Impact of Recent Acute Kidney Injury on Creatinine Clearance Estimation in Critically Ill Patients Undergoing Cardiac Surgery

Acute kidney injury (AKI), often present in critically ill patients and patients with cardiac dysfunction, may alter estimates of renal function. The impact of recent AKI on the accuracy of the Cockcroft-Gault creatinine clearance equation (CG-CrCl) before cardiac surgery is unknown. This single-center, retrospective study included patients who underwent cardiac surgery from 1 January 2006 through 30 June 2012 and whose 24-hour urine creatinine clearance (24hr-CrCl) was measured in the intensive care unit before surgery. We evaluated CG-CrCl accuracy by calculating absolute differences between 24hr-CrCl and CG-CrCl estimates. Clinical impact was signified by discrepancies in United States Food and Drug Administration (FDA) renal impairment stage indicated by 24hr-CrCl versus CG-CrCl estimates. Acute kidney injury was evaluated by using Kidney Disease: Improving Global Outcomes criteria. Of 161 patients, 93 (58%) had recent AKI: stage 1, 31 (33%); stage 2, 39 (42%); and stage 3, 23 (25%). In mL/min, the CG-CrCl overestimated 24hr-CrCl (absolute difference: total, -10 ± 25; no AKI, -7 ± 26; stage 1, -8 ± 17; stage 2, -16 ± 28; and stage 3, -10 ± 26; P=0.29). Renal impairment stages assigned by CG-CrCl did not match 24hr-CrCl in 70 (43%) of the 161 patients, especially those with recent AKI: no AKI, 24/68 (35%); stage 1, 13/31 (42%); stage 2, 23/39 (59%); and stage 3, 10/23 (43%). The CG-CrCl consistently overestimated 24hr-CrCl in critically ill patients before cardiac surgery. Clinicians should use the CG-CrCl cautiously when estimating renal function and medication dosages in this population

The triple helix of clinical, research, and education missions in academic health centers: A qualitative study of diverse stakeholder perspectives.

Introduction: Academic health centers are poised to improve health through their clinical, education, and research missions. However, these missions often operate in silos. The authors explored stakeholder perspectives at diverse institutions to understand challenges and identify alignment strategies. Methods: Authors used an exploratory qualitative design and thematic analysis approach with data obtained from electronic surveys sent to participants at five U.S. academic health centers (2017-18), with four different types of medical school/health system partnerships. Participants included educators, researchers, system leaders, administrators, clinical providers, resident/fellow physicians, and students. Investigators coded data using constant comparative analysis, met regularly to reconcile uncertainties, and collapsed/combined categories. Results: Of 175 participants invited, 113 completed the survey (65%). Three results categories were identified. First, five higher-order themes emerged related to aligning missions, including (a) shared vision and strategies, (b) alignment of strategy with community needs, (c) tension of economic drivers, (d) coproduction of knowledge, and (e) unifying set of concepts spanning all missions. Second, strategies for each mission were identified, including education (new competencies, instructional methods, recruitment), research (shifting agenda, developing partnerships, operations), and clinical operations (delivery models, focus on patient factors/needs, value-based care, well-being). Lastly, strategies for integrating each dyadic mission pair, including research-education, clinical operations education, and research-clinical operations, were identified. Conclusions: Academic health centers are at a crossroads in regard to identity and alignment across the tripartite missions. The study\u27s results provide pragmatic strategies to advance the tripartite missions and lead necessary change for improved patient health

Enhanced oxidative stress by alcohol use in HIV+ patients: possible involvement of cytochrome P450 2E1 and antioxidant enzymes

BACKGROUND: Alcohol consumption is prevalent amongst HIV positive population. Importantly, chronic alcohol use is reported to exacerbate HIV pathogenesis. Although alcohol is known to increase oxidative stress, especially in the liver, there is no clinical evidence that alcohol increases oxidative stress in HIV positive patients. The mechanism by which alcohol increases oxidative stress in HIV positive patients is also unknown. METHODS: To examine the effects of alcohol use on oxidative stress we recruited HIV+ patients who reported mild-to-moderate alcohol use. Strict inclusion and exclusion criteria were applied to reduce the effect of other therapeutic drugs metabolized via the hepatic system as well as the effect of co-morbidities such as active tuberculosis on the interaction between alcohol and HIV infection, respectively. Blood samples were collected from HIV-negative alcohol-users and HIV positive alcohol-users followed by collection of plasma and isolation and fractionation of monocytes from peripheral blood. We then determined oxidative DNA damage, glutathione level, alcohol level, transcriptional level of cytochrome P450 2E1 (CYP2E1) and several antioxidant enzymes, and plasma level of cytokines. RESULTS: Compared to HIV-negative alcohol users, HIV-positive alcohol users demonstrated an increase in oxidative DNA damage in both plasma and CD14+ monocytes, as well as, a relative increase in oxidized/reduced glutathione (GSSG/GSH) in plasma samples. These results suggest an increase in oxidative stress in HIV-positive alcohol users compared with HIV-negative alcohol users. We also examined whether alcohol metabolism, perhaps by CYP2E1, and antioxidant enzymes are involved in alcohol-mediated increased oxidative stress in HIV-positive patients. The results showed a lower plasma alcohol level, which was associated with an increased level of CYP2E1 mRNA in monocytes, in HIV-positive alcohol users compared with HIV-negative alcohol users. Furthermore, the transcription of major antioxidants enzymes (catalase, SOD1, SOD2, GSTK1), and their transcription factor, Nrf2, were reduced in monocytes obtained from HIV positive alcohol users compared to the HIV-negative alcohol user group. However, no significant change in levels of five major cytokines/chemokines were observed between the two groups. CONCLUSIONS: The data suggests that alcohol increases oxidative stress in HIV+ patients, perhaps through CYP2E1- and antioxidant enzymes-mediated pathways. The enhanced oxidative stress is accompanied by a failure of cellular antioxidant mechanisms to maintain redox homeostasis. Overall, the enhanced oxidative stress in monocytes may exacerbate HIV pathogenesis in HIV positive alcohol users

Games of Incomplete Information and Myopic Equilibria

A new concept of an equilibrium in games is introduced that solves an open question posed by A. Neyman

Covalently linked plasticizers: Triazole analogues of phthalate plasticizers prepared by mild copper-free "click" reactions with azide-functionalized PVC

Copper-free azide-alkyne click chemistry is utilized to covalently modify polyvinyl chloride (PVC). Phthalate plasticizer mimics di(2-ethylhexyl)-1H- triazole-4,5 dicarboxylate (DEHT), di(n-butyl)-1H-1,2,3-triazole-4,5- dicarboxylate (DBT), and dimethyl-1H-triazole-4,5-dicarboxylate (DMT) are covalently attached to PVC. DEHT, DBT, and DMT have similar chemical structures to traditional plasticizers di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), and dimethyl phthalate (DMP), but pose no danger of leaching from the polymer matrix and forming small endocrine disrupting chemicals. The synthesis of these covalent plasticizers is expected to be scalable, providing a viable alternative to the use of phthalates, thus mitigating dangers to human health and the environment. Covalently attached mimics of conventional phthalate plastacizers are synthesized on modified PVC by simple and scalable chemistry. Substitution of some of the chloride by azide, followed by thermal Huisgen cycloaddition with dialkyl acetylenedicarboxylates forms pendant triazoles bearing ortho esters resembling phthalate diesters. This copper-free cyclization is demonstrated at room temperature: first on small molecule models, then on PVC. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Impact of Recent Acute Kidney Injury on Creatinine Clearance Estimation in Critically Ill Patients Undergoing Cardiac Surgery

Acute kidney injury (AKI), often present in critically ill patients and patients with cardiac dysfunction, may alter estimates of renal function. The impact of recent AKI on the accuracy of the Cockcroft-Gault creatinine clearance equation (CG-CrCl) before cardiac surgery is unknown. This single-center, retrospective study included patients who underwent cardiac surgery from 1 January 2006 through 30 June 2012 and whose 24-hour urine creatinine clearance (24hr-CrCl) was measured in the intensive care unit before surgery. We evaluated CG-CrCl accuracy by calculating absolute differences between 24hr-CrCl and CG-CrCl estimates. Clinical impact was signified by discrepancies in United States Food and Drug Administration (FDA) renal impairment stage indicated by 24hr-CrCl versus CG-CrCl estimates. Acute kidney injury was evaluated by using Kidney Disease: Improving Global Outcomes criteria. Of 161 patients, 93 (58%) had recent AKI: stage 1, 31 (33%); stage 2, 39 (42%); and stage 3, 23 (25%). In mL/min, the CG-CrCl overestimated 24hr-CrCl (absolute difference: total, −10 ± 25; no AKI, −7 ± 26; stage 1, −8 ± 17; stage 2, −16 ± 28; and stage 3, −10 ± 26; P=0.29). Renal impairment stages assigned by CG-CrCl did not match 24hr-CrCl in 70 (43%) of the 161 patients, especially those with recent AKI: no AKI, 24/68 (35%); stage 1, 13/31 (42%); stage 2, 23/39 (59%); and stage 3, 10/23 (43%). The CG-CrCl consistently overestimated 24hr-CrCl in critically ill patients before cardiac surgery. Clinicians should use the CG-CrCl cautiously when estimating renal function and medication dosages in this population.</jats:p