tbuckley/cabot-search huggingface dataset:
Systemic Medication Associations with Presumed Advanced or Uncontrolled Primary Open-Angle Glaucoma
Authors: Wei Zheng, Thaddeus P. Dryja, Zhongyuan Wei, Dongying Song, Haijun Tian, Kristijan H. Kahler, Anthony P. Khawaja
Journal: Ophthalmology (2018)

To identify associations between systemic medications and primary open-angle glaucoma (POAG) requiring a procedure using United States insurance claims data in a hypothesis-generating study.Database study.In total, 6130 POAG cases (defined as patients with POAG undergoing a glaucoma procedure) were matched to 30 650 controls (defined as patients undergoing cataract surgery but without a coded glaucoma diagnosis, procedure, or medication) by age, gender, and region of residence.Participant prescription drug use was calculated for the 5-year period before the glaucoma procedure or cataract surgery. Separately for individual generic drugs and drug classes, logistic regression was used to assess the association with POAG status. This was done across all generic drugs and drug classes that were prescribed in at least 1% of cases and controls. Analyses were adjusted for age, sex, region of residence, employment status, insurance plan type, and the total number of drugs prescribed.Odds ratio (OR) and 95% confidence intervals (CIs) for the association between each drug or drug class and POAG.The median age of participants was 72 years, and 52% were women. We tested for associations of POAG with 423 drug classes and 1763 generic drugs, resulting in a total of 2186 statistical tests and a Bonferroni-adjusted significance threshold of P < 2.3 × 10-5. Selective serotonin reuptake inhibitors (SSRIs) were strongly associated with a reduced risk of POAG (OR, 0.70; 95% CI, 0.64-0.76; P = 1.0 × 10-15); the most significant drug in this class was citalopram (OR, 0.66; 95% CI, 0.57-0.77; P = 1.2 × 10-7). Calcium channel blockers were strongly associated with an increased risk of POAG (OR, 1.26; 95% CI, 1.18-1.35; P = 1.8 × 10-11); the most significant drug in this class was amlodipine (OR, 1.27; 95% CI, 1.18-1.37; P = 5.9 × 10-10).We present data documenting potential associations of SSRIs and calcium channel blockers with POAG requiring a procedure. Further research may be indicated to better evaluate any associates of serotonin metabolism or calcium channels in glaucoma, or establish whether the associations are due to variations in the patterns for prescribing these drugs.
Bayesian randomized trial comparing intensity modulated radiation therapy versus passively scattered proton therapy for locally advanced non-small cell lung cancer.
Authors: Zhongxing X. Liao, J. Jack Lee, Ritsuko Komaki, Daniel Richard Gomez, Michael O'Reilly, Pamela Allen, Frank V. Fossella, John Heymach, George R. Blumenschein, Noah C. Choi, Thomas Delaney, Stephen M. Hahn, Charles Lu, James D Cox, Radhe Mohan
Journal: Journal of Clinical Oncology (2016)

8500 Background: We assessed rates of and time to treatment failure (TF) [either grade ≥ 3 radiation pneumonitis (RP) or local recurrence (LR) within 12 months] in a Bayesian randomized trial of intensity-modulated radiotherapy (IMRT) vs. 3D proton therapy (3DPT), both with concurrent chemotherapy, for locally advanced non-small cell lung cancer (NSCLC). Methods: Assumptions for chosen sample size (n = 150) were that TF rate is log-normally distributed; IMRT will produce TF rates of 30% at 6 months (mos) and 40% at 12 mos; and 3DPT would reduce the TF rate by 10%. Pairs of IMRT and 3DPT plans were created for each patient. Patients were eligible for randomization only if both plans satisfied normal tissue constraints at the same radiation dose. Patients not eligible for randomization (NR) were treated with the modality producing the better plan. Patients denied coverage for protocol treatment were treated with the modality that was covered. Results: Of 255 enrolled patients, 149 were randomly allocated to IMRT (n = 92) or 3DPT (n = 57), and 106 received NRIMRT (n = 70) or NR3DPT (n = 36). Among randomized patients, patient characteristics were well balanced, but in 3DPT group, target volumes were larger (P= 0.071), and more patients received higher doses to tumors and had larger lung volumes receiving ≥ 30-80 Gy (V30-80 ) than that in IMRT group. TF rates at 12 mo were 20.7% in all, 15.6% in IMRT, and 24.6% in 3DPT groups; corresponding median times to TF were 10.5 mos in all, in IMRT, and 3DPT groups. RP rates were 8.7% in all, 7.2% in IMRT, and 11.0% in 3DPT groups. The median times to RP were 4.3, 4.5, and 4.0 mos in all, in IMRT, and in 3DPT. The incidence of LR were 23.5%, 22.8%, and 24.6% in all, in IMRT, and in 3DPT. The median times to LR were 13.0, 12.7, and 13.4 mos in all, in IMRT, and in 3DPT. Among nonrandomized patients, the IMRT group was younger (P= 0.013) and had higher-stage disease (P= 0.071); lung V20-40 was significantly lower in NR-3DPT patients, but was not different at other dose levels. The TF rates and time to TF were no different for NR-IMRT vs. NR-3DPT. Conclusions: No differences were found between IMRT vs. 3DPT in TF in this randomized trial. Clinical trial information: NCT00915005.
Clinical response observed in a phase I study in T cell lymphoma patients treated with anti-CD70 SIMPLE Antibody ARGX-110.
Authors: Jean-Marie Michot, Marie Maerevoet, Philippe Georges Aftimos, Sylvie Rottey, Christian Diego Rolfo, Fritz Offner, Luc Van Rompaey, Mahan Moshir, Hans de Haard, Karen Silence, Patrick Pauwels, Karen Zwaenepoel, Ahmad Awada, Dominique Bron, Vincent Ribrag
Journal: Journal of Clinical Oncology (2016)

7556 Background: Background: CD70 is a cell surface marker transiently expressed on activated B, T and dendritic cells. The interaction via its receptor CD27 results in survival, proliferation and lymphocyte differentiation. CD70 is chronically overexpressed in several hematological malignancies, often concomitantly with CD27, thereby mediating proliferation and survival of malignant cells. Immunohistochemistry on TCL patient samples confirmed overexpression of CD70 ( > 10% CD70+ tumor cells) in 40/73 PTCL (55%) and 15/21 CTCL (71%) samples. In 68% of these samples CD70 and CD27 were simultaneously expressed. Serum soluble CD27 levels were elevated compared to healthy subjects (670 ± 1096 vs 192 ± 44 IU/ml, respectively). ARGX-110 is a novel monoclonal antibody targeting and blocking CD70. ARGX-110 is glycoengineered and has potent effector functions (CDC, ADCP and enhanced ADCC). Methods: A phase I trial was initiated with ARGX-110, dose escalated to investigate safety, clinical pharmacology and determine the RP2D, in patients with CD70+ metastatic relapsed or refractory solid tumors and hematological malignancies. ARGX-110 was given at doses from 0.1 to 10 mg/kg IV every 3W. Results: 9 TCL patients were treated with ARGX-110 (3 Cutaneous TCL (CTCL) and 6 Peripheral TCL (PTCL)). 4/9 patients showed signal of activity. 2 patients with Sézary syndrome (treated at 0.1 and 10 mg/kg, respectively) had a > 90% reduction in the circulating malignant clone. Resolution of auto-immune hemolytic anemia, with concomitant reduction of LDH levels and increased Hb levels, was observed in 1 patient with AITL (5 mg/kg dose). This patient also reached radiological PR. Partial response in the skin, with a duration of > 5 months, was observed in one patient with Sézary syndrome (0.1 mg/kg) and in one patient with CTCL TFH lymphoma (TFH L; 5 mg/kg, received 14 doses, still on study). Conclusions: In the TCL patients treated with ARGX-110, we observed a biological and/or clinical response in 4/9 patients. These results support further investigation of ARGX-110 in TCL. Clinical trial information: NCT01813539.
Early season co-circulation of influenza A(H3N2) and B(Yamagata): interim estimates of 2017/18 vaccine effectiveness, Canada, January 2018
Authors: Danuta M Skowronski, Catharine Chambers, Gaston De Serres, James A Dickinson, Anne-Luise Winter, Rebecca Hickman, Tracy Chan, Agatha N Jassem, Steven J Drews, Hugues Charest, Jonathan B Gubbay, Nathalie Bastien, Yan Li, Mel Krajden
Journal: Eurosurveillance (2018)

Using a test-negative design, we assessed interim vaccine effectiveness (VE) for the 2017/18 epidemic of co-circulating influenza A(H3N2) and B(Yamagata) viruses. Adjusted VE for influenza A(H3N2), driven by a predominant subgroup of clade 3C.2a viruses with T131K + R142K + R261Q substitutions, was low at 17% (95% confidence interval (CI): -14 to 40). Adjusted VE for influenza B was higher at 55% (95% CI: 38 to 68) despite prominent use of trivalent vaccine containing lineage-mismatched influenza B(Victoria) antigen, suggesting cross-lineage protection.
Daratumumab Decreases Treg-Mediated Immunosuppression and Potentiates CD8+ T-Cell-Induced Killing of Chronic Lymphocytic Leukemia (CLL) Cells Ex Vivo
Authors: Alak Manna, Sharoon Akhtar, Paul Yi, Sameer A. Parikh, Wei Ding, Jose F. Leis, Victoria R. Alegria, Taimur Sher, Fabio Malavasi, Sikander Ailawadhi, Asher A. Chanan-Khan, Aneel Paulus
Journal: Blood (2017)
Metastatic Non-Uterine Leiomyosarcoma: Prognostic factors, Overall Survival and chemotherapy outcomes.
Authors: Sandra P. D'Angelo, Alexander Noor Shoushtari, Jonathan Landa, Deborah Kuk, Armando Jose Sanchez, Brittany Lala, Mark Andrew Dickson, Mrinal M. Gounder, Mary Louise Keohan, William D. Tap
Journal: Journal of Clinical Oncology (2015)

10574 Background: Non-uterine Leiomyosarcoma (LMS) is an aggressive, malignant tumor of mesenchymal origin whose natural history is poorly defined. We sought to evaluate clinical and treatment outcomes in patients (pts) with metastatic (met) disease. Methods: In a retrospective study using an institutional sarcoma database, we identified all pts with met non-uterine LMS treated at Memorial Sloan Kettering Cancer Center between 1983-2011 and collected their correlative clinical information.Kaplan-Meier method and Cox’s proportional-hazard models were used to determine overall survival (OS) from time of met and prognostic factors. Hazard ratios (HR) are listed with their 95% confidence intervals (CI). Objective responses to 1st chemotherapy were determined by RECIST 1.1. Results: We identified 214 pts: median age 56 (range 23-85), 80 (37%) male. Median OS was 2.6 years (yr) (range: 0.04-17 yr) with 14 yr of follow-up. Independent factors predictive of improved OS included age < 56, HR 0.70 (0.52-0.97) p = 0.03; primary tumor site in the retroperitoneum, HR 0.56 (0.34-0.93) p = 0.03; and < 3 met sites, HR 0.65 (0.47-0.9) p = .009. Most common regimens included anthracycline+alkylator (n = 47), gemcitabine-based regimens (n = 58), liposomal doxorubicin (dox) (n = 17) and dox (n = 15). Rates of complete response (CR) + partial response (PR), stable disease (SD), and progressive disease (PD) were 18%, 56% and 25%, respectively. Pts with CR/PR and SD had improved OS compared to those with PD, HR 0.25 (0.13-0.49, p < 0.001) and HR 0.46 (CI 0.28-0.76) p = 0.002, respectively. Regimen type did not impact OS. Conclusions: LMS is an aggressive malignancy with poor prognosis. Age < 56, primary tumors arising in the retroperitoneum and < 3 met sites were associated with improved OS. Patients with CR/PR/SD to first line chemotherapy had improved OS regardless of type of chemotherapy used. Molecular analysis of select pts with long-term OS may be warranted
Diagnosis and management of pemphigus: Recommendations of an international panel of experts
Authors: Dedee F. Murrell, Sandra Peña, Pascal Joly, Branka Marinovic, Takashi Hashimoto, Luis A. Diaz, Animesh A. Sinha, Aimee S. Payne, Maryam Daneshpazhooh, Rüdiger Eming, Marcel F. Jonkman, Daniel Mimouni, Luca Borradori, Soo-Chan Kim, Jun Yamagami, Julia S. Lehman, Marwah Adly Saleh, Donna A. Culton, Annette Czernik, John J. Zone, David Fivenson, Hideyuki Ujiie, Katarzyna Wozniak, Ayşe Akman-Karakaş, Philippe Bernard, Neil J. Korman, Frédéric Caux, Kossara Drenovska, Catherine Prost-Squarcioni, Snejina Vassileva, Ron J. Feldman, Adela Rambi Cardones, Johann Bauer, Dimitrios Ioannides, Hana Jedlickova, Francis Palisson, Aikaterini Patsatsi, Soner Uzun, Savas Yayli, Detlef Zillikens, Masayuki Amagai, Michael Hertl, Enno Schmidt, Valeria Aoki, Sergei A. Grando, Hiroshi Shimizu, Sharon Baum, Guiseppe Cianchini, Claudio Feliciani, Pilar Iranzo, Jose M. Mascaró, Cezary Kowalewski, Russell Hall, Richard Groves, Karen E. Harman, M. Peter Marinkovich, Emanual Maverakis, Victoria P. Werth
Journal: Journal of the American Academy of Dermatology (2018)
Out-of-Pocket Spending and Premium Contributions After Implementation of the Affordable Care Act
Authors: Anna L. Goldman, Steffie Woolhandler, David U. Himmelstein, David H. Bor, Danny McCormick
Journal: JAMA Internal Medicine (2018)

The Affordable Care Act (ACA) was associated with a reduced number of Americans who reported being unable to afford medical care, but changes in actual health spending by households are not known.To estimate changes in household spending on health care nationwide after implementation of the ACA.Population-based data from the Medical Expenditure Panel Survey from January 1, 2012, through December 31, 2015, and multivariable regression were used to examine changes in out-of-pocket spending, premium contributions, and total health spending (out-of-pocket plus premiums) after the ACA's coverage expansions on January 1, 2014. The study population included a nationally representative sample of US adults aged 18 to 64 years (n = 83 431). In addition, changes were assessed in the likelihood of exceeding affordability thresholds for each outcome and spending changes for income subgroups defined under the ACA to determine program eligibility at 138% or less, 139% to 250%, 251% to 400%, and greater than 400% of the federal poverty level (FPL).Implementation of the ACA's major insurance programs on January 1, 2014.Mean individual-level out-of-pocket spending and premium payments and the percentage of persons experiencing high-burden spending, defined as more than 10% of family income for out-of-pocket expenses, more than 9.5% for premium payments, and more than 19.5% for out-of-pocket plus premium payments.In this nationally representative survey of 83 431 adults (weighted frequency, 49.1% men and 50.9% women; median age, 40.3 years; interquartile range, 28.6-52.4 years), ACA implementation was associated with an 11.9% decrease (95% CI, -17.1% to -6.4%; P < .001) in mean out-of-pocket spending in the full sample, a 21.4% decrease (95% CI, -30.1% to -11.5%; P < .001) in the lowest-income group (≤138% of the FPL), an 18.5% decrease (95% CI, -27.0% to -9.0%; P < .001) in the low-income group (139%-250% of the FPL), and a 12.8% decrease (95% CI, -22.1% to -2.4%; P = .02) in the middle-income group (251%-400% of the FPL). Mean premium spending increased in the full sample (12.1%; 95% CI, 1.9%-23.3%) and the higher-income group (22.9%; 95% CI, 5.5%-43.1%). Combined out-of-pocket plus premium spending decreased in the lowest-income group only (-16.0%; 95% CI, -27.6% to -2.6%). The odds of household out-of-pocket spending exceeding 10% of family income decreased in the full sample (odds ratio [OR], 0.80; 95% CI, 0.70-0.90) and in the lowest-income group (OR, 0.80; 95% CI, 0.67-0.97). The odds of high-burden premium spending increased in the middle-income group (OR, 1.28; 95% CI, 1.03-1.59).Implementation of the ACA was associated with reduced out-of-pocket spending, particularly for low-income persons. However, many of these individuals continue to experience high-burden out-of-pocket and premium spending. Repeal or substantial reversal of the ACA would especially harm poor and low-income Americans.
Breast cancer patients have different levels of endogenous CD8 T cells capable of recognizing a HER2/neu peptide (E75) used as a cancer vaccine in clinical trials
Authors: Jarrod Holmes, Asna Amin, Matthew Hueman, Steven Khoo, Catherine Storrer, Yusuf Jama, Anna Smith, Dianna Craig, Alexander Stojadinovic, Sathibalan Ponniah, George Peoples
Journal: Cancer Research (2007)

1860    Introduction:  We are currently conducting clinical trials with the HER2/ neu  E75 peptide vaccine in clinically disease-free node-positive (NP) and node-negative (NN) breast cancer (BrCa) patients. Administration of the E75 peptide with GM-CSF stimulates clonal expansion of E75-specific CD8 T cells. The purpose of this study is to determine the levels of pre-existing immunity to E75 in BrCa patients.   Methods:  Pre-vaccination peripheral blood samples were collected from a total of 63 (25 NP and 38 NN) BrCa patients. HLA-A2:Ig dimer molecules were loaded with the HER2/ neu  peptide E75 and were used with anti-TcR and anti-CD8 antibodies to stain peripheral blood leukocytes immediately ex vivo. Samples were analyzed by flow cytometry and dimer+, E75-specific T cells reported as % of total CD8 +  cells.   Results:  Both NP (60%) and NN (44.7%) BrCa patients have pre-existing immunity to E75 peptide. Levels of E75-specific CD8 T cells were higher in the NP group compared to the NN group (0.8% [range 0-2.6%] vs. 0.43% [range 0-3.28%], P=0.04). Compared to NN patients, NP patients also had larger tumors (40% ≥T2 vs. 13%, P=0.025) and were higher grade (52% grade 3 vs. 26%, P neu  overexpression. Thirteen (21%) of patients had very high levels of pre-exisiting immunity (defined as E75-specific T cells >1%). This group with high dimer levels had more NP patients (76.9 vs. 30%, P=0.01), more patients with primary tumor ≥T2 (53.8% vs. 18%, P=0.01) and fewer patients that exhibited HER2/ neu  overexpression (7.7% vs. 39.5%, P=0.05).   Conclusions  :  We demonstrate evidence of pre-existing immunity to the E75 peptide in disease-free NP and NN BrCa patients. NP patients have greater levels of specific immunity than NN patients. Increased immunity in the NP group may be due to increased antigenic exposure from the larger tumors, positive lymph nodes, and higher grade tumors in this group. More NP patients received chemotherapy, therefore, the higher level of dimer may also be explained by decreased regulatory T cells post-chemotherapy. As the level of E75-specific T cells increased, HER2/ neu  overexpression decreased, implying a degree of protective immunity conferred by the presence of specific HER2/ neu  immunity.
Oncogenic manipulation and biologic selection for complete tumorigenic transformation of immortalized normal human bronchial epithelial cells
Authors: Mitsuo Sato, Woochang Lee, Luc Girard, Ruben D. Ramirez, David S. Shames, Adi F. Gazdar, Jerry W. Shay, John D. Minna
Journal: Cancer Research (2006)

2850   Despite the causality between human smoking and lung cancer (IARC, 2004), establishing reproducible and validated animal inhalation models for lung cancer induced by tobacco smoking has proven difficult. Here we report on two mouse strains suggested as possible models for lung tumorigenicity. Male A/J mice and Swiss SWR mice were whole-body exposed to diluted mainstream smoke from the standard reference cigarette 2R4F or to filtered fresh air (control), 6 hours per day, 5 days per week for 5 months, followed by a post-exposure period of 4 months. Smoke exposure was to whole smoke at concentrations of 120 or 240 μg total particulate matter (TPM)/l, to gas phase-depleted particle phase at 240 μg TPM/l, or to gas phase at a carbon monoxide concentration equivalent to 240 μg TPM/l. Lung tumor incidence and multiplicity were determined in the control and 240 μg TPM/l whole smoke groups at the end of the exposure period and in all groups at the end of the post-exposure period. At the end of the 5-month exposure period, a severe increase in neutrophils and macrophages in bronchoalveolar lavage fluid, indicating inflammation, was seen in the whole smoke groups. By the end of the 4-month post-exposure period, both inflammatory cell types had returned nearly to background levels. At the end of the 5-month exposure period, there was no difference in lung tumor response between smoke-exposed and control mice in both mouse strains. An enhanced lung tumor response was seen only after the 4-month post-exposure period: lung tumor incidence and multiplicity in the whole smoke groups was dose-dependently higher compared to controls by a factor of up to approximately 3-fold in A/J mice and a factor of up to approximately 2-fold in Swiss SWR mice. In A/J mice the lung tumor response was similar for gas phase-depleted particle phase and whole smoke at the same TPM concentration. In Swiss SWR mice, gas phase-depleted particle phase accounted for approximately 50% of the lung tumor response in the whole smoke group at the same TPM concentration. Gas phase failed to enhance lung tumor incidence and multiplicity in both mouse strains compared to controls. Microscopic examination of lung step serial sectioning in selected groups confirmed the macroscopic lung nodule assessment. Smoke exposure did not change the spontaneous lung tumor spectrum; bronchiolo-alveolar adenoma was the most prominent lung tumor type. There appears to be a need for a post-exposure period to see an increase in lung tumor incidence and multiplicity in both mouse strains. Further research is needed to evaluate the relevance of these models with regard to the human disease.
Oxidized cellulose as hemostatic agent to prevent bleeding after high-risk endoscopic resection of rectal laterally spreading tumor overlying hemorrhoids
Authors: Seiichiro Abe, Alvaro Martinez-Alcalá, K. Baig, Yutaka Saito, Klaus Mönkemüller
Journal: Endoscopy (2018)

A 58-year-old man with a history of a hypertension, coronary heart disease, and diabetes mellitus type II was referred for evaluation of a rectal tumor. The patient had undergone coronary artery stenting and was taking dual antiplatelet therapy. On colonoscopy he was found to have a laterally spreading tumor, granular type. The polypoid lesion extended from the anal verge, continued on top of internal hemorrhoids, and extended proximally 5 cm into the rectum, covering about two-thirds of the rectal circumference. The patient preferred endoscopic resection to a transrectal surgery procedure.
Abstract 15270: Plasma Cyclophilin A as a Useful Biomarker for Evaluation of the Effects of Balloon Pulmonary Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Katsuya Kozu, Kimio Satoh, Toru Shimizu, Tatsuo Aoki, Shunsuke Tatebe, Saori Yamamoto, Haruka Sato, Tomohiro Ohtsuki, Ryo Konno, Satoshi Miyata, Koichiro Sugimura, Hiroaki Shimokawa
Journal: Circulation (2017)

Background: Balloon pulmonary angioplasty (BPA) significantly improves hemodynamics and survival in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, there is...
Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism
Authors: Mark Y. Jeong, Ying H. Lin, Sara A. Wennersten, Kimberly M. Demos-Davies, Maria A. Cavasin, Jennifer H. Mahaffey, Valmen Monzani, Chandrasekhar Saripalli, Paolo Mascagni, T. Brett Reece, Amrut V. Ambardekar, Henk L. Granzier, Charles A. Dinarello, Timothy A. McKinsey
Journal: Science Translational Medicine (2018)

The histone deacetylase inhibitor ITF2357 (givinostat) prevents diastolic dysfunction by enhancing cardiac myofibril relaxation.