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PubMed | Veterans Affairs Central Office, Veterans Affairs Nebraska Western Iowa Health Care System, University of Nebraska Medical Center, Georgia4Emory University and University of Pittsburgh
Type: | Journal: JAMA surgery | Year: 2016

Growing consensus suggests that frailty-associated risks should inform shared surgical decision making. However, it is not clear how best to screen for frailty in preoperative surgical populations.To develop and validate the Risk Analysis Index (RAI), a 14-item instrument used to measure surgical frailty. It can be calculated prospectively (RAI-C), using a clinical questionnaire, or retrospectively (RAI-A), using variables from the surgical quality improvement databases (Veterans Affairs or American College of Surgeons National Surgical Quality Improvement Projects).Single-site, prospective cohort from July 2011 to September 2015 at the Veterans Affairs Nebraska-Western Iowa Heath Care System, a Level 1 Veterans Affairs Medical Center. The study included all patients presenting to the medical center for elective surgery.We assessed the RAI-C for all patients scheduled for surgery, linking these scores to administrative and quality improvement data to calculate the RAI-A and the modified Frailty Index.Receiver operator characteristics and C statistics for each measure predicting postoperative mortality and morbidity.Of the participants, the mean (SD) age was 60.7 (13.9) years and 249 participants (3.6%) were women. We assessed the RAI-C 10698 times, from which we linked 6856 unique patients to mortality data. The C statistic predicting 180-day mortality for the RAI-C was 0.772. Of these 6856 unique patients, we linked 2785 to local Veterans Affairs Surgeons National Surgical Quality Improvement Projects data and calculated the C statistic for both the RAI-A (0.823) and RAI-C (0.824), along with the correlation between the 2 scores (r=0.478; P<.001). Of these 2785 patients, there was sufficient data to calculate the modified Frailty Index for 1021, in which the C statistics were 0.865 (RAI-A), 0.797 (RAI-C), and 0.811 (modified Frailty Index). The correlation between the RAI-A and RAI-C was 0.547, and the correlations of the modified Frailty Index to the RAI-A and RAI-C were 0.300 and 0.26, respectively (all P<.001). A cutoff of RAI-C of at least 21 classified 18.3% patients as frail with a sensitivity of 0.50 and specificity of 0.82, whereas the RAI-A was less sensitive (0.25) and more specific (0.97), classifying only 3.7% as frail.The RAI-C and RAI-A represent effective tools for measuring frailty in surgical populations with predictive ability on par with other frailty tools. Moderate correlation between the measures suggests convergent validity. The RAI-C offers the advantage of prospective, preoperative assessment that is proved feasible for large-scale screening in clinical practice. However, further efforts should be directed at determining the optimal components of preoperative frailty assessment.


Petrosyan A.,Veterans Affairs Nebraska Western Iowa Health Care System | Petrosyan A.,University of Nebraska at Omaha | Ali M.F.,Veterans Affairs Nebraska Western Iowa Health Care System | Ali M.F.,University of Nebraska at Omaha | And 3 more authors.
Journal of Biological Chemistry | Year: 2012

Background: The Golgi docking mechanisms for transport vesicles carrying glycosyltransferases are largely unknown. Results: C1GalT1 utilizes GM130-GRASP65 when GRASP65 is available but GM130-Giantin without GRASP65, whereas C2GnT-M employs Giantin for Golgi targeting. Conclusion: The Golgi-targeting mechanism is glycosyltransferase-specific. Significance: Understanding the Golgi-targeting mechanisms of glycosyltransferases may help uncover altered glycosylation in some diseases. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.


Dusad A.,Veterans Affairs Nebraska Western Iowa Health Care System | Dusad A.,University of Nebraska Medical Center | Pedro S.,National Data Bank for Rheumatic Diseases | Mikuls T.R.,Veterans Affairs Nebraska Western Iowa Health Care System | And 6 more authors.
Arthritis and Rheumatology | Year: 2015

Objective To assess and compare the impact of total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). Methods Patients with rheumatologist-diagnosed arthritis undergoing primary TKA during 1999-2012 were identified. Indices of pain (overall, index knee, and contralateral knee) and health-related quality of life (HRQOL) were obtained in 3 consecutive 6-month intervals: preoperative (baseline), perioperative, and postoperative (recovery). Descriptive statistics and one-way analysis of variance were used to compare TKA outcomes by diagnosis. Effect sizes and standardized response means (SRMs) were calculated between baseline and recovery. Results Of the participating 18,897 patients, 834 of those with RA (5.3%) and 315 of those with OA (10.2%) had undergone index TKA at similar mean ages (65 and 68 years). Post-TKA, significant improvements were observed for most domains of pain, function, and HRQOL within both disease groups, with greater impact in OA. Based on the SRM, the maximum improvement was shown in index knee pain (SRM -1.33 in RA and -1.34 in OA; effect size -1.75 and -1.94, respectively). The Health Assessment Questionnaire II and the Short Form 36 physical component summary were the most responsive HRQOL indices in detecting post-TKA improvement in RA. A diagnosis of RA, lower income, and preoperative anxiety were independently associated with a lower degree of improvement in index knee pain following TKA. Conclusion TKA is highly effective in reducing clinically relevant knee pain (to a greater extent than its effect on other subjective HRQOL indices in patients with RA), although this improvement is less marked as compared to that among patients with OA. TKA serves as a "time machine" via which patients can return to a lifestyle with less disability, before the arthritis process catches up in RA. © 2015, American College of Rheumatology.


Thambidorai S.K.,Creighton University | Thambidorai S.K.,Veterans Affairs Nebraska Western Iowa Health Care System | Deshmukh A.R.,Creighton University | Deshmukh A.R.,Veterans Affairs Nebraska Western Iowa Health Care System | And 7 more authors.
International Journal of Cardiology | Year: 2011

Background: There is conflicting data regarding the mortality benefit of statins in patients with heart failure. The objectives of our study were to determine whether statin therapy is associated with decreased all-cause mortality and to assess the effect of incremental duration of therapy. Methods: We studied 10,510 consecutive patients from the Veterans Affairs health system with a diagnosis of heart failure from January 2002 through December 2006. Mean follow up was 2.66 years. Statin use and duration of therapy were identified. Veterans were classified into four groups based on duration of statin use during the study period (none, 1-25%, 26-75% and > 75% use of statins). Logistic regression was performed to identify the association between incident statin use and all-cause mortality following a diagnosis of heart failure. The Kaplan-Meier method was employed to assess for differences in survival time between the four statin use classifications. Results: Statin use was significantly associated with decreased all-cause mortality following a diagnosis of heart failure after controlling for age, gender, concurrent medications and comorbid diagnoses [χ 3 2 (N = 10,510) = 1077.82, p < 0.001]. The benefit was seen within a relatively short duration (within 1 year) after starting statins, and in patients with < 25% use of statins, there was no mortality benefit. Conclusion: Veterans who were not exposed to statin therapy at any time during the study period were 1.56 times more likely to suffer all-cause mortality. © 2010 Elsevier Ireland Ltd. All rights reserved.


Tsai J.,Veterans Affairs New England Mental Illness Research | Tsai J.,Yale University | Ramaswamy S.,Veterans Affairs Nebraska Western Iowa Health Care System | Ramaswamy S.,Creighton University | And 4 more authors.
American Journal of Community Psychology | Year: 2015

This study explored differences between homeless male veterans in metropolitan and micropolitan cities in Nebraska on sociodemographic, housing, clinical, and psychosocial characteristics as well as health service use. A convenience sample of 151 homeless male veterans (112 metropolitan, 39 micropolitan) were recruited from Veterans Affairs facilities and area shelters in Omaha, Lincoln, Grand Island, and Hastings in Nebraska. Research staff conducted structured interviews with homeless veterans. Results showed that compared to homeless veterans in metropolitans, those in micropolitans were more likely to be White, unmarried, living in transitional settings, and were far more transient but reported greater social support and housing satisfaction. Veterans in micropolitans also reported more medical problems, diagnoses of anxiety and personality disorders, and unexpectedly, were more likely to report using various health services and less travel time for services. Together, these findings suggest access to homeless and health services for veterans in micropolitan areas may be facilitated through Veterans Affairs facilities and community providers that work in close proximity to one another. Many homeless veterans in these areas are transient, making them a difficult population to study and serve. Innovative ways to provide outreach to homeless veterans in micropolitan and more rural areas are needed. © 2015, Society for Community Research and Action (outside the USA).


Aroor A.R.,University of Missouri | Restrepo R.J.,University of Missouri | Kharbanda K.K.,Veterans Affairs Nebraska Western Iowa Health Care System | Shukla S.D.,University of Missouri
Hepatology International | Year: 2014

Purpose: Ethanol binge augments liver injury after chronic ethanol consumption in humans, but the mechanism behind the enhanced liver injury by ethanol binge is not known. In this study we used a clinically relevant rat model in which liver injury is amplified by binge after chronic ethanol treatment and investigated the importance of histone modifications.Methods: Eight-week-old Sprague-Dawley rats were fed ethanol in a liquid diet for 4 weeks. Control rats were fed an isocaloric liquid diet. This was followed by three binge administrations of ethanol (intragastric 5 g/kg body weight, 12 h apart). In the control, ethanol was replaced by water. Four hours after the last binge administration, liver samples were analyzed for histone modifications and parameters of liver injury.Results: Chronic ethanol administration alone caused an increase in histone H3 ser10 and ser28 (H3S10 or S28) phosphorylation, and binge ethanol reduced their levels. Levels of dually modified phosphoacetylated histone H3 (H3AcK9/PS10) increased after acute binge ethanol and remained same after chronic ethanol binge. In contrast, histone H3 lysine-9 acetylation (H3AcK9) was not increased after chronic ethanol but increased significantly after acute binge and chronic ethanol binge. Increase in histone acetylation was accompanied by increased phospho-ERK1/2 in the nuclear extracts. Increased acetylation after chronic ethanol binge was also accompanied by increased protein levels of GCN5 histone acetyl transferase and a modest increase in HDAC3 in the nucleus. Histone lysine-9 dimethylation was significantly increased after chronic ethanol binge. Chronic ethanol binge also resulted in a decrease in the SAM:SAH ratio with a relative decrease of SAM levels and a corresponding increase in SAH levels.Conclusions: Ethanol binge after chronic ethanol altered the profile of site-specific histone modifications and may underlie the mechanism of augmented liver injury by chronic-ethanol-binge-treated rats. © 2014, Asian Pacific Association for the Study of the Liver.


PubMed | University of Missouri and Veterans Affairs Nebraska Western Iowa Health Care System
Type: Journal Article | Journal: Biomolecules | Year: 2015

Chronic alcoholics who also binge drink (i.e., acute on chronic) are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4%) for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart). Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9), dually modified phosphoacetylated histone H3 (H3AcK9/PS10), and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10) and H3 ser 28 (H3S28) increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.


Ali M.F.,Veterans Affairs Nebraska Western Iowa Health Care System | Ali M.F.,University of Nebraska Medical Center | Chachadi V.B.,Veterans Affairs Nebraska Western Iowa Health Care System | Chachadi V.B.,University of Nebraska Medical Center | And 4 more authors.
Journal of Biological Chemistry | Year: 2012

Core 2 N-acetylglucosaminyltransferase 1 (C2GnT1) is a key enzyme participating in the synthesis of core 2-associated sialyl Lewis x (C2-O-sLex), a ligand involved in selectin-mediated leukocyte trafficking and cancer metastasis. To accomplish that, C2GnT1 needs to be localized to the Golgi and this step requires interaction of its cytoplasmic tail (CT) with a protein that has not been identified. Employing C2GnT1 CT as the bait to perform a yeast two-hybrid screen, we have identified Golgi phosphoprotein 3 (GOLPH3) as a principal candidate protein that interacts with C2GnT1 and demonstrated that C2GnT1 binds to GOLPH3 via the LLRRR9 sequence in the CT. Confocal fluorescence microscopic analysis shows substantial Golgi co-localization of C2GnT1 and GOLPH3. Upon GOLPH3 knockdown, C2GnT1 is found mainly in the endoplasmic reticulum and decorated with complex-type N-glycans, indicating that the enzyme has been transported to the Golgi but is not retained. Also, we have found that a recombinant protein consisting of C2GnT1 CT1-16-Leu17-32-Gly33-42-GFP is localized to the Golgi although the same construct with mutated CT (AAAAA 9) is not. The data demonstrate that the C2GnT1 CT is necessary and sufficient for Golgi localization of C2GnT1. Furthermore, GOLPH3 knockdown results in reduced synthesis of C2-O-sLex associated with P-selectin glycoprotein ligand-1, reduced cell tethering to and rolling on immobilized P- or E-selectin, and compromised E-selectin-induced activation of spleen tyrosine kinase and cell adhesion to intercellular adhesion molecule-1 under dynamic flow. Our results reveal that GOLPH3 can regulate cell-cell interaction by controlling Golgi retention of C2GnT1.


PubMed | Veterans Affairs Nebraska Western Iowa Health Care System
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2012

Core 2 N-acetylglucosaminyltransferase 1 (C2GnT1) is a key enzyme participating in the synthesis of core 2-associated sialyl Lewis x (C2-O-sLe(x)), a ligand involved in selectin-mediated leukocyte trafficking and cancer metastasis. To accomplish that, C2GnT1 needs to be localized to the Golgi and this step requires interaction of its cytoplasmic tail (CT) with a protein that has not been identified. Employing C2GnT1 CT as the bait to perform a yeast two-hybrid screen, we have identified Golgi phosphoprotein 3 (GOLPH3) as a principal candidate protein that interacts with C2GnT1 and demonstrated that C2GnT1 binds to GOLPH3 via the LLRRR(9) sequence in the CT. Confocal fluorescence microscopic analysis shows substantial Golgi co-localization of C2GnT1 and GOLPH3. Upon GOLPH3 knockdown, C2GnT1 is found mainly in the endoplasmic reticulum and decorated with complex-type N-glycans, indicating that the enzyme has been transported to the Golgi but is not retained. Also, we have found that a recombinant protein consisting of C2GnT1 CT(1-16)-Leu(17-32)-Gly(33-42)-GFP is localized to the Golgi although the same construct with mutated CT (AAAAA(9)) is not. The data demonstrate that the C2GnT1 CT is necessary and sufficient for Golgi localization of C2GnT1. Furthermore, GOLPH3 knockdown results in reduced synthesis of C2-O-sLe(x) associated with P-selectin glycoprotein ligand-1, reduced cell tethering to and rolling on immobilized P- or E-selectin, and compromised E-selectin-induced activation of spleen tyrosine kinase and cell adhesion to intercellular adhesion molecule-1 under dynamic flow. Our results reveal that GOLPH3 can regulate cell-cell interaction by controlling Golgi retention of C2GnT1.


PubMed | Veterans Affairs New England Mental Illness Research and Veterans Affairs Nebraska Western Iowa Health Care System
Type: Comparative Study | Journal: American journal of community psychology | Year: 2015

This study explored differences between homeless male veterans in metropolitan and micropolitan cities in Nebraska on sociodemographic, housing, clinical, and psychosocial characteristics as well as health service use. A convenience sample of 151 homeless male veterans (112 metropolitan, 39 micropolitan) were recruited from Veterans Affairs facilities and area shelters in Omaha, Lincoln, Grand Island, and Hastings in Nebraska. Research staff conducted structured interviews with homeless veterans. Results showed that compared to homeless veterans in metropolitans, those in micropolitans were more likely to be White, unmarried, living in transitional settings, and were far more transient but reported greater social support and housing satisfaction. Veterans in micropolitans also reported more medical problems, diagnoses of anxiety and personality disorders, and unexpectedly, were more likely to report using various health services and less travel time for services. Together, these findings suggest access to homeless and health services for veterans in micropolitan areas may be facilitated through Veterans Affairs facilities and community providers that work in close proximity to one another. Many homeless veterans in these areas are transient, making them a difficult population to study and serve. Innovative ways to provide outreach to homeless veterans in micropolitan and more rural areas are needed.

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