Utility of a Benchmarking Report for Balancing Infection Prevention and Antimicrobial Stewardship in Children with Complicated Appendicitis.

OBJECTIVE: To develop a severity-adjusted, hospital-level benchmarking comparative performance report for postoperative organ space infection and antibiotic utilization in children with complicated appendicitis. BACKGROUND: No benchmarking data exist to aid hospitals in identifying and prioritizing opportunities for infection prevention or antimicrobial stewardship in children with complicated appendicitis. METHODS: This was a multicenter cohort study using NSQIP-Pediatric data from 16 hospitals participating in a regional research consortium, augmented with antibiotic utilization data obtained through supplemental chart review. Children with complicated appendicitis who underwent appendectomy from 07/01/2015 to 06/30/2020 were included. Thirty-day postoperative OSI rates and cumulative antibiotic utilization were compared between hospitals using observed-to-expected (O/E) ratios after adjusting for disease severity using mixed effects models. Hospitals were considered outliers if the 95% confidence interval for O/E ratios did not include 1.0. RESULTS: 1790 patients were included. Overall, the OSI rate was 15.6% (hospital range: 2.6-39.4%) and median cumulative antibiotic utilization was 9.0 days (range: 3.0-13.0). Across hospitals, adjusted O/E ratios ranged 5.7-fold for OSI (0.49-2.80, P=0.03) and 2.4-fold for antibiotic utilization (0.59-1.45, P<0.01). Three (19%) hospitals were outliers for OSI (1 high and 2 low performers), and eight (50%) were outliers for antibiotic utilization (5 high and 3 low utilizers). Ten (63%) hospitals were identified as outliers in one or both measures. CONCLUSIONS: A comparative performance benchmarking report may help hospitals identify and prioritize quality improvement opportunities for infection prevention and antimicrobial stewardship, as well as identify exemplar performers for dissemination of best practices.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Health Literacy and Health-care Resource Utilization Following Gastrostomy Tube Placement in Pediatric Patients.

INTRODUCTION: Parental health literacy and neighborhood socioeconomic disadvantage are associated with adverse health outcomes and increased health-care resource utilization in children. We sought to evaluate the association between community-level health literacy and neighborhood socioeconomic disadvantage and their relationships with outcomes of pediatric patients undergoing gastrostomy tube (GT) placement. METHODS: Pediatric patients who underwent GT placement from 2000 to 2019 were identified using the IBM MarketScan Research database. Claims data were merged with the health literacy index (HLI) and area deprivation index (ADI), measures of community-level health literacy and neighborhood socioeconomic disadvantage, respectively. We used multivariate logistic regression to estimate factors associated with postoperative 30- and 90-day ED visits (EVs) and 30-day readmissions. RESULTS: A total of 4374 pediatric patients underwent GT placement. In this cohort, 6.1% and 11.4% had 30-day and 90-day EV; and 30-day readmissions in 19.75%. HLI was lower in those with 30-(244.6 ± 6.1 versus 245.4 ± 6.1; P = 0.0482) and 90-(244.5 ± 5.8 versus 245.5 ± 6.1; P = 0.001) day EV, and 30-day readmission (244.5 ± 5.56 versus 245.4 ± 6.1; P = 0.001) related to GT. ADI was lower in those with 90-day EV (55.1 ± 13.1 versus 55.9 ± 14.6; P = 0.0244). HLI was associated with decreased odds of 30- (adjusted odds ratio: 0.968; 95% confidence interval: 0.941-0.997) and 90-day (adjusted odds ratio: 0.975; 95% confidence interval: 0.954-0.998) EV following GT placement. ADI was also significantly associated with 30 and 90-day EV following GT placement. CONCLUSIONS: In pediatric patients undergoing GT placement, higher ecologically-measured health literacy and neighborhood socioeconomic disadvantage are associated with decreased health-care resource utilization, as evidenced by decreased ED visits. Future studies should focus on the role of individual parental health literacy in outcomes of pediatric surgical patients.

Measuring Pectus Excavatum Severity, External Caliper, or Cross-Sectional Imaging: Family Perceptions.

INTRODUCTION: Patients with pectus excavatum (PE) often undergo cross-sectional imaging (CSI) to quantify severity for insurance authorization before surgical repair. The modified percent depth (MPD), an external caliper-based metric, was previously validated to be similar to the pectus index and correction index. This study explored family perceptions of CSI and MPD with respect to value and costs. METHODS: This is a cross-sectional survey study including families of patients enrolled in an ongoing prospective multicenter study evaluating the use of MPD as an alternative to CSI for quantifying PE severity. Families of PE patients who underwent both MPD and CSI completed a survey to determine their perceptions of MPD and costs of CSI. Responses were described and associations were evaluated using chi squared, Wilcoxon rank-sum test and logistic regression as appropriate. Statistical significance was set to 0.05. RESULTS: There were 136 surveys completed for a response rate of 88%. Respondents were confident in MPD (86%) and confident in its similarity to CSI (76%). Families of females were less confident in the measurements than males (55% versus 80%, P = 0.02; odds ratio 0.30 (0.11, 0.83). Obtaining CSI required time off work/school in 90% and a copay in 60%. Nearly half (49%) of respondents reported CSI was a time/financial hardship. Increasing copay led to decreased reassurance in CSI (55%: copay > $100 versus 77%: lower copay/75%: no copay; P = 0.04). CONCLUSIONS: From the family perspective, MPD is valuable in assessing the severity of PE. Obtaining CSI was financially burdensome, particularly for those with higher copays. MPD measurements provide high value at low cost in assessing the severity of PE.

Use of Antipseudomonal Antibiotics is not Associated with Lower Rates of Postoperative Drainage Procedures or More Favorable Culture Profiles in Children with Complicated Appendicitis: Results from a Multicenter Regional Research Consortium.

OBJECTIVE: To compare rates of postoperative drainage and culture profiles in children with complicated appendicitis treated with the two most common antibiotic regimens with and without antipseudomonal activity (piperacillin-tazobactam [PT] and ceftriaxone with metronidazole [CM]). SUMMARY OF BACKGROUND DATA: Variation in use of antipseudomonal antibiotics has been driven by a paucity of multicenter data reporting clinically relevant, culture-based outcomes. METHODS: Retrospective cohort study of patients with complicated appendicitis (7/2015-6/2020) using NSQIP-Pediatric data from 15 hospitals participating in a regional research consortium. Operative report details, antibiotic utilization, and culture data were obtained through supplemental chart review. Rates of 30-day postoperative drainage and organism-specific culture positivity were compared between groups using mixed effects regression to adjust for clustering after propensity matching on measures of disease severity. RESULTS: 1002 children met criteria for matching (58.9% received CM and 41.1% received PT). In the matched sample of 778 patients, children treated with PT had similar rates of drainage overall (PT: 11.8%, CM: 12.1%; OR 1.44 [OR:0.71-2.94]) and higher rates of drainage associated with growth of any organism (PT: 7.7%, CM: 4.6%; OR 2.41 [95%CI:1.08-5.39]) and Escherichia coli (PT: 4.6%, CM: 1.8%; OR 3.42 [95%CI:1.07-10.92]) compared to treatment with CM. Rates were similar between groups for drainage associated with multiple organisms (PT: 2.6%, CM: 1.5%; OR 3.81 [95%CI:0.96-15.08]) and Pseudomonas (PT: 1.0%, CM: 1.3%; OR 3.42 [95%CI:0.55-21.28]). CONCLUSIONS AND RELEVANCE: Use of antipseudomonal antibiotics is not associated with lower rates of postoperative drainage procedures or more favorable culture profiles in children with complicated appendicitis.

Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial.

BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023. CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

Cost of Pediatric Trauma: A Comparison of Non-Accidental and Accidental Trauma in Pediatric Patients.

BACKGROUND: Nonaccidental trauma (NAT) affects >100,000 children in the United States every year and is associated with significant mortality and morbidity. Little is known about the financial burden of NAT, particularly in comparison to accidental trauma (AT). We sought to compare hospital charges and outcomes between children presenting with NAT and AT. METHODS: Pediatric (<16 y) trauma hospitalizations from 2006 to 2018 were identified using the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) and Kid's Inpatient Sample (KID) databases. Hospitalizations were identified as NAT or AT based on ICD codes. Discharge weights were used to obtain national estimates and standardize them across the different sampling structures. Outcomes (hospital charges, length of stay (LOS), and mortality) were compared, and multivariate regression analyses were used to assess independent predictors of hospital charges and mortality. RESULTS: Fifty-eight Thousand Two Hundred Seventy-five pediatric hospitalizations were included with 17,954 (0.3%) categorized as NAT. Children with NAT were younger, more female, less likely to identify as White, and more under public insurance than those with AT. Hospital charges were significantly higher in patients with NAT ($27,100 versus $19,900, P < 0.0001). Mortality (4.9% versus 0.0%, P < 0.0001) and LOS (3.2 d versus 1.5 d, P < 0.0001) were significantly higher among patients with NAT. Multivariable regression analyses identified NAT as a predictor of higher hospital charges, mortality, and LOS. CONCLUSIONS: Nonaccidental trauma in pediatric patients is associated with significantly higher hospital charges, mortality, and LOS than accidental trauma. Ongoing research focused on the relative impact of known risk factors and resource utilization is needed.

Appendectomy by Pediatric Surgeons in North Carolina is Associated With Higher Charge Than General Surgeons.

INTRODUCTION: The delivery of pediatric surgical care for acute appendicitis involves general surgeons (GS) and pediatric surgeons (PS), but the differences in clinical practice are primarily undescribed. We examined charge differences between GS and PS for the treatment of pediatric acute appendicitis. METHODS: We performed a retrospective review of the North Carolina hospital discharge database (2013-2017) in pediatric patients (≤18 y) who had surgery for appendiceal pathology (acute or chronic appendicitis and other appendiceal pathology). We performed a bivariate analysis of surgical charges over the type of surgical providers (GS, PS, other specialty, and unassigned surgeons). RESULTS: Over the study period, 21,049 patients had appendicitis or other diseases of the appendix, and 15,230 (72.4%) underwent appendectomy. Patients who were operated on by PS were younger (10 y, interquartile range (IQR): 6-13 versus 13 y, IQR: 9-16, P < 0.001). Acute appendicitis was diagnosed in 2860 (44.3%) and 3173 (49.2%) of the PS and GS cohorts, respectively, P = 0.008. PS compared to GS performed a higher percentage of laparoscopic (n = 2,697, 89.4% versus n = 2,178, 65.5%) than open appendectomies (n = 280, 9.3% versus n = 1,118, 33.6%), P < 0.001. The overall hospital charges were $28,081 (IQR: $21,706-$37,431) and $24,322 (IQR: $17,906-$32,226) for PS and GS, respectively, P < 0.001. Surgical charges where higher for PS than GS, $12,566 (IQR: $9802-$17,462) and $8051 (IQR: $5872-$2331), respectively. When controlling for diagnosis, surgical approach, emergent status, age, and surgical cost of appendiceal surgery, and hospital charges following appendiceal surgery were $4280 higher for PS than GS (95% CI: 3874-4687). CONCLUSIONS: The total charge for operations for appendiceal disease is significantly higher for PS compared to GS. Pediatric surgeons had increased surgical charges compared to GS but decreased radiology charges. The specific reasons for these differences are not clearly delineated in this data set and persist after controlling for relevant covariates. However, these data demonstrate that increasing value in pediatric appendicitis may require specialty-based targets.

Prevention of postoperative atrial fibrillation in cardiac surgery: a quality improvement project.

PURPOSE: Postoperative atrial fibrillation (POAF) has an incidence of 20-60% in cardiac surgery. The Society of Cardiovascular Anesthesiologists and the European Association of Cardiothoracic Anaesthesiology Practice Advisory have recommended postoperative beta blockers and amiodarone for the prevention of POAF. By employing quality improvement (QI) strategies, we sought to increase the use of these agents and to reduce the incidence of POAF among our patients undergoing cardiac surgery. METHODS: This single-centre QI initiative followed the traditional Plan, Do, Study, Act (PDSA) cycle scientific methodology. A POAF risk score was developed to categorize all patients undergoing cardiac surgery as either normal or elevated risk. Risk stratification was incorporated into a preprinted prescribing guide, which recommended postoperative beta blockade for all patients and a postoperative amiodarone protocol for patients with elevated risk starting on postoperative day one (POD1). A longitudinal audit of all patients undergoing cardiac surgery was conducted over 11 months to track the use of prophylactic medications and the incidence of POAF. RESULTS: Five hundred and sixty patients undergoing surgery were included in the QI initiative from 1 December 2020 to 1 November 2021. The baseline rate of POAF across all surgical subtypes was 39% (198/560). The use of prophylactic amiodarone in high-risk patients increased from 13% (1/8) at the start of the project to 41% (48/116) at the end of the audit period. The percentage of patients receiving a beta blocker on POD1 did fluctuate, but remained essentially unchanged throughout the audit (34.8% in December 2020 vs 46.7% in October 2021). After 11 months, the overall incidence of POAF was 29% (24.9% relative reduction). Notable reductions in the incidence of POAF were observed in more complex surgical subtypes by the end of the audit, including multiple valve replacement (89% vs 56%), aortic repair (50% vs 33%), and mitral valve surgery (45% vs 33%). CONCLUSIONS: This single-centre QI intervention increased the use of prophylactic amiodarone by 28% for patients at elevated risk of POAF, with no change in the early postoperative initiation of beta blockers (46.7% of patients by POD1). There was a notable reduction in the incidence of POAF in patients at elevated risk undergoing surgery.

RéSUMé: OBJECTIF: Il y a une incidence de 20 à 60 % de fibrillation auriculaire postopératoire (FAPO) en chirurgie cardiaque. Dans un avis de pratique, la Society of Cardiovascular Anesthesiologists et l'European Association of Cardiothoracic Anaesthesiology ont recommandé l'utilisation de bêtabloquants et d'amiodarone en postopératoire pour la prévention du FAPO. En employant des stratégies d'amélioration de la qualité (AQ), nous avons cherché à augmenter l'utilisation de ces agents et à réduire l'incidence de FAPO chez nos patient·es bénéficiant d'une chirurgie cardiaque. MéTHODE: Cette initiative d'AQ monocentrique a suivi la méthodologie scientifique traditionnelle du cycle Plan, Do, Study, Act (PDSA), soit Planifier, Réaliser, Étudier, Agir. Un score de risque de FAPO a été mis au point pour catégoriser toute la patientèle bénéficiant d'une chirurgie cardiaque comme présentant un risque normal ou élevé. La stratification du risque a été intégrée dans un guide de prescription préimprimé, qui recommandait des bêtabloquants en période postopératoire pour tou·tes les patient·es et un protocole postopératoire d'amiodarone pour celles et ceux présentant un risque élevé et débutant à partir du premier jour postopératoire (JPO1). Une vérification longitudinale de toute la patientèle bénéficiant d'une chirurgie cardiaque a été menée sur une période de 11 mois afin de suivre l'utilisation de médicaments prophylactiques et l'incidence de FAPO. RéSULTATS: Cinq cent soixante personnes opérées ont été incluses dans l'initiative d'AQ entre le 1er décembre 2020 et le 1er novembre 2021. Le taux initial de FAPO pour tous les sous-types chirurgicaux était de 39 % (198/560). L'utilisation d'amiodarone prophylactique chez les patient·es à risque élevé est passée de 13 % (1/8) au début du projet à 41 % (48/116) à la fin de la période de vérification. Le pourcentage de patient·es recevant un bêtabloquant au JPO1 a fluctué, mais est resté fondamentalement inchangé tout au long de la période de vérification (34,8 % en décembre 2020 vs 46,7 % en octobre 2021). Après 11 mois, l'incidence globale de FAPO était de 29 % (réduction relative de 24,9 %). Des réductions notables de l'incidence de FAPO ont été observées dans des sous-types chirurgicaux plus complexes à la fin de la vérification, y compris le remplacement de plusieurs valves (89 % vs 56 %), la réparation aortique (50 % vs 33 %) et la chirurgie valvulaire mitrale (45 % vs 33 %). CONCLUSION: Cette intervention monocentrique d'amélioration de la qualité a augmenté l'utilisation de l'amiodarone prophylactique de 28 % chez les patient·es présentant un risque élevé de FAPO, sans changement dans l'amorce postopératoire précoce des bêtabloquants (46,7 % des patient·es au JPO1). Il y a eu une réduction notable de l'incidence de FAPO chez les patient·es à risque élevé bénéficiant d'une intervention chirurgicale.

The Impact of General Surgeons on Pediatric Surgical Practice in North Carolina: The Reality of Pediatric Surgical Care Delivery.

OBJECTIVE: The aim of this study was to define the training background of the actual surgical workforce providing care to pediatric patients in North Carolina (NC). BACKGROUND: Due to database limitations, pediatric surgical workforce studies have not included general surgeons (GS) who operate on children. Defining the role of GS in care delivery affects policy for clinical care and general and pediatric surgical training. METHODS: We performed a retrospective review of the NC Hospital Discharge Database (2011-2017), including pediatric patients (<18 years) undergoing the most frequent general surgery procedures. Descriptive and correlational analysis over surgical provider [Pediatric Surgeon (PS), GS], and other specialties (OSS), was performed using logistic regression modeling to identify factors associated with surgery by a PS. RESULTS: Of the 57,265 discharges analyzed, pediatric, general, and other specialty surgeons operated on 25,514 (44.6%), 18,581 (32.5%), and 9049 (15.8%), respectively. In a logistic regression model, PS had lower odds of operating on older patients [odds ratio (OR) 0.9, 95% confidence interval (CI) 0.90-0.91]. However, PS were more likely to operate on female patients (OR 1.58, 95% CI 1.53-1.65), Black (OR 1.49, 95% CI 1.43-1.56), and other minority patients (OR 1.23, 95% CI 1.17-1.29) when compared to white patients. PS were also more likely to operate on patients with private insurance (OR 1.38, 95% CI 1.33-1.43) compared to government insurance, and patients undergoing emergency surgery (OR 1.44, 95% CI 1.38-1.50). CONCLUSION: In NC, general surgeons performed a third of the operations on children. After controlling for covariates, pediatric surgeons in NC are more likely to operate on minority and emergency surgery patients, and this is the first study to describe this important practice pattern.

Emerging antenatal therapies for congenital diaphragmatic hernia-induced pulmonary hypertension in preclinical models.

Congenital diaphragmatic hernia (CDH)-related deaths are the largest contributor to in-hospital neonatal deaths in children with congenital malformations. Morbidity and mortality in CDH are directly related to the development of pulmonary hypertension (PH). Current treatment consists of supportive measures. To date, no pharmacotherapy has been shown to effectively reverse the hallmark finding of pulmonary vascular remodeling that is associated with pulmonary hypertension in CDH (CDH-PH). As such, there is a great need for novel therapies to effectively manage CDH-PH. Our review aims to evaluate emerging therapies, and specifically focuses on those that are still under investigation and not approved for clinical use by the Food and Drug Administration. Therapies were categorized into antenatal pharmacotherapies or antenatal regenerative therapies and assessed on their method of administration, safety profile, the effect on pulmonary vascular pathophysiology, and overall efficacy. In general, emerging antenatal pharmaceutical and regenerative treatments primarily aim to alleviate pulmonary vascular remodeling by restoring normal function and levels of key regulatory factors involved in pulmonary vascular development and/or in promoting angiogenesis. Overall, while these emerging therapies show great promise for the management of CDH-PH, most require further assessment of safety and efficacy in preclinical models before translation into the clinical setting. IMPACT: Emerging antenatal therapies for congenital diaphragmatic hernia-induced pulmonary hypertension (CDH-PH) show promise to effectively mitigate vascular remodeling in preclinical models. Further investigation is needed in preclinical and human studies to evaluate safety and efficacy prior to translation into the clinical arena. This review offers a comprehensive and up-to-date summary of emerging therapies currently under investigation in experimental animal models. There is no cure for CDH-PH. This review explores emerging therapeutic options for the treatment of CDH-PH and evaluates their impact on key molecular pathways and clinical markers of disease to determine efficacy in the preclinical stage.

Controlled Delivery of Slit3 Proteins from Alginate Microbeads Inhibits In Vitro Angiogenesis.

BACKGROUND: The Slit-Robo pathway is a key regulator of angiogenesis and cellular function in experimental models. Slit3 proteins exhibit both proangiogenic and antiangiogenic properties, but the exact mechanism remains unclear. It is theorized that Slit3 may be a potential treatment for vascular diseases and cancer. METHODS: Slit3 labeled with I-125 was encapsulated in microbeads composed of low-viscosity alginate of high-glucuronic acid content, first coated with poly-L-ornithine for various durations and finally with low-viscosity high mannuronic acid. Gamma counter was used to measure microbead encapsulation efficiency and Slit3 release. Markers of angiogenesis were assessed with Boyden chamber, scratch wound, and Matrigel tube formation assays using human umbilical vein and mouse endothelial cells. RESULTS: On incubation of Slit3-loaded microbeads, there was an initial burst phase release of Slit3 for the first 24 h followed by sustained release for 6 to 12 d. Microbead composition determined encapsulation efficiency and rate of release; Slit3 encapsulation was most efficient in microbeads with lower low-viscosity alginate of high-glucuronic acid content concentrations (1.5%) and no poly-L-ornithine coating. Compared with controls (media alone), Slit3 microbeads significantly inhibited in vitro cellular migration, endothelial cell migration for wound closure at 24 and 48 h and endothelial tube formation (P < 0.001, respectively). CONCLUSIONS: Slit3 can be effectively encapsulated and delivered via a controlled release pattern using alginate microbeads. Microbead encapsulation reduces in vitro endothelial tube formation and inhibits cellular migration to impair angiogenesis. Thus, Slit3 microparticles may be explored as a therapeutic option to mitigate tumor proliferation.

The impact of an enhanced recovery perioperative pathway for pediatric pectus deformity repair.

PURPOSE: Pediatric repair of chest wall deformities is associated with significant pain, morbidity, and resource utilization. We sought to determine outcomes of a perioperative enhanced recovery after surgery (ERAS) pathway for patients undergoing minimally invasive (Nuss) and traditional (Ravitch) corrective procedures. METHODS: Our ERAS protocol was implemented in 2015. We performed a retrospective review of patients for Nuss or Ravitch procedures before and after ERAS implementation. Combined and procedure segregated bivariate analyses were conducted on postoperative outcomes and resource utilization. RESULTS: There are 17 patients in the pre-intervention group (Nuss = 13 and Ravitch = 4) compared to 38 patients in the post-intervention group (Nuss = 28 and Ravitch = 10). Protocol implementation increased utilization of pre-operative non-narcotic medication. The combined and Nuss post-intervention groups had a significant decrease in epidural duration and time to enteral medications, but had increased total postoperative opioid usage. The Ravitch post-intervention group had a significant decrease in intra-operative narcotics and discharge pain scores. There were no differences in length of stay or complications. CONCLUSION: Implementation of our ERAS protocol standardized pectus perioperative care, but did not improve postoperative opioid usage, complications, or resource utilization. Alterations in the protocol may lead to achieving desired goals of better pain management and decreased resource utilization.

Echocardiography allows for analysis of pulmonary arterial flow in mice with congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a structural birth defect associated with pulmonary hypoplasia and pulmonary arterial hypertension (PAH). We hypothesize that echocardiography provides a method to assess real-time right ventricle (RV) function, remodeling, and pulmonary artery (PA) flow. MATERIALS AND METHODS: Slit3 wild-type (WT) (n = 6) and knockout (KO) (n = 5) mice were analyzed at 2-3 months of age. Mice were anesthetized using isoflurane. Echocardiography was performed to analyze left and right ventricular wall thickness, internal diameter (ID), and function. Color Doppler was used to analyze flow in the PA and across the tricuspid valve. RESULTS: There was significant RV dilation in the KO mice versus WT, with an average RVID of 1.99 mm versus 1.26 mm, respectively (P = 0.007). Flow in the PA of KO mice was altered compared to WT, with elevated PA velocity time indices, 30.68 mm versus 22.13 mm (P = 0.012), elevated PA peak velocities, 952.61 mm/s versus 628.73 mm/s (P = 0.003), and decreased pulmonary acceleration times, 8.94 ms versus 16.18 ms (P = 0.002), respectively. Pulmonary vascular resistance, calculated by measuring tricuspid regurgitation peak velocity and right ventricular outflow tract velocity time index, was increased in KO versus WT mice, 17.61 mm2/s versus 8.91 mm2/s (P = 0.003), respectively. CONCLUSIONS: Slit3 KO mice with CDH show evidence of PAH and resultant RV dilation. Using direct cardiac puncture, elevated RV systolic pressures have been demonstrated in KO mice as evidence of PAH. Echocardiography allows direct analysis of the PA and real-time RV function without sacrifice of the mouse. This mode of evaluation allows longitudinal study in mice with PAH and CDH.

Assessing the Benefits of Preoperative Thoracic Epidural Placement for Lung Transplantation.

OBJECTIVE: The authors investigated the effect of preoperative thoracic epidural (PreTE) catheter placement versus not placing a preoperative thoracic epidural catheter (NoPreTE) on the duration of postoperative ventilation time, time to become coherent (measured as time to become Confusion Assessment Method-intensive care unit [ICU] negative), opioid consumption, ICU length of stay (LOS), and hospital LOS. DESIGN: Retrospective cohort design. SETTING: Single institution, university hospital. PARTICIPANTS: Patients undergoing lung transplantation. COMPARISON GROUPS: PreTE group was defined as patients who received a thoracic epidural preoperatively. NoPreTE group was defined as patients who either received a thoracic epidural postoperatively or who did not receive a thoracic epidural postoperatively. MEASUREMENTS AND MAIN RESULTS: Fifty-six patients for the PreTE and 99 for NoPreTE groups were included in the study. After a excluding patients with postoperative ventilation times greater than 96 hours, preoperative thoracic epidural was associated with shorter time on the ventilator (19.1 hours v 30.6 hours; p < 0.001), time to become coherent (26.4 hours v 37.6 hours; p = 0.008), ICU LOS (6.4 days v 12.4 days; p = 0.018), and hospital LOS (15.9 days v 23.5 days; p = 0.04) compared to patients who did not receive a preoperative epidural. After controlling for single versus double lung transplantation and duration of cardiopulmonary bypass (CPB), differences in time to become coherent, ICU LOS, and hospital LOS became nonsignificant. Opioid consumption was significantly higher in those patients who did not receive a preoperative epidural. Despite a high rate of anticoagulation for CPB (89.5%), no neurologic complications or epidural hematomas were observed. CONCLUSION: For those lung transplant patients ventilated for less than 96 hours postoperatively, preoperative thoracic epidural placement is associated with shorter postoperative ventilator time and reduced opioid consumption. Time to become coherent postoperatively, ICU LOS, and hospital LOS also improved in this cohort, though the significance decreased after adjusting for possible confounders. A larger prospective study is necessary to confirm if timing of thoracic epidural placement alters time to become coherent postoperatively and ICU LOS.

A method for evaluating the murine pulmonary vasculature using micro-computed tomography.

BACKGROUND: Significant mortality and morbidity are associated with alterations in the pulmonary vasculature. While techniques have been described for quantitative morphometry of whole-lung arterial trees in larger animals, no methods have been described in mice. We report a method for the quantitative assessment of murine pulmonary arterial vasculature using high-resolution computed tomography scanning. METHODS: Mice were harvested at 2 weeks, 4 weeks, and 3 months of age. The pulmonary artery vascular tree was pressure perfused to maximal dilation with a radio-opaque casting material with viscosity and pressure set to prevent capillary transit and venous filling. The lungs were fixed and scanned on a specimen computed tomography scanner at 8-µm resolution, and the vessels were segmented. Vessels were grouped into categories based on lumen diameter and branch generation. RESULTS: Robust high-resolution segmentation was achieved, permitting detailed quantitation of pulmonary vascular morphometrics. As expected, postnatal lung development was associated with progressive increase in small-vessel number and arterial branching complexity. CONCLUSIONS: These methods for quantitative analysis of the pulmonary vasculature in postnatal and adult mice provide a useful tool for the evaluation of mouse models of disease that affect the pulmonary vasculature.

Effect of Perflubron-induced lung growth on pulmonary vascular remodeling in congenital diaphragmatic hernia.

PURPOSE: Congenital diaphragmatic hernia (CDH) involves lung hypoplasia and pulmonary hypertension (PH). Post-natal Perflubron ventilation induces lung growth. This phenomenon is called Perflubon-induced lung growth (PILG). However, it does not appear to ameliorate PH in CDH. We aim to determine the effect of PILG on pulmonary vascular remodeling in neonates with CDH and PH requiring extracorporeal membrane oxygenation (ECMO). METHODS: Lung tissue from four patients was obtained, three treated with PILG + ECMO, and one maintained on conventional ventilation + ECMO (control). The distribution of collagen was assessed with Masson's trichrome stain. Immunohistochemistry was done to assess cell proliferation and immunofluorescence to assess vascular morphology. RESULTS: Comparing PILG vs. control, there was an increase in vessel wall diameter (6.85 µm, 10.28 µm, and 10.35 µm vs. 4.34 µm), increase in collagen thickness in two PILG patients (35.66 µm, 14.23 µm, and 38.46 µm vs. 22.16 µm), and decrease in lumen diameter despite similar total area (48.99 µm, 41.74 µm, and 36.32 µm vs. 51.56 µm) for each PILG patient vs. the control patient, respectively. CONCLUSION: PILG does not appear to improve pulmonary vascular remodeling that occurs with PH. The findings are descriptive and will require larger samples to validate the significance of the findings. Overall, further studies will be required to identify the mechanistic causes of PH in CDH to create effective treatments.

A noninvasive hemoglobin monitor in the pediatric intensive care unit.

BACKGROUND: Critically ill pediatric patients frequently require hemoglobin monitoring. Accurate noninvasive Hb (SpHb) would allow practitioners to decrease anemia from repeated blood draws, traumatic blood draws, and a decreased number of laboratory Hb (LabHb) medical tests. The Food and Drug Administration has approved the Masimo Pronto SpHb and associated Rainbow probes; however, its use in the pediatric intensive care unit (PICU) is controversial. In this study, we define the degree of agreement between LabHb and SpHb using the Masimo Pronto SpHb Monitor and identify clinical and demographic conditions associated with decreased accuracy. MATERIALS AND METHODS: We performed a prospective, observational study in a large PICU at an academic medical center. Fifty-three pediatric patients (30-d and 18-y-old), weighing >3 kg, admitted to the PICU from January-April 2013 were examined. SpHb levels measured at the time of LabHb blood draw were compared and analyzed. RESULTS: Only 83 SpHb readings were obtained in 118 attempts (70.3%) and 35 readings provided a result of "unable to obtain." The mean LabHb and SpHb were 11.1 g/dL and 11.2 g/dL, respectively. Bland-Altman analysis showed a mean difference of 0.07 g/dL with a standard deviation of ±2.59 g/dL. Pearson correlation is 0.55, with a 95% confidence interval between 0.38 and 0.68. Logistic regression showed that extreme LabHb values, increasing skin pigmentation, and increasing body mass index were predictors of poor agreement between SpHb and LabHb (P < 0.05). Separately, increasing body mass index, hypoxia, and hypothermia were predictors for undetectable readings (P < 0.05). CONCLUSIONS: The Masimo Pronto SpHb Monitor provides adequate agreement for the trending of hemoglobin levels in critically ill pediatric patients. However, the degree of agreement is insufficient to be used as the sole indicator for transfusion decisions and should be used in context of other clinical parameters to determine the need for LabHb in critically ill pediatric patients.

Pediatric surgical care in Lilongwe, Malawi: outcomes and opportunities for improvement.

BACKGROUND: One of the objectives of the Millennium Development Goals is to improve child health. We describe the burden of pediatric surgical disease at a tertiary hospital in Malawi. METHODS: We conducted a retrospective analysis of a pediatric surgery database at Kamuzu Central Hospital in Malawi for the calendar year 2012. Variables included patient demographics, admission diagnosis, primary surgery and outcome. RESULTS: A total of 1170 pediatric patients aged 0-17 years were admitted to the surgical service during the study period. The mean age was 6.9 years, and 62% were male. Trauma was the most common indication for admission (51%, n = 596), and 67% (n = 779) of all patients were managed non-operatively. Neonates and patients managed non-operatively had a significantly increased risk of mortality. CONCLUSION: Only a third of patients admitted to the pediatric surgery service underwent surgery. More than half of patients with congenital anomalies did not undergo surgical intervention. Importantly, patients who underwent surgery had a survival advantage.

Aortic arch rupture in a patient with Marfan syndrome and previous aortic root repair: A stepwise approach to intraoperative catastrophe.

Marfan syndrome (MS) is an autosomal dominant connective tissue disease associated with significant morbidity and mortality due to progressive dilatation of the thoracic aorta which can lead to aortic rupture. Survival from an aortic rupture is predicated on immediate organized and goal directed care by both surgical and anesthesia teams. This case highlights how coordinated care from a cardiac operating room team, including early preparation of autologous blood products, expeditious placement of intravascular access for rapid high volume transfusion, and intentional communication between anesthesia, perfusion, surgery and nursing during the resuscitation in the OR, can all lead to an improved outcome.