tbuckley/cabot-search huggingface dataset:
The relevance of rising CA-125 levels within the normal range in predicting recurrence in patients with advanced stage ovarian cancer: A validation study
Authors: F. AbuShain, P. Escobar, S. Shahabi, C. Michener, R. Drake, P. G. Rose, P. E. Schwartz
Journal: Journal of Clinical Oncology (2009)

e16521 Background: Small published series suggested that three progressively rising CA-125 values, doubling of CA-125, and an absolute rise of 5 U/mL from the nadir, all while remaining in the normal range were highly associated with disease recurrence. This study aims to validate these proposed criteria in a larger population. Methods: We conducted a retrospective review of the records of patients with stages IIIC and IV epithelial ovarian cancer treated with primary surgery and adjuvant chemotherapy between 1994 and 2006. Only patients who had a complete response to chemotherapy verified by normal CT scan, CA-125 and physical examination were included. Nadir CA-125 level was defined as the first CA-125 measurement after completing chemotherapy. Available CA-125 values from diagnosis to recurrence or to last follow up were collected and evaluated for meeting any of the criteria above. Results: 91 patients with a median age of 59 (42 - 88) met the inclusion criteria. 82 patients had stage IIIC (90%) and 9 patients (10%) had stage IV. 86 patients (94.5%) had papillary serous histology and 88 patients had grade 3 (96.7%) disease. Median follow up was 43.7 months (12.6 - 156). Table 1 shows the number of patients who met any of the above CA-125 criteria in total and divided by the presence or absence of recurrence. There was no statistically significant difference in meeting any of the CA-125 criteria between the recurrence and no recurrence groups. Meeting at least one of the CA-125 criteria had 50% sensitivity, 65% specificity, and 86% positive predictive value for recurrence. The median time to recurrence in patients who met at least one CA-125 criteria was 3.8 months (0.2 - 12.4) and the median follow up time after meeting one of the CA 125 criteria in patients who did not recur was 88.5 months (10.4 - 188) Conclusions: Rising CA-125 levels within the normal range that meet any of the above criteria are highly predictive (86%) of recurrence within 12 months and closer observation is warranted. [Table: see text] No significant financial relationships to disclose.
Histologic diagnosis of pancreatic masses using 25-gauge endoscopic ultrasound needles with and without a core trap: a multicenter randomized trial
Authors: Ken Kamata, Masayuki Kitano, Satoru Yasukawa, Masatoshi Kudo, Yasutaka Chiba, Takeshi Ogura, Kazuhide Higuchi, Nobuyasu Fukutake, Reiko Ashida, Tomoaki Yamasaki, Hiroko Nebiki, Satoru Hirose, Noriyuki Hoki, Masanori Asada, Shujiro Yazumi, Makoto Takaoka, Kazuichi Okazaki, Fumihiro Matsuda, Yoshihiro Okabe, Akio Yanagisawa
Journal: Endoscopy (2016)

<b>Background and study aims: </b>Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with 25-gauge needles yields small volume samples that are mainly processed for cytology. Using 25-gauge needles with a core trap may overcome this limitation. This trial compared 25-gauge needles with and without a core trap in terms of their ability to obtain histologic samples from solid pancreatic masses. <b>Patients and methods: </b>Consecutive patients with solid pancreatic masses who presented to eight Japanese referral centers for EUS-FNA in April – September 2013 were randomized to undergo sampling with a 25-gauge needle with a core trap (ProCore) or a standard 25-gauge needle. Tissue samples were fixed in formalin and processed for histologic evaluation. For the purpose of this study only samples obtained with the first needle pass were used for comparison of: (i) accuracy for the diagnosis of malignancy, (ii) rate of samples with preserved tissue architecture adequate for histologic evaluation, and (iii) sample cellularity. <b>Results:</b> A total of 214 patients were enrolled. Compared to the first pass with a standard needle (n = 108), the first pass with the ProCore needle (n = 106) provided samples that were more often adequate for histologic evaluation (81.1 % vs. 69.4 %; <i>P</i> = 0.048) and had superior cellularity (rich/moderate/poor, 36 %/27 %/37 % vs. 19 %/26 %/55 %; <i>P</i> = 0.003). There were no significant differences between the two needles in sensitivity (75.6 % vs. 69.0 %, <i>P</i> = 0.337) and accuracy (79.2 % vs. 75.9 %,<i> P</i> = 0.561) for the diagnosis of malignancy. <b>Conclusions:</b> In patients with solid pancreatic masses, a 25-gauge EUS-FNA needle with a core trap provides histologic samples of better quality than a standard 25-gauge needle. There was no difference in accuracy for the diagnosis of malignancy between the needles. Clinical trial number: UMIN000010021.
Risk of Incident Diabetes Mellitus Associated With the Dosage and Duration of Oral Glucocorticoid Therapy in Patients With Rheumatoid Arthritis
Authors: Mohammad Movahedi, Marie‐Eve Beauchamp, Michal Abrahamowicz, David W. Ray, Kaleb Michaud, Sofia Pedro, William G. Dixon
Journal: Arthritis & Rheumatology (2015)

Objective To quantify the risk of incident diabetes mellitus (DM) associated with the dosage, duration, and timing of glucocorticoid (GC) use in patients with rheumatoid arthritis (RA). Methods We undertook a cohort study using 2 databases: a UK primary care database (the Clinical Practice Research Datalink [CPRD]) including 21,962 RA patients (1992–2009) and the US National Data Bank for Rheumatic Diseases (NDB) including 12,657 RA patients (1998–2013). Information on the dosage and timing of GC use was extracted. DM in the CPRD was defined using Read codes, at least 2 prescriptions for oral antidiabetic medication, or abnormal blood test results. DM in the NDB was defined through patient self‐reports. Data were analyzed using time‐dependent Cox models and a novel weighted cumulative dose (WCD) model that accounts for dosage, duration, and timing of treatment. Results The hazard ratio (HR) was 1.30 (95% confidence interval [95% CI] 1.17–1.45) and 1.61 (95% CI 1.37–1.89) in current GC users compared to nonusers in the CPRD and the NDB, respectively. A range of conventional statistical models consistently confirmed increases in risk with the GC dosage and duration. The WCD model showed that recent GC use contributed the most to the current risk of DM, while doses taken &gt;6 months previously did not influence current risk. In the CPRD, 5 mg of prednisolone equivalent dose for the last 1, 3, and 6 months was significantly associated with HRs of 1.20, 1.43, and 1.48, respectively, compared to nonusers. Conclusion GC use is a clinically important and quantifiable risk factor for DM. Risk is influenced by the dosage and treatment duration, although only for GC use within the last 6 months.
Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine and Guidance for Use as a Booster Dose
Authors: Jennifer Liang, Greg Wallace, Gina Mootrey
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

On March 24, 2015, the Food and Drug Administration licensed an additional combined diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP) and inactivated poliovirus (IPV) vaccine (DTaP-IPV) (Quadracel, Sanofi Pasteur Inc.). Quadracel is the second DTaP-IPV vaccine to be licensed for use among children aged 4 through 6 years in the United States (1). Quadracel is approved for administration as a fifth dose in the DTaP series and as a fourth or fifth dose in the IPV series in children aged 4 through 6 years who have received 4 doses of DTaP-IPV-Hib (Pentacel, Sanofi Pasteur) and/or DTaP (Daptacel, Sanofi Pasteur) vaccine (2,3). This report summarizes the indications for Quadracel vaccine and provides guidance from the Advisory Committee on Immunization Practices (ACIP) for its use.
3D Bioprinting Using a Templated Porous Bioink
Authors: James P. K. Armstrong, Madeline Burke, Benjamin M. Carter, Sean A. Davis, Adam W. Perriman
Journal: Advanced Healthcare Materials (2016)

3D tissue printing with adult stem cells is reported. A novel cell-containing multicomponent bioink is used in a two-step 3D printing process to engineer bone and cartilage architectures.
All health researchers should begin their training by preparing at least one systematic review
Authors: Kamal R Mahtani
Journal: Journal of the Royal Society of Medicine (2016)

One of the founding principles of evidence-based medicine is to use the best available evidence to inform decisions made by patients and clinicians. Systematic reviews have made significant contributions to the pool of best available evidence by systematically gathering, appraising and summarising evidence to answer a given healthcare question. Indeed, the current UK Chief Medical Officer, Dame Sally Davies, has emphasised that ‘by removing uncertainties in science and research, systematic reviews ensure that only the most effective and best value interventions are adopted by the NHS and social care providers’.
Clinical pharmacokinetics (PK) of EZN-2208, a novel anticancer agent, in patients (pts) with advanced malignancies: A phase I, first-in-human, dose-escalation study
Authors: Z. Guo, J. J. Wheler, A. Naing, S. Mani, S. Goel, M. Mulcahy, F. Gamza, C. Longley, A. Buchbinder, R. Kurzrock
Journal: Journal of Clinical Oncology (2008)

2556 Background: EZN-2208 is a water-soluble, polyethylene glycol (PEG) conjugate of SN38 that is active in solid tumors and lymphoma preclinical models, including an in vivo CPT-11-resistant tumor model. EZN-2208 accumulates in tumors, where it releases SN38. Methods: Pts with advanced solid tumors were enrolled to determine the safety, tolerability, PK, maximum tolerated dose, recommended dose, and preliminary evidence of antitumor activity of EZN-2208 administered as a 1-hour intravenous infusion every 3 weeks in a 3+3 escalating dose design. Pts homozygous for UGT1A1*28 were eligible after safety was established in non-homozygous pts. Dose escalation was based on drug-related toxicities observed during the first cycle. Plasma concentrations of EZN-2208 and SN38 were determined by HPLC using fluorescence detection. Pharmacokinetic parameters were estimated using a non-compartmental model analysis. Results: Ten pts (2 males; median age = 59 yrs [34–79 yrs]) were treated at doses of 1.25 (3 pts), 2.5 (3 pts), 5.0 (3 pts), and 10 (1 pt) mg/m2. All 10 pts were pretreated (median number of prior regimens = 5). Tumor types included colorectal (7 pts), gastric (1 pt), anal (1 pt), and breast (1 pt) cancers. Adverse events included grade 2 fatigue and grade 2 neutropenia. No dose-limiting toxicities were observed. Stable disease was observed in 3 pts; 2 of the pts had previously progressed while receiving irinotecan. Plasma PK in the first 3 cohorts (9 pts) is provided in the table below. Conclusions: EZN-2208, a novel agent, was well tolerated in pretreated pts with solid tumors. A qualitative assessment of the data indicates a rough proportionality in AUC vs dose. PK data demonstrated high AUC and prolonged exposure to SN38. Dose escalation is ongoing. Dosea (mg/m2) EZN-2208 b SN38 b Cmaxa (μg/mL) AUC(0-∞)a (h·μg/mL) Terminal t½ (h) Cmax(ng/mL) AUC(0-t)c (h·μg/mL) 1.25 22.4±5.8 645±152 30.1±6.3 32.9±42.1 504±393 2.5 26.1±15.9 891±713 43.8±20.2 14.8±8.0 569±337 5.0 40.6±14.7 1,414±559 53.7±20.7 54.9±33.6 1,026±229 a = SN38 equivalents; b = Mean ± standard deviation; c = AUC(0-t), t is time of last measurable concentration. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Enzon Pharmaceuticals Enzon Pharmaceuticals Enzon Pharmaceuticals
Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (D.O.S.E.) Registry: Analysis of outcomes and costs of epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment in cancer patients
Authors: A. Memisoglu, C. Peake, E. Buscaino, R. S. McKenzie, J. B. Forlenza, C. T. Piech
Journal: Journal of Clinical Oncology (2006)

16009 Background: NCCN anemia treatment guidelines recommend hemoglobin (Hb) levels be maintained between 11 and12 g/dL. To understand erythropoiesis-stimulating therapy (EST) dosing, outcomes and costs in cancer patients, data were analyzed from an ongoing prospective, observational registry (D.O.S.E. Registry) collecting real-world data on cancer patients treated for anemia in U.S. oncology clinics. Methods: Data were collected from participating hospital- and community-based outpatient oncology practices between 1/2004 and 11/2005. This analysis included adult patients who had received ≥2 doses of either EPO or DARB. Outcomes assessed included Hb values at weeks 4, 8, 12, and 16 following EST initiation. Drug cost was based on EST utilization and 2005 wholesale acquisition cost. Results: 652 patients (235 EPO, 417 DARB) from 32 sites were identified. Baseline characteristics of age, gender, Hb, tumor type and ferritin level were similar between treatment groups. The proportion of patients with iron supplementation at baseline was significantly higher in the DARB-treated group (EPO 18% v. DARB 31%, p &lt; 0.001). EPO-treated patients were maintained between 11 and 12 g/dL throughout the therapeutic duration ( Table ). Mean cumulative administered dose of EPO was 393,047 Units and DARB 1205 mcg, corresponding to an overall drug cost of $4,783 for EPO and $5253 for DARB (p = 0.001). Conclusions: These results demonstrate that EPO-treated patients maintained target Hb levels consistent with NCCN guidelines, which was not observed in the DARB-treated patients. Drug cost was significantly higher in the DARB group compared to the EPO group without considering the costs of iron supplementation. [Table: see text] [Table: see text]
The PI3K inhibitor BKM120 has potent antitumor activity in melanoma brain metastases in vitro and in vivo.
Authors: Friedegund Elke Meier, Heike Niessner, Jennifer Schmitz, Andreas Schmid, Carsten Calaminus, Bernd Pichler, Andrea Forschner, Keith Flaherty, Juergen Bernd Honegger, Reinhard Dummer, Ghazaleh Tabatabai, Benjamin Weide, Thomas K. Eigentler, Dirk Schadendorf, Leticia Quintanilla-Fend, Claus Garbe
Journal: Journal of Clinical Oncology (2013)

e20050 Background: In melanoma, the RAF-MEK-ERK and PI3K-AKT signaling pathways play a major role in melanoma progression and drug resistance. On the basis of significant improvement in overall survival, the BRAF inhibitor vemurafenib gained FDA approval for the treatment of patients with metastatic BRAFV600E mutated melanoma. However, vemurafenib appears to be less effective in melanoma brain metastases, and brain metastases are the most common cause of death in patients with metastatic melanoma. In our previous study we reported that the AKT survival pathway is hyperactivated in melanoma brain metastases. Methods: The current study aims to investigate the mechanisms of AKT hyperactivation and the antitumor activity of the PI3K inhibitor BKM120 in melanoma brain metastases in vitro and in vivo. Results: To simulate the tumor environment of brain metastases and extracerebral metastases, brain and matched extracerebral metastatic melanoma cells were stimulated by astrocyte- and fibroblast-conditioned medium, respectively. Both brain and extracerebral metastatic melanoma cells stimulated by astrocyte-conditioned medium showed higher AKT activation and invasiveness in a transwell matrigel invasion assay than cells stimulated by fibroblast-conditioned medium. The PI3K inhibitor BKM120 inhibited the phosphorylation of AKT and the growth of &gt;10 newly isolated cell lines derived from melanoma brain metastases achieving growth inhibition rates of up to 80%. These effects did not depend on BRAF, NRAS or KIT mutation status. Furthermore, BKM120 potently induced apoptosis in brain metastatic melanoma cells and significantly inhibited the tumor growth of human brain metastatic melanoma cells in the brain of nude mice as shown by MRI scans. Conclusions: Brain-derived factors induce hyperactivation of the AKT survival pathway and promote invasiveness and drug resistance of melanoma cells in the brain. The PI3K inhibitor BKM120 inhibits activation of the AKT survival pathway and demonstrates potent antitumor activity in melanoma brain metastases in vitro and in vivo.
Case 24-1972
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, John Noble, Richard B. Cohen
Journal: New England Journal of Medicine (1972)

Presentation of CaseA 48-year-old man was admitted to the hospital* because of dyspnea.He had been well until 10 months previously, when blurred vision developed; an ophthalmologist made a diagnosis of choroiditis. He took prednisone, 20 mg daily, irregularly for several weeks. A complete physical examination and an x-ray examination of the chest were negative. One month later fever and cough occurred, and a film of the chest showed pneumonitis in the right lower lobe. He was admitted to the hospital, where eight blood cultures yielded Candida albicans; no organisms were recovered in cultures of the urine, sputum, . . .
Abstract 18267: Ivabradine in Acute Heart Failure: A Therapeutic Means for Effective Heart Rate Control
Authors: Jens Treptau, Ole Jeske, Christian Napp, Akshay Menon, Bernhard Schieffer, Andreas Schaefer, Johann Bauersachs, Joern Tongers
Journal: Circulation (2015)

Background: In acute cardiac care elevated heart rates are related to morbidity and mortality. Heart rate control may be beneficial in critically ill patients, but heart rate-reducing ß-blockers or antiarrhythmic drugs alter inotropy and hemodynamics. We evaluated the use of ivabradine for heart rate control in acute heart failure with persistently elevated heart rates. Methods/Results: After acute ICU-admission for heart failure/cardiogenic shock, 68 patients (age 57+/-16 yrs, 49 male/19 female) were treated with ivabradine for heart rate control. ICU-admission resulted from myocardial ischemia (65%), decompensated heart failure (17%), valvular heart disease (4%) or other pathologies (7%); 17% of these patients had been resuscitated. Patients were critically ill: 29 required ≥1 catecholamine, 21 mechanical ventilation, 5 mechanical circulatory support (3 Impella microaxial pump, 1 extracorporal membrane oxygenation, 1 combined support), 4 received hemodialysis, and many a calcium sensitizer. In case of a persistently elevated heart rate after a 24hrs run-in phase (cut-off: &gt;80bpm, mean 100±15 bpm), ivabradine was initiated on-top of standard care (dosing: 5 mg/d, n=15; 10 mg/d, n=53). In 10 patients, the ivabradine dose could be increased, while in only 3 patients the dose had to be reduced or therapy terminated. Ivabradine treatment resulted in a significant reduction of heart rate (baseline 100±25 bpm; ICU day-2 82±12 bpm, p&lt;0.05; hospital discharge, 79±16 bpm, p&lt;0.01) without hemodynamic alteration (systolic/diastolic blood pressure at discharge: 111±16/63±10 mmHg). Overall ivabradine was well tolerated. Apart from one individual, all patients survived the intrahospital phase. Five patients were successfully bridged to LVAD-implantation. Follow-up revealed that ivabradine was continued in 52% and 43% of patients 30 and 180 days after hospital discharge. No serious adverse events were reported. Three patients had to be readmitted with acute cardiovascular events within 30 days and another 3 within 180 days of follow-up, whereas 7 patients died during 180-days follow-up. Conclusion: Early addition of ivabradine to standard intensive cardiac care is efficacious and safe in controlling elevated heart rates in acute heart failure.
SDF-1 Inhibition Using Spiegelmer® Nox-A12 As a Novel Strategy For Targeting AML Cells Within Their BM Microenvironment
Authors: Rodrigo Jacamo, Zhihong Zeng, Ye Chen, Yuexi Shi, Teresa McQueen, Anna Kruschinski, Marina Konopleva, Peter P. Ruvolo, Michael Andreeff
Journal: Blood (2013)
Treatment with abatacept prevents experimental dermal fibrosis and induces regression of established inflammation-driven fibrosis
Authors: Matthieu Ponsoye, Camelia Frantz, Nadira Ruzehaji, Carole Nicco, Muriel Elhai, Barbara Ruiz, Anne Cauvet, Sonia Pezet, Marie Laure Brandely, Frédéric Batteux, Yannick Allanore, Jérôme Avouac
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objective</h3> Activated T cells are the main component of the inflammatory skin infiltrates that characterise systemic sclerosis (SSc). Our aim was to investigate the efficacy of abatacept, which tempers T-cell activation, in reducing skin fibrosis in complementary mouse models of SSc. <h3>Methods</h3> The antifibrotic properties of abatacept were evaluated in the mouse models of bleomycin-induced dermal fibrosis and sclerodermatous chronic graft-versus-host disease, reflecting early and inflammatory stages of SSc. Thereafter, we studied the efficacy of abatacept in tight skin (Tsk-1) mice, an inflammation-independent mouse model of skin fibrosis. <h3>Results</h3> Abatacept efficiently prevented bleomycin-induced skin fibrosis and was also effective in the treatment of established fibrosis. In this model, abatacept decreased total and activated T-cell, B-cell and monocyte infiltration in the lesional skin. Abatacept did not protect CB17-SCID mice from the development of bleomycin-induced dermal fibrosis, which supports that T cells are necessary to drive the antifibrotic effects of abatacept. Upon bleomycin injections, skin interleukin (IL) 6 and IL-10 levels were significantly reduced upon abatacept treatment. Moreover, treatment with abatacept ameliorated fibrosis in the chronic graft-versus-host disease model, but demonstrated no efficacy in Tsk-1 mice. The tolerance of abatacept was excellent in the three mouse models. <h3>Conclusions</h3> Using complementary models, we demonstrate that inhibition of T-cell activation by abatacept can prevent and induce the regression of inflammation-driven dermal fibrosis. Translation to human disease is now required, and targeting early and inflammatory stages of SSc sounds the most appropriate for positioning abatacept in SSc.
Residual Risk of Stroke and Death in Anticoagulant-Treated Patients With Atrial Fibrillation
Authors: Ben Freedman, Carlos Martinez, Anja Katholing, Stephan Rietbrock
Journal: JAMA Cardiology (2016)

This study compares incidence of stroke among patients with warfarin-treated atrial fibrillation with the incidence among similar-risk patients without atrial fibrillation to distinguish if on-treatment stroke is attributable to treatment failure or baseline risk.