tbuckley/cabot-search huggingface dataset:
Correlation of T-cell response, clinical activity and regulatory T-cell levels in renal cell carcinoma patients treated with IMA901, a novel multi-peptide vaccine
Authors: H. Singh-Jasuja, S. Walter, T. Weinschenk, A. Mayer, P. Y. Dietrich, M. Staehler, A. Stenzl, S. Stevanovic, H. Rammensee, J. Frisch
Journal: Journal of Clinical Oncology (2007)

3017 Background: Cancer vaccines have been able to induce T-cell responses in cancer patients but rarely demonstrated a correlation of immune responses with clinical benefit. Here, we present immunological results of a phase 1 study with IMA901, a therapeutic cancer vaccine based on multiple novel synthetic tumor-associated peptides (TUMAP) identified as being naturally presented in primary renal cell carcinoma (RCC) tissues. Methods: The HLA peptidome of 32 primary RCC samples was systematically investigated using a combination of mass spectrometry, gene expression profiling and in vitro human T-cell assays. 9 HLA-A*02- and 1 HLA-DR- restricted TUMAPs derived from 9 different tumor antigens were selected and designated IMA901. 28 HLA-A*02-positive stage III/IV RCC patients were enrolled in a single arm, multicenter study and received 8 vaccinations on days 1, 2, 3, 8, 15, 22, 36, and 64 each consisting of 4.5 mg IMA901 (including a HBV-derived viral marker peptide) and 75 μg GM-CSF as immune adjuvant. T-cell responses using IFN-γ ELISPOT and HLA multimer analysis and CD4+ Foxp3+ regulatory T cell (Treg) levels were measured in peripheral blood. Results: In vivo IMA901- induced specific T-cell responses were detected to the HBV marker peptide (52% of 27 evaluable patients), at least one TUMAP (74%) or multiple TUMAPs (30%). T-cell responses were detectable already at day 15, peaked subsequently and were sustainable until follow-up in the majority of patients. Most importantly, patients eliciting multiple responses to TUMAPs significantly showed a higher clinical benefit rate (SD+PR; p=0.018) and lower Treg levels at study onset (p=0.016). No correlation of HBV marker peptide responses with either clinical benefit or Treg levels was observed. Conclusions: IMA901 rapidly induced T-cell responses in a majority of advanced RCC patients. A clinical mode of action is strongly supported by the significant correlation of multiple T-cell responses with clinical benefit. CD4+ Foxp3+ Tregs seem to play an active role in limiting the broadness of T-cell responses. Furthermore, our data suggest that we can predict in vivo immunogenicity of cancer vaccine antigens by our in vitro drug discovery approach. No significant financial relationships to disclose.
PFI is here to stay
Authors: B. McCloskey
Journal: BMJ (2002)

Uncertainty remains about efficacyEditor-The article by Lenzer and the associated commentary by Saver et al raise many serious issues, among which is the residual state of uncertainty concerning the efficacy of alteplase (tPA) in acute ischaemic stroke. 1 Confronted by opposing interpretations of the aggregate data published to date and the now known baseline imbalance in the severity of stroke in the National Institute of Neurological Diseases and Stroke (NINDS) trial, doctors are presented with a conundrum: what action do the data support?The reported unwillingness of the investigators and sponsor of the National Institute of Neurological Diseases and Stroke trial to provide data for additional analysis is disturbing.Emanuel et al have described seven requirements for the ethical conduct of clinical research, among which is social and scientific value. 2 Social value presupposes the public dissemination of research results.I have formulated a standard for the scientific and ethical review of trials that elaborates on this requirement. 3mplicit in this requirement is the necessity for the public dissemination of the complete dataset acquired during a clinical trial.This allows interested investigators to apply recognised analytic techniques in an attempt to resolve (or diminish) residual uncertainty concerning the clinical implications of the trial's results.This ethical requirement has not yet been met for the National Institute of Neurological Diseases and Stroke trial.
Factors Associated With Recurrence of Advanced Colorectal Adenoma After Endoscopic Resection
Authors: Antonio Facciorusso, Marianna Di Maso, Gaetano Serviddio, Gianluigi Vendemiale, Cristiano Spada, Guido Costamagna, Nicola Muscatiello
Journal: Clinical Gastroenterology and Hepatology (2016)
Cigarette Smoking, Alcohol Consumption, and Breast Cancer Risk
Authors: Dianne L. O'Connell, Barbara S. Hulka
 5, Lloyd E. Chambless, William E. Wilkinson, David C. Deubner
Journal: JNCI Journal of the National Cancer Institute (1987)

The effects of cigarette smoking and alcohol consumption on breast cancer risk were investigated in 276 primary, histologically confirmed breast cancer patients and 1,519 community-based comparison subjects identified in 1977 and 1978 in North Carolina. Data on both behaviors and other pertinent personal and medical characteristics were obtained by interview. Analytic methods included stratification and logistic regression. Among current cigarette smokers of 1-20 cigarettes per day and over 20 per day, the odds ratios (ORs) adjusted for age, race, alcohol consumption, estrogen use, and oral contraceptive use for breast cancer were 0.75 [95% confidence interval (CI) 0.52-1.09] and 0.57 (95% CI 0.30-1.08), respectively. A decrease in risk was not seen in former smokers. With respect to alcohol consumption, the adjusted OR for those having one drink or more per week compared to those having less than one was 1.45 (95% CI 0.99-2.12). If the comparison was ever versus never drinkers, the adjusted OR was 1.47 (95% CI 1.10-1.97); for current drinkers versus nondrinkers, the adjusted OR was 1.89 (95% CI 1.40-2.56). The ORs were adjusted for age, race, cigarette smoking, estrogen use, an oral contraceptive use. These data supports those reports showing an inverse association of cigarette smoking and a positive association of alcohol consumption with breast cancer risk.
Transcatheter Tricuspid Valve-in-Valve Implantation for the Treatment of Dysfunctional Surgical Bioprosthetic Valves
Authors: Doff B. McElhinney, Allison K. Cabalka, Jamil A. Aboulhosn, Andreas Eicken, Younes Boudjemline, Stephan Schubert, Dominique Himbert, Jeremy D. Asnes, Stefano Salizzoni, Martin L. Bocks, John P. Cheatham, Tarek S. Momenah, Dennis W. Kim, Dietmar Schranz, Jeffery Meadows, John D.R. Thomson, Bryan H. Goldstein, Ivory Crittendon, Thomas E. Fagan, John G. Webb, Eric Horlick, Jeffrey W. Delaney, Thomas K. Jones, Shabana Shahanavaz, Carolina Moretti, Michael R. Hainstock, Damien P. Kenny, Felix Berger, Charanjit S. Rihal, Danny Dvir
Journal: Circulation (2016)

Background— Off-label use of transcatheter aortic and pulmonary valve prostheses for tricuspid valve-in-valve implantation (TVIV) within dysfunctional surgical tricuspid valve (TV) bioprostheses has been described in small reports. Methods and Results— An international, multicenter registry was developed to collect data on TVIV cases. Patient-related factors, procedural details and outcomes, and follow-up data were analyzed. Valve-in-ring or heterotopic TV implantation procedures were not included. Data were collected on 156 patients with bioprosthetic TV dysfunction who underwent catheterization with planned TVIV. The median age was 40 years, and 71% of patients were in New York Heart Association class III or IV. Among 152 patients in whom TVIV was attempted with a Melody (n=94) or Sapien (n=58) valve, implantation was successful in 150, with few serious complications. After TVIV, both the TV inflow gradient and tricuspid regurgitation grade improved significantly. During follow-up (median, 13.3 months), 22 patients died, 5 within 30 days; all 22 patients were in New York Heart Association class III or IV, and 9 were hospitalized before TVIV. There were 10 TV reinterventions, and 3 other patients had significant recurrent TV dysfunction. At follow-up, 77% of patients were in New York Heart Association class I or II ( P &lt;0.001 versus before TVIV). Outcomes did not differ according to surgical valve size or TVIV valve type. Conclusions— TVIV with commercially available transcatheter prostheses is technically and clinically successful in patients of various ages across a wide range of valve size. Although preimplantation clinical status was associated with outcome, many patients in New York Heart Association class III or IV at baseline improved. TVIV should be considered a viable option for treatment of failing TV bioprostheses.
The Role Of Body Mass Index In Survival Outcome For Lymphoma Patients: US Intergroup Experience
Authors: Fangxin Hong, Thomas M Habermann, Leo I. Gordon, Howard S Hochster, Randy D. Gascoyne, Vicki A. Morrison, Richard I Fisher, Nancy L. Bartlett, Patrick J Stiff, Bruce D. Cheson, Michael Crump, Sandra J. Horning, Brad S. Kahl
Journal: Blood (2013)
Successful engraftment of T-cell-depleted haploidentical "three-loci" incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum
Authors: F Aversa, A Tabilio, A Terenzi, A Velardi, F Falzetti, C Giannoni, R Iacucci, T Zei, MP Martelli, C Gambelunghe
Journal: Blood (1994)
A phase II study of oxaliplatin and pemetrexed plus bevacizumab in advanced non-squamous non-small cell lung cancer (An International Oncology Network study, #I-04–015)
Authors: J. M. Waples, M. Auerbach, R. Steis, R. V. Boccia, R. G. Wiggans
Journal: Journal of Clinical Oncology (2008)

19018 Background: As single agents, oxaliplatin (OX) and pemetrexed (PEM) are active in patients (pts) with non-small cell lung cancer (NSCLC) and PEMhas synergistic effectiveness when combined with platinum-based drugs. Bevacizumab (BV) has an additive effect on many chemotherapy agents in several tumor types, including NSCLC. The purpose of this Phase II study is to evaluate the efficacy and safety of the combination of BV, OX and PEMas first-line treatment for NSCLC. The primary endpoint is progression-free survival (PFS). Methods: Pts with confirmed Stage IIIB/IV non-squamous NSCLC received 6 cycles of OX (120 mg/m2), PEM(500 mg/m2) and BV (15 mg/kg) on Day 1 of each 21-day cycle. Following 6 cycles, pts received BV alone every 21 days until PD or unacceptable toxicity. Results: At the time of analysis, 69 pts have been enrolled, 67 have received study medication, and 58 are evaluable for response. Pt characteristics include: gender male/female, 44/25; median age 63 yrs (range 43–86); ECOG PS 0/1, 33/36; and race Caucasian/Black/Hispanic, 64/4/1. Median number of cycles administered is 6 (range 1–24). PFS is 7.8 months (95% CI, 5.3 to 8.4). Median survival is 16.7 months (95% CI, 10.5 to 20). Fifteen pts had a PR for an overall response rate of 26% (95% CI, 15 to 39), though 34 pts (58.6%) have SD. The most common G3 toxicities were fatigue (9%), dehydration (9%), hyperglycemia (6%), back pain (6%), neutropenia (4.5%), dyspnea (4.5%), arthralgia (4.5%), headache (4.5%) and pleuritic pain (4.5%). G4 toxicities were neutropenia (3%), dyspnea (3%), pulmonary embolism (3%), hyperglycemia (1.5%), febrile neutropenia (1.5%) and thrombocytopenia (1.5%). Nine pts remain on study. Ten pts died; 5 PD, 3 adverse events (2 hypoxia, 1 cerebral vascular accident), 1 respiratory failure and 1 pulmonary embolism. Conclusions: The median survival of 16 months is encouraging compared to expectations of <1 year in most studies in this population. Treatment led to 84% of pts having a response or SD. This may explain the higher than expected median survival for a relatively well-tolerated regimen. No significant financial relationships to disclose.
AAP urges pediatricians to act against child poverty
Authors: Michael McCarthy
Journal: BMJ (2016)

Pediatricians should assess the financial status of all the families of children they see and connect those in need with appropriate community resources, the American Academy of Pediatrics (AAP) said in a policy statement on tackling child poverty, published Wednesday 9 March.1

The statement added that pediatricians should advocate for public policies that reduce poverty’s impact on child health, emphasizing, “The AAP considers child poverty in the United States unacceptable and detrimental to the health and well-being of children and is committed to its elimination.”

Roughly one in five (21.1%) children in the US live in poor households, defined as having household incomes below 100% of the federal poverty …
Oxaliplatin can be safely infused at a rate of 1mg/m<sup>2</sup>/min.
Authors: Andrea Cercek, Vivian Park, Rona D. Yaeger, Diane Lauren Reidy, Nancy E. Kemeny, Zsofia Kinga Stadler, Neil Howard Segal, Anna M. Varghese, Leonard Saltz
Journal: Journal of Clinical Oncology (2015)

e14665 Background: Shorter oxaliplatin infusion time would shorten overall treatment time, decompress crowded chemotherapy units, and improve patient satisfaction. Oxaliplatin at a dose of 85mg/m2 is administered over 120 minutes in the standard FOLFOX regimen. An alternative regimen is CapeOx (capecitabine plus oxaliplatin) in which the dose of oxaliplatin is 130mg/m2, also infused over 120 minutes. Not shortening the length of oxaliplatin infusion has been based in large part on concern for hypersensitivity reactions (HSRs) if infused too quickly. Methods: We first reviewed our institutional experience to assure that the rates of HSR were not increased in the Cape Ox regimen, using computerized pharmacy records to identify all patients who received oxaliplatin at our institution between January 1, 2011 and December 31, 2013. Our institutional (pharmacy) adverse drug reporting program was used to identify all HSRs. We then instituted a new policy, as a quality improvement initiative, to infuse all non-research doses of oxaliplatin at a set rate of 1mg/m2/min. The incidence of HSRs with the new infusion rate was actively monitored. An IRB waiver was obtained to review and report the outcomes. Results: Of the 2097 unique patients retrospectively reviewed who had previously received oxaliplatin over 120 minutes, 1936 had received a dose of 85mg/m2 (+/- 10%) and 161 at a dose of 130mg/m2. The incidence of HSRs in the 85 mg/m2 group was 11% vs 7% in the 130 mg/m2 (faster infusion rate) group. For simplicity, we rounded 130mg/m2 over 120 minutes to a rate of 1 mg/m2/min. Then, between Dec 1, 2014 and Jan 23, 2015, 326 unique patients received oxaliplatin, with all doses given at a rate of 1mg/m2/min. The incidence of HSR in patients treated at this fixed infusion rate was 4.6%. Conclusions: Infusing oxaliplatin at a rate of 1mg/m2/min does not increase the rate of HSRs and does not compromise patient safety. Updated data on a six month large volume experience will be presented at the meeting.
Abstract 3552: Abnormal Glucose Regulation is Associated with Lipid-Rich Plaque: Involvement of Insulin Resistance
Authors: Tetsuya Amano, Tatsuaki Matsubara, Tadayuki Uetani, Michio Nanki, Nobuyuki Marui, Masataka Kato, Kosuke Arai, Kiminobu Yokoi, Hirohiko Ando, Soichiro Kumagai, Hideki Ishii, Hideo Izawa, Toyoaki Murohara
Journal: Circulation (2007)

Background:  Abnormal glucose tolerance (AGT) has emerged an important determinant of cardiovascular risk. We hypothesized that AGT would be associated with coronary plaque instability.   Methods:  Conventional and integrated backscatter intravascular ultrasound (IB-IVUS) using 40-MHz (motorized pullback 0.5mm/s) intravascular catheter was performed to 153 consecutive patients with 358 coronary lesions. The percentage of fibrous area (% FA) and the percentage of lipid area (% LA) were automatically calculated by IB-IVUS system. Following the WHO criteria, the subjects were classified into the diabetic group, the impaired glucose tolerance (IGT) group, and the normal glucose tolerance group. We defined the cut-off point for the lipid-rich plaque as % LA>44 % or % FA th  percentile of % LA or the 25 th  percentile of % FA in this study population. Insulin resistance (IR) was defined as the homeostasis model assessment of IR (HOMA-IR).   Results:  There were no significant differences in the baseline characteristics except for HOMA-IR, and in the conventional IVUS parameters among the three groups. In the IB-IVUS analysis, as compared with the normal glucose tolerance group, the diabetic group and the IGT group showed a significant increase in % LA (35 ± 16 %, p=0.005 and 36 ± 19 %, p=0.006 vs. 29 ± 16 %) and a significant decrease in % FA (60 ± 14 %, p=0.003 and 59 ± 15 %, p=0.004 vs. 65 ± 12 %). The lipid-rich plaque rate was significantly associated with an increasing HOMA-IR in the tertile (p ANOVA=0.008). On logistic regression analysis after adjusting for confounding and coronary risk factors, HOMA-IR (>3.4) was significantly associated with the lipid-rich plaque (OR 1.79, 95% CI 1.03–3.13, p=0.04).   Conclusions:  Coronary lesions in patients with AGT are associated with lipid-rich plaque, which might be on the basis of the increased IR in these patients.
Abstract 147: Glucagon-like Peptide-1 Receptor Activation Reverses Cardiac Mitochondrial Remodeling In Advanced Type 2 Diabetes Via Suppression Of Nox4.
Authors: Akio Monji, Yasuko K Bando, Toko Mitsui, Morihiko Aoyama, Haruya Kawase, Toyoaki Murohara
Journal: Circulation Research (2013)

PURPOSE: Damaged cardiac mitochondria are one of the critical features of diabetic cardiomyopathy. We indeed demonstrated that diet-induced type 2 diabetes mellitus (T2DM) exhibited cardiac mitochondria remodeling, which were reversed by glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex4) (submitted as another abstract to BCVS 2013); however, it remains unclear whether the mitochondrial remodeling induced by diabetes may be reversible even at an advanced disease stage and Ex4 may be strong enough to exhibit the cardioprotective effects on such a progressive T2DM. Methods and Results: Genetic T2DM model (KKAy mice of which casual blood glucose levels is more than 30 mmol/L) were allocated into exendin-4 (Ex4, 24 nmole/kg/day for 40 days; KK-Ex4) and vehicle groups (KK-v). In KK-v, their systolic left-ventricular (LV) function was normal range, whereas they exhibited diastolic LV dysfunction and myocardial hypertrophy, which were ameliorated by Ex4. Myocardial fibrosis and cardiac steatosis (detected by Oil-red-O-staining and anti-ceramide antibody) were reduced in KK-ex4. Transmission electron microscopy revealed that Ex-4 normalized cardiac mitochondrial remodeling in terms of morphology, size, and number observed in KK-v. Ex4 attenuated mitochondrial damage which was detected by its specific dye mitotracker-red and alternatively monitored by mitofusin (Mfn)1/Mfn2 ratio. DHE staining revealed that Ex-4 reduced cardiac oxidative stress observed in KK-v. Ex4 modulated cardiac oxidative stress balance by reduction of NOX4 level; whereas it had no influence on NOX2 level and antioxidative molecules (SOD, thioredoxin, glutathione peroxidase), contrarily to those cases observed in diet-induced T2DM heart. Conclusions: Mitochondrial remodeling induced by T2DM was found to be reversible even at an advanced disease stage and Ex4 was strong enough to exhibit the cardioprotective effects on such a progressive T2DM by attenuating cardiac oxidative stress, at least in part, by suppression of NOX4.
Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From Neurofibromatosis Type 2–Associated Vestibular Schwannomas
Authors: Jaishri O. Blakeley, Xiaobu Ye, Dan G. Duda, Chris F. Halpin, Amanda L. Bergner, Alona Muzikansky, Vanessa L. Merker, Elizabeth R. Gerstner, Laura M. Fayad, Shivani Ahlawat, Michael A. Jacobs, Rakesh K. Jain, Christopher Zalewski, Eva Dombi, Brigitte C. Widemann, Scott R. Plotkin
Journal: Journal of Clinical Oncology (2016)

Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VSs) resulting in deafness and brainstem compression. This study evaluated efficacy and biomarkers of bevacizumab activity for NF2-associated progressive and symptomatic VSs.Bevacizumab 7.5 mg/kg was administered every 3 weeks for 46 weeks, followed by 24 weeks of surveillance after treatment with the drug. The primary end point was hearing response defined by word recognition score (WRS). Secondary end points included toxicity, tolerability, imaging response using volumetric magnetic resonance imaging analysis, durability of response, and imaging and blood biomarkers.Fourteen patients (estimated to yield > 90% power to detect an alternative response rate of 50% at alpha level of 0.05) with NF2, with a median age of 30 years (range, 14 to 79 years) and progressive hearing loss in the target ear (median baseline WRS, 60%; range 13% to 82%), were enrolled. The primary end point, confirmed hearing response (improvement maintained ≥ 3 months), occurred in five (36%) of 14 patients (95% CI, 13% to 65%; P < .001). Eight (57%) of 14 patients had transient hearing improvement above the 95% CI for WRS. No patients experienced hearing decline. Radiographic response was seen in six (43%) of 14 target VSs. Three grade 3 adverse events, hypertension (n = 2) and immune-mediated thrombocytopenic purpura (n = 1), were possibly related to bevacizumab. Bevacizumab treatment was associated with decreased free vascular endothelial growth factor (not bound to bevacizumab) and increased placental growth factor in plasma. Hearing responses were inversely associated with baseline plasma hepatocyte growth factor (P = .019). Imaging responses were associated with high baseline tumor vessel permeability and elevated blood levels of vascular endothelial growth factor D and stromal cell-derived factor 1α (P = .037 and .025, respectively).Bevacizumab treatment resulted in durable hearing response in 36% of patients with NF2 and confirmed progressive VS-associated hearing loss. Imaging and plasma biomarkers showed promising associations with response that should be validated in larger studies.
Review of<i>Manual of Botulinum Toxin Therapy, 2nd ed</i>
Authors: Krishnan Padmakumari Sivaraman Nair
Journal: JAMA Neurology (2016)

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Effects of thermoresponsivity and softness on skin penetration and cellular uptake of polyglycerol-based nanogels
Authors: Fiorenza Rancan, Mazdak Asadian-Birjand, Serap Dogan, Christina Graf, Luis Cuellar, Stefanie Lommatzsch, Ulrike Blume-Peytavi, Marcelo Calderón, Annika Vogt
Journal: Journal of Controlled Release (2016)