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Koyner J.L.,University of Chicago | Arthur J.M.,Medical University of South Carolina | Shaw A.D.,Vanderbilt University | Tumlin J.A.,University of Tennessee at Chattanooga | And 4 more authors.
Journal of the American Society of Nephrology | Year: 2015

Clinicians have access to limited tools that predict which patients with early AKI will progress to more severe stages. In early AKI, urine output after a furosemide stress test (FST), which involves intravenous administration of furosemide (1.0 or 1.5mg/kg), can predict the development of stage 3 AKI.Wemeasured several AKI biomarkers in our previously published cohort of 77 patients with early AKI who received an FST and evaluated the ability of FST urine output and biomarkers to predict the development of stage 3 AKI (n=25 [32.5%]), receipt of RRT (n=11 [14.2%]), or inpatient mortality (n=16 [20.7%]). With an area under the curve (AUC)±SEM of 0.87±0.09 (P<0.0001), 2-hour urine output after FST was significantly better than each urinary biomarker tested in predicting progression to stage 3 (P<0.05). FST urine output was the only biomarker to significantly predict RRT (0.86±0.08; P=0.001). Regardless of the end point, combining FST urine output with individual biomarkers using logistic regression did not significantly improve risk stratification (DAUC, P>0.10 for all). When FST urine output was assessed in patients with increased biomarker levels, the AUC for progression to stage 3 improved to 0.90±0.06 and the AUC for receipt of RRT improved to 0.91±0.08. Overall, in the setting of early AKI, FST urine output outperformed biochemical biomarkers for prediction of progressive AKI, need for RRT, and inpatient mortality. Using a FST in patients with increased biomarker levels improves risk stratification, although further research is needed. © 2015 by the American Society of Nephrology.


Chretien K.C.,Washington Veterans Affairs Medical Center | Chretien K.C.,George Washington University | Farnan J.M.,University of Chicago | Greysen S.R.,University of California at San Francisco | And 2 more authors.
Academic Medicine | Year: 2011

Purpose: To assess faculty perceptions of professional boundaries and trainee-posted content on social networking sites (SNS). Method: In June 2010, the Clerkship Directors in Internal Medicine conducted its annual survey of U.S. and Canadian member institutions. The survey included sections on demographics and social networking. The authors used descriptive statistics and tests of association to analyze the Likert scale responses and qualitatively analyzed the free-text responses. Results: Of 110 institutional members, 82 (75%) responded to the survey. Of the 40 respondents who reported current or past SNS use, 21 (53%) reported receiving a "friend request" from a current student and 25 (63%) from a current resident. Of these, 4 (19%) accepted the student request and 12 (48%) accepted the resident request. Sixty-three of 80 (79%) felt it was inappropriate to send a friend request to a current student, 61 (76%) to accept a current student's request, 42 (53%) to become friends with a current resident, and 61 (81%) to become friends with a current patient. Becoming friends with a former student, former resident, or colleague was perceived as more appropriate. Younger respondents were less likely to deem specific student behaviors inappropriate (odds ratio [OR] 0.18-0.79; adjusted OR 0.12-0.86, controlling for respondents' sex, rank, and SNS use), although none reached statistical significance. Conclusions: Some internal medicine educators are using SNSs and interacting with trainees online. Their perceptions on the appropriateness of social networking behaviors provide some consensus for professional boundaries between faculty and trainees in the digital world. Copyright © by the Association of American Medical Colleges.


Chretien J.-P.,Health Integrated | Chretien K.C.,Washington Veterans Affairs Medical Center
Journal of General Internal Medicine | Year: 2013

Many American military personnel who served in the Iraq and Afghanistan wars will need long-term management of war-related conditions. There is pressing need for expertise in veterans' care outside of the Military Health System (MHS) and Department of Veterans Affairs (VA), as many will seek care elsewhere: Veterans receive free MHS care only while on active duty; enhanced eligibility for VA healthcare ends 5 years after military discharge; many veterans eligible for VA healthcare use non-VA services instead; and the Affordable Care Act will expand Medicaid coverage for uninsured veterans. Families of veterans also may need care for conditions related to war service. Most medical schools lack veteran-focused curricula beyond VA clerkships, which often do not provide specific training on service-related conditions. The VA, Department of Defense (DoD), veterans groups, and medical professional organizations should partner to develop technical competencies in veteran and family health care for clinicians at all career stages, and cultural competencies to ensure contextually appropriate care. National and state licensing boards should assess these competencies formally. Partnerships between VA, DoD, and the community for care delivery can improve transitions and the quality of veterans' post-deployment care. © 2013 Society of General Internal Medicine.


Chawla L.S.,Washington Veterans Affairs Medical Center | Chawla L.S.,George Washington University | Herzog C.A.,University of Minnesota | Costanzo M.R.,Midwest Heart Specialists Advocate Medical Group | And 5 more authors.
Journal of the American College of Cardiology | Year: 2014

Structural heart disease is highly prevalent in patients with chronic kidney disease requiring dialysis. More than 80% of patients with end-stage renal disease (ESRD) are reported to have cardiovascular disease. This observation has enormous clinical relevance because the leading causes of death for patients with ESRD are of cardiovascular disease etiology, including heart failure, myocardial infarction, and sudden cardiac death. The 2 systems most commonly used to classify the severity of heart failure are the New York Heart Association (NYHA) functional classification and the American Heart Association (AHA)/American College of Cardiology (ACC) staging system. With rare exceptions, patients with ESRD who do not receive renal replacement therapy (RRT) develop signs and symptoms of heart failure, including dyspnea and edema due to inability of the severely diseased kidneys to excrete sodium and water. Thus, by definition, nearly all patients with ESRD develop a symptomatology consistent with heart failure if fluid removal by RRT is delayed. Neither the AHA/ACC heart failure staging nor the NYHA functional classification system identifies the variable symptomatology that patients with ESRD experience depending upon whether evaluation occurs before or after fluid removal by RRT. Consequently, the incidence, severity, and outcomes of heart failure in patients with ESRD are poorly characterized. The 11th Acute Dialysis Quality Initiative has identified this issue as a critical unmet need for the proper evaluation and treatment of heart failure in patients with ESRD. We propose a classification schema based on patient-reported dyspnea assessed both pre- and post-ultrafiltration, in conjunction with echocardiography. © 2014 by the American College of Cardiology Foundation.


Koyner J.L.,University of Chicago | Shaw A.D.,Vanderbilt University | Chawla L.S.,Washington Veterans Affairs Medical Center | Hoste E.A.J.,Ghent University | And 5 more authors.
Journal of the American Society of Nephrology | Year: 2015

Tissue inhibitor metalloproteinase-2 (TIMP-2) and IGF-binding protein-7 (IGFBP7) have been validated for risk stratification in AKI. However, the association of urinary TIMP-2 and IGFBP7 with longterm outcomes is unknown.We evaluated the 9-month incidence of a composite end point of all-cause mortality or the need for RRT in a secondary analysis of a prospective observational international study of critically ill adults. Two predefined [TIMP-2]z[IGFBP7] cutoffs (0.3 for high sensitivity and 2.0 for high specificity) for the development of AKI were evaluated. Cox proportional hazards models were used to determine risk for the composite end point. Baseline [TIMP-2]z[IGFBP7] values were available for 692 subjects, of whom 382 (55.2%) subjects developed stage 1 AKI (defined by Kidney Disease Improving Global Outcomes guidelines) within 72 hours of enrollment and 217 (31.4%) subjects met the composite end point. Univariate analysis showed that [TIMP-2]z[IGFBP7].2.0 was associated with increased risk of the composite end point (hazard ratio [HR], 2.11; 95% confidence interval [95% CI], 1.37 to 3.23; P,0.001). In a multivariate analysis adjusted for the clinical model, [TIMP-2]z[IGFBP7] levels.0.3 were associated with death or RRT only in subjects who developed AKI (compared with levels 0.3: HR, 1.44; 95% CI, 1.00 to 2.06 for levels.0.3 to 2.0; P=0.05 and HR, 2.16; 95% CI, 1.32 to 3.53 for levels.2.0; P=0.002). In conclusion, [TIMP-2]z[IGFBP7]measured early in the setting of critical illness may identify patients with AKI at increased risk for mortality or receipt of RRT over the next 9 months. Copyright © 2015 by the American Society of Nephrology.


Seebach C.L.,Washington Veterans Affairs Medical Center | Kirkhart M.,Loyola University Maryland | Lating J.M.,Loyola University Maryland | Wegener S.T.,Johns Hopkins Hospital | And 3 more authors.
Pain | Year: 2012

Consistent evidence supports a significant association between lower positive affect and higher negative affect and increased pain and disability in adults with chronic pain. However, examining this relation in surgical populations has received little empirical consideration. The primary purpose of this study was to determine whether preoperative and postoperative positive and negative affect predict pain, disability, and functional status after spine surgery. A secondary objective was to assess the relation of depression to postoperative outcomes compared with positive and negative affect. Participants were 141 patients treated by spine surgery for lumbar or cervical degeneration. Data collection occurred at baseline and 6 weeks and 3 months postoperatively. Affect was measured with the Positive and Negative Affect Schedule. Multivariable mixed-model linear regression analyses found that preoperative variables were not predictive of postoperative pain, disability and functional status. However, multivariable postoperative analysis found that 6-week positive affect predicted functional status, and 6-week negative affect predicted pain interference and pain-related disability at 3 months following surgery. Postoperative depression demonstrated statistically significant and stronger associations with pain intensity, pain interference, and pain-related disability at 3-month follow-up, as compared with negative affect. Results suggest that positive affect and depression are important variables to target when seeking to improve postoperative outcomes in a spine surgery population. Recommendations include postoperative screening for positive affect and depression, and treating depression as well as focusing on rehabilitation strategies to bolster positive affect so as to improve functional outcomes after spine surgery. © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.


Shi S.-R.,University of Southern California | Taylor C.R.,University of Southern California | Fowler C.B.,Washington Veterans Affairs Medical Center | Mason J.T.,Washington Veterans Affairs Medical Center
Proteomics - Clinical Applications | Year: 2013

Tissue-based proteomic approaches (tissue proteomics) are essential for discovering and evaluating biomarkers for personalized medicine. In any proteomics study, the most critical issue is sample extraction and preparation. This problem is especially difficult when recovering proteins from formalin-fixed, paraffin-embedded (FFPE) tissue sections. However, improving and standardizing protein extraction from FFPE tissue is a critical need because of the millions of archival FFPE tissues available in tissue banks worldwide. Recent progress in the application of heat-induced antigen retrieval principles for protein extraction from FFPE tissue has resulted in a number of published FFPE tissue proteomics studies. However, there is currently no consensus on the optimal protocol for protein extraction from FFPE tissue or accepted standards for quantitative evaluation of the extracts. Standardization is critical to ensure the accurate evaluation of FFPE protein extracts by proteomic methods such as reverse phase protein arrays, which is now in clinical use. In our view, complete solubilization of FFPE tissue samples is the best way to achieve the goal of standardizing the recovery of proteins from FFPE tissues. However, further studies are recommended to develop standardized protein extraction methods to ensure quantitative and qualitative reproducibility in the recovery of proteins from FFPE tissues. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Fowler C.B.,Washington Veterans Affairs Medical Center | O'Leary T.J.,Veterans Health Administration | Mason J.T.,Washington Veterans Affairs Medical Center
Expert Review of Proteomics | Year: 2013

Archival formalin-fixed, paraffin-embedded (FFPE) tissue and their associated diagnostic records represent an invaluable source of retrospective proteomic information on diseases for which the clinical outcome and response to treatment are known. However, analysis of archival FFPE tissues by high-throughput proteomic methods has been hindered by the adverse effects of formaldehyde fixation and subsequent tissue histology. This review examines recent methodological advances for extracting proteins from FFPE tissue suitable for proteomic analysis. These methods, based largely upon heat-induced antigen retrieval techniques borrowed from immunohistochemistry, allow at least a qualitative analysis of the proteome of FFPE archival tissues. The authors also discuss recent advances in the proteomic analysis of FFPE tissue; including liquid-chromatography tandem mass spectrometry, reverse phase protein microarrays and imaging mass spectrometry. © 2013 Informa UK Ltd.


Breceda E.Y.,Washington Veterans Affairs Medical Center | Breceda E.Y.,Georgetown University | Dromerick A.W.,Washington Veterans Affairs Medical Center | Dromerick A.W.,Georgetown University
Current Opinion in Neurology | Year: 2013

Advancements in neurorehabilitation have shifted treatment away from nonspecific activity regimens and amphetamines. As the body of knowledge grows, evidence-based practice using interventions targeted at specific subgroups becomes progressively more feasible. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.


Schwartz B.L.,Washington Veterans Affairs Medical Center
Psychiatry research | Year: 2013

Individuals with schizophrenia are impaired in processing social signals such as facial expressions of emotion. Perceiving facial expressions is a complex process that depends on a distributed neural network of regions involved in affective, cognitive, and visual processing. We examined repetition priming, a non-conscious form of perceptual learning, to explore the visual-perceptual processes associated with perceiving facial expression in people with schizophrenia. Functional magnetic resonance imaging (fMRI) was also employed to probe the sensitivity of face-responsive regions in the ventral pathway to the repetition of stimuli. Subjects viewed blocks of novel and repeated faces displaying fear expressions and neutral expressions and identified each face as male or female. Gender decisions were faster for repeated encoding relative to initial encoding of faces, indicating significant priming for facial expressions. Priming was normal in schizophrenia patients, but, as expected, recognition memory for the expressions was impaired. Neuroimaging findings showed that priming-related activation for patients was reduced in the left fusiform gyrus, relative to controls, regardless of facial expression. The findings suggest that schizophrenia patients have altered neural sensitivity in regions of the ventral visual processing stream that underlie early perceptual learning of objects and faces. Published by Elsevier Ireland Ltd.

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