National Institutes Of Health Roadmap Research Articles

MP41-02 TUMOR SIZE IS ASSOCIATED WITH GROWTH KINETICS IN SMALL RENAL MASSES ON ACTIVE SURVEILLANCE

You have accessJournal of UrologyCME1 Apr 2023MP41-02 TUMOR SIZE IS ASSOCIATED WITH GROWTH KINETICS IN SMALL RENAL MASSES ON ACTIVE SURVEILLANCE Maximilian Pallauf, Michael Rezaee, Roy Elias, Tina Wlajnitz, Sean A. Fletcher, Khalid Alkhatib, Peter Chang, Andrew A. Wagner, James M. McKiernan, Mohammad E. Allaf, Phillip M. Pierorazio, and Nirmish Singla Maximilian PallaufMaximilian Pallauf More articles by this author , Michael RezaeeMichael Rezaee More articles by this author , Roy EliasRoy Elias More articles by this author , Tina WlajnitzTina Wlajnitz More articles by this author , Sean A. FletcherSean A. Fletcher More articles by this author , Khalid AlkhatibKhalid Alkhatib More articles by this author , Peter ChangPeter Chang More articles by this author , Andrew A. WagnerAndrew A. Wagner More articles by this author , James M. McKiernanJames M. McKiernan More articles by this author , Mohammad E. AllafMohammad E. Allaf More articles by this author , Phillip M. PierorazioPhillip M. Pierorazio More articles by this author , and Nirmish SinglaNirmish Singla More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) is an accepted treatment strategy for small renal masses (SRM) <4 cm. Intervention is recommended for SRMs exceeding growth rates (GR) of 0.5 cm/year. We sought to identify clinical factors predictive of GR >0.5 cm/year for SRM on AS. METHODS: We queried the prospective, multi-institutional Delayed Intervention and Surveillance for SRM (DISSRM) registry for patients enrolled in AS. We tabulated clinical factors, including age, sex, and tumor size, and quantified GRs of SRMs between study enrollment and delayed intervention, metastasis, death, or last follow-up, whichever occurred first. GR was defined by the change in tumor size over time between the first and latest imaging. We defined growth progression as a GR in excess of 0.5 cm/year. We used recurrent-event multivariable Cox-regression modeling to test the associations between clinical factors and growth progression; age and tumor size were handled as time-varying covariates. Tumor size was tested as a continuous and dichotomized variable based on a cutoff of 2 cm, endorsed by the AUA guidelines. To account for GR variability within the first few months of AS, we excluded follow-up visits earlier than six months. RESULTS: Between 2009 and 2022, 591 patients were initially enrolled onto AS within the DISSRM registry, of whom 332 were on AS for at least six months. The median follow-up time of patients who continued AS was 4.0 years (IQR 2.6-6.1). Sixty-six patients (20%) exhibited growth progression, but no patient developed metastatic disease. Fifty patients (15%) underwent delayed intervention. While age and sex were not associated with growth progression, tumor size was an independent predictor of growth progression on multivariable analysis (HR 2.61 (95% CI 2.16-3.15), p<0.001). On dichotomization of tumor size, we found that tumors ≥ 2 cm were significantly associated with growth progression compared to those <2 cm (HR 4.29 (95% CI 2.43-7.61), p<0.001) (Figure). The mean GR for tumors ≥ 2 cm was 0.21 cm/year (±0.31) vs. 0.06 cm/year (±0.26) for those <2 cm. CONCLUSIONS: Larger tumor size is independently associated with clinically meaningful growth progression (GR >0.5 cm/year) for SRMs on AS. Identifying clinical factors predictive of growth kinetics for SRMs is important to guide patient counseling by informing personalized strategies of AS versus intervention. Source of Funding: This publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR003098 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH.Pallauf M gratefully acknowledges the support of the Paracelsus Medical University Research and Innovation Fund (2022-FIRE-004-Pallauf). © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e554 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maximilian Pallauf More articles by this author Michael Rezaee More articles by this author Roy Elias More articles by this author Tina Wlajnitz More articles by this author Sean A. Fletcher More articles by this author Khalid Alkhatib More articles by this author Peter Chang More articles by this author Andrew A. Wagner More articles by this author James M. McKiernan More articles by this author Mohammad E. Allaf More articles by this author Phillip M. Pierorazio More articles by this author Nirmish Singla More articles by this author Expand All Advertisement PDF downloadLoading ...

4013 Does dietary fat composition predict short-term elevations in lipid levels in adults on a modified Atkins diet?

OBJECTIVES/GOALS: The modified Atkins diet (MAD) is used in the management of drug-resistant epilepsy in adults. Some patients on MAD show an increase in serum levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. We explored whether dietary fat composition predicts short-term elevations in serum lipid levels in diet-naïve adults who begin MAD. METHODS/STUDY POPULATION: Participants self-reported their diet intake with 3-day food records at baseline, 1 month and 2 months. Food records were analyzed using Nutrition Data System for Research software. Fasting serum levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides were also collected and LDL level calculated at baseline, 1 month, and 2 months. RESULTS/ANTICIPATED RESULTS: 38 patients submitted complete food records at each study visit (baseline, 1 month, and 2 month). Compared to baseline diet intake, there was a significant reduction in daily carbohydrate intake at 1 and 2 months months (p&lt;0.001). There was also a significant increase in daily saturated fatty acid (SFA) intake at 1 and 2 months (p&lt;0.001), daily mono-unsaturated fatty acid (MUFA) intake at 1 and 2 months (p&lt;0.001), and daily cholesterol intake at 1 month (p&lt;0.05) and 2 months (p&lt;0.001), but no change in daily poly-unsaturated fatty acid (PUFA) intake over time. Compared to baseline, there was a significant increase in serum LDL at 1 month (p&lt;0.001) and 2 months (p&lt;0.01) and an increase in serum TC at 1 month (p&lt;0.01) but not 2 months. DISCUSSION/SIGNIFICANCE OF IMPACT : Despite a significant increase in total fat, saturated fat and mono-unsaturated fat intake as well as an increase in total cholesterol and LDL levels following MAD initiation, dietary fat composition appears to minimally predict serum lipid values in the short term. CONFLICT OF INTEREST DESCRIPTION: Tanya McDonald has received speaking honoraria from Nutricia North America. Bobbie Henry-Barron receives grants from Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research, Nutricia and Vitaflo. Diane Vizthum receives grants from the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Mackenzie C. Cervenka has received grant support from Nutricia North America, Vitaflo, Army Research Laboratory, The William and Ella Owens Medical Research Foundation and BrightFocus Foundation. She receives speaking honoraria from LivaNova, Epigenix, Nutricia North America and the Glut1 Deficiency Foundation and performs consulting with Nutricia North America and Sage Therapeutics and receives Royalties from Demos Health.

Developing Mediterranean and Western Diets for an Anti-Inflammatory Feeding Trial (P12-017-19)

ObjectivesDesign a research diet that can be used to evaluate the relationship between nutrition and inflammation in a randomized, cross-over study in adults. MethodsDietary components were established for a Mediterranean menu and a Western menu based on a literature review. Three-day menu cycles were planned using the established components. Recipes were developed and adapted to meet menu goals at the 2000 calorie level. Proportional increments of menu items at the 2000 kcal level were used to establish 2500, 3000, and 3500 daily kcal levels to allow for varying energy requirements of participants. Meal plans were analyzed using Nutrition Data System for Research 2017 (NDSR). Healthy Eating Index was calculated using NDSR data. Results100% of grains in the Mediterranean diet, none in the Western diet, were whole grains. Sweets and pastries were included in the Western diet daily but not the Intervention diet. Mean HEI score for the three-day menu cycle was 91.1 and 37.2 for the Mediterranean and Western diet, respectively. Preliminary results from three participants fed both diets for 6 days: All three participants consumed within 5% of the planned diet with the exception of one participant, who, during the Mediterranean diet cycle, consumed 64%. Mean HEI calculated for actual participant intake (n = 3, 6 days each) was: 89.7 Mediterranean, 36.4 Western ConclusionsThe Mediterranean diet had a 10-fold higher ratio of omega-6: omega-3 fat than Western. A three-day menu cycle was planned and met goals for an anti-inflammatory feeding study. Recruitment is ongoing to study the feasibility of providing a Mediterranean style and Western style diet to adults with asthma in Baltimore City. Mean HEI for the first three recruits was similar to that of the planned menu, indicating that lack of strict diet adherence did not alter HEI goal of the diet. Although diet design was successful, there were challenges to feeding study participants that must be considered in future feeding studies. Adequate freezer space is key in food preparation and delivery. Acceptability of foods in the Mediterranean diet may effect diet compliance in those who typically eat a Western diet. Dietary restrictions and allergies excluded potential study subjects. Funding SourcesThis publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH. Supporting Tables, Images and/or Graphs▪

Novel Cell Adhesion/Migration Pathways Are Predictive Markers of HDAC Inhibitor Resistance in Cutaneous T Cell Lymphoma

Background: Treatment for Cutaneous T Cell Lymphoma (CTCL) is generally not curative. Therefore, selecting a therapy that is both effective and tolerable is critical to clinical decision-making. Histone deacetylase inhibitors (HDACi), epigenetic modifier drugs, are commonly used but effective in only ~30% of patients. There are no predictive markers of HDACi response and the histone acetylation landscape in CTCL remains unmapped. We sought to identify pre-treatment molecular markers of resistance in CTCL that progressed on HDACi therapy. Methods: Purified T cells from 39 pre/post-treatment peripheral blood samples and skin biopsies from 20 patients were subjected to RNA-seq and ChIP-seq for histone acetylation marks (H3K14/9ac, H3K27ac). We correlated significant differences in histone acetylation with gene expression in HDACi-resistant/sensitive CTCL. We extended these findings in additional CTCL patient cohorts (RNA-seq, microarray), and using ELISA in matched CTCL patient plasma. Findings: Resistant CTCL exhibited high levels of histone acetylation, which correlated with increased expression of 338 genes (FC≥2, FDR<0.05), including some novel to CTCL: BIRC5 (anti-apoptotic); RRM2 (cell cycle); TXNDC5, GSTM1 (redox); and CXCR4, LAIR2 (cell adhesion/migration). Several of these, including LAIR2, were elevated pre-treatment in HDACiresistant CTCL. In CTCL patient plasma (n=6), LAIR2 protein was also elevated (p<0.01) compared to controls. Interpretation: This study is the first to connect genome-wide differences in chromatin acetylation and gene expression to HDACi-resistance in primary CTCL. Our results identify novel markers with high pre-treatment expression, such as LAIR2, as predictors of HDACi-resistance in CTCL. Funding Statement: This work was supported by NIH grants CA156690, CA188286 (J.E.P.), the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences (NCATS) (Pilot Award to J.E.P.), and Siteman Cancer Center (CA091842) (Pilot Award to J.E.P.) grants. Sequencing provided by the Genome Technology Access Center, which is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1 TR000448 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The ICTS is funded by the NIH’s NCATS Clinical and Translational Science Award (CTSA) program grant #UL1 TR002345. Declaration of Interests: N. Mehta-Shah reports research funding from Celgene, Verastem Pharmaceuticals, Roche/Genentech, and Bristol Myers Squibb and is a consultant for Kiowa Hakka Kirin. K. R. Carson is also employed by Flatiron Health. A. C. Musiek reports research funding from Pfizer, Helsinn, miRagen, Solgenix, Kyowa, Elorac, and Actelion and is also on the advisory boards for Actelion and Kyowa. No potential conflicts of interest were disclosed by the other authors. Ethics Approval Statement: De-identified peripheral blood draws or skin punch biopsies were obtained from patients seen at the Washington University School of Medicine Cutaneous Lymphoma Clinic under IRB-approved protocols with patients providing informed consent. Peripheral blood was also drawn from healthy volunteers at WUSM with IRB approval.

A Spatial-Temporal Analysis of Organ-Specific Lupus Flares in Relation to Fine Particulate Matter Pollution and Temperature

Objectives: We performed a spatial-time cluster analysis of the Hopkins Lupus Cohort with the goal of identifying potential clusters of SLE organ specific flares and their relation to temperature changes and fine particulate matter pollution (PM2.5). Methods: 1261 patients who fulfilled the SLICC classification criteria for SLE and who had recorded home addresses were included in the analysis. Disease activity was expressed as the Lupus Activity Index. Assessment of rash, joint involvement, serositis, neurologic, pulmonary, renal, and hematologic activity was quantified on a 0-3 VAS. An organ specific flare was defined as an increase in visual analogue scale (VAS) of 1 point or more compared to the previous visit. Average temperature and PM2.5 exposure over a period of 10 days prior to patient visit were obtained. Spatiotemporal cluster detection was conducted using the SaTScan software. Regression models were used for adjustment and included age, sex, and race, as well as PM2.5 and temperature. Results: Three statistically significant (p<0.05) unadjusted clusters were identified for joint flares, four rash flare clusters, one hematologic flare cluster, four neurologic flare clusters, three serositis flare clusters, four renal flare clusters, and five pulmonary flare clusters. Most of the identified clusters changed in significance, temporal, or spatial extent after adjusting for temperature, PM2.5 concentration, and individual covariates. Conclusions: We describe the first space-time clusters of lupus organ-specific disease activity. Seasonal, as well as multi-year cluster patterns were identified, differing in extent and location for the various organ-specific flare types. Further study focusing on each individual lupus organ-specific activity will be required to better understand the driving forces behind these observed changes. Funding Statement: The Hopkins Lupus Cohort is supported by a grant from the National Institute of Health (NIH AR 43727 and 69572). This publication was also made possible by Grant Number UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Dr. George Stojan is a Jerome L. Greene Foundation Scholar. Dr. Frank Curriero is supported by NIH grant R01AI123931. Declaration of Interests: The authors state: None. Ethics Approval Statement: The Hopkins Lupus Cohort has been approved by the Johns Hopkins University School of Medicine Institutional Review Board and complies with the Health Insurance Portability and Accountability Act.

The Role of Patient Financial Assistance Programs in Reducing Costs for Cancer Patients.

Limited transparency exists regarding eligibility and benefits for patient financial assistance programs (PAPs). To describe oral anticancer medication costs, insurance coverage, and the degree of financial assistance provided by PAPs. This was a retrospective study of prescription anticancer medication costs and PAP coverage. The study used data from an academic cancer center's specialty pharmacy. Medication, cost, and coverage data were collected from the specialty pharmacy database for prescriptions filled from January 2013 to November 2015. Prescriptions with missing copayments, insurance, or financial assistance amounts were excluded. Descriptive statistics summarized prescription characteristics. Of 9,388 anticancer medication prescriptions filled, 8,212 (87%) had complete cost data and were included. The 5 most common medications prescribed were capecitabine (20%), temozolomide (13%), enzalutamide (10%), letrozole (6%), and tamoxifen (4%). Most prescriptions were covered by commercial insurance or Part D (41.6%, n = 3,418). The median copayment was $20 per prescription (interquartile range [IQR] = $10.00-$80.30). When considering all prescriptions that received PAP assistance, the median amount of financial assistance provided by PAPs per prescription was $411.0 (IQR = $302.80-$523.40), amounting to 15% of the median prescription cash price. When considering all prescriptions, the median amount of financial assistance provided by PAPs per prescription was $0, and the mean was $79.30 (SD = $389.90). A minority of prescriptions received financial assistance from PAPs. The proportion of financial assistance was small relative to the price billed to insurance. PAPs play a modest role in reducing anticancer prescription-related costs. Support of this project by The Duke Biostatistics Core was made possible by Grant Number UL1TR001117 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Zullig is supported by a VA Health Services Research and Development (HSR&D) Career Development Award (CDA 13-025). Zullig also reports a financial relationship with Novartis. Zafar reports financial relationships with Novartis, Genentech-Roche, and Vivor. Vlastelica, Shankaran, and Wolf have nothing to disclose. The views in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, Duke University, NCATS, or NIH. This abstract was previously presented at the 2016 ASCO Annual Meeting; Chicago, Illinois; June 3-7, 2016. Study concept and design were contributed by Zafar, Zullig, and Vlastelica, with assistance from Shankaran. Vlastelica and Wolf took the lead in data collection, along with Zafar, and data interpretation was performed by Zullig, Zafar, and Wolf, along with Vlastelica and Shankaran. The manuscript was written and revised by Zullig and Zafar, along with the other authors.

Joseph C. Wu: Envisioning Personalized Medicine and Clinical Trials in a Dish.

If he develops heart disease in the future, Joseph Wu envisions his physicians selecting the ideal medication for him by first testing drugs on his “mini-me” surrogates – dishes of beating heart cells created from his own stem cells. Joseph C. Wu Growing up in Southern California, Wu helped his father grow Asian specialty pears. Now, as director of the Stanford Cardiovascular Institute in Palo Alto, California, he grows cardiomyocytes for a wide range of applications – disease modeling, drug discovery, medication safety testing, and possible regenerative therapy. Since coming to Stanford in 2004, Wu has worked with both human embryonic stem (ES) cells and human induced pluripotent stem (iPS) cells. Using ES cells, Dr Wu’s laboratory is addressing several important technical challenges in stem cell technology, including how to improve cardiac differentiation efficiency,1 control potential tumorigenicity,2 and avoid immune rejection.3 For iPS cells, his laboratory has shown that iPS cell-derived cardiomyocytes can be used to elucidate the molecular mechanisms of familial dilated cardiomyopathy and hypertrophic cardiomyopathy.4–6 In a paper designated the best basic science manuscript in Circulation in 2014, Wu used a library of iPS cell-derived cardiomyocytes to show that patterns of drug-induced cardiotoxicity differed among healthy controls and patients with long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy, indicating that the system might be a more accurate predictor of adverse drug responses than current assays and screening tests.7 In Circulation Research , he recently described the opportunities to use iPS cell-derived cardiomyocytes to advance the scientific understanding and treatment of sudden cardiac death.8 The Stanford Cardiovascular Institute is currently creating a biobank of patient-specific, deidentified iPS cell lines from healthy controls and patients with a wide range of cardiovascular diseases, which will benefit the research community and patients alike.9 …

Substance use, mental health and incarceration among Mexican-American young adult men with a history of gang membership

s / Drug and Alcohol Dependence 146 (2015) e202–e284 e243 resource for tracking marijuana use behaviors and attitudes towards marijuana use in near real-time. Financial support: This publicationwasmadepossible byGrant Numbers UL1 RR024992 andKL2 RR024994 from theNational Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research and by K02DA021237 from the NIH. Other support includes an NIH Career Development Award awarded to Dr. Cavazos-Rehg (NIDA, K01DA025733) and NIDA, R01 DA032843, an NIH Midcareer Investigator Award awarded to Dr. Bierut (K02 DA021237), R01 DA031288 awarded to Dr. Grucza. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.126 Substance use, mental health and incarceration among Mexican-American young adult men with a history of gang membership Alice Cepeda1, Avelardo Valdez1,2, Kathryn M. Nowotny3 1 School of Social Work, University of Southern California, Los Angeles, CA, United States 2 Sociology, University of Southern California, Los Angeles, CA, United States 3 Sociology, University of Colorado Boulder, Boulder,

Bioinformatics for the Human Microbiome Project

Microbes inhabit virtually all sites of the human body, yet we know very little about the role they play in our health. In recent years, there has been increasing interest in studying human-associated microbial communities, particularly since microbial dysbioses have now been implicated in a number of human diseases [1]–[3]. Dysbiosis, the disruption of the normal microbial community structure, however, is impossible to define without first establishing what “normal microbial community structure” means within the healthy human microbiome. Recent advances in sequencing technologies have made it feasible to perform large-scale studies of microbial communities, providing the tools necessary to begin to address this question [4], [5]. This led to the implementation of the Human Microbiome Project (HMP) in 2007, an initiative funded by the National Institutes of Health Roadmap for Biomedical Research and constructed as a large, genome-scale community research project [6]. Any such project must plan for data analysis, computational methods development, and the public availability of tools and data; here, we provide an overview of the corresponding bioinformatics organization, history, and results from the HMP (Figure 1).

A Case Study for Large-Scale Human Microbiome Analysis Using JCVI’s Metagenomics Reports (METAREP)

As metagenomic studies continue to increase in their number, sequence volume and complexity, the scalability of biological analysis frameworks has become a rate-limiting factor to meaningful data interpretation. To address this issue, we have developed JCVI Metagenomics Reports (METAREP) as an open source tool to query, browse, and compare extremely large volumes of metagenomic annotations. Here we present improvements to this software including the implementation of a dynamic weighting of taxonomic and functional annotation, support for distributed searches, advanced clustering routines, and integration of additional annotation input formats. The utility of these improvements to data interpretation are demonstrated through the application of multiple comparative analysis strategies to shotgun metagenomic data produced by the National Institutes of Health Roadmap for Biomedical Research Human Microbiome Project (HMP) (http://nihroadmap.nih.gov). Specifically, the scalability of the dynamic weighting feature is evaluated and established by its application to the analysis of over 400 million weighted gene annotations derived from 14 billion short reads as predicted by the HMP Unified Metabolic Analysis Network (HUMAnN) pipeline. Further, the capacity of METAREP to facilitate the identification and simultaneous comparison of taxonomic and functional annotations including biological pathway and individual enzyme abundances from hundreds of community samples is demonstrated by providing scenarios that describe how these data can be mined to answer biological questions related to the human microbiome. These strategies provide users with a reference of how to conduct similar large-scale metagenomic analyses using METAREP with their own sequence data, while in this study they reveal insights into the nature and extent of variation in taxonomic and functional profiles across body habitats and individuals. Over one thousand HMP WGS datasets and the latest open source code are available at http://www.jcvi.org/hmp-metarep.

Ultrasound Is Superior to Magnetic Resonance Imaging for Detecting Peripheral Nerve Pathology in Mononeuropathies and Brachial Plexopathies (P06.149)

Objective: Compare accuracy of magnetic resonance imaging (MRI) and ultrasound (US) in detecting peripheral nerve pathology. Background It is unknown whether MRI or US is superior for detecting peripheral nerve pathology. Design/Methods: We reviewed charts of 141 cases referred for neuromuscular US between 6/2007 and 10/2011 for suspected upper and lower extremity mononeuropathy(ies) or brachial plexopathy, excluding idiopathic carpal tunnel syndrome and ulnar neuropathy at the elbow, and identified cases who underwent MRI of the same limb for the same indication as the US. Imaging results were compared to the gold standard of surgical or, if unavailable, clinical/electrodiagnostic evaluation. Results: We identified 52 cases evaluated with both MRI and US. Focal nerve pathology was established in 46 and excluded in six by surgical (39) or clinical/electrodiagnostic evaluation (13). Diagnoses included peripheral nerve sheath tumors (18), traumatic (10) or idiopathic (8) neuropathy, fibrosis (4), compression by ganglion/synovial cysts (4) or other soft-tissue structures (3), non-nerve soft tissue tumor (3), intraneural granuloma (1) and vasculitis (1). US was more sensitive than MRI (93 vs. 70%) and equally specific (both 83%). Pathology accurately identified on US but not MRI included nerve enlargement (7), peripheral nerve sheath tumor (3), compression by anomalous muscle (1), and a hemangioma identified as non-nerve pathology on US but not MRI. Of these 12 cases with inaccurate MRI but not US, eight (67%) had lesions larger than two centimeters; only two lesions were outside the field of view of the MRI. In three cases classified as accurate for a single lesion on both MRI and US, US identified 11 additional lesions (multifocal neurofibromas, nerve enlargements, and fibrous thickening) not seen on MRI. Conclusions: Ultrasound is more sensitive, has equivalent specificity, and may better identify multifocal lesions than MRI in suspected mononeuropathies and brachial plexopathies. Supported by: This publication was made possible in part by the Washington University Neuromuscular Research Fund and the Grant Number UL1RR024992 from the NIH-National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Disclosure: Dr. Zaidman has nothing to disclose. Dr. Seelig has nothing to disclose.

Approaching sepsis solutions using the National Institutes of Health Roadmap*

Approaching sepsis solutions using the National Institutes of Health Roadmap*

Comparison of the Occupational Therapy Research Agenda With the National Institutes of Health Roadmap for Medical Research

Comparison of the Occupational Therapy Research Agenda With the National Institutes of Health Roadmap for Medical Research

The role of organizational affiliations and research networks in the diffusion of breast cancer treatment innovation.

The National Institutes of Health (NIH) sees provider-based research networks and other organizational linkages between academic researchers and community practitioners as promising vehicles for accelerating the translation of research into practice. This study examines whether organizational research affiliations and teaching affiliations are associated with accelerated diffusion of sentinel lymph node biopsy (SLNB), an innovation in the treatment of early-stage breast cancer. Surveillance Epidemiology and End Results-Medicare data were used to examine the diffusion of SLNB for treatment of early-stage breast cancer among women aged 65 years and older diagnosed between 2000 and 2002, shortly after Medicare approved and began reimbursing for the procedure. In this population, patients treated at an organization affiliated with a research network--the American College of Surgeons Oncology Group (ACOSOG) or other National Cancer Institute (NCI) cooperative groups--were more likely to receive the innovative treatment (SLNB) than patients treated at unaffiliated organizations (odds ratio: 2.70, 95% confidence interval: 1.77-4.12; odds ratio: 1.84, 95% confidence interval: 1.26-2.69, respectively). Neither hospital teaching status nor surgical volume was significantly associated with differences in SLNB use. Patients who receive cancer treatment at organizations affiliated with cancer research networks have an enhanced probability of receiving SLNB, an innovative procedure that offers the promise of improved patient outcomes. Study findings support the NIH Roadmap and programs such as the NCI's Community Clinical Oncology Program, as they seek to accelerate the translation of research into practice by simultaneously accelerating and broadening cancer research in the community.

National Institute of Nursing Research Has Widened the Blue Highway of Translation Research

Congratulations the authors for clearly connecting the grand achievements and potential in science contemporary health research needs, specifically the need advance translational science. Woods and Magyary (2010) aptly underscore the quality improvement barriers created by restricted pathways between efficacy research and broad utilization of evidence improve clinical decision making. It was these narrow blue highways (Westfall, Mold, & Fagnan, 2007) that precipitated the National Institutes of Health (NIH) reinvent major portions of the health research enterprise in the 2004 NIH Roadmap, using Clinical and Translational Science Awards (CTSAs) as a key design. With this letter, I briefly describe activities that match the authors' recommendations and highlight recent activities already set in motion. Now only 7 years after the NIH Roadmap, nurse scientists are building a new infrastructure with significant funding from National Institute of Nursing Research (NINR)/NIH. This new structure is intended be our super highway as a national research network in translational science. This entity, the Improvement Science Research Network (ISRN, n.d.; Fohn, 2009), directly addresses Woods and Magyary's (2010) wise recommendation that magnify . . . efforts seek out and obtain funding support nursing's leadership and participation in collaborative endeavors through practice-based translational research networks that are interdisciplinary or primarily focused on nursing (p. 20). The ISRN proposal was a response NIH Request for Applications (RFA) Number RFA-OD-09-004, Recovery Act Limited Competition for NIH Grants: Research and Research Infrastructure Grand Opportunities (RC2). To the great benefit of nursing, the NINR was a participating organization, providing opportunity for nurses lead in collaborative, practice-based research. The RFA called for projects to support high impact ideas that lend themselves short-term funding, and may lay the foundation for new fields of investigation (NIH Grants Guide, 2009). With opportunity for large budgets (minimum of $1 million per year for 2 years), these were known as Grand Opportunity or GO grants. The NIH requested novel approaches in areas that addressed specific knowledge gaps, scientific opportunities, new technologies, data generation, or research methods that would benefit from an influx of funds quickly advance the area in significant ways. Applicants were requested propose either a specific research question or propose the creation of a unique infrastructure/resource designed accelerate scientific progress in the future (NIH Grants Guide, 2009). The ISRN proposed the latter. With the NIH/NINR funding, the ISRN has become a national research infrastructure that provides a test bed for the nascent field of improvement science (Fohn, 2009). Because of the very nature of health care improvement, the ISRN is interprofessional; because of the very nature of health care systems, it is decidedly focused. It offers a research coordinating center with a solid foundation in the decade-old Academic Center for Evidence-Based Practice (ACE). Key strategies include harnessing the energy created by the improvement and patient safety movements and capturing the motion created by the emphasis on clinical excellence such as the Magnet Recognition Program. The ISRN capitalizes on the core values of CTSAs, including community engagement through academic-practice partnership and commitment of moving knowledge through T1, T2, T3, and so forth. In addition, the ISRN honors the need for rigor in quality improvement testing (Berenholtz, Needham, Lubomski, Goeschel, & Pronovost, 2010) by applying scientific standards the evaluation of improvement strategies. To these ends, the ISRN has accomplished the following: (a) established stakeholder-based research priorities in improvement science, (b) coalesced almost 200 research associates, (c) created a forum for advancing capacity in improvement research methods (Improvement Science Summit), (d) launched three multisite improvement research studies, and (e) crafted a cyber environment for capacity building and conduct of multisite improvement research. …

Bridging science and practice in child welfare and children’s mental health service systems through a two-decade research center trajectory

• Summary: Over the past two decades, research on social work practice has experienced substantial growth in the United States, indicated by both the establishment of the Society for Social Work Research in 1994 and increased funding from the National Institutes of Health (NIH). Recently, this growth has carried an increasing emphasis on research to establish the evidence base for social work practice and an emphasis on understanding dissemination and implementation of evidence-based interventions or practice models in usual care settings within service systems that have historic and professional linkages to the social work discipline, such as child welfare and mental health. • Findings: This article illustrates this growth and emphases on evidence-based practice in the social work research areas, child abuse and neglect, child welfare and child mental health through the two-decade experience of a large-scale and multi-disciplinary research center in San Diego County, California, the Child and Adolescent Services Research Center (CASRC). Evidence for understanding and improving care in these two service systems served by social work practice has been developed through center studies of clinical epidemiology, mental health services, effectiveness of evidence-based interventions, and the dissemination and implementation of these interventions in usual care settings. • Applications: This evolving research agenda was shown to be well linked to the NIH Roadmap initiative and highly competitive for NIH funding.

In the NEWS A ROUNDUP OF NEWS AND INFORMATION FROM OUR COMMUNITY

In the NEWS A ROUNDUP OF NEWS AND INFORMATION FROM OUR COMMUNITY

Family Medicine in the Research Revolution

National Institutes of Health (NIH) funding has contributed to improvements in the health of the nation, but the pace of progress, particularly in the war on cancer, has been frustratingly slow. Departments of family medicine receive less NIH funding than all other specialties. Although numerous factors contribute to low family medicine funding levels, persistent undervaluing of primary care plays a paramount role. Fueled by the harsh reality that our nation's health is unconscionably poor, we are entering a new era in our nation's research enterprise, a virtual research revolution. The 3 components of this revolution are the NIH roadmap, personalized medicine, and the Clinical and Translational Science Awards. Each of these elements will contribute to a growing emphasis on translational research. Translational research demands formation of innovative structures in academic health centers (AHCs) to enable them to address questions of vital relevance to improving public health. Service research, funded by the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, and foundations, defines a new approach to research with high potential to improve the health of communities. To be a part of the research revolution, departments must rely on senior researchers to secure funding and provide mentorship for junior investigators. Junior investigators must relentlessly pursue answers to questions of direct relevance to improving health. Finally, department chairs have the obligation to identify research mentors, find ways to fund research gaps, and create a culture of scholarship and investigation. Advocating for AHCs to commit to improving the health of the regions they serve can have a substantial impact on the types of questions that centers choose to study and, ultimately, on the health of the communities they serve.

Pharmacokinetic/ Pharmacodynamic‐Driven Drug Development

The drug discovery and development enterprise, traditionally an industrial juggernaut, has spanned into the academic arena that is partially motivated by the National Institutes of Health Roadmap highlighting translational science and medicine. Because drug discovery and development represents a pipeline of basic to clinical investigations, it meshes well with the "bench to the bedside" prime directive of translational medicine. The renewed interest in drug discovery and development in academia provides an opportunity to rethink the hiearchary of studies with the hope of improving the staid approaches that have been criticized for lacking innovation. One area that has received limited attention concerns the use of pharmacokinetic and pharmacodynamic studies in the drug-development process. Using anticancer drug development as a focus, this review will address past and current deficencies in how pharmacokinetic/pharmacodynamic studies are conducted and offer new strategies that might bridge the gap between preclinical and clinical trials.

IT &amp; informatics in translational research: a case study

IT &amp; informatics in translational research: a case study