tbuckley/cabot-search huggingface dataset:
Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM).
Authors: Omid Hamid, Jeffrey Alan Sosman, Donald P. Lawrence, Ryan J. Sullivan, Nageatte Ibrahim, Harriet M. Kluger, Peter D. Boasberg, Keith Flaherty, Patrick Hwu, Marcus Ballinger, Ahmad Mokatrin, Marcin Kowanetz, Daniel S. Chen, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2013)

9010 Background: mM is an immunotherapy responsive disease where PD-L1 overexpression is prevalent. MPDL3280A, a human monoclonal antibody containing an engineered Fc-domain designed to optimize efficacy and safety, targets PD-L1, blocking PD-L1 from binding its receptors, including PD-1 and B7.1. Initial antitumor activity observed during dose escalation supported further expansion in mM with MPDL3280A as monotherapy and in combination with targeted therapy. Methods: Pts with mM of any histologic subtype received MPDL3280A administered IV q3w for up to 1 y. Objective response rate (ORR) was assessed by RECIST v1.1. Reported ORR includes u/cCR and u/cPR. In addition, a separate Ph 1b was initiated to evaluate the safety and efficacy of MPDL3280A with vemurafenib (vem) in pts with BRAF-V600 mutated mM. Results: As of Jan 10, 2013, 45 mM pts were treated at ≤1 (n=4), 10 (n=10), 25 (n=20) and 20 mg/kg (n=11) and evaluable for safety. Median pt age was 63 y (range 21-83 y), 100% were PS 0-1, 91% had prior surgery and 64% received prior systemic therapy. Pts received MPDL3280A treatment for a median duration of 127 days (range 1-282). The incidence of all G3/4 AEs, regardless of attribution, was 33%, including hyperglycemia (7%), elevated ALT (7%) and elevated AST (4%). No G3-5 pneumonitis was reported. No treatment-related deaths occurred on study. 35 mM pts who initiated treatment at doses of 1-20 mg/kg and enrolled prior to Jul 1, 2012, were evaluable for efficacy. An ORR of 26% (9/35) was observed, with all RECIST responses ongoing or improving. Further, some responding pts experienced tumor shrinkage within days of initial treatment. The 24-week PFS was 35%. Several additional pts had delayed antitumor activity after apparent radiographic progression and were counted as PD for the above analyses. Analysis of mandatory archival tumors showed a correlation between PD-L1 status and efficacy. Further, of three initial pts treated with MPDL3280A and vem, 2 experienced tumor shrinkage, including 1 CR. Conclusions: MPDL3280A was well tolerated as monotherapy, and durable ORs were observed. Therefore, further assessment of MPDL3280A as monotherapy and combination therapy is warranted. Clinical trial information: NCT01375842.
Inconsistent Approaches to Research Involving Cognitively Impaired Adults: Why the Broad View of Substituted Judgment Is Our Best Guide
Authors: Mark Yarborough
Journal: The American Journal of Bioethics (2015)

"Inconsistent Approaches to Research Involving Cognitively Impaired Adults: Why the Broad View of Substituted Judgment Is Our Best Guide." The American Journal of Bioethics, 15(10), pp. 66–67
The Relationship of Early Maternal Separation to Borderline Personality in Children and Adolescents: A Pilot Study
Authors: Susan J. Bradley
Journal: American Journal of Psychiatry (1979)

The author compared 14 child and adolescent borderline patients, diagnosed by the criteria of Gunderson and Singer (1), with a control population for history of separation from the mother or significant caretaker before age 10. The borderline patients experienced a statistically greater number of separations than the psychotic controls, the nonpsychotic psychiatric controls, and the nonpsychiatrically-referred delinquent controls before age 5 but not between ages 5 and 10. The author concludes that the study provides statistical support for the theoretic role of disruption of the early infant-mother bond in borderline pathology.
Cardiac Troponin and Risk Stratification in Ischemic Heart Disease
Authors: Chiara Melloni, Matthew T. Roe
Journal: New England Journal of Medicine (2015)

Early, first-generation and second-generation cardiac troponin assays were shown to improve the accuracy of the diagnosis of acute myocardial infarction and enhance the risk stratification of patients with suspected ischemic symptoms by means of a more precise identification of myocardial necrosis.1,2 The first universal definition of myocardial infarction, published in 2000, defined laboratory thresholds for the designation of elevated cardiac troponin values to clarify the diagnosis of myocardial infarction in a patient with suspected myocardial ischemia.3 In a similar fashion, the guidelines for unstable angina and non–ST-segment elevation myocardial infarction in the United States and Europe incorporated cardiac troponin . . .
Abstract 2373: Diet Plus Pravastatin Treatment Reduces The Risk Of Cardiovascular Disease And Total Mortality In Patients With Metabolic Syndrome: Sub-analysis From A Large-scale Primary Prevention Trial With Pravastatin (MEGA Study)
Authors: Teruhiko Matsushima, Susumu Koseki, Haruo Nakamura
Journal: Circulation (2007)

Background: The metabolic syndrome is related to an increased risk of cardiovascular disease (CVD), as reported by numerous studies. In this analysis, we investigated the relationship between the metabolic syndrome (MetSyn) and CVD risk in hypercholesterolemic patients and the effect of pravastatin treatment in the MEGA Study population. Methods: The MetSyn was defined according to modified National Cholesterol Education Program (NCEP) criteria, namely, the presence of three or more risk factors: 1)obesity (body mass index ≥25 kg/m 2 ), 2)hypertriglyceridemia (≥150 mg/dL), 3)low HDL cholesterol (&lt;40 mg/dL in men and &lt;50 mg/dL in women), 4)hypertension (SBP≥130 mmHg and/or DBP≥85 mmHg), 5)hyperglycemia (fasting glucose ≥100 mg/dL). The risk of CVD and total mortality was compared in patients with and without MetSyn. The effect of pravastatin plus diet therapy in the patients with MetSyn was compared to those without MetSyn, and moreover these comparisons were conducted in two groups, divided according to their LDL cholesterol levels (cut point: 156.9 mg/dL). Results: A total of 2,636 (33.7%) of the 7,832 hypercholesterolemic patients enrolled in MEGA had MetSyn. A 1.9 times higher incidence of CVD was found in the patients with, compared to those without, MetSyn. The risk of CVD in patients with MetSyn was very similar to that in patients with high LDL cholesterol (≥156.9 mg/dL) and with low LDL cholesterol (&lt;156.9 mg/dL). Notably, a 36% significant risk reduction for CVD and 50% risk reduction for total mortality were observed in the patients with MetSyn treated with pravastatin plus diet treatment compared to diet therapy alone. Moreover, the greatest CVD risk reduction was observed in the high LDL-C group with MetSyn compared to those without MetSyn (Hazard ratio 0.44 vs. 0.56, respectively, interaction p=0.07). Conclusion: Metabolic syndrome increases the risk of CVD regardless of the presence or absence of hypercholesterolemia. Diet plus pravastatin treatment is effective for the prevention of CVD for patients with hypercholesterolemia and MetSyn.
Neonatal invasive fungal infection in England 2004–2010
Authors: C. Oeser, S. Vergnano, R. Naidoo, M. Anthony, J. Chang, P. Chow, P. Clarke, N. Embleton, N. Kennea, S. Pattnayak, B. Reichert, T. Scorrer, I. Tiron, T. Watts, M. Sharland, P.T. Heath
Journal: Clinical Microbiology and Infection (2014)
Mayo clinic gastroenterology and hepatology board review
Authors: Stephen C. Hauser, Darrell S. Pardi, John J. Poterucha
Journal: Hepatology (2004)

The Mayo Clinic Gastroenterology and Hepatology Board Review has been designed to provide a review of core essential knowledge in gastroenterology, hepatology, and relevant related areas of radiology, pathology, endoscopy, and nutrition. Clinical knowledge to enhance patient management, rather than the latest scientific advances, is emphasized. For those preparing for their board examination, certification or recertification, case-based presentations and numerous board examination-type single best-answer questions with annotated answers are provided, and abundant figures, images and tables are also included.
Electron microscopic analysis of asbestos body cores from the Belgian urban population
Authors: E Moulin, N Yourassowsky, P Dumortier, P De Vuyst, JC Yernault
Journal: European Respiratory Journal (1988)

Typical ferruginous bodies considered as asbestos bodies (AB) were collected from the lungs of 19 asbestos-exposed and 25 non-exposed urban subjects. Of the 319 body cores analysed by energy dispersive spectrometry (EDS), 315 were asbestos. The non-asbestos cores were talc and crystalline silica. 89.2% of the asbestos cores were commercial amphiboles (amosite/crocidolite), 7% were chrysotile and 3.8% were non-commercial amphiboles (anthophyllite/tremolite). The commercial amphibole bodies were found in exposed and non-exposed subjects and chrysotile bodies mostly in exposed subjects. The non-commercial amphibole bodies were detected in non-exposed patients with low lung AB levels; this background contamination would be more difficult to detect in lungs containing large amounts of bodies due to occupational exposure. Chrysotile bodies and tremolite/anthophyllite bodies were not observed together. We suggest that in Belgium the source of non-commercial amphiboles exposure is not contamination by chrysotile.
Randomized trial assessing the addition of interferon alpha-2a to fluorouracil and leucovorin in advanced colorectal cancer. Colorectal Cancer Working Party of the United Kingdom Medical Research Council.
Authors: M T Seymour, M L Slevin, D J Kerr, D Cunningham, R D James, J A Ledermann, T J Perren, W A McAdam, P G Harper, J P Neoptolemos, M Nicholson, A M Duffy, R J Stephens, S P Stenning, I Taylor
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine the effects of interferon alpha-2a (IFN alpha) on the efficacy and toxicity of fluorouracil (FUra) and leucovorin (LV) in patients with advanced colorectal cancer. PATIENTS AND METHODS Two hundred sixty chemotherapy-naive patients were randomized to FUra/LV alone or FUra/LV plus IFN alpha. All patients received: LV 200 mg/m2 intravenous (IV) infusion over 2 hours, then FUra 400 mg/m2 i.v. bolus plus 400 mg/m2 i.v. infusion over 22 hours, all repeated on day 2. Treatment was every 2 weeks for up to 12 cycles. Patients randomized to IFN alpha received 6 x 10(6) IU subcutaneously every 48 hours throughout. Objective response (OR) and toxicity were assessed conventionally; in addition, palliative benefit and adverse effects were assessed using quality-of-life (QoL) questionnaires. RESULTS There were no differences in OR rate, progression-free survival, or overall survival. OR rates in assessable patients were as follows: FUra/LV alone (n = 104), complete or partial response (OR) = 27%, no change (NC) = 34%; FUra/LV/IFN alpha (n = 101), OR = 28%, NC = 30%. Median survival was 10 months in both arms. Dose-limiting FUra toxicities were not significantly increased by co-administration of IFN alpha, and the delivered FUra dose-intensity was not significantly reduced. However, QoL was adversely affected: patients on IFN alpha were less likely to report improvement in pretreatment physical and psychologic symptoms, and more likely to report new or worsening symptoms. CONCLUSION IFN alpha, at a dose that impaired QoL, did not improve the efficacy of FUra/LV. The power of this trial is sufficient to exclude with 95% confidence a benefit of 15% in OR or 10 weeks in median survival. Accordingly, we cannot recommend the use of IFN alpha as a clinical modulator of FUra/LV in the treatment of advanced colorectal cancer.
How important are the common factors in psychotherapy? An update
Authors: Bruce E. Wampold
Journal: World Psychiatry (2015)

The common factors have a long history in the field of psychotherapy theory, research and practice. To understand the evidence supporting them as important therapeutic elements, the contextual model of psychotherapy is outlined. Then the evidence, primarily from meta‐analyses, is presented for particular common factors, including alliance, empathy, expectations, cultural adaptation, and therapist differences. Then the evidence for four factors related to specificity, including treatment differences, specific ingredients, adherence, and competence, is presented. The evidence supports the conclusion that the common factors are important for producing the benefits of psychotherapy.
Abstract 2218: Impact of Low Molecular Weight Heparin on Bleeding, Need for Transfusion and 6-month Survival in Elderly Patients (75 years of age or older) with Acute Myocardial iInfarction. Data from the FAST-MI Registry of the French Society of Cardiology.
Authors: Eric Durand, François Schiele, Tabassome Simon, Jean-Philippe Godenir, Jean-Pierre Cambou, Xavier Tabone, Geneviève Mulak, Nicolas Danchin
Journal: Circulation (2007)

There are conflicting results as regards the impact of low molecular weight heparin (LMWH) on bleeding and mortality in elderly patients. Aim: to compare in-hospital mortality in pts with AMI according to type of heparin used. Methods: FAST-MI is a nationwide French registry carried out over a one-month period in the fall 2005, including consecutive pts with AMI admitted to CCUs =75 years and had received heparin therapy. Of those, 301 received unfractionated heparin (UFH) only, 398 LMWH only and 185 both UFH and LMWH. UFH only patients were slightly older (83 vs 82 years, p&lt;0.01) and patients on LMWH only more often had NSTEMI: 65% vs 55% (UFH) and 50% (UFH+LMWH), p&lt;0.01). Major bleeding was found in 6.3% (UFH), 2.3% (LMWH) and 2.7% (UFH+LMWH) (p&lt;0.02). Blood transfusion was used in 10% (UFH), 4.8% (LMWH) and 4.3% (UFH+LMWH) (p&lt;0.01). After x-variate adjustment, compared with UFH only, the need for transfusion was significantly lower (p&lt;0.03) for LMWH OR=0.45 (95%CI: 0.25–0.85) and for UFH+LMWH OR=0.44 (0.19–1.01) and major bleeding was also reduced (OR=0.39; 95%CI: 0.17–0.89, for LMWH and OR=0.47; 95%CI: 0.17–1.31, for UFH+LMWH). Six-month survival was 73% for UFH, 85% for LMWH and 82% for UFH+LMH (p&lt;0.001, Figure ). Using Cox x-variate analysis, use of LMWH remained associated with improved 6-month survival: OR=0.65 (95%CI: 0.46–0.92) for LMWH alone, and OR=0.69 (95%CI: 0.45–1.05) for UFH+LMWH, in comparison with UFH alone. Conclusion: in a “real world” population hospitalised for AMI, the use of LMWH was associated with a reduced risk of bleeding complications and improved survival.
The Benefit of Heparin Reversal With Protamine During Carotid Endarterectomy
Authors: Claudio Baracchini, Enzo Ballotta
Journal: JAMA Surgery (2015)

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Bone mineral density and inflammatory and bone biomarkers after darunavir–ritonavir combined with either raltegravir or tenofovir–emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial
Authors: Jose I Bernardino, Amanda Mocroft, Patrick W Mallon, Cedrick Wallet, Jan Gerstoft, Charlotte Russell, Peter Reiss, Christine Katlama, Stephane De Wit, Laura Richert, Abdel Babiker, Antonio Buño, Antonella Castagna, Pierre-Marie Girard, Genevieve Chene, Francois Raffi, Jose R Arribas
Journal: The Lancet HIV (2015)
Pilot Study of Low-Dose Interleukin-11 in Patients With Bone Marrow Failure
Authors: Razelle Kurzrock, Jorge Cortes, Deborah A. Thomas, Sima Jeha, Susan Pilat, Moshe Talpaz
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Interleukin-11 (IL-11) is a thrombopoietic cytokine that attenuates postchemotherapy thrombocytopenia at doses of 50 μg/kg/d subcutaneously. Very little is known about the activity of IL-11 in patients with bone marrow failure states. PATIENTS AND METHODS: Our preliminary experience with IL-11 at doses of 50 μg/kg/d suggested that patients with bone marrow failure developed significant peripheral and pulmonary edema after the prolonged dosing necessary for treating these conditions. We, therefore, initiated a study of low-dose IL-11 (starting dose, 10 μg/kg/d). RESULTS: Sixteen patients were assessable for response. Six patients had diploid cytogenetics; the others had a variety of chromosomal abnormalities. Six (38%) of 16 patients showed a platelet response to IL-11, and two had a multilineage response (to IL-11 alone, n = 1; to IL-11 plus G-CSF and erythropoietin, n = 1). The median increase in peak platelet counts was 95 × 10 9 /L above baseline in the responders (range, increase of 55 × 10 9 /L to 130 × 10 9 /L above baseline). Responders included five of 11 patients with myelodysplasia and one of four patients with aplastic anemia. Response durations were 12, 13, 14+, 25, 30, and 30+ weeks. Side effects of IL-11 were mild (peripheral edema, n = 7; conjunctival injection, n = 7; myalgia, n = 1; all grade 1). Seven patients had no side effects. CONCLUSION: Our pilot study suggests that administration of low-dose IL-11 (10 μg/kg/d) can raise platelet counts without significant toxicity in selected thrombocytopenic patients with bone marrow failure.
Abstract 16420: Human Cardiac Stem Cells (hCSCs) Carrying the Mother DNA Constitute a Novel Class of Resident Stem Cells With Markedly Superior Growth Reserve
Authors: Yingnan Bai, Donato Cappetta, Domenico D'Amario, Hanqiao Zheng, Caludia Fiorini, Alex Matsuda, Barbara Ogórek, James Kostyla, Virginia Caballero, Toru Hosoda, Fumihiro Sanada, David A D'Alessandro, Robert E Michler, Annarosa Leri, Roberto Bolli, Piero Anversa, Jan Kajstura
Journal: Circulation (2011)

Cell therapy for the failing heart requires recognition of the most powerful cell for myocardial regeneration. Here, we established whether hCSCs divide by symmetric and asymmetric DNA segregation,...
Patterns of Use of Chemotherapy for Breast Cancer in Older Women: Findings From Medicare Claims Data
Authors: Xianglin Du, James S. Goodwin
Journal: Journal of Clinical Oncology (2001)

PURPOSE: There is little population-based information available on the use of chemotherapy in women with breast cancer. This study describes the use of chemotherapy through analysis of Medicare claims and determines the correlates of chemotherapy use. PATIENTS AND METHODS: We used the merged Surveillance, Epidemiology, and End Results–Medicare database and identified women ≥ 65 years of age diagnosed with breast cancer in 1991 and 1992. Chemotherapy was ascertained from Medicare claims through procedure codes for chemotherapy made within 24 months of the diagnosis. RESULTS: In women with stages I, II, III, and IV breast cancer, the percentage receiving chemotherapy within 24 months of diagnosis was 5.1%, 19.5%, 33.9%, and 35.2%, respectively. Most women receiving chemotherapy had two to 12 claims; the median number was eight. Use of chemotherapy decreased significantly with age across all tumor stages; eg, in women with stage III cancer, the use of chemotherapy declined from 49% in those aged 65 to 69 years to 10% in those ≥ 80 years old. In a multivariate analysis, there was little variation by ethnicity. Chemotherapy use was highest (70%) in women aged 65 to 69 years with node-positive and estrogen receptor–negative tumors and lowest (5%) in those with node-negative and estrogen receptor–positive tumors. Compared with those without comorbid diseases, patients with a comorbidity score of 2 had significantly lower use of chemotherapy. CONCLUSION: Medicare claims data seem to provide valuable information on the use of chemotherapy for breast cancer in older women. However, external validation of the accuracy and completeness of these data is required before any firm conclusion can be drawn.
Air Pollution and Preterm Birth in the U.S. State of Georgia (2002–2006): Associations with Concentrations of 11 Ambient Air Pollutants Estimated by Combining Community Multiscale Air Quality Model (CMAQ) Simulations with Stationary Monitor Measurements
Authors: Hua Hao, Howard H. Chang, Heather A. Holmes, James A. Mulholland, Mitch Klein, Lyndsey A. Darrow, Matthew J. Strickland
Journal: Environmental Health Perspectives (2015)

Previous epidemiologic studies suggest associations between preterm birth and ambient air pollution.We investigated associations between 11 ambient air pollutants, estimated by combining Community Multiscale Air Quality model (CMAQ) simulations with measurements from stationary monitors, and risk of preterm birth (< 37 weeks of gestation) in the U.S. state of Georgia.Birth records for singleton births ≥ 27 weeks of gestation with complete covariate information and estimated dates of conception between 1 January 2002 and 28 February 2006 were obtained from the Office of Health Indicators for Planning, Georgia Department of Public Health (n = 511,658 births). Daily pollutant concentrations at 12-km resolution were estimated for 11 ambient air pollutants. We used logistic regression with county-level fixed effects to estimate associations between preterm birth and average pollutant concentrations during the first and second trimester. Discrete-time survival models were used to estimate third-trimester and total pregnancy associations. Effect modification was investigated by maternal education, race, census tract poverty level, and county-level urbanicity.Trimester-specific and total pregnancy associations (p < 0.05) were observed for several pollutants. All the traffic-related pollutants (carbon monoxide, nitrogen dioxide, PM2.5 elemental carbon) were associated with preterm birth [e.g., odds ratios for interquartile range increases in carbon monoxide during the first, second, and third trimesters and total pregnancy were 1.005 (95% CI: 1.001, 1.009), 1.007 (95% CI: 1.002, 1.011), 1.010 (95% CI: 1.006, 1.014), and 1.011 (95% CI: 1.006, 1.017)]. Associations tended to be higher for mothers with low educational attainment and African American mothers.Several ambient air pollutants were associated with preterm birth; associations were observed in all exposure windows.Hao H, Chang HH, Holmes HA, Mulholland JA, Klein M, Darrow LA, Strickland MJ. 2016. Air pollution and preterm birth in the U.S. state of Georgia (2002-2006): associations with concentrations of 11 ambient air pollutants estimated by combining Community Multiscale Air Quality Model (CMAQ) simulations with stationary monitor measurements. Environ Health Perspect 124:875-880; http://dx.doi.org/10.1289/ehp.1409651.