tbuckley/cabot-search huggingface dataset:
Abstract 13714: Association between Intensively Controlled Low-density Lipoprotein Cholesterol and Clinical Outcomes in Patients with Peripheral Artery Disease after Angioplasty
Authors: Jung-Hee Lee, Dong-Ho Shin, Jung-Sun Kim, Byeong-Keuk Kim, Myeong-Ki Hong, Yangsoo Jang, Donghoon Choi, Young-Guk Ko
Journal: Circulation (2014)

Objective:  The purpose of this study was to evaluate the association between intensively controlled low-density lipoprotein (LDL) cholesterol and clinical outcomes in patients with peripheral artery disease (PAD).   Background:  Although statin medication is recommend for reducing atherosclerotic cardiovascular events, the achieved LDL cholesterol levels are diverse. There are little data about the relation between achieved LDL cholesterol levels and clinical outcomes in PAD patients.   Methods:  The study population consisted of 242 patients with PAD who underwent percutaneous transluminal angioplasty (PTA) from 2011 through 2012. We categorized the patients according to the achieved LDL cholesterol level at 4 months after PTA [well-controlled LDL group (LDL level≤70mg/dL, n=114) and uncontrolled LDL group (LDL level>70mg/dL, n=128)]. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) defined as a composite of cardiac death, myocardial infarction, stroke, target lesion revascularization, and unplanned amputation.   Results:  Baseline characteristics including age, sex, BMI, history of hypertension, diabetes, strokes, previous vascular disease and pre-procedural lipid profiles are similar between each group. There was significant difference in achieved LDL cholesterol level between the two groups (55.7±10.6 vs. 92.9±20.6mg/dl, p    Conclusions:  Intensively controlled LDL cholesterol level significantly reduced MACCE in patients with PAD after PTA.
Feasibility of high-dose chemotherapy (HDCT) with doble autologous stem cell transplantation (ASCT) for Ewing and soft tissue sarcomas
Authors: J. Fernández Plana, A. López Pousa, A. Sureda Balari, X. González Farré, D. Páez López-Bravo, A. Tibau Martorell, J. Pérez Altozano, J. López López, A. Barnadas Molins
Journal: Journal of Clinical Oncology (2008)

21501 Background: To improve long-term outcome of metastatic sarcoma patients (pts), we started a tandem ASCT program in compassionate use. Its feasibility is analyzed. Methods: From January/2004 to April/2007, 11 pts (8 males, age 29 [19 - 51] years) were included: 7 Ewing, 2 rabdomyosarcoma, 1 sinovial and 1 leiomyosarcoma. Patients included in the program were those with CR or PR after conventional chemotherapy (CT). Median treatment lines before transplant was 1 (1–3). Conditioning regimen for both ASCTs was ICE protocol (HDCT) (ifosfamide 2,500 mg/m2 iv × 4 d, carboplatin 360 mg/m2 iv × 4 d., etoposide 310 mg/m2 iv × 4 d.). A minimum number of 4 × 106 CD34+/kg cels were collected. Results: 5 pts were in CR, 5 in PR just before ASCT. 1 pt that achieved a PR after CT, presented with an early progression just before the first ASCT. All pts underwent the first procedure. Post-transplant toxicity: grade (G) 4 neutropenia: (11d [7d-14d]), G4 thrombocytopenia: (7.7d [4–12]), G 3–4 gastrointestinal (GI) toxicity in 6 (54%) and severe venooclusive disease in 2 (18%) pts. All pts developed neutropenic fever. Two pts (18%) died from transplant related mortality (TRM). 3 other pts (27%) didn't proceed to 2nd intensive course due to early progression after first ASCT. Time interval between procedures was 3.6 (2–7) months. Second ASCT toxicity was: neutropenia G IV 11.5 (9–14) d and thrombocytopenia G4 5.8 (2–14) d. One pt (16%) developed G3 GI toxicity. TRM was 0%. With a median follow-up for all pts of 14.5 (1–35) months after the first transplant, 4 are alive (36%), 1 in CR, 3 in PR and 7 are death (63%). Conclusions: This tandem procedure is feasible but rather toxic: G 3–4 GI toxicity are higher than expected as well as TRM. Progression rate after the first ASCT procedure is not negligible. Other options should be sought for this bad-prognosis pts. No significant financial relationships to disclose.
Targeted hypoglossal neurostimulation (THN) to treat obstructive sleep apnea (OSA). A one year safety and efficacy trial
Authors: Gimbada Mwenge, Philippe Rombaux, Myriam Dury, Benoit Lengele, Daniel Rodenstein
Journal: European Respiratory Journal (2012)

Patients with severe OSA non-compliant to CPAP need an alternative treatment. We performed a one-year safety and efficacy study of a new therapy using unilateral THN. The system was implanted in 13 (12 males) out of 14 patients aged 50 ± 10 yo, BMI 31 ± 3 kg/m² with severe OSA refusing CPAP. After surgery two patients had asymptomatic hemitongue paresis lasting two and three months. One patient was not implanted due to a missmatch between the electrode and the pulse generator. There were no other surgery-related adverse events.  The main efficacy outcomes were the apnea-hypopnea index (AHI), the 4% oxygen desaturation index (ODI) and the movement arousal index (MAI). Diagnostic data showed AHI 45 ± 18, ODI 29 ± 20 and MAI 37 ± 13. The Total Sleep Time (TST) was 414 ± 85 min. After one year, AHI was 21 ± 16, ODI 15 ± 16, and MAI 25 ± 14, all p  There were no serious adverse events. Three electrodes failures in two subjects led to treatment interruptions. One patient had his IPG replaced due to malfunction, and there was one twiddler phenomenon.  There was a trend towards improvements of the Epworth Sleepiness Scale (from 11 ± 6 to 8 ± 4, p 0.09) and of the Fatigue Severity Scale (5 ± 2 to 4 ± 2, p 0.09). Patients found the THN treatment more pleasant and comfortable than CPAP.  Conclusion: THN is safe and efficient in most OSA patients.
Phase III study (PRIME/20050203) of panitumumab (pmab) with FOLFOX compared with FOLFOX alone in patients (pts) with previously untreated metastatic colorectal cancer (mCRC): Pooled safety data
Authors: S. Siena, J. Tabernero, R. L. Burkes, J. Cassidy, D. Cunningham, M. E. Barugel, Y. Humblet, C. McPhie, M. Shing, J. Douillard
Journal: Journal of Clinical Oncology (2008)

4034 Background: Pmab is a fully human anti-EGFr monoclonal antibody (MAb) with activity as a single agent in refractory mCRC. PRIME study is the first global, phase III trial investigating a fully human anti-EGFr MAb combined with FOLFOX as first-line treatment (tx) for pts with mCRC. Methods: This is a randomized, multicenter, phase III study with pt eligibility criteria which include: histologically/cytologically-confirmed adenocarcinoma of the colon or rectum with metastatic disease; no prior chemotherapy or systemic therapy for mCRC; ECOG performance status (PS) 0 to 2. No EGFr staining is required for inclusion. Pts are randomized 1:1 to receive either pmab 6.0 mg/kg Q2W + FOLFOX4 Q2W (Pmab+FOLFOX4) or FOLFOX4 Q2W alone. The primary endpoint is progression-free survival. Secondary endpoints include overall survival, objective response rate, time to progression, duration of response, and safety. PRIME study endpoints will be investigated by the pts’ KRAS mutational status in both arms as a potential biomarker for pmab activity in combination with FOLFOX as first-line tx for pts with mCRC. The study has multiple, planned safety interim analyses conducted by an independent Data Monitoring Committee (DMC), with the latest safety interim analysis including 601 pts of approximately 1150 target accrual. Results: 302 pts are in the Pmab+FOLFOX4 arm and 299 pts are in the FOLFOX4 arm. Of all pts, 63 % are men, median age is 62 years (range, 27- 83), ECOG PS 0: 57 %, PS 1: 38 %, PS 2: 5 %. Of all pts, 99 % received tx with at least 1 cycle of study therapy, and 39 % have stopped study tx. Median follow-up time was 15 weeks. Adverse events of interest are shown (table). Conclusions: After the safety interim analysis of the first 601 pts conducted by the DMC, PRIME study continues per protocol. PRIME study has reached the enrollment goal and updated pooled safety data for approximately 900 pts will be presented. Adverse Events of Interest: Pooled Analysis of 601 pts Adverse Event MedDRA terms Any Grade - n (%) CTC AE v3.0 Grade 3/4 - n (%) CTC AE v3.0 Skin and subcutaneous tissue SOC * 324 (54) 67 (11) Diarrhea 261 (43) 58 (10) Nausea 233 (39) 16 (3) Neutropenia 226 (38) 147 (25) Fatigue 162 (27) 25 (4) Hypomagnesaemia 68 (11) 11 (2) Dehydration 28 (5) 14 (2) Infection 4 (1) 0 (0) * SOC = system organ class. There was 1 investigator-reported adverse event of infusion reaction (grade 1). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen, AstraZeneca, Eli Lilly, Merck Serono, Roche, sanofi-aventis Amgen Abraxis, Amgen, AstraZeneca, Eli Lilly, Merck, Ortho Biotech, Roche, sanofi-aventis Amgen, Roche, sanofi-aventis Amgen
Helping cancer-family caregivers with end-of-life home symptom management: Initial evaluation of an automated symptom monitoring and coaching system.
Authors: Kathi Mooney, Patricia Berry, Bob Wong, Gary Donaldson
Journal: Journal of Clinical Oncology (2014)

85 Background: Family caregivers face the task of providing end of life care (EOL) in the home setting and need effective caregiving support. Although not previously tested in EOL care, automated symptom monitoring has shown promise for cancer patients on active treatment. This study tests an automated monitoring and coaching system for family caregivers during home hospice. Methods: Family Caregivers (FC) of hospice cancer patients (PT) (N=243 dyads) were monitored daily using an automated telephone symptom monitoring system, and randomly assigned to receive the symptom care intervention (SC) (N=119) or usual care (UC) (N=124). All FCs called the monitoring system daily, reporting by proxy, past 24 hour presence, severity and FC distress on 11 common PT symptoms (0–10 scale). In addition, FCs reported their own fatigue, sleep, mood and anxiety severity (0-10 scale). The SC intervention FCs received automated tailored symptom care coaching based on reported patterns; in addition symptoms moderate or greater generated alerts to their hospice nurse. Results: Most FCs and PTs were White (95; 94%), 66% of FCs and 48% of PTs were female with the Mean age for FCs 60 and 73 for PTs. Most frequent PT symptoms were fatigue (70%), pain (64%), poor appetite (54%), anxiety (39%), and change in thinking (38%). PT symptom severity levels were highly related to FC distress. Preliminary analyses indicates that FC vitality (FC combined symptoms) improved more in the SC group (p=.003, mixed effects model). Furthermore PT symptom severity, categorized as Mild (&lt;=3), Moderate (4-6), or Severe (&gt;=7), provided strong preliminary evidence of SC intervention benefit in each of the first four weeks in hospice care and overall (p=.003). Rapid onset of the SC benefit was suggested by Kaplan-Meier analysis of time to first all-zero symptom profile (p=.06 log-rank). The benefit of the SC intervention continued throughout the hospice stay until the last several days of life when there was no difference with UC. Conclusions: This is the first reported evaluation of automated symptom monitoring in home EOL care and provides strong preliminary evidence of benefit for cancer family caregivers and patients. Clinical trial information: NCT02112461.
Correlation of right ventricular ejection fraction with tricuspid annular plane systolic excursion by electrocardiogram-gated 320 slice CT in chronic thromboembolic pulmonary hypertension
Authors: Toshihiko Sugiura, Nobuhiro Tanabe, Nobusada Funabashi, Naoko Kawada, Yukiko Matsuura, Takayuki Juzyo, Rintaro Nishimura, Ayumi Sekine, Norituki Yanagawa, Seiichiro Sakao, Yasunori Kasahara, Koichiro Tatsumi
Journal: European Respiratory Journal (2011)

Purpose:  There is a strong correlation between right ventricular ejection fraction (RVEF) and tricuspid annular plane systolic fraction (TAPSE) determined by echocardiography in subjects with pulmonary hypertension (PH). However, it is unknown whether there a correlation between RVEF and TAPSE determined by 320-slice CT. We tested whether TAPSE measured by enhance ECG-gated volume 320-slice CT correlates with RVEF and correlates with pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) obtained by right heart catheterization (RHC) in chronic thromboembolic pulmonary hypertension (CTEPH) subjects.   Materials and methods:  33 subjects (11 male, 61±10 yrs) with CTEPH underwent enhanced retrospective ECG-gated volume 320-slice CT (Aquilion ONE, Toshiba) and RHC. CT images were reconstructed every 5% from 0-95% of the R-R interval and a series of apical 4-chanber images. TAPSE was measured from systolic displacement of the RV freewall and tricuspid annular plane junction. RV end-systolic and end-diastolic true volumes were measured from 3-dimensional reconstruction and used to calculate RVEF.   Results:  TAPSE and RVEF were 14.5±3.5mm and 47.0±14.3%, respectively. In RHC, mean PAP (mPAP) and PVR were 41±12 mmHg and 683±364 dyne sec cm -5 , respectively. The correlation coefficient of TAPSE with RVEF was 0.78 (P   Conclusions:  TAPSE by ECG-gated 320-slice CT correlated strongly with RVEF and significantly with mPAP and PVR acquired by RHC in subjects with CTEPH.
P15 Non-invasive assessment of hepatic fibrosis in prior non-responders to hepatitis C virus treatment—a comparison of eight marker panels of liver fibrosis
Authors: S Tanwar, E Ellis, C Herold, W Rosenberg
Journal: Gut (2010)

Introduction  The detection of advancing fibrosis in patients who have previously failed standard therapy for hepatitis C virus (HCV) is important both for ascertaining prognosis and stratifying patients for further treatment with emerging therapies. Whilst liver biopsy remains the reference standard, non-invasive markers of liver fibrosis may be able to reduce the need for liver biopsy in this group of patients.  Method  80 previous non-responders to pegylated interferon and ribavirin (46 male, 34 female, age 24–98 years, mean 48.9) were recruited from five centres. Serum was taken at the time of liver biopsy. Seven tests of liver fibrosis and simple biochemical markers were compared. These were: Hyaluronic acid (HA); Indirect tests: APRI, Forn9s, Fib-4; Tests including HA: SHASTA, Hepascore, Fibrometer and ELF test. Area under receiver operating characteristic curves (AUROC) were plotted for minimal fibrosis (F0–1 vs F2–6), mild fibrosis (F0–2 vs F3–6), moderate fibrosis (F0–3 vs F4–6), and severe fibrosis/cirrhosis (F0–4 vs F5–6).  Results  AUROCs (and asymptotic 95% confidence intervals) are presented for each test for minimal, mild and severe fibrosis.  ELF was best at detecting lesser degrees of fibrosis and was better than the indirect marker panels either with or without HA. ELF and Hepascore were best at detecting advanced fibrosis, but other panels performed adequately with similar AUCs.  Conclusion  In this cohort of previous non-responders to HCV treatment, the ability to discriminate advanced fibrosis appears to be similar amongst most of the markers tested. In contrast, of the eight markers tested in this study, the ELF panel appears to have the most consistent diagnostic performance across all stages of fibrosis and performs well in the detection of minimal and mild fibrosis. ELF testing would permit stratification of previous non-responders for further anti-HCV and anti-fibrotic therapy and for screening for complications of cirrhosis.
Alternating chemotherapy and twice-daily thoracic radiotherapy in limited-stage small-cell lung cancer: a pilot study of the Eastern Cooperative Oncology Group.
Authors: D H Johnson, A T Turrisi, A Y Chang, R Blum, P Bonomi, D Ettinger, H Wagner
Journal: Journal of Clinical Oncology (1993)

PURPOSE This pilot study was undertaken to determine the efficacy and feasibility of alternating cisplatin and etoposide with multiple daily fractions of thoracic radiotherapy (TRT) in patients with limited-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS Thirty-four SCLC patients received four courses of cisplatin (30 mg/m2/d x 3) plus etoposide (120 mg/m2/d x 3) (PE) every 3 weeks. TRT was administered twice daily (1.5 Gy per fraction) for 5 consecutive days in the week after cycles 1, 2, and 3 of chemotherapy (total TRT dose, 45 Gy). Patients who achieved a complete response (CR) received one course of late-intensification (LI) treatment consisting of cyclophosphamide (4 g/m2) and etoposide (900 mg/m2). Prophylactic cranial irradiation (PCI) was optional. RESULTS Nineteen of 32 assessable patients achieved a CR (59%) and 12 had a partial response (38%), for an overall response rate of 97% (95% confidence interval [CI], 84% to 99%). Median survival was 18 months, while 2-year progression-free survival was 47%. Leukopenia &lt; or = 1,000/microL occurred in 12% of induction treatment cycles. Severe esophagitis was uncommon. Pulmonary fibrosis that was asymptomatic or minimally symptomatic was observed in eight patients (25%). There was one episode of adult respiratory distress syndrome (ARDS) during LI chemotherapy. Life-threatening neutropenia (&lt; or = 500/microL) developed in all patients who underwent LI chemotherapy, with a median duration of 10 days (range, 8 to 19). Two patients died of sepsis during LI chemotherapy. CONCLUSION Alternating PE and TRT as performed in this trial is an effective brief induction regimen for limited-stage SCLC. However, this particular regimen did not appear to be substantially different in terms of efficacy or toxicity compared with regimens using concurrent chemotherapy and standard-fraction TRT. LI chemotherapy was associated with unacceptable toxicity and did not appear to have a favorable impact on survival.
Randomized, double-blind, placebo-controlled phase II study of carboplatin and paclitaxel with or without vorinostat, a histone deacetylase inhibitor (HDAC), for first-line therapy of advanced non-small cell lung cancer (NCI 7863)
Authors: S. S. Ramalingam, M. Maitland, P. Frankel, A. E. Argiris, M. Koczywas, B. Gitlitz, I. Espinoza-Delgado, E. E. Vokes, D. R. Gandara, C. P. Belani
Journal: Journal of Clinical Oncology (2009)

8004 Background: Vorinostat, a HDAC inhibitor, enhances paclitaxel and platinum-mediated anti-cancer activity in preclinical studies by enhanced tubulin acetylation and DNA fragmentation respectively. Promising activity with carboplatin (C), paclitaxel (P), and vorinostat in patients with advanced NSCLC in the phase I study (Ramalingam et al, Clin Cancer Res, 2007) prompted this placebo-controlled, randomized phase II study. Methods: Pts. with stage IIIB (wet) or IV NSCLC, performance status (PS) 0/1, no prior therapy and adequate bone marrow, renal and hepatic function were randomized (2:1) for therapy with PC with either vorinostat or placebo. Treatment consisted of C: AUC=6 mg/ml.min; and P 200 mg/m 2 both given on day 3 along with either vorinostat (400 mg PO QD) or placebo on days 1–14 of each 3 wk cycle to a maximum of 6 cycles. The estimated sample size to demonstrate a 50% improvement in response rate for vorinostat over placebo was 93 pts. (one-sided P, type I error 10%). Results: Ninety-four pts. were enrolled (vorinostat-64; placebo-32). Pts. baseline characteristics were similar between the two arms (median age 64, male 60%, PS 0 40%, brain mets 16%). Median # cycles: vorinostat-3.5; placebo - 4. The confirmed response rate was superior with vorinostat over placebo (34% vs. 12.5%, P = 0.02). At the time of analysis, the preliminary median PFS for vorinostat and placebo were 5.75 and 4.1 m respectively (ITT). Follow up for survival is ongoing. Common grade 3/4 toxicities (vorinostat vs. placebo): neutropenia (44% vs. 47%); thrombocytopenia (33% vs. 16%); fatigue (13% vs. 3%); hyponatremia (21% vs. 6%); diarrhea (5% vs. 0). Discontinuation from study after cycle 1 was higher with vorinostat (27% vs. 16%). Biomarker studies on baseline tumor tissue and peripheral blood cells are ongoing. Conclusions: Administration of vorinostat with carboplatin and paclitaxel resulted in a significantly superior response rate for pts.with advanced NSCLC. HDAC inhibition is a novel therapeutic strategy for treatment of NSCLC. Supported by ASCO Career Development Award to S.S.Ramalingam, and NCI NO1-CM-62209, NO1-CM-62201, NO1-CM-62208. [Table: see text]
HD10: Investigating reduction of combined modality treatment intensity in early stage Hodgkin’s lymphoma. Interim analysis of a randomized trial of the German Hodgkin Study Group (GHSG)
Authors: V. Diehl, C. Brillant, A. Engert, R. P. Mueller, H. K. Mueller-Hermelink, R. Hermann, B. Doerken, L. Kanz, R. Greil, B. Pfistner
Journal: Journal of Clinical Oncology (2005)

6506 Background: Early stage Hodgkin's lymphoma (HL) in stages I-II without risk factors currently is successfully treated with combined modality of chemotherapy (usually ABVD) followed by involved field irradiation (IF) in most study groups, reaching complete remission rates higher than 90%. In the HD10 trial the GHSG investigated if the number of ABVD cycles as well as IF-radiotherapy (RT) dose could be safely reduced. Methods: 1131 patients (pts) with early stage disease (stage I,II without risk factors) were randomized between 4 cycles vs. 2 cycles of ABVD and 30 Gy IF vs. 20 Gy IF in a 2x2 factorial design between 5/1998 and 5/2002. Primary endpoint was freedom from treatment failure (FFTF). Results: The second interim analysis conducted in August 2003 comprised of 847 pts (75%) that were well balanced between treatments arms concerning baseline characteristics. Complete remission rates were high with 98.4% of all pts while progressive disease or no change was observed in 0.9% of cases. Relapse rate was 2.5%, thirteen patients died during the study (1.5%). The most common WHO grade 3/4 toxicity during CT was leukopenia with 19% (4xABVD: 22%, 2xABVD: 15%). RT was well tolerated with dysphagia in 2.3%. So far ten secondary neoplasias were reported: 1AML, 4 NHL and 5 solid tumors. FFTF after a median observation time of two years was 96.6% with no statistical differences between CT of 4xABVD vs. 2xABVD or RT of 30Gy IF vs. 20Gy IF. Overall survival was 98.5% without any statistical differences in CT and RT comparisons either. Conclusions: Further analysis will show if these promising interim results will allow to reduce further therapy intensity in combined modality treatment of early stage HL both in terms of the composition of drugs (ABVD->AV in HD13) as well as RT dose. No significant financial relationships to disclose.
Neuropathy and Efficacy Of Weekly Subcutaneous Bortezomib In Myeloma and AL Amyloidosis
Authors: Surbhi Sidana, Beth Faiman, Paul Elson, Mitchell R Smith, Robert M Dean, Jason Valent, Christy Samaras, Hien K. Duong, Debbie Hastings, Kellie Bruening, Frederic J. Reu
Journal: Blood (2013)
Chemogenetic disconnection of monkey orbitofrontal and rhinal cortex reversibly disrupts reward value
Authors: Mark A G Eldridge, Walter Lerchner, Richard C Saunders, Hiroyuki Kaneko, Kristopher W Krausz, Frank J Gonzalez, Bin Ji, Makoto Higuchi, Takafumi Minamimoto, Barry J Richmond
Journal: Nature Neuroscience (2015)