bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Nephrotoxicity Associated with Once-Daily Administration of Aminoglycoside
Authors: Nodoushani Mojgan , Nicolau David P , Hitt Catherine M , Quintiliani Richard , Nightingale Charles H 
Published: July 2017

Objective: To determine the potential risk factors associated with nephrotoxicity in patients receiving once-daily aminoglycoside (ODA) therapy. Design: Case series. Setting: Large community teaching hospital. Patients: Twenty-five patients considered nephrotoxic during ODA therapy. Main Outcome Measures: This study is a retrospective chart review of patients in whom nephrotoxicity developed during ODA therapy. Nephrotoxicity was defined as a rise in serum creatinine (SCr) concentration of 0.5 mg/dL or more above the preaminoglycoside baseline value. Patients were identified from our institutional ODA database. Based on the previously identified risk factors for aminoglycoside-associated nephrotoxicity with conventional aminoglycoside therapy published by Bertino et al., a data collection tool was developed. Collected data included demographic information, concurrently administered drugs, diagnostic agents used, and potential comorbidity risk factors. Results: Similar to what has been found in patients receiving conventional aminoglycoside regimens, numerous risk factors, such as the concomitant use of cephalosporins, loop diuretics, intravenous contrast dye, angiotensin-converting enzyme inhibitors, and nonsteroidal antiinflammatory drugs, may have been responsible for the rise in SCr observed in our study population. In addition, common comorbidity risk factors in this population were pleural effusion, pneumonia, decrease in systolic blood pressure to less than 80 mm Hg, and preexisting renal disease. Conclusions: Nephrotoxicity is the result of multifactorial processes and is not solely due to the ODA administration technique.
Tissue-type plasminogen activator regulates macrophage activation and innate immunity
Authors: Mantuano Elisabetta , Azmoon Pardis , Brifault Coralie , Banki Michael A. , Gilder Andrew S. , Campana Wendy M. , Gonias Steven L. 
Published: July 2017

Key PointsTissue-type plasminogen activator inhibits the activity of the innate immune system in macrophages in vitro and in vivo in mice. Suppression of macrophage proinflammatory responses by tPA requires the NMDA receptor.
Joint analysis of left ventricular expression and circulating plasma levels of Omentin after myocardial ischemia
Authors: Saddic Louis A. , Nicoloro Sarah M. , Gupta Olga T. , Czech Michael P. , Gorham Joshua , Shernan Stanton K. , Seidman Christine E. , Seidman Jon G. , Aranki Sary F. , Body Simon C. , Fitzgibbons Timothy P. , Muehlschlegel Jochen D. 
Published: July 2017

Abstract
Background
Omentin-1, also known as Intelectin-1 (ITLN1), is an adipokine with plasma levels associated with diabetes, obesity, and coronary artery disease. Recent studies suggest that ITLN1 can mitigate myocardial ischemic injury but the expression of ITLN1 in the heart itself has not been well characterized. The purpose of this study is to discern the relationship between the expression pattern of ITLN1 RNA in the human heart and the level of circulating ITLN1 protein in plasma from the same patients following myocardial ischemia.

Methods
A large cohort of patients (n = 140) undergoing elective cardiac surgery for aortic valve replacement were enrolled in this study. Plasma and left ventricular biopsy samples were taken at the beginning of cardiopulmonary bypass and after an average of 82 min of ischemic cross clamp time. The localization of ITLN1 in epicardial adipose tissue (EAT) was also further characterized with immunoassays and cell fate transition studies.

Results
mRNA expression of ITLN1 decreases in left ventricular tissue after acute ischemia in human patients (mean difference 280.48, p = 0.001) whereas plasma protein levels of ITLN1 increase (mean difference 5.24, p < 0.001). Immunohistochemistry localized ITLN1 to the mesothelium or visceral pericardium of EAT. Epithelial to mesenchymal transition in mesothelial cells leads to a downregulation of ITLN1 expression.

Conclusions
Myocardial injury leads to a decrease in ITLN1 expression in the heart and a corresponding increase in plasma levels. These changes may in part be due to an epithelial to mesenchymal transition of the cells that express ITLN1 following ischemia.
Trial Registration Clinicaltrials.gov ID: NCT00985049
Automating the Determination of Prostate Cancer Risk Strata From Electronic Medical Records
Authors: Gregg Justin R. , Lang Maximilian , Wang Lucy L. , Resnick Matthew J. , Jain Sandeep K. , Warner Jeremy L. , Barocas Daniel A. 
Published: July 2017

Purpose Risk stratification underlies system-wide efforts to promote the delivery of appropriate prostate cancer care. Although the elements of risk stratum are available in the electronic medical record, manual data collection is resource intensive. Therefore, we investigated the feasibility and accuracy of an automated data extraction method using natural language processing (NLP) to determine prostate cancer risk stratum. Methods Manually collected clinical stage, biopsy Gleason score, and preoperative prostate-specific antigen (PSA) values from our prospective prostatectomy database were used to categorize patients as low, intermediate, or high risk by D’Amico risk classification. NLP algorithms were developed to automate the extraction of the same data points from the electronic medical record, and risk strata were recalculated. The ability of NLP to identify elements sufficient to calculate risk (recall) was calculated, and the accuracy of NLP was compared with that of manually collected data using the weighted Cohen’s κ statistic. Results Of the 2,352 patients with available data who underwent prostatectomy from 2010 to 2014, NLP identified sufficient elements to calculate risk for 1,833 (recall, 78%). NLP had a 91% raw agreement with manual risk stratification (κ = 0.92; 95% CI, 0.90 to 0.93). The κ statistics for PSA, Gleason score, and clinical stage extraction by NLP were 0.86, 0.91, and 0.89, respectively; 91.9% of extracted PSA values were within ± 1.0 ng/mL of the manually collected PSA levels. Conclusion NLP can achieve more than 90% accuracy on D’Amico risk stratification of localized prostate cancer, with adequate recall. This figure is comparable to other NLP tasks and illustrates the known tradeoff between recall and accuracy. Automating the collection of risk characteristics could be used to power real-time decision support tools and scale up quality measurement in cancer care.
Survival Disparities by Hospital Volume Among American Women With Gynecologic Cancers
Authors: Seagle Brandon-Luke L. , Strohl Anna E. , Dandapani Monica , Nieves-Neira Wilberto , Shahabi Shohreh 
Published: July 2017

Purpose We describe survival disparities among women with uterine, ovarian, or cervical cancer by cancer-specific mean annual hospital volume. Methods National Cancer Database 1998-2011 uterine (n = 441,863), ovarian (n = 223,017), and cervical (n = 146,698) cancer data sets were used. Cancer-specific mean annual hospital volumes were calculated. Overall survival (OS) was plotted by hospital volume using restricted mean OS times from Cox regression. Results Uterine, ovarian, and cervical cancers were reported from 1,651, 1,633, and 1,600 hospitals, respectively. Median values of mean annual hospital volumes among hospitals were 8.6 (interquartile range [IQR], 2.6 to 20.8), 4.4 (IQR, 1.4 to 10.3), and 2.4 (IQR, 0.6 to 6.6) for uterine, ovarian, and cervical cancers, respectively. Increased hospital volume was associated with increased OS among women with stage III to IV high-grade serous ovarian cancer, stage II to IV squamous or adenocarcinoma cervical cancer, and stage I to IV endometrioid, clear cell, serous, or carcinosarcoma uterine cancers (all P < .03). Differential OS between women treated at higher- versus lower-volume cancer centers exceeded 5, 5, and 13 months among women with advanced endometrial, ovarian, or cervical cancer, respectively (all P < .001). Hospital volume was not associated with OS among patients with stage II to IV cervical cancer treated with brachytherapy ( P = .17). Use of adjuvant therapies decreased OS disparities by hospital volume among women with advanced ovarian or endometrial cancer. Conclusion Increased delivery of brachytherapy for treatment of cervical cancer may decrease survival disparities by hospital volume. Standardization of adjuvant therapies may diminish survival disparities by hospital volume among women with advanced ovarian or endometrial cancer. In addition, survival of American women with gynecologic cancer may be increased by centralization of care.
Chart Review Versus an Automated Bioinformatic Approach to Assess Real-World Crizotinib Effectiveness in Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer
Authors: Bui Nam , Henry Solomon , Wood Douglas , Wakelee Heather A. , Neal Joel W. 
Published: July 2017

Purpose The efficacy of targeted therapies such as crizotinib in anaplastic lymphoma kinase–positive non–small-cell lung cancer has been well established by multiple clinical trials. However, clinical trials involve highly selected participants, and manual data curation is resource intensive. With the increasing use of electronic medical records, there is potential for the development of electronic algorithms that could quickly generate outcomes data, but the validation of such algorithms requires comparison with historical methods, such as retrospective chart review. Materials and Methods Using a cohort of patients with anaplastic lymphoma kinase–positive non–small-cell lung cancer, we performed manual chart review to retrospectively evaluate time on treatment (TOT) for crizotinib and cytotoxic chemotherapies. Thirty-three patients were identified, with a total of 70 regimens administered. We developed a computational algorithm to mine electronic charts for crizotinib therapy data and correlated that with manually curated data. Results Among the 24 patients who received crizotinib, the median TOT was 8.5 months. The computational algorithm was able to extract TOT data for 15 out of 24 patients treated with crizotinib (62.5%). Most of the patients for whom data could not be automatically extracted were treated within a clinical trial. Pearson’s correlation coefficient between the two methods was 0.39 ( P = .15); however, there were five outliers as a result of incorrect provider notation and nonstandard treatment patterns that severely skewed the correlation. Conclusion An automated method of extracting patient TOT is feasible but requires additional optimizations to handle outliers. We are currently working on improving the algorithm to better correct for outliers. Automated generation of treatment data potentially represents a viable approach to perform retrospective outcomes analysis.
Visualization of Cancer and Cardiovascular Disease Co-Occurrence With Network Methods
Authors: Duarte Christine W. , Lindner Volkhard , Francis Sanjeev A. , Schoormans Dounya 
Published: July 2017

Purpose Cancer and cardiovascular disease (CVD) are common causes of morbidity and mortality, and measurement and interpretation of their co-occurrence rate have important implications for public health and patient care. Here, we present the raw and adjusted co-occurrence rates of cancer and CVD in the overall population by using a visually intuitive network approach. Methods By using baseline survey and linked health outcome data from 490,842 individuals age 40 to 69 years from the UK Biobank, we recorded diagnoses between 1997 and 2014 of specific cancers and specific CVDs ascertained through hospital claims. We measured raw and adjusted rates of CVD for the following groups: individuals with Hodgkin or non-Hodgkin lymphoma, lung and trachea cancer, uterus cancer, colorectal cancer, prostate cancer, breast cancer, or no recorded diagnosed cancer during this time period. Analysis accounted for age, sex, and behavioral risk factors, without regard to the order of occurrence of cancer and CVD. Results A significantly increased rate of CVD was found in patients with multiple types of cancers, including Hodgkin and non-Hodgkin lymphoma and lung and trachea, uterus, colorectal, and breast cancer, compared with patients without cancer by using age and sex-adjusted models. Increased co-occurrence for many CVD categories remained after correction for behavioral risk factors. Construction of co-occurrence networks highlighted heart failure as a shared CVD diagnosis across multiple cancer types, including breast cancer, lung cancer, non-Hodgkin lymphoma, and colorectal cancer. Smoking, physical activity, and other lifestyle factors accounted for some but not all of the increased co-occurrence for many of the CVD diagnoses. Conclusion Increased co-occurrence of several common CVD conditions is seen widely across multiple malignancies, and shared diagnoses, such as heart failure, were highlighted by using network methods.
Epidemiologic Analysis Along the Mevalonate Pathway Reveals Improved Cancer Survival in Patients Who Receive Statins Alone and in Combination With Bisphosphonates
Authors: El-Refai Sherif M. , Brown Joshua D. , Arnold Susanne M. , Black Esther P. , Leggas Markos , Talbert Jeffery C. 
Published: July 2017

Purpose Cohort studies report associations between statin use and improved survival in patients with cancer. We used pharmacoepidemiologic methods to evaluate the survival of patients with cancer who received statins alone or in ostensibly synergistic drug combinations. Materials and Methods Patients with cancer who were diagnosed from 2010 to 2013 were identified in a large health care claims database. The rate of all-cause death up to 1 year after diagnosis was compared by Cox proportional hazard regression. Sensitivity analyses included age stratification, statin type and intensity, and comparison with or without bisphosphonates and dipyridamole. Results Among 312,907 identified patients with cancer, treatment groups included statin users (n = 65,440), nonstatin users who received medications that block cholesterol absorption (n = 9,289), and nonusers (n = 226,007). Statin use before diagnosis was associated with improved overall survival compared with no treatment (hazard ratio [HR], 0.85; 95% CI, 0.80 to 0.91) and specifically in patients with leukemia, lung, or renal cancers. Nonstatin users had increased overall survival compared with no treatment (HR, 0.73; 95% CI, 0.62 to 0.85); when stratified, this difference held true only for pancreatic cancer and leukemia. No differences were observed between statin and nonstatin groups. Bisphosphonate use alone had no effect (n = 4,528), but patients who used both statins and bisphosphonates (n = 4,090) had increased survival compared with no treatment (HR, 0.60; 95% CI, 0.45 to 0.81). The effect of the combination of dipyridamole and statin use (n = 651) was not significant compared with no treatment. Conclusion This study suggests that the combination of statins with drugs that affect isoprenylation, such as bisphosphonates, improves survival in patients with cancer. Consideration of pathway-specific pharmacology allows for hypotheses testing with the pharmacoepidemiologic approach. Prospective evaluation of these findings warrants clinical investigation and preclinical mechanistic studies.
Feasibility and Acceptability of a Web Site to Promote Survivorship Care in Survivors of Hodgkin Disease
Authors: Underhill Meghan L. , Hong Fangxin , Jones Tarsha , Sprunck-Harrild Kim , Walsh Sarah K. , Boyajian Richard , Berry Donna L. , Partridge Ann 
Published: July 2017

Purpose Evaluate rates of enrollment, completion, and patient-reported acceptability of an educational survivorship-care Web site for survivors of Hodgkin disease (HD). Patients and Methods The study was a mixed-method evaluation design. Eligible participants were adults who had completed treatment of a primary diagnosis of HD ≥ 2 years before enrollment. Patients were recruited through postal mail and telephone and were asked to review a Web site, complete an adapted version of the Acceptability E-scale (total score of 24 or greater indicates acceptability), and respond to a structured telephone or e-mail interview to discuss experiences with the Web site. Results Of 259 potentially eligible participants identified by medical record review, 124 survivors had confirmed contact with study staff and were invited to participate; 63 people (50.8%; 90% CI, 43% to 59%) enrolled; 37 participants (58.7%) were men. The median age at time of enrollment was 51.0 years (range, 29.3 to 80.0 years), and the median time since completion of treatment of HD was 14.9 years (range, 3 to 38.75 years). Overall, 82.5% of those enrolled viewed all Web site content. Forty-eight participants completed the acceptability survey, which resulted in a mean acceptability score of 26.5 (standard deviation, 3.5). The majority of enrollees (67%) completed a follow-up interview. Conclusion Overall, HD survivor participants viewed the content and reviewed it favorably. A Web-based intervention is a promising way to provide survivors of HD with information about how to manage the long-term and late effects from cancer and treatment, and provide trusted survivorship resources.
Next-Generation Sequencing Reveals Potentially Actionable Alterations in the Majority of Patients With Lymphoid Malignancies
Authors: Goodman Aaron M. , Choi Michael , Wieduwilt Matthew , Mulroney Carolyn , Costello Caitlin , Frampton Garrett , Miller Vincent , Kurzrock Razelle 
Published: July 2017

Purpose Next-generation sequencing (NGS) identifies potentially targetable alterations by US Food and Drug Administration (FDA)–approved drugs and/or by available experimental agents that may not have otherwise been contemplated. Many targeted drugs have been developed for diverse solid cancers; a smaller number of genomically targeted drugs have been approved for lymphoid malignancies. Materials and Methods We analyzed NGS results from 60 patients with various lymphoid malignancies and found 224 alterations (median per patient, three alterations). Results Forty-nine patients (82%) had potentially actionable alterations with the use of FDA-approved drugs and/or experimental therapies; only 11 patients (18%) had no theoretically actionable alterations. Only three patients (5%) had an alteration for which an approved drug in the disease is available (on label); 45 patients (75%) had an alteration for which an approved drug is available for another disease (off label). The median number of alterations per patient potentially actionable by an FDA-approved drug was one. Of note, 19 (32%) of 60 patients had intermediate to high tumor mutational burden, which may predict response to certain immunotherapy agents. Conclusion NGS identifies alterations that may be pharmacologically tractable in most patients with lymphoid malignancies, albeit with drugs that have usually been developed in the context of solid tumors. These observations merit expanded exploration in the clinical trials setting.
Circulating Tumor DNA Analysis and Functional Imaging Provide Complementary Approaches for Comprehensive Disease Monitoring in Metastatic Melanoma
Authors: Wong Stephen Q. , Raleigh Jeanette M. , Callahan Jason , Vergara Ismael A. , Ftouni Sarah , Hatzimihalis Athena , Colebatch Andrew J. , Li Jason , Semple Timothy , Doig Kenneth , Mintoff Christopher , Sinha Devbarna , Yeh Paul , Silva Maria Joao , Alsop Kathryn , Thorne Heather , Bowtell David D. , Gyorki David E. , Arnau Gisela Mir , Cullinane Carleen , Kee Damien , Brady Benjamin , Kelleher Fergal , Dawson Mark A. , Papenfuss Anthony T. , Shackleton Mark , Hicks Rodney J. , McArthur Grant A. , Sandhu Shahneen , Dawson Sarah-Jane 
Published: July 2017

Purpose Circulating tumor DNA (ctDNA) allows noninvasive disease monitoring across a range of malignancies. In metastatic melanoma, the extent to which ctDNA reflects changes in metabolic disease burden assessed by 18F-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) is unknown. We assessed the role of ctDNA analysis in combination with FDG-PET to monitor tumor burden and genomic heterogeneity throughout treatment. Patients and Methods We performed a comprehensive analysis of serial ctDNA and FDG-PET in 52 patients who received systemic therapy for metastatic melanoma. Next-generation sequencing and digital polymerase chain reaction were used to analyze plasma samples from the cohort. Results ctDNA levels were monitored across patients with mutant BRAF, NRAS, and BRAF/NRAS wild type disease. Mutant BRAF and NRAS ctDNA levels correlated closely with changes in metabolic disease burden throughout treatment. TERT promoter mutant ctDNA levels also paralleled changes in tumor burden, which provide an alternative marker for disease monitoring. Of note, subcutaneous and cerebral disease sites were not well represented in plasma. Early changes in ctDNA and metabolic disease burden were important indicators of treatment response. Patients with an early decrease in ctDNA post-treatment had improved progression-free survival compared with patients in whom ctDNA levels remained unchanged or increased over time (hazard ratio, 2.6; P = .05). ctDNA analysis contributed key molecular information through the identification of putative resistance mechanisms to targeted therapy. A detailed comparison of the genomic architecture of plasma and multiregional tumor biopsy specimens at autopsy revealed the ability of ctDNA to comprehensively capture genomic heterogeneity across multiple disease sites. Conclusion The findings highlight the powerful role of ctDNA in metastatic melanoma as a complementary modality to functional imaging that allows real-time monitoring of both tumor burden and genomic changes throughout therapy.