Antithrombin III infusion improves anticoagulation in congenital diaphragmatic hernia patients on extracorporeal membrane oxygenation.

PURPOSE: Achieving effective anticoagulation during neonatal extracorporeal membrane oxygenation (ECMO) without increasing the risk of hemorrhage remains challenging. The use of antithrombin III (AT-III) for this purpose has been examined, but studies have been limited to intermittent bolus dosing. We aimed to evaluate the efficacy and safety of an institutionally developed AT-III continuous infusion protocol in neonates receiving ECMO for the treatment of congenital diaphragmatic hernia (CDH). METHODS: In this single center, retrospective study, all neonates with a CDH who received ECMO support during the study period were included. Data on anticoagulation labs and therapy, life-threatening bleeding, and circuit changes were analyzed. RESULTS: Eleven patients were divided into two groups: patients with AT-III continuous infusion (n = 5) and without (n = 6). There were no differences in the gestational age (p = 0.29), sex (p = 1.00), ECMO duration (p = 0.59), or initial AT-III levels (p = 0.76) between groups. Patients in the AT-III infusion group had on average 18.5% higher AT-III levels (p < 0.0001). Patients receiving continuous AT-III infusions spent a significantly higher percentage of ECMO time within the therapeutic range, measured using anti-Factor Xa levels (64.9±4.2% vs. 29.1±8.57%, p = 0.008), and required fewer changes to the heparin infusion rate (6.48±0.88 vs 2.38±0.36 changes/day changes/day, p = 0.005). Multivariate analysis revealed continuous infusion of AT-III did not increase the rate of intracranial or surgical bleeding (p = 0.27). CONCLUSION: AT-III as a continuous infusion in CDH neonates on ECMO provides a decreased need to modify heparin infusion and more consistent therapeutic anticoagulation without increasing the risk of life-threatening bleeding.

VEGF blockade enables oncolytic cancer virotherapy in part by modulating intratumoral myeloid cells.

Understanding the host response to oncolytic viruses is important to maximize their antitumor efficacy. Despite robust cytotoxicity and high virus production of an oncolytic herpes simplex virus (oHSV) in cultured human sarcoma cells, intratumoral (ITu) virus injection resulted in only mild antitumor effects in some xenograft models, prompting us to characterize the host inflammatory response. Virotherapy induced an acute neutrophilic infiltrate, a relative decrease of ITu macrophages, and a myeloid cell-dependent upregulation of host-derived vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, bevacizumab and r84, the latter of which binds VEGF and selectively inhibits binding to VEGF receptor-2 (VEGFR2) but not VEGFR1, enhanced the antitumor effects of virotherapy, in part due to decreased angiogenesis but not increased virus production. Neither antibody affected neutrophilic infiltration but both partially mitigated virus-induced depletion of macrophages. Enhancement of virotherapy-mediated antitumor effects by anti-VEGF antibodies could largely be recapitulated by systemic depletion of CD11b(+) cells. These data suggest the combined effect of oHSV virotherapy and anti-VEGF antibodies is in part due to modulation of a host inflammatory reaction to virus. Our data provide strong preclinical support for combined oHSV and anti-VEGF antibody therapy and suggest that understanding and counteracting the innate host response may help enable the full antitumor potential of oncolytic virotherapy.

Vascular endothelial growth factor receptor-2 inhibition in experimental murine colitis.

BACKGROUND: In the setting of inflammatory bowel disease, inflammation is associated with a simultaneous increase in angiogenesis; moreover, elevated vascular endothelial growth factor (VEGF) levels implicate angiogenesis as a pathologic contributor to disease severity. We hypothesize that selectively inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) in a model of murine colitis will reduce angiogenesis, resulting in decreased inflammation and disease severity, providing mechanistic insight into the role of pathologic angiogenesis in IBD. MATERIALS AND METHODS: In a dextran sodium sulfate model of murine colitis, anti-VEGFR2 monoclonal antibody (DC101) or placebo was administered. Clinical assessments followed by histologic and molecular tissue analysis were performed to quantify inflammation, microvessel density (MVD), VEGF and VEGFR2 gene expression, and phosphorylated mitogen-activated protein kinase protein expression. RESULTS: Weight loss began after d 6 with the treatment group demonstrating a more favorable percent weight change. Inflammation and MVD were similar between cohorts, both increasing in parallel toward a plateau. VEGF and VEGFR2 messenger RNA expression were not significantly different, but phosphorylated mitogen-activated protein kinase was elevated in the DC101 cohort (P = 0.03). CONCLUSIONS: Despite a more favorable weight change profile in the treated group, no difference was observed between cohorts regarding clinical disease severity. However, a parallel rise in inflammation and MVD was observed coinciding with weight loss, suggesting their relationship in IBD. VEGFR2 downstream signaling was significantly elevated in the treated cohort, possibly by VEGF-independent signal transduction. Early and effective inhibition of angiogenesis by limiting downstream VEGF signaling or targeting multiple angiogenic pathways may block angiogenesis, thereby reducing disease severity and provide evidence toward the mechanism and clinical benefit of antiangiogenics in the setting of IBD.

Neonatal venoarterial and venovenous ECMO.

ECMO remains an important support tool in the treatment of neonates with reversible congenital cardiopulmonary diseases. There are specific circumstances that call for either venoarterial (VA) or venovenous (VV) ECMO in neonates. While limited by the infant's the size and gestational age, ECMO can confer exceptional survival rates to a number of neonates who can often develop without devastating complications. However, it remains a labor and time intensive endeavor, which may be impractical or unattainable in resource-limited environments. While adult and pediatric ECMO indications and equipment options have expanded in recent years, neonatal ECMO continues to be a niche subspecialty requiring specific expertise and technical skill, especially considering the ever-changing neonatal physiology in the setting of cardiopulmonary support. It is critical to recognize the unique approaches to cannulation options, imaging, vessel management, anticoagulation, and monitoring protocols to achieve optimal outcomes. Thus, it becomes nearly impossible to separate the role of pediatric surgeons from the continuous involvement with and management of neonatal ECMO patients. This necessitates that pediatric surgeons in ECMO centers continue to hone their expertise and remain heavily involved in neonatal ECMO. This section reviews the most critical current approaches and unresolved controversies in neonatal ECMO with special attention to the practical aspects and decisions a surgeon faces in initiation and termination of neonatal ECMO.

Impact of institutional prophylaxis guidelines on rates of pediatric venous thromboembolism following trauma-A multicenter study from the pediatric trauma society research committee.

BACKGROUND: A paucity of data exists with regard to the incidence, management, and outcomes of venous thromboembolism (VTE) in injured children. We sought to determine the impact of institutional chemoprophylaxis guidelines on VTE rates in a pediatric trauma population. METHODS: A retrospective review of injured children (≤15 years) admitted between 2009 and 2018 at 10 pediatric trauma centers was performed. Data were gathered from institutional trauma registries and dedicated chart review. The institutions were surveyed as to whether they had chemoprophylaxis guidelines in place for high-risk pediatric trauma patients, and outcomes were compared based on the presence of guidelines using χ 2 analysis ( p < 0.05). RESULTS: There were 45,202 patients evaluated during the study period. Three institutions (28,359 patients, 63%) had established chemoprophylaxis policies during the study period ("Guidelines"); the other seven centers (16,843 patients, 37%) had no such guidelines ("Standard"). There were significantly lower rates of VTE in the Guidelines group, but these patients also had significantly fewer risk factors. Among critically injured children with similar clinical presentations, there was no difference in VTE rate. Specifically within the Guidelines group, 30 children developed VTE. The majority (17/30) were actually not indicated for chemoprophylaxis based on institutional guidelines. Still, despite protocols only one VTE patient in the guidelines group who was indicated for intervention ended up receiving chemoprophylaxis prior to diagnosis. No consistent ultrasound screening protocol was in place at any institution during the study. CONCLUSION: The presence of an institutional policy to guide chemoprophylaxis for injured children is associated with a decreased overall frequency of VTE, but this disappears when controlling for patient factors. However, the overall efficacy is impacted by a combination of deficits in guideline compliance and structure. Further prospective data are needed to help determine the ideal role for chemoprophylaxis and protocols in pediatric trauma. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

EGFR inhibition fails to suppress vascular proliferation and tumor growth in a Ewing's sarcoma model.

BACKGROUND: Expression of epidermal growth factor receptor (EGFR), a potent regulator of cellular homeostasis, is associated with aggressive tumor behavior. The mechanism by which EGFR inhibition functions is unclear, with controversial results demonstrating an effect on the tumor cells, endothelial cells, or pericytes. EGFR activation has been linked to the expression of vascular endothelial growth factor (VEGF), a known mitogen of angiogenesis, but the relationship between these factors and their effect on tumor vessel development is vague. We hypothesized that using an EGFR inhibitor on a human Ewing's sarcoma model would inhibit tumor growth by suppressing vessel proliferation. METHODS: A cell proliferation assay was performed on the Ewing's sarcoma (SK-NEP-1) cell line. Tumor cells were implanted intrarenally in athymic mice. Animals received daily gavage with vehicle or gefitinib 1 wk following implantation. Mice (n = 12/cohort) were euthanized 6 wk following implantation. Remaining mice were maintained without treatment for 2 wk. Vascular changes were assessed by angiography and immunohistochemically. EGFR and vascular endothelial growth factor (VEGF) expression were quantified using quantitative polymerase chain reaction (qPCR). RESULTS: Gefitinib suppressed in vitro cell growth with an IC(50) = 1.36 µM. Minimal tumor growth suppression was noted at 6 wk (6.01 ± 1.2 g in control versus 4.61 ± 0.9 g treated, P = 0.36). After cessation of gefitinib, tumor growth was increased in both groups (7.37 ± 1.62 g versus 6.77 ± 1.53 g, P = 0.79). Microvessel density was unchanged despite EGFR inhibition (161,000 ± 16,000 pixels versus 135,000 ± 18,000 pixels, P = 0.31). At 6 wk, the vascular maturity index was similar in both groups (3.63 ± 1.12 versus 4.09 ± 1.71, P = 0.83). A downward trend in EGFR expression (49% of control) and an upward trend in VEGF levels (50% of control) occurred in the treated group. CONCLUSIONS: EGFR expression was suppressed in cultured cells and xenograft tumors. Despite a cytotoxic effect on cell lines, gefitinib had little effect on tumor growth. No effects on the tumor vasculature were noted in the setting of EGFR suppression, suggesting that angiogenesis induced by SK-NEP-1 cells is refractory to EGFR inhibition. Interestingly, the resulting increase in VEGF expression following EGFR blockade, provides an alternative pro-angiogenic pathway promoting tumor survival.

Running the Obstacle Course: Improving the Utilization of Bariatric Surgery in Adolescent Obesity.

The obesity epidemic in the adolescent population continues to worsen despite increased awareness. Although there is an improved understanding of the role of bariatric surgery in the treatment of obesity in adolescents, a number of barriers still prevent its widespread utilization. The lack of formal obesity-focused education in the training curricula of primary care providers (PCPs), coupled with variable distribution of comprehensive resources, creates an inhospitable environment for effective anti-obesity treatment in adolescents. In addition, racial disparities and variability in insurance coverage contribute to the complexity of this problem. The coronavirus disease 2019 (COVID-19) pandemic has exacerbated the rate of childhood obesity and emphasized the need for bariatric surgery as an adjunctive treatment. This article highlights 3 barriers to bariatric surgery: (1) hesitation to refer for surgery; (2) limitation in available resources; and (3) racial disparities in anti-obesity treatment. Potential systemic solutions to such obstacles are examined.

Venous thromboembolic risk stratification in pediatric trauma: A Pediatric Trauma Society Research Committee multicenter analysis.

BACKGROUND: Venous thromboembolism (VTE) in injured children is rare, but its consequences are significant. Several risk stratification algorithms for VTE in pediatric trauma exist with little consensus, and all are hindered in development by relying on registry data with known inaccuracies. We performed a multicenter review to evaluate trauma registry fidelity and confirm the effectiveness of one established algorithm across diverse centers. METHODS: Local trauma registries at 10 institutions were queried for all patients younger than 18 years admitted between 2009 and 2018. Additional chart review was performed on all "VTE" cases and random non-VTE controls to assess registry errors. Corrected data were then applied to our prediction algorithm using 10 real-time variables (Glasgow Coma Scale, age, sex, intensive care unit admission, transfusion, central line placement, lower extremity/pelvic fracture, major surgery) to calculate VTE risk scores. Contingency table classifiers and the area under a receiver operator characteristic curve were calculated. RESULTS: Registries identified 52,524 pediatric trauma patients with 99 episodes of VTE; however, chart review found that 13 cases were misclassified for a corrected total of 86 cases (0.16%). After correction, the algorithm still displayed strong performance in discriminating VTE-fated encounters (sensitivity, 69%; area under the receiver operating characteristic curve, 0.96). Furthermore, despite wide institutional variability in VTE rates (0.04-1.7%), the algorithm maintained a specificity of >91% and a negative predictive value of >99.7% across centers. Chart review also revealed that 54% (n = 45) of VTEs were directly associated with a central line, usually femoral (n = 34, p < 0.001 compared with upper extremity), and that prophylaxis rates were underreported in the registries by about 50%; still, only 19% of the VTE cases had been on prophylaxis before diagnosis. CONCLUSION: The VTE prediction algorithm performed well when applied retrospectively across 10 diverse pediatric centers using corrected registry data. These findings can advance initiatives for VTE screening/prophylaxis guidance following pediatric trauma and warrant prospective study. LEVEL OF EVIDENCE: Clinical decision rule evaluated in a single population, level III.

Parental attitudes toward bariatric surgery in adolescents with obesity.

BACKGROUND: Parental underestimation of the severity and risks of their child's obesity and parents' potential implicit weight bias contribute to the reluctance to consider bariatric surgery for their adolescent children with obesity. Despite evidence for safety and efficacy of bariatric surgery in adolescents, pediatric providers may be hesitant or uncomfortable to discuss the benefits and refer patients for surgical evaluation. Understanding these barriers is an essential step toward effective long-term care in this patient population. OBJECTIVES: We hypothesized that parental views on bariatric surgery are primarily influenced by personal experiences with bariatric surgery, their implicit bias, understanding of health risks of obesity, and counseling by pediatric providers. SETTING: Data were collected and analyzed at an academic medical center in the United States. METHODS: After a retrospective chart review of 192 adolescents with obesity, a telephone survey of patients' parents was conducted. RESULTS: Parents of 71.4% of patients who received outpatient weight loss counseling had accurate recollection of that event. Only 12.8% of parents who were referred to lifestyle programs successfully enrolled. Neither prior personal exposure to bariatric surgery nor enrollment of the child in a lifestyle program increased parents' likelihood to consider bariatric surgery for their child (P = .10 and .70, respectively). Most parents (84.6%) who were counseled by their pediatric provider about bariatric surgery would consider it, compared with only 34.5% of the parents who did not receive counseling (P < .001). CONCLUSIONS: Counseling by pediatric providers, not involvement in lifestyle programs or exposure to bariatric surgery, increased parents' willingness to consider bariatric surgery for their child. Given the current recommendations to incorporate bariatric surgery as a treatment modality in severe adolescent obesity, earlier counseling about the role of surgery by pediatric providers is essential. More detailed provider education on the current state of bariatric surgery in the treatment of severe adolescent obesity is also necessary.

Complications of bariatric surgery in adolescents.

Over the past decade, outcomes data have demonstrated the benefit of bariatric surgery in achieving both sustained weight loss and reversal of co-morbidities. Comparing these data to contemporary known risks of adolescent bariatric surgery informs the patients and providers considering bariatric procedures and provides insight into potential ways to reduce and manage complications. The goal of this article is to review the common surgical and postoperative complications following bariatric procedures and discuss approaches to improve their safety. A systematic review identifying bariatric surgery complications in adolescents was conducted. The review focused on the data relevant to adolescent bariatric surgery. However, when necessary, adult studies were used to address the gaps in available pediatric information. The data pertaining to the intraoperative, short term, and long term surgically related and nutritional related complications show that complication are declining with increasing experience. Specific recommendations and strategies to avoid major complications of bariatric surgery in adolescents are offered.

Two conventional protein kinase C isoforms, alpha and beta I, are involved in the ATP-induced activation of volume-regulated anion channel and glutamate release in cultured astrocytes.

Volume-regulated anion channels (VRACs) are activated by cell swelling and are permeable to inorganic and small organic anions, including the excitatory amino acids glutamate and aspartate. In astrocytes, ATP potently enhances VRAC activity and glutamate release via a P2Y receptor-dependent mechanism. Our previous pharmacological study identified protein kinase C (PKC) as a major signaling enzyme in VRAC regulation by ATP. However, conflicting results obtained with potent PKC blockers prompted us to re-evaluate the involvement of PKC in regulation of astrocytic VRACs by using small interfering RNA (siRNA) and pharmacological inhibitors that selectively target individual PKC isoforms. In primary rat astrocyte cultures, application of hypoosmotic medium (30% reduction in osmolarity) and 20 microM ATP synergistically increased the release of excitatory amino acids, measured with a non-metabolized analog of L-glutamate, D-[(3)H]aspartate. Both Go6976, the selective inhibitor of Ca(2+)-sensitive PKCalpha, betaI/II, and gamma, and MP-20-28, a cell permeable pseudosubstrate inhibitory peptide of PKCalpha and betaI/II, reduced the effects of ATP on D-[(3)H]aspartate release by approximately 45-55%. Similar results were obtained with a mixture of siRNAs targeting rat PKCalpha and betaI. Surprisingly, down-regulation of individual alpha and betaI PKC isozymes by siRNA was completely ineffective. These data suggest that ATP regulates VRAC activity and volume-sensitive excitatory amino acid release via cooperative activation of PKCalpha and betaI.

Bariatric Surgery Needs a Seat at the Children's Table: Bridging the Perception and Reality of the Role of Bariatric Surgery in the Treatment of Obesity in Adolescents.

The long-term morbidity of obesity in adolescents is well recognized nationally and represents a major health concern for the population of the near future. Traditional medical management of obesity focuses on addressing behavioral modification, dietary and exercise programs, and, to a lesser degree, pharmaceuticals. Although these strategies are relatively effective, they suffer from the lack of sustained benefit, a high relapse rate, and, in case of pharmacotherapy, potentially dangerous adverse effects. Bariatric surgery in adolescents has often been characterized as a risky intervention with unknown long-term benefits. However, recent data establish that a sustained, clinically meaningful effect on weight loss, as well as a reduction in chronic morbidities related to obesity, can be achieved. The role of bariatric surgery as an accepted adjunctive strategy in the treatment of obesity in adolescents is becoming more recognized; however, a number of barriers exist that prevent the timely evaluation of adolescents with obesity for potential surgical intervention. We examine these barriers in light of recent advancements to help better define the role of bariatric surgery in the treatment of obesity in adolescent population.

The evaluation of clopidogrel use in perioperative general surgery patients: a prospective randomized controlled trial.

BACKGROUND: The perioperative safety profile of clopidogrel, a potent antiplatelet agent used in the management of cardiovascular disease, is unknown, and there are no evidence-based guidelines recommending for either its interruption or continuation at this time. The aim of this study was to determine whether patients who are maintained on clopidogrel before general surgical procedures are at increased risk of perioperative bleeding complications. METHODS: Patients receiving clopidogrel at the time of elective general surgery were randomized to either discontinue clopidogrel 1 week before surgery (group A) or continue clopidogrel into surgery (group B). All other antiplatelet and anticoagulant agents were discontinued before surgery. The primary end points were perioperative bleeding requiring intraoperative or postoperative transfusion of blood or blood components and bleeding-related readmission, reoperation, or mortality within 90 days of surgery. The secondary end points were perioperative myocardial infarction or cerebrovascular accidents within 90 days of surgery. RESULTS: Thirty-nine patients were enrolled and underwent 43 general surgical operations. Twenty-one procedures were randomized to group A and 22 to group B. The most commonly performed individual procedures were open inguinal hernia repair (23%), laparoscopic cholecystectomy (21%), open ventral hernia repair (15%), laparoscopic ventral hernia repair (11%), and laparoscopic inguinal hernia repair (9%). No perioperative mortalities, bleeding events requiring blood transfusion, or reoperations occurred. One readmission for intra-abdominal hematoma requiring percutaneous drainage occurred in each group (group A: 4.8% vs group B: 4.5%; P = 1.0). No myocardial infarctions or cerebrovascular accidents were observed or reported. CONCLUSIONS: The outcomes from this prospective study suggest that, patients undergoing commonly performed elective general surgical procedures can be safely maintained on clopidogrel without increased perioperative bleeding risk.

Angiogenesis and Vascular Endothelial Growth Factor-A Expression Associated with Inflammation in Pediatric Crohn's Disease.

BACKGROUND AND AIMS: Angiogenesis is a component of chronic inflammatory diseases including inflammatory bowel disease. Some studies describe increased angiogenesis associated with acute disease in adult Crohn's disease and ulcerative colitis, while animal models aid investigations of mechanism and pathophysiology of angiogenesis. We aim to explore the role of angiogenesis and its pathways in pediatric Crohn's disease. METHODS: Surgical specimens were obtained from pediatric Crohn's disease (both inflamed and non-inflamed regions of ileum) and control patients. Samples were examined for inflammation, microvessel density, and molecular expression of vascular endothelial growth factor-A, platelet-derived growth factor-ß, angiopoietin-1, and angiopoietin-2. RESULTS: Angiogenesis and inflammation were increased in parallel in Crohn's disease compared to controls. We also discovered increased angiogenesis in Crohn's disease tissue that was relatively free of inflammatory disease. Vascular endothelial growth factor-A gene expression (P = 0.034) was elevated in Crohn's disease over controls, while gene expression of platelet-derived growth factor-ß (P = 0.069), angiopoietin-1 (P = 0.206), and angiopoietin-2 (P = 0.082) was not significantly elevated. CONCLUSIONS: We confirm that inflammation-associated angiogenesis is upregulated in pediatric Crohn's disease. This population also exhibits elevated mucosal angiogenesis at the surgical margin with limited inflammation. This suggests that angiogenesis is an additional pathologic characteristic to potentially identify normal mucosa and margins of surgical resection that are uninvolved with disease and, furthermore, may have implications for monitoring complete disease remission. We further identify the vascular endothelial growth factor-A pathway involvement in the disease process, which may serve as a future molecular target for anti-angiogenic therapy in inflammatory bowel disease.

Pretreatment with anti-VEGF therapy may exacerbate inflammation in experimental acute colitis.

AIM: Our previous investigations of angiogenesis in inflammatory bowel disease showed that vascular endothelial growth factor (VEGF) blockade reduced colonic neovascularization and inflammation. We hypothesized that pretreatment with bevacizumab, a monoclonal anti-VEGF antibody, would attenuate the severity of angiogenesis and inflammation in a murine model of colitis. METHODS: C57BL/6 mice were treated with intraperitoneal injections of bevacizumab (250 µg/dose) before induction of colitis with dextran sulfate sodium (DSS). The colons were examined at predetermined time points. Colonic inflammation and microvessel density were assessed microscopically. RESULTS: All mice acutely developed melena and weight loss (18.8% ± 1.1% control vs 20.2% ± 1.1% treated, P = .37) and regained a similar weight percentage after the recovery (26.5% ± 4.0% vs 20.9% ± 4.4%, P = .37). Microvessel density acutely increased in both groups in response to DSS, with a trend toward inhibited angiogenesis in the treated group at the conclusion of the acute phase (194,100 ± 14,240 vs 149,400 ± 17,590 µm(2), P = .11). Bevacizumab-treated mice exhibited significantly increased inflammation after the acute phase (8.3 ± 0.8 vs 13.0 ± 2.0, P = .05), but were similar to control after the recovery (7.3 ± 1.5 vs 5.5 ± 1.0, P = .27). CONCLUSIONS: Preemptive VEGF inhibition does not significantly attenuate angiogenesis and, in fact, worsens inflammation in a model of acute colitis. Preventive VEGF blockade may disrupt healing and exacerbate injury via alternative angiogenic or inflammatory pathways.

Cessation of clopidogrel before major abdominal procedures.

OBJECTIVE: To determine whether timing of clopidogrel bisulfate cessation influences outcome after abdominal operations. METHODS: A review was performed of 104 patients receiving clopidogrel who underwent abdominal operations between March 2003 and March 2009. Patients were grouped by last clopidogrel use: group A (<7 days) and group B (≥7 days). RESULTS: Of 104 patients, 43 were in group A and 61 were in group B. Overall, 6 deaths occurred (group A, 5 patients [12%] vs group B, 1 [2%]; P = .03) and 27 patients required intensive care unit admission (group A, 16 patients [37%] vs group B, 11 [18%]; P = .03). Twenty-one patients developed a postoperative bleeding complication; 19 complications were managed by blood transfusion and 2 required reoperation. Group A vs group B had significantly increased rates of postoperative bleeding requiring blood transfusion (13 patients [30%] vs 8 [13%]; P = .03). No significant difference in postoperative bleeding resulting in reoperation or mortality was demonstrated. Timing of clopidogrel cessation within 7 days did not affect postoperative bleeding risk. Eighty-nine patients (86%) underwent elective operations (group A, 30 patients [70%] vs group B, 59 [97%]; P < .001). While elective patients in group A vs those in group B demonstrated a trend toward increased risk of postoperative bleeding requiring transfusion (7 patients [23%] vs 8 [14%]; P = .25), no significant difference in intensive care unit admission (group A, 6 patients [20%] vs group B, 9 [15%]; P = .31) or mortality (1 [3%] vs 1 [2%]; P = .62) was demonstrated. CONCLUSIONS: While clopidogrel use within 7 days of an operation significantly increased the risk of postoperative bleeding, most bleeding episodes were successfully managed by transfusion without an increase in bleeding-related mortality or necessity for reoperation. After controlling for operative urgency, no significant difference in mortality or intensive care unit admission was demonstrated in patients undergoing elective procedures. High-risk patients undergoing elective operations may not require preoperative clopidogrel cessation. When clopidogrel cessation is warranted, 7 days before the procedure is recommended. Perioperative risk does not vary by timing of cessation within 7 days of an operation.