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BACKGROUND Thrombosis in the neonatal population is rare, but increasing. Its incidence and management are not well understood. OBJECTIVES To investigate the incidence, associated factors, and management of thrombosis in the neonatal intensive care unit (NICU) population. PATIENTS/METHODS We performed a retrospective cohort study of infants admitted to a Pediatrix Medical Group-affiliated NICU from 1997 through 2015. We determined the prevalence of venous and arterial thrombosis, and assessed demographic characteristics and known risk factors. Categorical variables were compared with the Pearson χ2 test and continuous variables with Wilcoxon rank-sum tests. Stepwise logistic regression was used to identify associated factors. The primary outcome was incidence of thrombosis. Secondary analyses investigated correlations between clinical and demographic characteristics and thrombosis. RESULTS Among 1 158 755 infants, we identified 2367 (0.20%) diagnosed with thrombosis. In a multivariable regression analysis, prematurity, male sex, congenital heart disease, sepsis, ventilator support, vasopressor receipt, central venous catheter, invasive procedures, and receipt of erythropoietin were associated with increased risk of thrombosis, while Black race and Hispanic ethnicity were associated with reduced risk. The majority of infants diagnosed with thrombosis (73%) received no anticoagulation, but anticoagulant use in infants with thrombosis was higher than those without (27% versus 0.2%, P

Objective Congenital vascular malformations are a heterogeneous group of lesions with the potential to cause significant lifelong morbidity in children. Diagnosis and treatment of these lesions may be complex and require a multidisciplinary approach. Sclerotherapy is widely used for the treatment of low-flow vascular malformations (LFVMs) as an alternative to surgical resection in adults; however, limited data of its use in a pediatric setting are available. The purpose of this study was to evaluate the efficacy and safety of sclerotherapy for pediatric LFVMs. Methods In this retrospective study, we reviewed our multidisciplinary vascular malformations team database for all patients younger than 18 years treated for congenital vascular malformations from 2008 to 2017. Of these, patients with LFVM treated with foam sclerotherapy were included. Dynamic contrast-enhanced magnetic resonance imaging was used to select patients for sclerotherapy by the multidisciplinary team. Foam sclerotherapy was performed with either polidocanol or sodium tetradecyl sulfate. Patients' characteristics, including demographics, presenting symptoms, and anatomic location of malformation, were assessed. Outcomes included treatment response, number of procedures, and postprocedural complications. Results The 61 patients with 61 LFVMs included 27 boys (44.3%) and 34 girls (55.7%), with mean age of 10.3 years (standard deviation, ± 5.3 years). The cohort included 32 venous (52.5%), 16 lymphatic (26.2%), and 8 mixed venous and lymphatic (13.1%) malformations along with 5 (8.2%) associated with Klippel-Trenaunay syndrome. Primary indications for intervention included pain and swelling (n = 12 [19.6%]), pain alone (n = 23 [37.7%]), swelling alone (n = 15 [24.6%]), functional impairment (n = 8 [13.1%]), and bleeding (n = 3 [4.9%]). Anatomic distributions varied, with 13 head and neck (21.3%), 5 truncal (8.2%), 10 upper extremity (16.4%), 27 lower extremity (44.3%), and 6 diffuse (9.8%). Among the head and neck lesions, 8 (13.1%) extended to the face; and of the extremity lesions, 5 (8.2%) extended to the hand and 17 (27.9%) to the foot. Overall, sclerotherapy resulted in significant improvement or complete resolution of symptoms in 53 patients (86.9%). Complications were observed in seven patients (11.4%); six cases (9.8%) of superficial skin ulceration resolved without intervention, and one infection (1.6%) required antibiotics. No patients experienced adverse hemodynamic consequences or venous thromboembolism. Conclusions This series of pediatric LFVMs, the largest of its kind to date, demonstrates that sclerotherapy with foam-based agents effectively reduces symptoms with an acceptable rate of complications. Further study is needed to determine the optimal sclerosing agents for individual subsets of LFVMs in the pediatric population.

Pediatric patients require massive transfusion (MT) in a variety of settings. Multiple studies of adult MT support balanced ratio transfusion to improve outcomes; however, it is unclear if these findings can be extrapolated to pediatric populations. The use of balanced transfusion ratios, MT protocols, hemostatic adjuncts, and even the definition of a MT in children are all open questions. This review presents details of care from current practices in pediatric MT and summarizes practice strategies while providing insight from our single-center experience.PubMed, EMBASE, and Web of Science were searched using MeSH index and free-text terms for articles from 1946 to 2017. Articles were independently reviewed by two reviewers. Studies were assessed for definition of MT, factors predicting MT, MT complications, blood product ratios, hemostatic adjuncts, protocol logistics, and clinical outcomes.A heterogeneous composite of 29 articles was included in the analysis. Of these, 45% reported a formal transfusion protocol or adopted one during the study. Seven unique definitions of pediatric MT were reported; the most common was1 total blood volume within 24 hours. A total of 18,369 patients were assessed, and 1,163 received MT (6.3%). Overall mortality for patients requiring MT in studies reporting mortality was high (range 14.7% to 51.2%). We identified 14 patients receiving MT at our center with an age range of 8 months to 18 years and average transfusion of 38.1 mL/kg red blood cells (range: 22.1 mL/kg to 156.7 mL/kg).Current practices of pediatric MT demonstrate a variety of site-specific interventions with a persistently high mortality rate. A national focus on improving techniques of MT in children has the potential to save the lives of these children.Systematic review, levels IV and V.

BACKGROUND: No independent comparisons, with midterm follow-up, of standard arteriovenous grafts (SAVGs) and immediate-access arteriovenous grafts (IAAVGs) exist. The goal of this study was to compare “real-world” performance of SAVGs and IAAVGs. METHODS: Consecutive patients who underwent placement of a hemodialysis graft between November 2014 and April 2016 were retrospectively identified from the electronic medical record and Vascular Quality Initiative database at two tertiary centers. Only primary graft placements were included for analysis. Patients were divided into two groups based on the type of graft implanted. Patients’ comorbidities, graft configuration, operative characteristics, and follow-up were collected and analyzed with respect to primary and secondary patency. Additional outcomes included graft-related complications, time to first cannulation, time to tunneled catheter removal, catheter-related complications, and overall survival. Patency was determined from the time of the index procedure; χ(2), Kaplan-Meier, and Cox regression analyses were used, with the P value set as significant at < .05. RESULTS: There were 210 grafts identified, 148 SAVGs and 62 IAAVGs. At baseline, the patients’ characteristics were similar between groups, except for a greater prevalence of preoperative central venous occlusions in the IAAVG group (16.3% vs6.8%; P < .04). Of the IAAVG group, 50 were Acuseal (W. L. Gore & Associates, Flagstaff, Ariz) and 12 were Flixene (Atrium Medical Corporation, Hudson, NH). Primary patency was similar at both 1 year (SAVG, 39.4%; IAAVG, 56.7%; P = .4) and 18 months (SAVG, 29.0%; IAAVG, 43.7%; P = .4). Secondary patency was similar at 1 year (SAVG, 50.7%; IAAVG, 52.1%; P = .73) and 18 months (SAVG, 42.3%; IAAVG, 46.3%; P = .73). Overall survival was 48% at 24 months. IAAVG patients required fewer overall additional procedures to maintain patency (mean number of procedures, 0.99 for SAVGs vs 0.61 for IAAVGs; P = .025). There was no difference in occurrence of steal syndrome (SAVG, 6.8%; IAAVG, 8.1%; P = .74) or graft infection (SAVG, 19.0%; IAAVG, 12.0%; P = .276). Seventy-five percent of all grafts were successfully cannulated, with shorter median time to first cannulation in the IAAVG group (6 days; interquartile range [IQR], 1–19 days) compared with the SAVG group (31 days; IQR, 26–47 days; P < .01). Of all pre-existing catheters, 65.75% were removed, with a shorter median time until catheter removal in the IAAVG cohort at 34 days (IQR, 22–50 days) vs 49 days (IQR, 39–67 days) in the SAVG group (P < .01). Catheter-related complications occurred less frequently in the IAAVG group (16.4% vs 2.9%; P < .045). CONCLUSIONS: IAAVGs allow earlier cannulation and tunneled catheter removal, thereby significantly decreasing catheter-related complications. Patency and infection rates were similar between SAVGs and IAAVGs, but fewer secondary procedures were performed in IAAVGs.

Bleeding and thrombosis in critically ill infants and children is a vexing clinical problem. Despite the relatively low incidence of bleeding and thrombosis in the overall pediatric population relative to adults, these critically ill children face unique challenges to hemostasis due to extreme physiologic derangements, exposure of blood to foreign surfaces and membranes, and major vascular endothelial injury or disruption. Caring for pediatric patients on extracorporeal support, recovering from solid organ transplant or invasive surgery, and after major trauma is often complicated by major bleeding or clotting events. As our ability to care for the youngest and sickest of these children increases, the gaps in our understanding of the clinical implications of developmental hemostasis have become increasingly important. We review the current understanding of the development and function of the hemostatic system, including the complex and overlapping interactions of coagulation proteins, platelets, fibrinolysis, and immune mediators from the neonatal period through early childhood and to young adulthood. We then examine scenarios in which our ability to effectively measure and treat coagulation derangements in pediatric patients is limited. In these clinical situations, adult therapies are often extrapolated for use in children without taking age-related differences in pediatric hemostasis into account, leaving clinicians confused and impacting patient outcomes. We discuss the limitations of current coagulation testing in pediatric patients before turning to emerging ideas in the measurement and management of pediatric bleeding and thrombosis. Finally, we highlight opportunities for future research which take into account this developing balance of bleeding and thrombosis in our youngest patients.

Background Phyllodes tumors are fibroepithelial breast lesions that are uncommon in women and rare among children. Due to scarcity, few large pediatric phyllodes tumor series exist. Current guidelines do not differentiate treatment recommendations between children and adults. We examined national guideline adherence for children and adults. Methods We queried the NCDB (2004–2014) for female patients with phyllodes tumor histology, excluding patients with missing age or survival data. Patients were stratified by age (pediatric Results We identified 2787 cases of phyllodes tumor (2725 adult, 62 pediatric). Median age was 17 years in children and 52 years in adults. Margin positivity rates and median tumor size were similar between adults and children. Treatment was discordant with NCCN guidelines in 28.6% of adults and 14.5% of children through use of axillary staging, chemotherapy, adjuvant endocrine therapy, and radiotherapy. Five-year and ten-year survival were comparable between both groups. Conclusion Children and adults present with similarly sized phyllodes tumors. Trends reveal high margin positivity rates, and overtreatment with regional axillary staging and systemic adjuvant therapies. Particularly in children, treatment decisions must consider risks of adjuvant therapy including radiation-related second primary cancers, given uncertain benefit. Type of Study Retrospective Comparative Study. Level of Evidence Level III.

Cardiopulmonary bypass (CPB) is essential for the repair of many congenital cardiac defects in infants but is associated with significant derangements in hemostasis and systemic inflammation. As a result, hemorrhagic complications and thrombosis are major challenges in the management of children requiring CPB or extracorporeal membrane oxygenation. Conventional clinical laboratory tests capture individual hemostatic derangements (low platelets, elevated fibrinogen) but fail to describe the complex, overlapping interactions among the various components of coagulation, including cellular interactions, contact activation, fibrinolysis, and inflammation. Given recent advances in analytic tools for identifying protein-protein interactions in the plasma proteome, we hypothesized that an unbiased proteomic analysis would help identify networks of interacting proteins for further investigation in pediatric CPB.Infants up to 1 y of age were enrolled. Plasma samples were collected at 0, 1, 4, and 24 h after CPB. Mass spectrometry was used to identify proteins undergoing changes in concentration after CPB, and STRING and ToppGene tools were used to identify biological networks. Two-dimensional difference gel electrophoresis identified changes in protein concentrations. Inflammatory markers were assessed by enzyme-linked immunosorbent assay at the same time points.Ten infants with cardiac anomalies requiring surgery and CPB were enrolled; no major complications were recorded (median age, 127.5 d; interquartile range, 181.25 d). Using two-dimensional difference gel electrophoresis,1400 individual protein spots were observed, and 89 proteins demonstrated change in concentration30% with P 0.02 when comparing 1, 4, or 24 h to baseline. Among protein spots with significant changes in concentration after CPB, 29 were identified with mass spectrometry (33%). In our interrogation of functional associations among these differentially expressed proteins, our results were dominated by the acute phase response, coagulation, and cell signaling functional categories. Among cytokines analyzed by enzyme-linked immunosorbent assay, IL-2, IL-8, and IL-10 were elevated at 4 h but normalized by 24 h, whereas IL-6 was persistently elevated.Infants manifest a robust response to CPB that includes overlapping, complex pathways. Further investigation of interactions among immune, coagulation, and cell signaling systems may lead to novel therapeutics or biomarkers useful in the management of infants requiring CPB.

This study aimed to define morbidities and costs related to modern-day medical care for children with vascular anomalies. We reviewed the 2003–2009 Kids’ Inpatient Database for pediatric patients (age

OBJECTIVES To examine the effect of implementing postcatheterization ultrasound (US) on femoral arterial thrombosis detection rates and factors associated with thrombosis in infants. BACKGROUND Although femoral arterial thrombosis is an uncommon complication of cardiac catheterization, it can cause limb threatening complications. Previous studies assessing the utility of postprocedure US to detect thrombosis in infants have utilized US as an adjunct to standard clinical detection methods, are small scale, or include small cohorts of infants within older populations. METHODS We reviewed institutional records of patients 0-12 months undergoing catheterization from 2007 to 2016. Demographics and procedural data were compared between the thrombosis and non-thrombosis group. Pre- and post-US groups were compared for detected thrombosis rate. Using univariate and multivariable analyses, we identified factors associated with thrombosis. RESULTS In total, 270 patients underwent 509 catheterizations, with 40 (7.9%) documented thromboses. The rate of thrombus detection in patients younger than 6 months increased from 8.3% to 23.4% (P = 0.006) after implementing routine US. On multivariable analysis, lower weight (P

The breadth of technical skills included in general surgery training continues to expand. The current competency-based training model requires assessment tools to measure acquisition, learning, and mastery of technical skill longitudinally in a reliable and valid manner. This study describes a novel skills assessment tool, the Omni, which evaluates performance in a broad range of skills over time.The 5 Omni tasks, consisting of open bowel anastomosis, knot tying, laparoscopic clover pattern cut, robotic needle drive, and endoscopic bubble pop, were developed by general surgery faculty. Component performance metrics assessed speed, accuracy, and quality, which were scaled into an overall score ranging from 0 to 10 for each task. For each task, ANOVAs with Scheffé's post hoc comparisons and Pearson's chi-squared tests compared performance between 6 resident cohorts (clinical years (CY1-5) and research fellows (RF)). Paired samples t-tests evaluated changes in performance across academic years. Cronbach's alpha coefficient determined the internal consistency of the Omni as an overall assessment.The Omni was developed by the Department of Surgery at Duke University. Annual assessment and this research study took place in the Surgical Education and Activities Lab.All active general surgery residents in 2 consecutive academic years spanning 2015 to 2017.A total of 62 general surgery residents completed the Omni and 39 (67.2%) of those residents completed the assessment in 2 consecutive years. Based on data from all residents' first assessment, statistically significant differences (p0.05) were observed among CY cohorts for bowel anastomosis, robotic, and laparoscopic task metrics. By pair-wise comparisons, mean bowel anastomosis scores distinguished CY1 from CY3-5 and CY2 from CY5. Mean robotic scores distinguished CY1 from RF, and mean laparoscopic scores distinguished CY1 from RF, CY3, and CY5 in addition to CY2 from CY3. Mean scores in performance on the knot tying and endoscopic tasks were not significantly different. Statistically significant improvement in mean scores was observed for all tasks from year 1 to year 2 (all p0.02). The internal consistency analysis revealed an alpha coefficient of 0.656.The Omni is a novel composite assessment tool for surgical technical skill that utilizes objective measures and scoring algorithms to evaluate performance. In this pilot study, 3 tasks demonstrated discriminative ability of performance by CY, and all 5 tasks demonstrated construct validity by showing longitudinal improvement in performance. Additionally, the Omni has adequate internal consistency for a formative assessment. These results suggest the Omni holds promise for the evaluation of resident technical skill and early identification of outliers requiring intervention.

Blunt cerebrovascular injury (BCVI) is a rare consequence of blunt trauma. There appears to be benefit to an aggressive approach to screening for BCVI due to catastrophic sequelae of unrecognized injury. However, screening for BCVI carries extensive cost and oncologic risk to young patients. Foundational BCVI studies examined adults primarily, leaving question to the effectiveness of these criteria in children. We sought to evaluate BCVI screening criteria developed in primarily adult populations using a nationally representative pediatric dataset.We queried the 2008-2014 National Trauma Data Bank for patients with BCVI. Patients were stratified by age (adults18yrs, pediatric≤18yrs). Screening factors from the Modified Denver Criteria and Modified Memphis Criteria (GCS≤8, C1C3 cervical fracture, cervical subluxation, seatbelt sign, basilar skull fracture, mid-facial fracture, mandibular fracture, significant blood loss, coma, stroke, and hanging) were examined using univariate analysis and backwards-stepwise logistic regression to verify predictors of BCVI.Blunt injury occurred in 2,174,244 adults and 422,181 children; 5970 adults and 809 children sustained BCVI. In univariate analysis, all screening factors correlated with BCVI in both groups (p 0.001). When comparing BCVI patients, children more commonly experienced GCS≤8, seatbelt sign, basilar skull fracture, mid-facial fracture, mandibular fracture, and coma (p 0.05). In multivariable analysis, seatbelt sign was not associated with pediatric BCVI.Many adult-associated BCVI risk factors apply to children. Although children more commonly experience seatbelt sign, it does not independently cause increased BCVI risk. Given the rarity of pediatric BCVI, prospective multi-institutional studies are warranted to establish screening criteria specific to children.

Endovascular approaches have replaced open surgical revascularization in most patients with mesenteric ischemia; however, flush ostial occlusions may not be amenable to traditional antegrade access. Retrograde mesenteric stenting has been previously described, but this technique requires a formal laparotomy and dissection of the proximal superior mesenteric artery. We present here a modification of this technique that requires only a "mini-laparotomy" and no open vascular repair of the superior mesenteric artery as well as a review of our initial institutional experience with this procedure. Our approach differs from previously described work by minimizing mesenteric dissection, avoiding the need for repair of an arteriotomy, and limiting the size of the laparotomy incision in this population of profoundly comorbid patients.

Background Renal medullary carcinoma (RMC) is an aggressive malignancy seen predominantly in young males with sickle cell trait. RMC is poorly understood, with fewer than 220 cases described in the medical literature to date. We used a large national registry to define the typical presentation, treatments, and outcomes of this rare tumor. Methods The National Cancer Database was queried for patients under 40 years of age diagnosed with RMC from 1998 to 2011. An analysis of patient and tumor characteristics, treatment details, and overall survival (OS) was undertaken, and factors associated with mortality were identified using multivariable regression analysis. Results In total, 159 patients with RMC were identified, of whom a majority were male (71%), African American (87%), and had metastatic disease (71%). Median tumor size was 6 cm and median survival was 7.7 months. Most patients underwent surgery (60%) and chemotherapy (65%). Few patients received radiation (12%). Patients with metastatic disease had a significantly worse median survival (4.7 vs. 17.8 months, P < 0.001) and were less likely to receive surgery (42% vs. 91%, P < 0.001). Age and tumor size did not appear to impact OS. Conclusion In the largest cohort to date of patients with RMC, we found a dismal median survival of less than 8 months. Age and tumor size were not associated with OS. Metastatic disease at presentation was the main negative prognostic indicator in RMC and was present in a majority of patients at the time of diagnosis.

Post-operative atrial fibrillation (POAF) is common after cardiac surgery. However, few studies examine the effect on early and late outcomes following thoracic aortic surgery. Patients (n=993) who underwent proximal aortic surgery, without pre-operative atrial fibrillation (n=135), at a single

Objective The 2010 endovascular aneurysm repair (EVAR) trial 2 (EVAR 2) reported that patients with comorbidity profiles rendering them unfit for open aneurysm repair who underwent EVAR did not experience a survival advantage compared with those who did not undergo intervention. These patients experienced a 30-day mortality of 7.3%, whereas reports from similar cohorts reported far lower mortality rates. The primary objective of our study was to compare the incidence of 30-day mortality in low- and high-risk patients undergoing EVAR in a contemporary data set, using patient risk stratification criteria from EVAR 2. Secondarily, we sought to identify risk factors associated with a disproportionate contribution to 30-day mortality risk. Methods Data were obtained from the 2005 to 2013 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data Files (N = 24,813). Patients were included in the high-risk cohort with the presence of renal, respiratory, or cardiac preoperative criteria alone or in combination. Renal impairment criteria were defined as dialysis and creatinine concentration >2.26 mg/dL. Respiratory impairment criteria included history of chronic obstructive pulmonary disease and preoperative ventilator support. Cardiac impairment criteria included history of myocardial infarction, congestive heart failure, angina, and prior coronary intervention. Patient and procedural characteristics and 30-day postoperative outcomes were compared using Pearson χ 2 tests for categorical variables and Wilcoxon rank sum tests for continuous variables. Results Among 24,813 patients undergoing EVAR, 12,043 (48%) patients were characterized as high risk (at least one impairment criterion); 12,770 (52%) patients were stratified as low risk. The 30-day mortality rate was 1.9% in the high-risk cohort compared with the 7.3% reported by EVAR 2, and it was higher in the high-risk cohort compared with the low-risk cohort (1.9% vs 0.9%; P P = .005; cardiac OR, 1.55; 95% CI, 1.14-2.10; P = .005), the presence of renal criteria disproportionately increased the odds of mortality threefold (OR, 3.42; 95% CI, 2.31-5.09; P Conclusions Contemporary 30-day mortality after EVAR in high-risk patients is substantially lower than that reported in the EVAR 2 trial. Whereas low- and high-risk stratification by current comorbidity criteria is appropriate, attention needs to be paid to disproportionate risk contribution from renal disease to mortality compared with cardiac and pulmonary comorbidities. Given the lower mortality risk than previously described, patients stratified as high risk should be thoughtfully considered for definitive EVAR.

Background: Venous thromboembolism (VTE) is an uncommon but clinically significant postoperative complication in children. Incidence of VTE in pediatric patients ranges from 34-58 per 10,000 hospitalized children1. Due to rarity of these events, there is limited information about the factors predisposing children to VTE after surgery. We queried a national surgical database to identify risks and outcomes associated with VTE in pediatric surgical patients. Methods: The National Surgical Quality Improvement Program-Pediatric (NSQIP) is a prospectively collected database that records pediatric surgical information, surgical approaches, and 30 day patient outcomes. The database was queried for the years 2012-2013 to identify pediatric patients (age < 18) who had received surgical intervention and were diagnosed with postoperative VTE. Because of their separate coding in NSQIP, we defined VTE as including venous thromboembolism, or pulmonary embolism (PE) diagnosed radiographically within 30 days of operation. To reduce non-random differences between patients we used propensity scores based on age, sex, race, BMI, and ASA classification to match patients in a 1:2 ratio using the nearest neighbor method. Using univariate and multivariate analysis, we identified preoperative risk factors associated with VTE. Results: In total, 130 patients were identified who developed VTE postoperatively (VTE n=122, PE n=7, BOTH PE + VTE n= 1) from this database of 114,395 patients. There were 104 patients with VTE that also had complete entries and were subsequently analyzed in this study. Surgical specialties treating patients in this analysis included cardiothoracic surgery, general surgery, neurosurgery, orthopedic surgery, otolaryngology, plastic surgery, and urology. Eighty-one unique operative CPT codes were identified for patients with VTE. Patients who developed VTE had increased operative time, anesthesia time, and total length of stay (all p < 0.001). Multivariate analysis demonstrated that pneumonia (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.3 - 2.29), Central Line Associated Bloodstream Infection (CLABSI) (OR 1.69, 95% CI 1.18 - 2.42), sepsis (OR 1.47, 95% CI 1.18 - 1.82), septic shock (OR 1.36, 95% CI 1.06 - 1.75), and current solid or hematologic malignancy or active treatment of malignancy (OR 1.30, 95% CI 1.08 - 1.58) were all statistically significant risk factors associated with development of VTE (all p < 0.05). Conclusions: Postoperative VTE risk is significantly increased in children with malignancy or severe infections. Further research is needed to understand the mechanism between malignancy, systemic inflammation, and VTE risk in children. These findings may help to identify patients in need of prophylactic treatment in order to reduce postoperative thrombotic risk in pediatric patients. References: 1. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics. 2009;124(4):1001-1008. Disclosures No relevant conflicts of interest to declare.

Purpose: Circulating cell-free DNA in blood may originate from cell necrosis, apoptosis, or NETosis. NETosis is a recently described inflammatory process in which neutrophils release a meshwork of DNA fibers called neutrophil extracellular traps (NETs) to attack microorganisms. Higher levels of cell-free DNA have been observed in patients with sepsis and malignancy, and it may be linked to arterial thrombosis as well. We examined changes in cell-free DNA in infants who experienced acute, iatrogenic thrombosis of the femoral artery after arterial catheterization to better understand the role of cell-free DNA in clot formation. Methods: Plasma samples were collected from infants < 1 year of age with congenital heart disease during cardiac catheterization. Post-procedurally, femoral artery thrombus formation at the site of sheath insertion was detected by ultrasound. Cell-free DNA was quantified at two time points (before and after arterial catheterization) in three infants who developed femoral artery thrombus after catheterization and three age-matched controls. Cell-free DNA was also quantified from plasma of normal adults as a comparison. Results: At baseline,cell-free DNA level for the infant cohort was similar to that in normal adults (13.9 ng/mL vs. 10.3 ng/mL, p = 0.20, Figure). After arterial catheterization, cell-free DNA was increased from baseline in all infants (51.0 ng/mL vs. 13.9 ng/ml, p = 0.004). However, infants who developed femoral artery thrombus after catheterization did not demonstrate higher cell-free DNA after arterial injury, compared to the control group (47.1 ng/mL vs. 54.9 ng/ml, p = 0.83). Conclusions: Cell-free DNA is significantly and consistently elevated in infants after arterial catheterization. As part of NETosis, cell-free DNA may serve as an inflammatory mediator in infants who experience arterial injury. We plan to confirm the findings of this pilot study in a larger human infant cohort as well as in a piglet model of vascular injury. Figure Cell-free DNA levels in infants, before and after arterial catheterization, in comparison to normal adults. Figure. Cell-free DNA levels in infants, before and after arterial catheterization, in comparison to normal adults. Disclosures No relevant conflicts of interest to declare.

More than 30 years after demonstration that survival after breast conservation surgery (BCS) and adjuvant radiotherapy is equivalent to survival after mastectomy,1 significant variability in the implementation of BCS remains, particularly in the rates of reoperation for margins. Breast conservation surgery is the most common oncologic operation performed in the United States, with a measurable financial and physical burden caused by repeated excisions. In this issue of JAMA Surgery, the study by Isaacs et al2 reports a mean 90-day reoperation rate of 30.9% from 2003 to 2013 in New York State, with a significant decrease over time from 38.5% to 23.1%. This study shows that almost onethird of the reoperations results in mastectomy. In 2014, Wilke et al3 similarly demonstrated that within the National Cancer Database from 2004 to 2010, the rates of repeated operations after BCS decreased from 25% to 22%. This change is seen within the context of efforts to define adequate margins for BCS.4 The recent Society for Surgical Oncology–American Society for Radiation Oncology (SSOASTRO) consensus guidelines encourage the use of “no ink on tumor” as the current standard in an era of multimodal treatment and evolving understanding of tumor biology along with tumor burden. In fact, this approach to reexcisions echoes the conclusion of Fisher et al5(p1722) in 1986 after review of pathologic findings from the National Surgical Adjuvant Breast Project that “it is most appropriate to regard lines of resection involved only when cancer is transected,” because subjective designations of close margins resulted in second operations with a low yield of residual cancer. Isaacs et al2 report notable intersurgeon variability, with rates of reoperations ranging from 0% to 100%. Studies have shown significant surgeon and institutional variation in clinical practice,6 althoughwithout data regardingmarginwidth, the proportion of this variation attributable to interpretation ofmargin status isunknown. Sourcesof inconsistencymay include surgeon training and volume, radiographic evaluation, andpathologic processing. In addition, subjective elements of surgeon bias may play a role because the authors’ multivariable analysis demonstrated that repeated excisions were significantlymore likely inyoungerpatients and thosewith fewer comorbidities.2 Establishing a rational, evidence-based approach to reexcision as originally proposedbyFisher et al5 and that has been supported by the new SSO-ASTRO guidelines has the potential to provide substantial national cost savings by eliminating reexcisions for closebutnegativemargins.7As theseguidelines for margin status are widely adopted, identification of persistent outliers to these guidelines and assessment of the effect of this practice change on surgical outcomes and value of care for early stage breast cancer should remain important goals.