardial infarction on the coronary care unit.
Abstract 18674: Effects of Erythropoietin during Hemorrhagic Shock in a Swine Model
Authors: Kasen Whitehouse, Vesna Borovnik Lesjak, Yang Miao, Alvin Baetiong, Sathya Velmurugan, Brian Currie, Jeejabai Radhakrishnan, Raúl J Gazmuri
Journal: Circulation (2012)

Background: Erythropoietin (EPO) has recently been shown to activate cell survival mechanisms in a broad array of organs and tissues including the heart, brain, kidney, liver, and skin. We developed a swine model of hemorrhagic shock (HS) of increasing severity to investigate whether erythropoietin - through these mechanisms - could help attenuate tissue injury and improve survival. Methods: Two HS protocols were developed in two series of 24 male pigs each. In an initial series, 50% of the estimated blood volume (BV) was withdrawn (BW) over 30 minutes ( Series-50% ); in a subsequent series an additional 15% BV was withdrawn over an additional 30 minutes to a total of 65% BV removal ( Series-65% ). At 90 minutes, normal saline - threefold the BV withdrawn - was given over 240 minutes in both series followed by blood reinfusion (BR). Within each group, pigs were randomized to receive EPO (5,000 U/kg) or NaCl intraosseously after having withdrawn 10% of the BV. Results: Overall survival measured at the end of BR was 87.5% in Series-50% and 25% in Series-65% with no differences between EPO and NaCl (Table). The greater HS severity in Series-65% was evidenced by a lower mean aortic pressure, development of lactic acidosis, and lower oxygen consumption (VO2) at the end of HS. However, these manifestations of increased shock severity appeared to have been attenuated by EPO (Table). Conclusions: Despite comparable survival outcomes, the present study supports the possibility that EPO could exert beneficial hemodynamic effects under conditions of anaerobic metabolism; a possibility currently being investigated by examining whether EPO could be effective in reducing organ dysfunction in combination with therapies able to increase survival.
A 56 year old woman with syncope, weakness, and refractory hypotension
Authors: A. George, M. Phillips, L. Sweeney, C. Colombo
Journal: BMJ (2015)

A 56 year old woman with hypothyroidism after total thyroidectomy presented to the emergency department after an episode of near syncope. When she arrived she had hypotension and atrial fibrillation, with a rapid ventricular response. She reported a history of progressive weakness, weight loss, polyuria, polydipsia, anorexia, and fatigue. Urine analysis was positive for leucocyte esterase and pyuria. She was admitted to the intensive care unit with a diagnosis of severe sepsis of urinary source and atrial fibrillation with a rapid ventricular response. After aggressive fluid resuscitation and the administration of intravenous antibiotics, her heart spontaneously converted to a normal rhythm and she appeared well perfused but remained hypotensive. Review of her medical record showed that her therapeutic thyroxine replacement had recently been decreased because of low thyrotrophin. On perusal of her records from an another facility it was noted that she had undergone pituitary mass resection and irradiation 20 years earlier.

After empirical treatment with thyroid hormone and glucocorticoids her hypotension resolved. On hospital day four she demonstrated haemodynamic stability and was transferred to the ward. On hospital day five she manifested dilute polyuria (urine osmolality of …
Update: Influenza Activity — United States, October 1, 2017–February 3, 2018
Authors: Alicia P. Budd, David E. Wentworth, Lenee Blanton, Anwar Isa Abd Elal, Noreen Alabi, John Barnes, Lynnette Brammer, Erin Burns, Charisse N. Cummings, Todd Davis, Brendan Flannery, Alicia M. Fry, Shikha Garg, Rebecca Garten, Larisa Gubareva, Yunho Jang, Krista Kniss, Natalie Kramer, Stephen Lindstrom, Desiree Mustaquim, Alissa O’Halloran, Sonja J. Olsen, Wendy Sessions, Calli Taylor, Xiyan Xu, Vivien G. Dugan, Jacqueline Katz, Daniel Jernigan
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Influenza activity in the United States began to increase in early November 2017 and rose sharply from December through February 3, 2018; elevated influenza activity is expected to continue for several more weeks. Influenza A viruses have been most commonly identified, with influenza A(H3N2) viruses predominating, but influenza A(H1N1)pdm09 and influenza B viruses were also reported. This report summarizes U.S. influenza activity* during October 1, 2017-February 3, 2018,† and updates the previous summary (1).
Mortality, Morbidity, and Developmental Outcomes in Infants Born to Women Who Received Either Mefloquine or Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy: A Cohort Study
Authors: María Rupérez, Raquel González, Ghyslain Mombo-Ngoma, Abdunoor M. Kabanywanyi, Esperança Sevene, Smaïla Ouédraogo, Mwaka A. Kakolwa, Anifa Vala, Manfred Accrombessi, Valérie Briand, John J. Aponte, Rella Manego Zoleko, Ayôla A. Adegnika, Michel Cot, Peter G. Kremsner, Achille Massougbodji, Salim Abdulla, Michael Ramharter, Eusébio Macete, Clara Menéndez
Journal: PLoS Medicine (2016)

Little is known about the effects of intermittent preventive treatment of malaria in pregnancy (IPTp) on the health of sub-Saharan African infants. We have evaluated the safety of IPTp with mefloquine (MQ) compared to sulfadoxine-pyrimethamine (SP) for important infant health and developmental outcomes.In the context of a multicenter randomized controlled trial evaluating the safety and efficacy of IPTp with MQ compared to SP in pregnancy carried out in four sub-Saharan countries (Mozambique, Benin, Gabon, and Tanzania), 4,247 newborns, 2,815 born to women who received MQ and 1,432 born to women who received SP for IPTp, were followed up until 12 mo of age. Anthropometric parameters and psychomotor development were assessed at 1, 9, and 12 mo of age, and the incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were determined until 12 mo of age. No significant differences were found in the proportion of infants with stunting, underweight, wasting, and severe acute malnutrition at 1, 9, and 12 mo of age between infants born to women who were on IPTp with MQ versus SP. Except for three items evaluated at 9 mo of age, no significant differences were observed in the psychomotor development milestones assessed. Incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were similar between the two groups. Information on the outcomes at 12 mo of age was unavailable in 26% of the infants, 761 (27%) from the MQ group and 377 (26%) from the SP group. Reasons for not completing the study were death (4% of total study population), study withdrawal (6%), migration (8%), and loss to follow-up (9%).No significant differences were found between IPTp with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes. The poorer performance on certain psychomotor development milestones at 9 mo of age in children born to women in the MQ group compared to those in the SP group may deserve further studies.ClinicalTrials.gov NCT00811421.
First-line systemic therapy in metastatic non-small cell lung cancer (mNSCLC) patients treated at National Comprehensive Cancer Network (NCCN) institutions: An analysis from the NCCN Oncology Outcomes Database Project.
Authors: J. L. Vandergrift, R. Mamet, C. Zornosa, M. E. Reid, M. S. Rabin, D. S. Ettinger, G. P. Kalemkerian, G. A. Otterson, J. C. Niland, K. Pisters
Journal: Journal of Clinical Oncology (2010)

7634 Background: The NCCN Clinical Practice Guidelines (GL) allow many systemic therapy options for patients (pts) with mNSCLC. The primary aims of this analysis were to identify first-line regimens for the treatment of mNSCLC pts and examine concordance with NCCN NSCLC GL. Methods: The database was queried to identify pts with mNSCLC treated with first-line systemic therapy at 8 NCCN institutions presenting between September 2006 and March 2009. Pt characteristics, regimens utilized, and GL concordance were analyzed. Systemic therapy was categorized as cytotoxic doublet (CD), combination cytotoxic/targeted therapy (C/T), targeted therapy alone (T), or cytotoxic single agent (SA). Results: A total of 983 eligible pts were identified, as follows: 51% male; median age 64 years; performance status (PS) was documented in 77% (82% PS 0 or 1; 11% PS 2; 7% PS 3 or 4). There were 729 pts (74%) treated with systemic therapy, 123 (17%) of which participated in a clinical trial. Most common reasons for not receiving therapy were death prior to treatment (37%), therapy was not recommended (35%), or unknown (20%). For PS 3 or 4 pts not enrolled in a clinical trial, 20/48 (42%) received systemic therapy. Systemic therapy administered: 437 CD (60%), 139 C/T (19%), 94 T (13%), and 46 SA (6%). A platin-agent was used in 96% of CDs, with carboplatin in 83%. Paclitaxel (45%), gemcitabine (22%), docetaxel (15%) and pemetrexed (9%) were the most common partner agents. Of 600 pts with adenocarcinoma, 50 (8%) were treated with pemetrexed. Bevacizumab with carboplatin and either paclitaxel or docetaxel were the most common C/Ts (85% of C/T, 16% of all treated). Erlotinib was the most common T (92% of T, 12% of all treated). Analyses of EGFR mutation testing and concordance to NCCN NSCLC GLs are underway. Conclusions: The majority of pts with mNSCLC were treated with first-line systemic therapy and 17% participated in a clinical trial. Though not included in the NCCN GL prior to 2010, treatment of PS 3 or 4 pts and first-line therapy including erlotinib were observed. Few pts with adenocarcinoma received pemetrexed in the first-line setting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems, Merck Genentech, Lilly Abbott Laboratories, Abraxis BioScience, Genentech, Lilly, Pfizer
The cellular composition of the human immune system is shaped by age and cohabitation
Authors: Edward J Carr, James Dooley, Josselyn E Garcia-Perez, Vasiliki Lagou, James C Lee, Carine Wouters, Isabelle Meyts, An Goris, Guy Boeckxstaens, Michelle A Linterman, Adrian Liston
Journal: Nature Immunology (2016)
Toxicity, Radiation Sensitivity Modification, and Combined Drug Effects of Ascorbic Acid With Misonidazole In Vivo on FSall Murine Fibrosarcomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P Okunieff, H D Suit
Journal: JNCI Journal of the National Cancer Institute (1987)

Ascorbic acid (ASC) has been shown to radioprotect nonmalignant tissue and to enhance the effects of misonidazole (MISO) on hypoxic cells in vitro. Since ASC is minimally toxic, it is an interesting candidate for improving the radiotherapeutic gain factor in vivo. The in vivo radiomodifying effects of ASC on a C3H/fSed murine fibrosarcoma (FSaII), on normal skin, and on bone marrow were determined with the use of the tumor growth delay and TCD50 (i.e., radiation dose required to control 50% of treated tumors for a minimum of 120 days) assays and the RD50 (i.e., dose required to cause a peak skin reaction of 2 in 50% of treated hind limbs) and LD50 (i.e., whole-body radiation lethal dose) assays, respectively. ASC was buffered to pH 7.35 and delivered ip at a dose of 4.5 mg g-1 body weight. ASC did not modify tumor growth delay induced by radiation or the TCD50 [87.1 Gy (control) vs. 85.6 Gy (ASC)]. Normal tissues, however, were radioprotected by ASC. RD50 values for 2+ acute skin reactions were 46.4 and 55.7 Gy for control and ASC-treated subjects, respectively; LD50 (30 days) values were 7.2 and 8.5 Gy. The enhancement ratios for skin and bone marrow were 1.20 and 1.18, and 95% confidence limits were (1.07 ... 1.34) and (1.14 ... 1.23), respectively. The therapeutic gain factor was 1.22 calculated as the ratio of the TCD50 and the reference normal tissue (RD50 or LD50). When ASC and MISO were combined, ASC reduced the in vivo radiosensitizing effects of MISO.
Fatty acid metabolism is altered in non-alcoholic steatohepatitis independent of obesity
Authors: Paula Walle, Markus Takkunen, Ville Männistö, Maija Vaittinen, Maria Lankinen, Vesa Kärjä, Pirjo Käkelä, Jyrki Ågren, Mika Tiainen, Ursula Schwab, Johanna Kuusisto, Markku Laakso, Jussi Pihlajamäki
Journal: Metabolism (2016)
Group-Level Symptom Networks in Depression—Reply
Authors: Claudia D. van Borkulo, Denny Borsboom, Robert A. Schoevers
Journal: JAMA Psychiatry (2016)

creases from 515 to 344) and the strong regularization penalty; both networks lose almost all of their connections and, in that trivial sense, become more alike.As shown in our article, 1 when using procedures that have less effect on power (like partialling out general level of functioning or weakening the regularization parameter), differences between groups become more, rather than less, pronounced.Although we believe that it is not very likely that the associations between symptoms are substantially different for individual patients, intraindividual analyses are needed to test this.In addition, intraindividual analyses are warranted to determine whether symptoms are associated over time within patients.Therefore, we gladly reveal that the Netherlands Study of Depression and Anxiety, 3 from which we drew our sample, recently started a new wave of measures in which 400 of its nearly 3000 participants are studied with Ecological Momentary Assessment 4 over 2 weeks.The aim of this study is to provide more insight into the association between intraindividual and interindividual differences, which will lead to an increased understanding of how nomothetic and idiographic analyses are related.
Abstract 13782: Atrioventricular Junction Elongation and Ion Channel Remodelling Leads to Slowing of Atrioventricular Conduction in Heart Failure
Authors: Theodora Nikolaidou, Xue Cai, Joseph Yanni, Andrew J Atkinson, Halina Dobrzynski, George Hart, Mark R Boyett
Journal: Circulation (2013)

The atrioventricular junction (AVJ) maintains synchronised atrioventricular conduction and protects from ventricular tachycardia, as well as bradycardia. Heart failure (HF) is a major killer worldw...
Occult ovarian cancers at the time of risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers
Authors: T. R. Rebbeck, T. M. Friebel, S. M. Domchek
Journal: Journal of Clinical Oncology (2009)

1508 Background: Risk-reducing salpingo-oophorectomy (RRSO) is widely used for cancer risk reduction in women with BRCA1 or BRCA2 (BRCA1/2) mutations. Occult ovarian cancers (OOC) detected at the time of RRSO have been reported, but there is wide variability in reported prevalence rates. Methods: We evaluated a prospective cohort of 647 women from 18 centers who underwent RRSO between 2001 and 2007 after a positive genetic test for disease-associated BRCA1/2 mutations. We estimated the prevalence of OOC. Results: Mean follow-up from genetic testing to RRSO was 1.01 years. OOC was detected in 16 of 647 women (2%). The mean age of women in whom OOC was detected was 51.7 versus 46.6 in women undergoing RRSO in whom OOC was not detected (p = 0.017). Twelve of the 16 OOCs (75%) were diagnosed in women with a BRCA1 mutation. Two OOCs were detected on RRSO prior to age 40, both in BRCA1 mutation carriers. Thirty eight percent of women with OOC had stage I cancer, as opposed to 10% of women in the PROSE database diagnosed with ovarian cancer outside of screening (p = 0.006). Among the 283 women in whom pathology reports were available for central review, 71% of RRSO were performed at the respective PROSE sites (i.e. major genetic referral centers), while 29% of RRSO were performed at local sites (i.e. community hospitals). Ovarian and fallopian tube tissues removed at RRSO at major genetics referral centers were significantly more likely to have been examined in toto compared to specimens obtained at nonreferral centers (76% vs. 24%, p &lt; 0.001). Conclusions: RRSO reduces cancer risk and mortality in BRCA1/2 mutation carriers. Our results confirm that OOC is present at RRSO in BRCA1/2 mutation carriers, and suggest that OOC are more frequent after age 40 and are of a more favorable stage than cancers found outside the context of RRSO. Despite the fact that we examined surgeries after 2001, an unacceptably high proportion of pathologic examinations did not adequately examine ovaries and fallopian tubes obtained at RRSO. Failure to perform adequate pathological examination may overlook OOC and have clinical consequences for women undergoing RRSO. No significant financial relationships to disclose.
Uridine glucuronosyltransferase 2B7 polymorphisms and epirubicin pharmacokinetics
Authors: M. B. Sawyer, A. Scarfe, K. Tonkin, A. A. Joy, S. Damaraju, V. Damaraju, E. N. Pituskin, J. Hanson, M. Clemons, J. R. Mackey
Journal: Journal of Clinical Oncology (2006)

13071 Background: Epirubicin (epi) is a widely used anthracycline for the treatment of breast cancer. In contrast to its optical isomer doxorubicin, epi is predominantly glucuronidated by uridine glucuronosyltransferase 2B7 (UGT2B7). UGT2B7 has a T to C polymorphism at position -161 in the enhancer region which correlated with efficacy of morphine glucuronidation (Sawyer et al. Clin Pharmcol Ther 2003). Methods: We performed a prospective pharmacogenetic study of FEC100 (5-fluorouracil 500 mg/m 2 , Epi 100 mg/m 2 and cyclophosphamide 500 mg/m 2 ) given every 3 wks in early stage breast cancer pts. Drug levels were drawn at 1 and 24 hrs. We have determined levels of epi, epi-glucuronide (epiG), epirubicinol (epiol), and epiol-glucuronide (epiolG) in 78 of the 120 pts. The levels of epi and its metabolites were measured using an HPLC with fluorescence detection using the method of Fogli et al with modifications. Patient characteristics-median (range): age 50 (28 - 67), sex 77 F/ 1 M, baseline AST 22 U/L (13–66), ALT 20 U/L (5–90), bilirubin 7 umol/L (2–24), creatinine 73 umol/L (51–126). Results: 14 pts were TT homozygotes, 45 were CT heterozygotes, and 19 were CC homozygotes. Concentrations (ng/ml, median (range)) of epi, epiG, epiol, and epiolG at 1 hr respectively were 91 (39–481), 280 (0–981) 76 (14–212) 76 (0–276). There was no relationship between epiG concentration and genotype: 315 (median) TT, 263 CT, 288 CC. Patients with a TT genotype had a lower epiol concentrations (median, ng/ml) at 24 hr: 12 TT, 23 CT, 25 CC; p = 0.04. Conclusions: This analysis shows a relationship between UGT2B7 genotype and epi pharmacokinetics. We are completing analysis of all 120 samples and plan to perform a formal NONMEM analysis. No significant financial relationships to disclose.
High Levels of Wilms' Tumor Gene (wt1) mRNA in Acute Myeloid Leukemias Are Associated With a Worse Long-Term Outcome
Authors: Lothar Bergmann, Cornelius Miething, Ulrich Maurer, Jürgen Brieger, Tunca Karakas, Eckhart Weidmann, Dieter Hoelzer
Journal: Blood (1997)