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Pulsatility Inhibits Non-Pulsatile Laminar Flow Induced-Degradation of IκBα in Endothelial Cells
e62
J Am Coll Surg
Scientific Forum: 2016 Clinical Congress
RESULTS: Among 91 patients (mean age, 64 years; 45% with diabetes), the mean elevation in glucose from preoperative to POD1 was similar between patients with and without diabetes (16 vs 15 mg/dL). Both groups showed a rise in CRP and IL-6 by POD1; however, this rise was not different between those with and without diabetes. After linear regression, rise in either inflammatory marker by POD1 was not associated with hyperglycemia. CONCLUSIONS: Perioperative hyperglycemia was not associated with the elevations seen in IL-6 and CRP by POD1 in this cohort. The mechanism linking hyperglycemia and poor outcomes remains unclear. These findings weaken the likelihood that inflammation is the unifying factor explaining why patients without diabetes have worse outcomes in the setting of hyperglycemia. Other potential factors to consider include: possible under-diagnosis of diabetes and under-treatment with insulin.
Pulsatility Inhibits Non-Pulsatile Laminar Flow Induced-Degradation of IkBa in Endothelial Cells Jiro Kurita, MD, Erik Benitez, MD, Bauer E Sumpio, MD, FACS Nippon Medical School, Tokyo, Japan INTRODUCTION: Nuclear factor-kB (NFkB), which is crucial in regulating inflammatory pathway of atherosclerosis is inhibited by IkBa protein. Phosphorylation of IkBa causes activation of NFkB by degrading IkBa via ubiquitin proteasome system (UPS). Shear stress is known to effect on activation of NFkB but the impact of the different types of mechanical forces are not well-defined. The aim of this study was to investigate the mechanism of the degradation of IkBa in endothelial cells (ECs) exposed to laminar flow with the presence or absence of pulsatility. METHODS: Confluent, serum starved bovine aortic ECs were subjected to 4h of non-pulsatile laminar flow (LF) or pulsatile forward flow (PF) with or without MG132, an UPS inhibitor. Western blot analysis of total, phospho-IkBa, intra-nuclear, and -cytoplasmic NFkB was performed. IkBa activity was based on the ratio of phosphorylated to total IkBa. Fold change compared to static control at 0 h was calculated. RESULTS: Exposure to LF for 4h significantly decreased the levels of IkBa (52.021.7%; p<0.05) but not to PF (86.28.9%; NS). But addition of MG132 failed to inhibit the LF induced-decrease in the level of IkBa (46.518.2%; p<0.05). LF significantly increased the level of p/t-IkBa (5.03.6; p<0.05) but not PF (2.10.9; NS). However, not only LF but also PF did not cause any change of the level of NFkB in Cytoplasm or Nuclear. CONCLUSIONS: The localization of NFkB was stable in ECs exposed to unidirectional flow in spite of the presence or absence of pulsatility. However, the pulsatility produced different effects on activity of IkBa. The degradation of IkBa under LF occurs via an alternative, UPS-independent pathway.
Regional Variation in the Cost of Infra-Inguinal Lower Extremity Bypass Surgery: National Study Besma Nejim, MBChB, MPH, Tammam Obeid, MD, Isibor J Arhuidese, MD, MPH, Satinderjit S Locham, MD, Oluwadamilola O Onasanya, MBChB, MPH, Joseph K Canner, MHS, Mahmoud Malas, MD, MHS, FACS Johns Hopkins University School of Medicine, Baltimore, MD INTRODUCTION: Infra-inguinal lower extremity bypass (LEB) remains the gold standard revascularization procedure for lower limbs. The cost of LEB substantially varies based on patient characteristics and comorbidities. We sought to assess regional variation in cost using a large national database. METHODS: We analyzed all patients who underwent LEB in the Premier database (2009-2015). Patients with concurrent cardiac surgery were excluded. Multivariable linear regression model was used to examine total in-hospital cost adjusting for patient demographics, clinical characteristics and hospital factors. RESULTS: A total of 32,224 patients were identified. Critical limb ischemia was present in 39.3% of the cohort. Mean age was 66.4 (12.7) years. The average total in-hospital LEB cost was Table. Multivariable Linear Regression Analysis of Total InHospital Cost Adjusted for Inflation
Factors
Age>65 vs age65 years female vs male sex Race White Black Hispanic Other Regions South Midwest Northeast West Teaching vs nonteaching hospital Urban vs rural hospital Critical Limb Ischemia vs claudicants Major amputation History of CHF
Adjusted mean difference, USD
95% Confidence Interval
p Value
713
495 e 930
<0.001
506
285 e 728
<0.001
Ref 2,245 3,958 612
1,935 e 2,552 2,613 e 5,302 296 e 927
<0.001 <0.001 <0.001
Ref 2,183 4,961 5,417 537
1,886 4,646 5,075 294
e e e e
<0.001 <0.001 <0.001 <0.001
-241 2,216
36,257 5,897
2,480 5,276 5,760 780
(-590) e 109 1,996 e 2,435
0.177 <0.001
35,245 e 37,269 <0.001 5,450 e 6,344
<0.001
Total n¼28, 832 after excluding influential points by Tukey Method.
J Am Coll Surg
Scientific Forum: 2016 Clinical Congress
RESULTS: Among 91 patients (mean age, 64 years; 45% with diabetes), the mean elevation in glucose from preoperative to POD1 was similar between patients with and without diabetes (16 vs 15 mg/dL). Both groups showed a rise in CRP and IL-6 by POD1; however, this rise was not different between those with and without diabetes. After linear regression, rise in either inflammatory marker by POD1 was not associated with hyperglycemia. CONCLUSIONS: Perioperative hyperglycemia was not associated with the elevations seen in IL-6 and CRP by POD1 in this cohort. The mechanism linking hyperglycemia and poor outcomes remains unclear. These findings weaken the likelihood that inflammation is the unifying factor explaining why patients without diabetes have worse outcomes in the setting of hyperglycemia. Other potential factors to consider include: possible under-diagnosis of diabetes and under-treatment with insulin.
Pulsatility Inhibits Non-Pulsatile Laminar Flow Induced-Degradation of IkBa in Endothelial Cells Jiro Kurita, MD, Erik Benitez, MD, Bauer E Sumpio, MD, FACS Nippon Medical School, Tokyo, Japan INTRODUCTION: Nuclear factor-kB (NFkB), which is crucial in regulating inflammatory pathway of atherosclerosis is inhibited by IkBa protein. Phosphorylation of IkBa causes activation of NFkB by degrading IkBa via ubiquitin proteasome system (UPS). Shear stress is known to effect on activation of NFkB but the impact of the different types of mechanical forces are not well-defined. The aim of this study was to investigate the mechanism of the degradation of IkBa in endothelial cells (ECs) exposed to laminar flow with the presence or absence of pulsatility. METHODS: Confluent, serum starved bovine aortic ECs were subjected to 4h of non-pulsatile laminar flow (LF) or pulsatile forward flow (PF) with or without MG132, an UPS inhibitor. Western blot analysis of total, phospho-IkBa, intra-nuclear, and -cytoplasmic NFkB was performed. IkBa activity was based on the ratio of phosphorylated to total IkBa. Fold change compared to static control at 0 h was calculated. RESULTS: Exposure to LF for 4h significantly decreased the levels of IkBa (52.021.7%; p<0.05) but not to PF (86.28.9%; NS). But addition of MG132 failed to inhibit the LF induced-decrease in the level of IkBa (46.518.2%; p<0.05). LF significantly increased the level of p/t-IkBa (5.03.6; p<0.05) but not PF (2.10.9; NS). However, not only LF but also PF did not cause any change of the level of NFkB in Cytoplasm or Nuclear. CONCLUSIONS: The localization of NFkB was stable in ECs exposed to unidirectional flow in spite of the presence or absence of pulsatility. However, the pulsatility produced different effects on activity of IkBa. The degradation of IkBa under LF occurs via an alternative, UPS-independent pathway.
Regional Variation in the Cost of Infra-Inguinal Lower Extremity Bypass Surgery: National Study Besma Nejim, MBChB, MPH, Tammam Obeid, MD, Isibor J Arhuidese, MD, MPH, Satinderjit S Locham, MD, Oluwadamilola O Onasanya, MBChB, MPH, Joseph K Canner, MHS, Mahmoud Malas, MD, MHS, FACS Johns Hopkins University School of Medicine, Baltimore, MD INTRODUCTION: Infra-inguinal lower extremity bypass (LEB) remains the gold standard revascularization procedure for lower limbs. The cost of LEB substantially varies based on patient characteristics and comorbidities. We sought to assess regional variation in cost using a large national database. METHODS: We analyzed all patients who underwent LEB in the Premier database (2009-2015). Patients with concurrent cardiac surgery were excluded. Multivariable linear regression model was used to examine total in-hospital cost adjusting for patient demographics, clinical characteristics and hospital factors. RESULTS: A total of 32,224 patients were identified. Critical limb ischemia was present in 39.3% of the cohort. Mean age was 66.4 (12.7) years. The average total in-hospital LEB cost was Table. Multivariable Linear Regression Analysis of Total InHospital Cost Adjusted for Inflation
Factors
Age>65 vs age65 years female vs male sex Race White Black Hispanic Other Regions South Midwest Northeast West Teaching vs nonteaching hospital Urban vs rural hospital Critical Limb Ischemia vs claudicants Major amputation History of CHF
Adjusted mean difference, USD
95% Confidence Interval
p Value
713
495 e 930
<0.001
506
285 e 728
<0.001
Ref 2,245 3,958 612
1,935 e 2,552 2,613 e 5,302 296 e 927
<0.001 <0.001 <0.001
Ref 2,183 4,961 5,417 537
1,886 4,646 5,075 294
e e e e
<0.001 <0.001 <0.001 <0.001
-241 2,216
36,257 5,897
2,480 5,276 5,760 780
(-590) e 109 1,996 e 2,435
0.177 <0.001
35,245 e 37,269 <0.001 5,450 e 6,344
<0.001
Total n¼28, 832 after excluding influential points by Tukey Method.