Antifibrinolytics Are Not Associated With Reduced Blood Loss in Minimally-Invasive Endoscopic-Assisted Craniectomy for Repair of Single-Suture Craniosynostosis.

ABSTRACT: Minimally-invasive endoscopic-assisted craniectomy (EAC) achieves similar functional and cosmetic outcomes, whereas reducing morbidity risk that is often associated with complex cranial vault reconstruction. Antifibrinolytics (AF) usage to limit blood loss and transfusion requirements during complex cranial vault reconstruction has been studied extensively; however, studies are limited for AF therapy in EAC. The aim of this single-center retrospective observational cohort pilot study was to evaluate whether the use of AF was associated with reduced blood loss in infants undergoing EAC. The authors hypothesized that there would be no difference in blood loss between patients who received AF and those that did not receive AF during EAC. Non-syndromic patients who underwent single-suture EAC were retrospectively evaluated. Primary outcome measure was intraoperative calculated blood loss (mL/kg). Secondary outcome measures included perioperative red blood cells transfusion volumes, number of blood donor exposures, and pediatric intensive care unit and total hospital length of stay. Study cohort demographic and outcome data were analyzed; Fisher exact test was used for categorical data, Student t test was used for continuous data. A P value of <0.05 was considered statistically significant. Forty-nine EAC patients were included in the study with 34 patients in the AF cohort and 15 patients in the non-AF cohort. There were no significant differences in demographics between the 2 groups. Additionally, there was no significant difference in intraoperative calculated blood loss or any secondary outcome measure. In our single-suture EAC study cohorts, AF administration was not associated with a decrease in blood loss when compared to those that did not receive AF therapy.

Non-Invasive Venous waveform Analysis (NIVA) for volume assessment during complex cranial vault reconstruction: A proof-of-concept study in children.

BACKGROUND: Non-Invasive Venous waveform Analysis (NIVA) is novel technology that captures and analyzes changes in venous waveforms from a piezoelectric sensor on the wrist for hemodynamic volume assessment. Complex cranial vault reconstruction is performed in children with craniosynostosis and is associated with extensive blood loss, potential life-threatening risks, and significant morbidity. In this preliminary study, we hypothesized that NIVA will provide a reliable, non-invasive, quantitative assessment of intravascular volume changes in children undergoing complex cranial vault reconstruction. OBJECTIVE: To present proof-of-concept results of a novel technology in the pediatric population. METHODS: The NIVA prototype was placed on each subject's wrist, and venous waveforms were collected intraoperatively. Estimated blood loss and fluid/blood product administration were recorded in real time. Venous waveforms were analyzed into a NIVA value and then correlated, along with mean arterial pressure (MAP), to volume changes. Concordance was quantified to determine if the direction of change in volume was similar to the direction of change in MAP or change in NIVA. RESULTS: Of 18 patients enrolled, 14 had usable venous waveforms, and there was a significant correlation between change in NIVA value and change in volume. Change in MAP did not correlate with change in volume. The concordance between change in MAP and change in volume was less than the concordance between change in NIVA and change in volume. CONCLUSION: NIVA values correlate more closely to intravascular volume changes in pediatric craniofacial patients than MAP. This initial study suggests that NIVA is a potential safe, reliable, non-invasive quantitative method of measuring intravascular volume changes for children undergoing surgery.

Normal Saline solutions cause endothelial dysfunction through loss of membrane integrity, ATP release, and inflammatory responses mediated by P2X7R/p38 MAPK/MK2 signaling pathways.

Resuscitation with 0.9% Normal Saline (NS), a non-buffered acidic solution, leads to increased morbidity and mortality in the critically ill. The goal of this study was to determine the molecular mechanisms of endothelial injury after exposure to NS. The hypothesis of this investigation is that exposure of endothelium to NS would lead to loss of cell membrane integrity, resulting in release of ATP, activation of the purinergic receptor (P2X7R), and subsequent activation of stress activated signaling pathways and inflammation. Human saphenous vein endothelial cells (HSVEC) incubated in NS, but not buffered electrolyte solution (Plasma-Lyte, PL), exhibited abnormal morphology and increased release of lactate dehydrogenase (LDH), adenosine triphosphate (ATP), and decreased transendothelial resistance (TEER), suggesting loss of membrane integrity. Incubation of intact rat aorta (RA) or human saphenous vein in NS but not PL led to impaired endothelial-dependent relaxation which was ameliorated by apyrase (hydrolyzes ATP) or SB203580 (p38 MAPK inhibitor). Exposure of HSVEC to NS but not PL led to activation of p38 MAPK and its downstream substrate, MAPKAP kinase 2 (MK2). Treatment of HSVEC with exogenous ATP led to interleukin 1ß (IL-1ß) release and increased vascular cell adhesion molecule (VCAM) expression. Treatment of RA with IL-1ß led to impaired endothelial relaxation. IL-1ß treatment of HSVEC led to increases in p38 MAPK and MK2 phosphorylation, and increased levels of arginase II. Incubation of porcine saphenous vein (PSV) in PL with pH adjusted to 6.0 or less also led to impaired endothelial function, suggesting that the acidic nature of NS is what contributes to endothelial dysfunction. Volume overload resuscitation in a porcine model after hemorrhage with NS, but not PL, led to acidosis and impaired endothelial function. These data suggest that endothelial dysfunction caused by exposure to acidic, non-buffered NS is associated with loss of membrane integrity, release of ATP, and is modulated by P2X7R-mediated inflammatory responses.

Follow-up imaging of traumatic vertebral artery dissections is unnecessary in asymptomatic patients.

OBJECTIVE: Routine computed tomography (CT) imaging in trauma patients has led to increased recognition of blunt vertebral artery injuries (BVIs). We sought to determine the prevalence of strokes, injury progression, and need for intervention in patients with BVI. METHODS: Consecutive patients presenting with BVI during 2 years were identified from the institutional trauma registry. Inpatient records, imaging studies, and follow-up data were reviewed in detail from the electronic medical record. RESULTS: There were 76 BVIs identified in 70 patients (64% male; mean age, 47 ± 19 years); bilateral injuries occurred in 6 patients. Five patients who arrived at the hospital intubated had evidence of posterior circulation infarcts on admission CT, whereas one additional patient had evidence of a posterior circulation infarct attributed to complications of late spinal surgery. Four of the five patients with infarcts on admission CT survived to discharge, but only one had residual stroke symptoms. Minor (grade 1 or grade 2) injuries occurred in 25 (36%) patients; severe (grade 3 or grade 4) injuries occurred in 45 (64%). Twelve patients died of associated injuries (eight with severe BVI, four with minor BVI). Stepwise logistic regression analysis selected age (odds ratio, 1.14; confidence interval, 1.04-1.25; P < .001) and intubation on arrival (odds ratio, 450.4; confidence interval, 17.41-1645.51; P < .001) as independent predictors of hospital stroke and death. Of the 58 surviving to discharge, 31 (53%) returned for follow-up CT scans. Six of 10 (60%) patients with minor injuries had resolution or improvement compared with 3 of 21 (14%) with severe injuries (P = .027). One patient (10%) with a minor BVI and two patients (10%) with severe BVI had radiologic progression, but none were clinically significant. During a mean follow-up of 15 ± 13 months, none of the study patients had treatment (surgical or interventional) for BVI, and there were no delayed strokes. Only five patients in this series had vertebral pseudoaneurysms, which limits conclusions about this type of BVI. CONCLUSIONS: These data suggest that BVI-related strokes are present at the time of admission and do not have clinical sequelae. No late strokes occurred in this series, and no surgical or interventional treatments were required even in the presence of radiographic worsening. The relatively few cases of vertebral pseudoaneurysms in this series limit any conclusions about these specific lesions. However, these data indicate that follow-up imaging of nonaneurysmal BVI is not necessary in adults who are found to be asymptomatic on follow-up.

Nanotechnology Enabled Modulation of Signaling Pathways Affects Physiologic Responses in Intact Vascular Tissue.

IMPACT STATEMENT: Subarachnoid hemorrhage (SAH) is associated with vasospasm that is refractory to traditional vasodilators, and inhibition of vasospasm after SAH remains a large unmet clinical need. SAH causes changes in the phosphorylation state of the small heat shock proteins (HSPs), HSP20 and HSP27, in the vasospastic vessels. In this study, the levels of HSP27 and HSP20 were manipulated using nanotechnology to mimic the intracellular phenotype of SAH-induced vasospasm, and the effect of this manipulation was tested on vasomotor responses in intact tissues. This work provides insight into potential therapeutic targets for the development of more effective treatments for SAH induced vasospasm.

Unregulated saphenous vein graft distension decreases tissue viscoelasticity.

OBJECTIVES: Unregulated intraoperative distension of human saphenous vein (SV) graft leads to supraphysiologic luminal pressures and causes acute physiologic and cellular injury to the conduit. The effect of distension on tissue viscoelasticity, a biophysical property critical to a successful graft, is not well described. In this investigation, we quantify the loss of viscoelasticity in SV deformed by distension and compare the results to tissue distended in a pressure-controlled fashion. MATERIALS AND METHODS: Unmanipulated porcine SV was used as a control or distended without regulation and distended with an in-line pressure release valve (PRV). Rings were cut from these tissues and suspended on a muscle bath. Force versus time tracings of tissue constricted with KCl (110 mM) and relaxed with sodium nitroprusside (SNP) were fit to the Hill model of viscoelasticity, using mean absolute error (MAE) and r2-goodness of fit as measures of conformity. RESULTS: One-way ANOVA analysis demonstrated that, in tissue distended manually, the MAE was significantly greater and the r2-goodness of fit was significantly lower than both undistended tissues and tissues distended with a PRV (p<0.05) in KCl-induced vasoconstriction and SNP-induced vasodilation. CONCLUSIONS: Unregulated manual distension of SV graft causes loss of viscoelasticity and such loss may be mitigated with the use of an in-line PRV.

Upper Extremity Pulse Pressure Predicts Amputation-Free Survival after Lower Extremity Bypass.

Increased pulse pressure reflects pathologic arterial stiffening and predicts cardiovascular events and mortality. The effect of pulse pressure on outcomes in lower extremity bypass patients remains unknown. We thus investigated whether preoperative pulse pressure could predict amputation-free survival in patients undergoing lower extremity bypass for atherosclerotic occlusive disease. An institutional database identified 240 included patients undergoing lower extremity bypass from 2005 to 2014. Preoperative demographics, cardiovascular risk factors, operative factors, and systolic and diastolic blood pressures were recorded, and compared between patients with pulse pressures above and below 80 mm Hg. Factors were analyzed in bi- and multivariable models to assess independent predictors of amputation-free survival. Kaplan-Meier analysis was performed to evaluate the temporal effect of pulse pressure ≥80 mm Hg on amputation-free survival. Patients with a pulse pressure ≥80 mm Hg were older, male, and had higher systolic and lower diastolic pressures. Patients with pulse pressure <80 mm Hg demonstrated a survival advantage on Kaplan-Meier analysis at six months (log-rank P = 0.003) and one year (P = 0.005) postoperatively. In multivariable analysis, independent risk factors for decreased amputation-free survival at six months included nonwhite race, tissue loss, infrapopliteal target, and preoperative pulse pressure ≥80 mm Hg (hazard ratio 2.60; P = 0.02), while only tissue loss and pulse pressure ≥80 mm Hg (hazard ratio 2.30, P = 0.02) remained predictive at one year. Increased pulse pressure is independently associated with decreased amputation-free survival in patients undergoing lower extremity bypass. Further efforts to understand the relationship between increased arterial stiffness and poor outcomes in these patients are needed.

Prediction of Prolonged Ventilation after Coronary Artery Bypass Grafting: Data from an Artificial Neural Network.

OBJECTIVES: The need for mechanical ventilation 24 hours after coronary artery bypass grafting (CABG) is considered a morbidity by the Society of Thoracic Surgeons. The purpose of this investigation was twofold: to identify simple preoperative patient factors independently associated with prolonged ventilation and to optimize prediction and early identification of patients prone to prolonged ventilation using an artificial neural network (ANN). METHODS: Using the institutional Adult Cardiac Database, 738 patients who underwent CABG since 2005 were reviewed for preoperative factors independently associated with prolonged postoperative ventilation. Prediction of prolonged ventilation from the identified variables was modeled using both "traditional" multiple logistic regression and an ANN. The two models were compared using Pearson r2 and area under the curve (AUC) parameters. RESULTS: Of 738 included patients, 14% (104/738) required mechanical ventilation ≥ 24 hours postoperatively. Upon multivariate analysis, higher body-mass index (BMI; odds ratio [OR] 1.10 per unit, P < 0.001), lower ejection fraction (OR 0.97 per %, P = 0.01) and use of cardiopulmonary bypass (OR 2.59, P = 0.02) were independently predictive of prolonged ventilation. The Pearson r2 and AUC of the multivariate nominal logistic regression model were 0.086 and 0.698 ± 0.05, respectively; analogous statistics of the ANN model were 0.159 and 0.732 ± 0.05, respectively.BMI, ejection fraction and cardiopulmonary bypass represent three simple factors that may predict prolonged ventilation after CABG. Early identification of these patients can be optimized using an ANN, an emerging paradigm for clinical outcomes modeling that may consider complex relationships among these variables.

Calcification of Human Saphenous Vein Associated with Endothelial Dysfunction: A Pilot Histopathophysiological and Demographical Study.

While the pathophysiology and clinical significance of arterial calcifications have been studied extensively, minimal focus has been placed on venous calcification deposition. In this study, we evaluated the association between calcium deposition in human saphenous vein (HSV), endothelial function, and patient demographic risk factors. Fifty-four HSV segments were collected at the time of coronary artery bypass graft (CABG) surgery. The presence or absence of calcium deposits was visualized using the Von Kossa staining method. Endothelial function was determined by measuring muscle tissue contraction with phenylephrine and relaxation with carbachol in a muscle bath. Additional segments of vein underwent histologic evaluation for preexisting intimal thickness and extracellular matrix (ECM) deposition. Patient demographics data were obtained through our institution's electronic medical record, with patient consent. Calcium was present in 16 of 54 samples (29.6%). Veins with calcium deposits had significantly greater intimal-to-medial thickness ratios (p = 0.0058) and increased extracellular collagen deposition (p = 0.0077). Endothelial relaxation was significantly compromised in calcified veins vs. those without calcium (p = 0.0011). Significant patient risk factors included age (p = 0.001) and preoperative serum creatinine (p = 0.017). Calcified veins can be characterized as having endothelial dysfunction with increased basal intimal thickness and increased ECM deposition. Patient risk factors for calcium deposits in veins were similar to those for arteries, namely, advanced age and kidney disease. Further studies are needed to determine the effect of preexisting vein calcification on short- and long-term graft patency.

Hyperlactemia Predicts Surgical Mortality in Patients Presenting With Acute Stanford Type-A Aortic Dissection.

OBJECTIVE: Inspired by the limited facility of the Penn classification, the authors aimed to determine a rapid and optimal preoperative assessment tool to predict surgical mortality after acute Stanford type-A aortic dissection (AAAD) repair. DESIGN: Patients who underwent an attempted surgical repair of AAAD were determined using a de-identified single institution database. The charts of 144 patients were reviewed retrospectively for preoperative demographics and surrogates for disease severity and malperfusion. Bivariate analysis was used to determine significant (p≤0.05) predictors of in-hospital and 1-year mortality, the primary endpoints. Receiver operating characteristic curve generation was used to define optimal cut-off values for continuous predictors. SETTING: Single center, level 1 trauma, university teaching hospital. PARTICIPANTS: The study included 144 cardiac surgical patients with acute type-A aortic dissection presenting for surgical correction. INTERVENTIONS: Surgical repair of aortic dissection with preoperative laboratory samples drawn before patient transfer to the operating room or immediately after arterial catheter placement intraoperatively. MEASUREMENTS AND MAIN RESULTS: The study cohort comprised 144 patients. In-hospital mortality was 9%, and the 1-year mortality rate was 17%. Variables that demonstrated a correlation with in-hospital mortality included an elevated serum lactic acid level (odds ratio [OR] 1.5 [1.3-1.9], p<0.001), a depressed ejection fraction (OR 0.91 [0.86-0.96], p = .001), effusion (OR 4.8 [1.02-22.5], p = 0.04), neurologic change (OR 5.3 [1.6-17.4], p = 0.006), severe aortic regurgitation (OR 8.2 [2.0-33.9], p = 0.006), and cardiopulmonary resuscitation (OR 6.8 [1.7-26.9], p = 0.01). Only an increased serum lactic acid level demonstrated a trend with 1-year mortality using univariate Cox regression (hazard ratio 1.1 [1.0-1.1], p = 0.006). Receiver operating characteristic analysis revealed optimal cut-off lactic acid levels of 6.0 mmol/L and 6.9 mmol/L for in-hospital and 1-year mortality, respectively. CONCLUSION: Lactic acidosis, ostensibly as a surrogate for systemic malperfusion, represents a novel, accurate, and easily obtainable preoperative predictor of short-term mortality after attempted AAAD repair. These data may improve identification of patients who would not benefit from surgery.

Local Delivery of PHD2 siRNA from ROS-Degradable Scaffolds to Promote Diabetic Wound Healing.

Small interfering RNA (siRNA) delivered from reactive oxygen species-degradable tissue engineering scaffolds promotes diabetic wound healing in rats. Porous poly(thioketal-urethane) scaffolds implanted in diabetic wounds locally deliver siRNA that inhibits the expression of prolyl hydroxylase domain protein 2, thereby increasing the expression of progrowth genes and increasing vasculature, proliferating cells, and tissue development in diabetic wounds.

Aortic arch involvement worsens the prognosis of type B aortic dissections.

OBJECTIVE: Medical management of acute aortic dissections limited to the descending thoracic aorta (AD-desc) is associated with acceptable outcomes. Uncertainty remains about whether acute type B aortic dissections involving the aortic arch (AD-arch) have an increased risk of retrograde extension into the ascending aorta or other dissection-related complications. This study compared outcomes of AD-arch with AD-desc managed medically. METHODS: Consecutive patients admitted from 2005 to 2014 with acute aortic dissections not involving the ascending aorta were retrospectively analyzed. Primary end points included dissection-related death and operative intervention. RESULTS: The study included 99 patients (63% men; mean age, 60 ± 14 years) with acute aortic dissections. Dissections were limited to the aorta distal to the left subclavian artery (AD-desc) in 79 patients (80%), and 20 (20%) had involvement of the left subclavian (n = 16), left common carotid (n = 1), or innominate (n = 3) arteries (AD-arch). Dissections ended proximal to the celiac artery in 30 patients (30%), between the celiac artery and aortic bifurcation in 36 (36%), and distal to the aortic bifurcation in 33 (33%). During medical management, further proximal extension into the arch occurred in two AD-arch patients and one AD-desc patient (P < .05), but proximal dissection into the ascending aorta occurred in only one AD-arch patient with Marfan disease. Compared with patients with AD-desc, those with AD-arch were younger (53 ± 12.5 vs 62 ± 16 years; P < .01) and had more frequent early interventions (40% vs 19%; P = .047), cardiac complications (35% vs 11%; P < .01), and neurologic events (25% vs 6%; P < .01). Seven AD-arch patients (35%) and nine AD-desc patients (11%) died of dissection-related causes (P < .01). Among survivors, late interventions were performed in four of eight AD-arch patients (50%) and in six of 58 AD-desc patients (10%; P = .02). Medical treatment without intervention was successful in four AD-arch patients (20%) and in 52 AD-desc patients (66%; P < .001). Multivariate logistic regression retained arch involvement as the sole predictor of dissection-related death (odds ratio, 4.2; 95% confidence interval, 1.3-13.4) and failure of medical treatment (odds ratio, 7.7; 95% confidence interval, 2.5-29). The distal extent of dissection had no bearing on outcome. CONCLUSIONS: AD-arch dissections are associated with a higher risk of cardiac and neurologic events, need for early intervention, and dissection-related death than AD-desc dissections. Because further proximal dissections into the ascending aorta were rare in this study, medical management appears to be safe as the initial treatment of AD-arch dissections. However, surgeons should be aware of the increased risk of complications and the potential need for urgent interventions in these patients.

Red cell distribution width is a novel biomarker that predicts excess body-mass index loss 1 year after laparoscopic Roux-en-Y gastric bypass.

INTRODUCTION: Bariatric surgery is the most effective method for producing sustained weight loss, improving obesity-associated comorbidities and reducing inflammation in the morbidly obese population. The red cell distribution width (RDW) is a novel marker of inflammation that is usually reported as part of a complete blood count. In this study, we tested our hypothesis that red cell distribution width might represent a novel biomarker predictive of excess body-mass index loss (EBMIL) following laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Five hundred and forty-seven LRYGB patients included from a single institution were individually reviewed, noting both preoperative RDW and percent excess BMI loss at 6 months and 1 year post-LRYGB (%EBMIL180 and %EBMIL365, respectively). Bivariate and multivariate linear regression analysis was conducted between age, gender, initial body-mass index (BMI0) and RDW and each of the two endpoints, to assess the independence of RDW as a predictor of postoperative success. RESULTS: The median RDW was 13.9 (13.3-14.6) %, and median EBMIL180 and EBMIL365 were 55.4 (45.2-66.7) % and 71.3 (58.9-87.8) %, respectively. After controlling for age, gender and BMI0, RDW was associated with %EBMIL365 (B = -1.4 [-2.8 to -0.002] %, P = .05), but not %EBMIL180 (B = -0.6 [-1.6 to 0.5] %, P = .30. Upon Kruskal-Wallis analysis, patients with a preoperative RDW > 15.0 % had significantly lower %EBMIL than those in the <13.0 % (P < .001) and 13.0-15.0 % (P < .01) strata. CONCLUSIONS: RDW is predictive of EBMIL at 1 year following LRYGB. This represents a novel preoperative biomarker that may provide clinically useful prognostic information.

Preoperative Predictors of 30-Day Mortality and Prolonged Length of Stay after Above-Knee Amputation.

BACKGROUND: The above-knee amputation (AKA) is an operation of last resort with high postoperative morbidity and mortality. This study identifies preoperative risk factors predictive of both 30-day mortality and extended length of stay (LOS) in AKA patients. METHODS: Two hundred ninety-five AKA patients from 2004 to 2013 from a single institution were retrospectively reviewed using a deidentified electronic medical record. Rationally selected factors potentially influencing 30-day mortality and LOS were chosen, including demographics, etiologies, vascular surgical history, lifestyle factors, comorbidities, and laboratory values. Variables trending with one of the end points on bivariate analysis (P ≤ 0.10) were entered into multivariate forward stepwise regression models to determine independence as a risk factor (P ≤ 0.05). Subgroup analysis of AKA patients without a traumatic, burn, or malignant etiology was similarly conducted. RESULTS: Within the 295 patient cohort, 60% of the patients were male, 18% were African American, mean age was 58 years and mean body mass index was 28 kg/m(2). The 30-day mortality rate was 9%, and mean postoperative LOS of discharged patients was 9.3 days. Upon logistic regression, thrombocytopenia (platelet count < 250 × 10(6)/mL, P < 0.001, odds ratio 6.1) and preoperative septic shock (P = 0.02, odds ratio 5.1) were identified as independent risk factors for 30-day mortality. Upon linear regression, burn etiology (P < 0.001, B = 15.8 days), leukocytosis (white blood cell count > 12 × 10(6)/mL, P < 0.001, B = 6.2 days), and guillotine amputation (P < 0.001, B = 7.6 days) were independently associated with prolonged LOS. Excluding patients with AKAs due to trauma, burn, or malignancy, only thrombocytopenia (platelet count < 250 × 10(6)/mL, P < 0.001, odds ratio 10.2) and leukocytosis (white blood cell count > 12 × 10(6)/mL, P = 0.01, B = 5.2 days) were independent risk factors for in-hospital mortality and prolonged LOS, respectively. CONCLUSIONS: Preoperative septic shock and thrombocytopenia are independent risk factors for 30-day mortality after AKA, while burn etiology, leukocytosis, and guillotine amputation contribute to prolonged LOS. Awareness of these risk factors may help enhance both preoperative decision making and expectations of the hospital admission.

Brilliant blue FCF is a nontoxic dye for saphenous vein graft marking that abrogates response to injury.

BACKGROUND: Injury to saphenous vein grafts during surgical preparation may contribute to the subsequent development of intimal hyperplasia, the primary cause of graft failure. Surgical skin markers currently used for vascular marking contain gentian violet and isopropanol, which damage tissue and impair physiologic functions. Brilliant blue FCF (FCF) is a nontoxic dye alternative that may also ameliorate preparation-induced injury. METHODS: Porcine saphenous vein (PSV) was used to evaluate the effect of FCF on physiologic responses in a muscle bath. Cytotoxicity of FCF was measured using human umbilical venous smooth muscle cells. Effect of FCF on the development of intimal hyperplasia was evaluated in organ culture using PSV. Intracellular calcium fluxes and contractile responses were measured in response to agonists and inhibitors in rat aorta and human saphenous vein. RESULTS: Marking with FCF did not impair smooth muscle contractile responses and restored stretch injury-induced loss in smooth muscle contractility of PSV. Gentian violet has cytotoxic effects on human umbilical venous smooth muscle cells, whereas FCF is nontoxic. FCF inhibited intimal thickening in PSV in organ culture. Contraction induced by 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate and intracellular calcium flux were inhibited by FCF, oxidized adenosine triphosphate, KN-62, and brilliant blue G, suggesting that FCF may inhibit the purinergic receptor P2X7. CONCLUSIONS: Our studies indicated that FCF is a nontoxic marking dye for vein grafts that ameliorates vein graft injury and prevents intimal thickening, possibly due to P2X7 receptor inhibition. FCF represents a nontoxic alternative for vein graft marking and a potentially therapeutic approach to enhance outcome in autologous transplantation of human saphenous vein into the coronary and peripheral arterial circulation.

Impaired weight loss in laparoscopic adjustable gastric banding patients over 50 years of age: diabetes mellitus as an independent risk factor.

INTRODUCTION: Laparoscopic adjustable gastric banding (LAGB) represents a safe and effective bariatric procedure, particularly for patients over 50. Preoperative risk factors for impaired post-LAGB excess weight loss are not well characterized for this population. This study aimed to identify demographics, characteristics or comorbidities associated with excess weight loss at 6 and 12 months postoperatively (EWL180 and EWL365, respectively) for these patients. METHODS: One hundred and seventeen LAGB patients >50 years of age from 2005 to 2014 were retrospectively reviewed for factors potentially associated with EWL180 and EWL365. Rationally selected variables chosen for analysis included age, race, gender, initial body mass index and preoperative weight loss; comorbidities assessed included hypertension, psychiatric disorders and diabetes mellitus (DM). Variables correlated with EWL180 or EWL365 on bivariate linear regression analysis (P ≤ .05) were input into multivariate linear regression analysis to confirm independent association. RESULTS: Preoperative DM (B = -9.1% EWL; 95% CI -13.6, -4.5%; P < .001) and African-American race (B = -8.8% EWL; 95% CI -17.3, -0.3%; P = .05) were independent risk factors for impaired EWL180. Only DM was a risk factor for impaired EWL365 (B = -9.7% EWL; 95% CI -17.7, -1.8%; P = .02). CONCLUSIONS: LAGB is a successful operation in patients >50 years of age. Preoperative DM is an independent risk factor for impaired EWL in this cohort.

Prediction of excess weight loss after laparoscopic Roux-en-Y gastric bypass: data from an artificial neural network.

INTRODUCTION: Laparoscopic Roux-en-Y gastric bypass (LRYGB) has become the gold standard for surgical weight loss. The success of LRYGB may be measured by excess body mass index loss (%EBMIL) over 25 kg/m(2), which is partially determined by multiple patient factors. In this study, artificial neural network (ANN) modeling was used to derive a reasonable estimate of expected postoperative weight loss using only known preoperative patient variables. Additionally, ANN modeling allowed for the discriminant prediction of achievement of benchmark 50% EBMIL at 1 year postoperatively. METHODS: Six hundred and forty-seven LRYGB included patients were retrospectively reviewed for preoperative factors independently associated with EBMIL at 180 and 365 days postoperatively (EBMIL180 and EBMIL365, respectively). Previously validated factors were selectively analyzed, including age; race; gender; preoperative BMI (BMI0); hemoglobin; and diagnoses of hypertension (HTN), diabetes mellitus (DM), and depression or anxiety disorder. Variables significant upon multivariate analysis (P < .05) were modeled by "traditional" multiple linear regression and an ANN, to predict %EBMIL180 and %EBMIL365. RESULTS: The mean EBMIL180 and EBMIL365 were 56.4 ± 16.5 % and 73.5 ± 21.5%, corresponding to total body weight losses of 25.7 ± 5.9% and 33.6 ± 8.0%, respectively. Upon multivariate analysis, independent factors associated with EBMIL180 included black race (B = -6.3%, P < .001), BMI0 (B = -1.1%/unit BMI, P < .001), and DM (B = -3.2%, P < .004). For EBMIL365, independently associated factors were female gender (B = 6.4%, P < .001), black race (B = -6.7%, P < .001), BMI0 (B = -1.2%/unit BMI, P < .001), HTN (B = -3.7%, P = .03), and DM (B = -6.0%, P < .001). Pearson r(2) values for the multiple linear regression and ANN models were 0.38 (EBMIL180) and 0.35 (EBMIL365), and 0.42 (EBMIL180) and 0.38 (EBMIL365), respectively. ANN prediction of benchmark 50% EBMIL at 365 days generated an area under the curve of 0.78 ± 0.03 in the training set (n = 518) and 0.83 ± 0.04 (n = 129) in the validation set. CONCLUSIONS: Available at https://redcap.vanderbilt.edu/surveys/?s=3HCR43AKXR, this or other ANN models may be used to provide an optimized estimate of postoperative EBMIL following LRYGB.

Independent Preoperative Predictors of Prolonged Length of Stay after Laparoscopic Appendectomy in Patients Over 30 Years of Age: Experience from a Single Institution.

Prompt discharge after laparoscopic appendectomy (LA) is a marker of quality of care, fiscally desirable and feasible in select patients. Patients over 30 comprise a more heterogeneous cohort known to experience worse outcomes after LA. We aimed to identify easily available preoperative risk factors portending a postoperative length of stay ≥2 days among patients above age 30. In this investigation, 296 included patients from a single institution who underwent LA for acute appendicitis from 2010 to 2014 were retrospectively reviewed for preoperative demographics, laboratory studies, comorbidities, presentation characteristics, radiographic finding, and other rationally selected factors for association with postoperative length of stay ≥2 days. Bivariate and multivariate analysis was conducted to determine independent risk factors, which were subsequently modeled via receiver-operating characteristic curve generation and Kaplan-Meier analysis. "Classic" presentation [odds ratio (OR) = 0.5, P = .02], elevated red cell distribution width (RDW; OR = 1.5/% increase, P = 0.004) as well as evidence of rupture on CT (OR = 6.9, P < 0.001) were independently associated with postoperative length of stay ≥ 2 days. Modeling length of stay using these factors generated an area under the curve of 0.713 ± 0.037. Kaplan-Meier analysis of "classic" presentation, elevated RDW, and evidence of rupture on CT through the fifth postoperative day generated log-rank P values of 0.02, 0.05, and ≤ 0.001, respectively. In summary, lack of "classic" presentation, elevated RDW, and CT evidence of rupture are novel risk factors for prolonged postoperative length of stay in LA patients over 30. These findings may help target patients most appropriate for prompt discharge.

MK2 inhibitory peptide delivered in nanopolyplexes prevents vascular graft intimal hyperplasia.

Autologous vein grafts are commonly used for coronary and peripheral artery bypass but have a high incidence of intimal hyperplasia (IH) and failure. We present a nanopolyplex (NP) approach that efficiently delivers a mitogen-activated protein kinase (MAPK)-activated protein (MAPKAP) kinase 2 inhibitory peptide (MK2i) to graft tissue to improve long-term patency by inhibiting pathways that initiate IH. In vitro testing in human vascular smooth muscle cells revealed that formulation into MK2i-NPs increased cell internalization, endosomal escape, and intracellular half-life of MK2i. This efficient delivery mechanism enabled MK2i-NPs to sustain potent inhibition of inflammatory cytokine production and migration in vascular cells. In intact human saphenous vein, MK2i-NPs blocked inflammatory and migratory signaling, as confirmed by reduced phosphorylation of the posttranscriptional gene regulator heterogeneous nuclear ribonucleoprotein A0, the transcription factor cAMP (adenosine 3',5'-monophosphate) element-binding protein, and the chaperone heat shock protein 27. The molecular effects of MK2i-NPs caused functional inhibition of IH in human saphenous vein cultured ex vivo. In a rabbit vein transplant model, a 30-min intraoperative graft treatment with MK2i-NPs significantly reduced in vivo IH 28 days posttransplant compared with untreated or free MK2i-treated grafts. The decrease in IH in MK2i-NP-treated grafts in the rabbit model also corresponded with decreased cellular proliferation and maintenance of the vascular wall smooth muscle cells in a more contractile phenotype. These data indicate that nanoformulated MK2 inhibitors are a promising strategy for preventing graft failure.

Prediction of in-hospital mortality after ruptured abdominal aortic aneurysm repair using an artificial neural network.

OBJECTIVE: Ruptured abdominal aortic aneurysm (rAAA) carries a high mortality rate, even with prompt transfer to a medical center. An artificial neural network (ANN) is a computational model that improves predictive ability through pattern recognition while continually adapting to new input data. The goal of this study was to effectively use ANN modeling to provide vascular surgeons a discriminant adjunct to assess the likelihood of in-hospital mortality on a pending rAAA admission using easily obtainable patient information from the field. METHODS: Of 332 total patients from a single institution from 1998 to 2013 who had attempted rAAA repair, 125 were reviewed for preoperative factors associated with in-hospital mortality; 108 patients received an open operation, and 17 patients received endovascular repair. Five variables were found significant on multivariate analysis (P < .05), and four of these five (preoperative shock, loss of consciousness, cardiac arrest, and age) were modeled by multiple logistic regression and an ANN. These predictive models were compared against the Glasgow Aneurysm Score. All models were assessed by generation of receiver operating characteristic curves and actual vs predicted outcomes plots, with area under the curve and Pearson r(2) value as the primary measures of discriminant ability. RESULTS: Of the 125 patients, 53 (42%) did not survive to discharge. Five preoperative factors were significant (P < .05) independent predictors of in-hospital mortality in multivariate analysis: advanced age, renal disease, loss of consciousness, cardiac arrest, and shock, although renal disease was excluded from the models. The sequential accumulation of zero to four of these risk factors progressively increased overall mortality rate, from 11% to 16% to 44% to 76% to 89% (age ≥ 70 years considered a risk factor). Algorithms derived from multiple logistic regression, ANN, and Glasgow Aneurysm Score models generated area under the curve values of 0.85 ± 0.04, 0.88 ± 0.04 (training set), and 0.77 ± 0.06 and Pearson r(2) values of .36, .52 and .17, respectively. The ANN model represented the most discriminant of the three. CONCLUSIONS: An ANN-based predictive model may represent a simple, useful, and highly discriminant adjunct to the vascular surgeon in accurately identifying those patients who may carry a high mortality risk from attempted repair of rAAA, using only easily definable preoperative variables. Although still requiring external validation, our model is available for demonstration at https://redcap.vanderbilt.edu/surveys/?s=NN97NM7DTK.