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Nonoperative management of acute appendicitis is a safe and effective alternative to appendectomy, though rates of treatment failure and disease recurrence are significant. The purpose of this study was to determine whether COVID-19-positive children with acute appendicitis were more likely to undergo nonoperative management when compared to COVID-19-negative peers and to compare clinical outcomes and healthcare use for these groups.A retrospective cohort study of children18 years with acute appendicitis across 45 US Children's Hospitals during the first 12 months of the COVID-19 pandemic was performed. Operative management was defined as appendectomy or percutaneous drain placement, whereas nonoperative management was defined as admission with antibiotics alone. Multivariable hierarchical logistic regression using an exact matched cohort was used to determine the association between COVID-19 positivity and nonoperative management. The secondary outcomes included intensive care unit admission, mechanical ventilation, length of stay, nonoperative management failure rates, and hospital variation in nonoperative management.Of 17,481 children in the cohort, 581 (3.3%) were positive for COVID-19. The odds of nonoperative management was significantly higher in the COVID-19-positive group (adjusted odds ratio [95% confidence interval]: 13.4 [10.7-16.8], P.001). Patients positive for COVID-19 had increased odds of intensive care unit admission (adjusted odds ratio [95% confidence interval]: 3.78 [2.01-7.12], P.001) and longer length of stay (median 2 days vs 1 day, P.001). Hospital rates of nonoperative management ranged from 0% to 100% for COVID-19-positive patients and 0% to 42% for COVID-19-negative patients.Children with concurrent acute appendicitis and COVID-19 positivity are significantly more likely to undergo nonoperative management. Both groups experience infrequent nonoperative management failure rates and rare intensive care unit admissions. Marked hospital variability in nonoperative management practices was demonstrated.

More than twenty years ago, the Accreditation Council for Graduate Medical Education and the American Board of Medical Specialties began the conversion of graduate medical education from a structure- and process-based model to a competency-based framework. The educational outcomes assessment tool, known as the Milestones, was introduced in 2013 for seven specialties and by 2015 for the remaining specialties, including pediatric surgery. Designed to be an iterative process with improvements over time based on feedback and evidence-based literature, the Milestones started the evolution from 1.0 to 2.0 in 2016. The formation of Pediatric Surgery Milestones 2.0 began in 2019 and was finalized in 2021 for implementation in the 2022-2023 academic year. Milestones 2.0 are fewer in number and are stated in more straightforward language. It incorporated the harmonized milestones, subcompetencies for non-patient care and non-medical knowledge that are consistent across all medical and surgical specialties. There is a new Supplemental Guide that lists examples, references and links to other assessment tools and resources for each subcompetency. Milestones 2.0 represents a continuous process of feedback, literature review and revision with goals of improving patient care and maintaining public trust in graduate medical education's ability to self-regulate. LEVEL OF EVIDENCE: V.

The insurance status of pediatric trauma patients is associated with access to post-discharge resources, including inpatient rehabilitation. Our goal was to understand the impact of changes in insurance coverage on access to post-acute care resources for pediatric trauma patients.We utilized the National Trauma Data Bank from 2012 to 2016 for all pediatric trauma patients with a highest body region abbreviated injury score2. Our primary outcome was hospital discharge disposition location. We used multivariable regression to adjust for salient patient and trauma center characteristics. Additionally, we performed a sensitivity analysis including only high-volume hospitals to examine the relationship between the magnitude of facility level expansion in coverage and changes in patient disposition.We identified 195,649 pediatric trauma patients meeting inclusion criteria. From 2012 to 2016 the proportion of patients with Medicaid (35% versus 39%, P0.001) and private insurance (39% versus 45%, P0.001) increased. Increased discharges with home health (HH) (+0.6% adjusted risk difference 2012 to 2016, P0.001) and decreased discharges to inpatient rehabilitation and skilled nursing facilities (-0.6% adjusted risk difference 2012 to 2016, P = 0.01) were associated with changes in insurance coverage. After stratifying high volume facilities by magnitude of increase in Medicaid and private insurance, we found that, for all groups, discharge to inpatient rehabilitation and skilled nursing facilities decreased (P0.01).Expanded insurance coverage for children was paradoxically associated with decreased discharge to inpatient rehabilitation and skilled nursing facilities after severe traumatic injury. These findings suggest that additional barriers may drive limitations in access to pediatric post-discharge services.

The objective of this study was to develop a portal natural language processing approach to aid in the identification of postoperative venous thromboembolism events from free-text clinical notes.We abstracted clinical notes from 25,494 operative events from 2 independent health care systems. A venous thromboembolism detected as part of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was used as the reference standard. A natural language processing engine, easy clinical information extractor-pulmonary embolism/deep vein thrombosis (EasyCIE-PEDVT), was trained to detect pulmonary embolism and deep vein thrombosis from clinical notes. International Classification of Diseases (ICD) discharge diagnosis codes for venous thromboembolism were used as baseline comparators. The classification performance of EasyCIE-PEDVT was compared with International Classification of Diseases codes using sensitivity, specificity, area under the receiver operating characteristic curve, using an internal and external validation cohort.To detect pulmonary embolism, EasyCIE-PEDVT had a sensitivity of 0.714 and 0.815 in internal and external validation, respectively. To detect deep vein thrombosis, EasyCIE-PEDVT had a sensitivity of 0.846 and 0.849 in internal and external validation, respectively. EasyCIE-PEDVT had significantly higher discrimination for deep vein thrombosis compared with International Classification of Diseases codes in internal validation (area under the receiver operating characteristic curve: 0.920 vs 0.761; P.001) and external validation (area under the receiver operating characteristic curve: 0.921 vs 0.794; P.001). There was no significant difference in the discrimination for pulmonary embolism between EasyCIE-PEDVT and ICD codes.Accurate surveillance of postoperative venous thromboembolism may be achieved using natural language processing on clinical notes in 2 independent health care systems. These findings suggest natural language processing may augment manual chart abstraction for large registries such as NSQIP.

Children with ulcerative colitis (UC) may undergo a staged approach for restorative proctocolectomy and ileal pouch anal anastomosis (IPAA). Previous studies in adults suggest a decreased morbidity with delayed pouch creation, but pediatric studies are limited. We compared outcomes for delayed versus early pouch construction in children.Patients with UC undergoing IPAA were selected from the National Surgical Quality Improvement Program Pediatric database from 2012 to 2018. Patients were categorized as early (2-stage) or delayed (3-stage) pouch construction based on Current Procedural Terminology codes. Our primary outcome was any adverse event. We used a multivariable logistic regression model to assess the relationship between timing of pouch creation and adverse events.We identified 371 children who underwent IPAA: 157 (42.3%) had early pouch creation and 214 (57.6%) had a delayed pouch. Those with an early pouch creation were more likely to have exposure to immunosuppressants (11% vs. 5%, p = 0.017) and steroids (30% vs. 10%, p 0.001) at the time of surgery. After controlling for patient characteristics, there were no significant differences in adverse events between the two groups.Children undergoing early pouch creation have increased exposure to steroids and immune suppressants; nevertheless, no differences in adverse events were identified.II.

Background The effect of the consolidation of neonatal pediatric surgical cases to limited surgeons within a hospital is unknown. We elected to model the distribution of complex neonatal procedures using an economic measure of market concentration, the Herfindahl-Hirschmann Index (HHI), and study its effect on outcomes of index pediatric surgical operations. Methods We used data from 49 US children's hospitals between 2007 and 2017 for the following procedures: congenital diaphragmatic hernia repair (CDH), esophageal atresia and tracheoesophageal fistula repair (EA/TEF), and pull-through for Hirschsprung disease (HD). Mixed effects logistic regression modeling was used to adjust for salient patient characteristics to determine the effect of HHI on in-hospital mortality, condition-specific one-year re-operation, and one-year unplanned readmissions. Results A total of 2270 infants were identified who underwent surgery for the three conditions of interest. On multivariable analysis, increasing HHI was not associated with differences in mortality or condition-specific re-operation within the first year. A decrease in the number of unplanned readmissions at highly concentrated centers was seen for HD (RR 0.8 CI (0.69–0.97), p = 0.02) and CDH (RR 0.4 CI (0.28–0.71), p Conclusions Pediatric surgical specialization did not affect mortality or condition-specific re-operation. However, it did decrease the number of unplanned readmissions following CDH repairs and pull-throughs for HD. Study design Retrospective Cohort Study. Level of Evidence Level II.

There is increasing need to avoid excess opioid prescribing after surgery. We prospectively assessed overprescription in our hospital system and used these data to design a quality improvement intervention to reduce overprescription.Beginning in January 2017, an e-mail-based survey to assess the quantity of opioids used postoperatively as well as patient-reported pain control was sent to all surgical patients in a 23-hospital system. In January 2018, as a quality improvement initiative, guidelines were given to surgeons based on patient consumption data. Prescription and consumption were then tracked prospectively. Wilcoxon signed-rank, analysis of variance, and Cuzick trend tests were used to assess for overprescription and changes over time in opioid prescribing and consumption.We included 2239 patients in our cohort. The amount prescribed (median [IQR]: 30 [24-45] versus 18 [12-30], P 0.001) and consumed (median [IQR]: 12 [7-20] versus 8 [3-15], P 0.001) each decreased between the first and last quarter studied. Academic hospitals prescribed fewer opioids than nonacademic hospitals (median [IQR]: 24[15-40] versus median [IQR]: 30 [20-45], P 0.001). There was no difference in the quantity of opioids consumed between patients treated at academic and nonacademic facilities (median [IQR]: 10[3-19] versus 10.5 [4-20], P = 0.08). Patients consumed a median of 42% of the opioids prescribed, and there was no significant trend in the percent consumed over time (P = 0.8).Patients used far fewer opioids than prescribed after common adult general surgery procedures. When surgeons were provided with patient consumption data, the number of opioids prescribed decreased significantly.

Purpose We sought to examine the short-term outcomes following single-stage repair of rectoperineal and rectovestibular fistulae in infants and identify risk factors for wound complication. Methods Patients with a rectoperineal or rectovestibular fistula treated with a single-stage repair beyond the neonatal period (>30days of age) at a pediatric colorectal center (2011–2016) were reviewed. Results 36 patients with a rectoperineal and 7 patients with a rectovestibular fistula were repaired using the Posterior Sagittal Anorectoplasty (PSARP) approach. Median follow-up was 31months. The median age and weight at the time of repair were 166days and 6.5kg. Four patients (11%) suffered a wound complication (3 rectoperineal, 1 rectovestibular). Two required a diverting colostomy to allow wound healing. Two patients suffered skin separation managed with local wound care. All 4 patients experienced satisfactory wound healing without anoplasty stricture. Two different patients developed a stricture of the neo-anus. Age and weight at time of repair, gender, and presence of a genitourinary anomaly were not associated with wound complications. Conclusion Delayed single-stage repair of rectoperineal and rectovestibular fistulae can be performed safely in infants beyond the newborn period. With attentive treatment, satisfactory healing can be anticipated if a wound complication is encountered. Level of Evidence Retrospective Comparative Study, Level III.

Background Machine-learning can elucidate complex relationships/provide insight to important variables for large datasets. This study aimed to develop an accurate model to predict neonatal surgical site infections (SSI) using different statistical methods. Methods The 2012–2015 National Surgical Quality Improvement Program-Pediatric for neonates was utilized for development and validations models. The primary outcome was any SSI. Models included different algorithms: full multiple logistic regression (LR), a priori clinical LR, random forest classification (RFC), and a hybrid model (combination of clinical knowledge and significant variables from RF) to maximize predictive power. Results 16,842 patients (median age 18 days, IQR 3–58) were included. 542 SSIs (4%) were identified. Agreement was observed for multiple covariates among significant variables between models. Area under the curve for each model was similar (full model 0.65, clinical model 0.67, RF 0.68, hybrid LR 0.67); however, the hybrid model utilized the fewest variables (18). Conclusions The hybrid model had similar predictability as other models with fewer and more clinically relevant variables. Machine-learning algorithms can identify important novel characteristics, which enhance clinical prediction models.

Background The optimal time to reinsert central venous catheters (tCVC) after a documented central line associated blood stream infection (CLABSI) is unclear. The goal of this study is to identify risk factors for children who develop persistent bacteremia after tCVC removal due to CLABSI. Methods We performed a retrospective cohort study from a tertiary children's hospital. Children who underwent removal of a tCVC due to CLABSI were included in our analysis. Our primary outcome was persistent bacteremia after tCVC removal defined by a persistently positive blood culture. Salient patient demographic and clinical factors were extracted from the medical record. Results A total of 140 patients met inclusion criteria and 27 (19%) had a persistent CLABSI after removal of the tCVC. There were no significant differences between the patients who cleared their bacteremia and those who develop persistent bacteremia. The median (IQR) time to positive blood culture after tCVC removal was 2.7 days (1.7– 4.0). Conclusions We did not identify any patient risk factors distinguishing between a child who will clear a CLABSI versus develop a persistent CLABSI after tCVC removal. Blood stream infection clearance was rapid after tCVC removal, supporting a brief line holiday prior to tCVC reinsertion. Level of Evidence Level III Retrospective Case-Control Study

Purpose Awareness of equestrian related injury remains limited. Studies evaluating children after equestrian injury report under-utilization of safety equipment and rates of operative intervention as high as 33%. Methods We hypothesized that helmets are underutilized during equestrian activity and lack of use is associated with increased traumatic brain injury. We queried the trauma database of a level one pediatric trauma center for all cases of equestrian and rodeo related injury from 2005 to 2015. Analysis was conducted using SAS 9.4. Results Of 312 children identified, 142 were assessed for use of a helmet. Only 28 children (19.7%) had documented use of a helmet. Most injuries occurred while riding a horse (83%) or bull (13%) with traumatic brain injury being the most common injury (51%). Helmet use was associated with decreased ISS (7.1 vs. 11.3, p p =0.03), and ICU admission (10.7% vs. 29%, p =0.05). Multivariable analysis reveals lack of helmet use to be an independent predictor of TBI (OR 2.5, 95% CI 1.1–6.3). Conclusion Helmets are underutilized by children during equestrian related activity. Increased awareness of TBI and education encouraging helmet use may decrease morbidity associated with equestrian activities. Level of Evidence Retrospective comparative study, Level III.

Background/purpose The purpose of this study was to study the effect of trisomy 21 (T21) on enterocolitis rates and bowel function among children with Hirschsprung disease (HD). Methods A retrospective cohort study of patients with HD treated at our tertiary children's hospital (2000–2015) and a cohort of patients with HD treated in our pediatric colorectal center (CRC) (2011–2015) were performed. Results 26/207 (13%) patients with HD had T21. 70 (41%) with HD alone were diagnosed with enterocolitis episodes compared to 9 (38%) with HD+T21 ( p =0.71). 55/207 patients were managed in the CRC. 11/55 patients (20%) had HD+T21. 25 (58%) with HD had one or more enterocolitis episodes compared to 4 (36%) with HD+T21 ( p =0.20). Number of hospitalizations for enterocolitis was similar between all groups. Toilet training was assessed in 32 CRC patients (25 HD, 7 HD+T21). One child with HD+T21 was toilet trained by age 4years versus 12 with HD ( p =0.20). Laxative or enema therapy was required for constipation management in 57% HD versus 64% HD+T21. Conclusion Enterocolitis rates in children with HD+T21 did not differ from rates in children with HD alone. The majority of patients with CRC follow-up had constipation requiring laxative or enema therapy, which demonstrates the need for consistent postoperative follow-up. Level of Evidence: Retrospective Study – Level II.

Esophageal atresia (EA) without tracheoesophageal fistula is characterized typically by a long gap between the discontinuous upper and lower esophageal pouches. In these challenging patients, initial esophagoesophagostomy is often not possible due to excessive tension produced when approximating the two pouches. This tension poses significant risk for pouch retraction, anastomotic leak, mediastinitis, and subsequent esophageal stricture. Consequently, multiple strategies exist to induce pouch lengthening and to achieve full continuity of native esophageal tissue, which if not accomplished, requires interpositions of stomach, small bowel, or colon to establish deglutition. One strategy involves a two-staged approach: first, after a period of growth into early infancy, the two esophageal pouches are suture-approximated without anastomosis, and second, repeat surgery is performed to establish luminal continuity once tension between the pouches has resolved. Esophageal growth and continuity are thereby achieved. Here, we describe an innovative, staged treatment approach for long-gap EA in two premature babies who initially underwent suture-approximation of the esophageal pouches at 3 months of age, followed by catheter-based magnetic compression anastomosis 10 weeks later. In both babies, the magnetic procedure allowed preservation of the gained full esophageal length, established successful esophageal canalization, created a leak-free anastomosis, and prevented the need for additional thoracotomy to accomplish these goals.

Our goal is to identify the impact of time to surgical intervention on the outcomes of infants with gastroschisis.After institutional review board approval, we performed a retrospective review of the medical records of all infants admitted to our institution from 2001 to 2010. Transport, bowel stabilization, and closure times were defined as the time from birth to admission, admission to the first-documented operative intervention, and first operative intervention to abdominal closure, respectively. Outcomes included age at full enteral feeds, total parental nutrition days, ventilator days, and hospital length of stay. Multivariate analysis was used to identify independent predictors of the outcomes.One hundred eighteen infants with gastroschisis were included in our study. Transport and bowel stabilization times were not predictive of any outcome. However, the time to abdominal wall closure and postnatal gastrointestinal complications were independently predictive of age at full enteral feeds, total parenteral nutrition days, and hospital length of stay.Time to surgical evaluation/bowel stabilization was not predictive of any clinically relevant outcomes in infants with gastroschisis. These data demonstrate that potential benefits from prenatal regionalization of infants with gastroschisis are not supported by decreased time to operative intervention.

Purpose In animal models, the small intestine responds to massive small bowel resection (SBR) through a compensatory process termed adaptation , characterized by increases in both villus height and crypt depth. This study seeks to determine whether similar morphologic alterations occur in humans after SBR. Methods Clinical data and pathologic specimens of infants who had both an SBR for necrotizing enterocolitis and an ostomy takedown from 1999 to 2009 were reviewed. Small intestine mucosal morphology was compared in the same patients at the time of SBR and at the time of ostomy takedown. Results For all samples, there was greater villus height (453.6 ± 20.4 vs 341.2 ± 12.4 μ m, P μ m, P r = 0.36, P Conclusion Mucosal adaptation after SBR in human infants is similar to what is observed in animal models. These findings validate the use of animal models of SBR used to understand the molecular mechanisms of this important response.

Purpose The objective of our study was to quantify mucosal bacterial DNA within specimens from neonates undergoing small bowel resection for necrotizing enterocolitis (NEC). Methods We obtained clinical information and pathologic specimens from all infants diagnosed with NEC who underwent surgical treatment at our institution from 1999 to 2008. Bacterial and human DNA were isolated from paraffin-embedded surgical specimens, and real time polymerase chain reaction was used to amplify bacterial and human genes. Linear regression was used to quantify the amount of human and bacterial DNA in our specimens. Results From a cohort of 50 infants, we identified 23 infants who underwent both surgical resection and subsequent intestinal reanastomosis. Thirteen (59%) of the neonates had Bell stage III NEC, and 9 (41%) had stage II. There was significantly more bacterial DNA in the resection specimens than in the reanastomosis specimens. This corresponds to a median (interquartile range) increase of 1.81 (1.11-4.69)-fold bacterial DNA in the resection specimen compared with the reanastomosis specimen ( P Conclusion There is more bacterial DNA in infants with acute NEC compared with the same infants after the NEC had clinically resolved. These findings underscore the potential relevance of adherent or invasive bacteria across the bowel wall in the pathogenesis of NEC.

Purpose The purpose of the study was to determine if first rib fractures are associated with an increased incidence of thoracic vascular injury in pediatric patients. Methods The medical records of all children diagnosed with a first rib fracture or a central vascular injury after blunt trauma treated at a state-designated level 1 pediatric trauma center from 2000 to 2009 were reviewed. Results Thirty-three children (0.27% of patients; mean age, 10.9 ± 0.9 years) were identified with either a first rib fracture or thoracic vascular injury owing to blunt trauma. Thirty-two children had a first rib fracture, and only 1 child (3%) had significant thoracic vascular injury. Mediastinal abnormalities (indistinct aortic knob) were identified in 3 children, 2 with first rib fracture on initial chest radiograph. Despite a normal cardiovascular examination result, 25 (74%) children with a normal mediastinum on screening chest radiograph underwent computed tomography. No child with a normal mediastinum on initial chest radiograph was found to have associated intrathoracic injuries requiring further intervention. In children with first rib fractures and a normal mediastinum by screening chest x-ray, the negative predictive value for thoracic vascular injury was 100%. Conclusions Children with first rib fractures without mediastinal abnormality on chest radiograph require no further workup for thoracic vascular injury.

In 2001, in response to an overwhelming increase in patient visits for various pediatric abscesses, burns, and other wounds, an ambulatory burn and procedural sedation program (Pediatric Acute Wound Service, or PAWS) was developed to minimize operating room utilization. The purpose of this study is to report our initial 7-year experience with the PAWS program.The hospital records of all children managed through PAWS from 2001 to 2007 were reviewed. Outcomes measured include patient demographics, number and location of visits per patient, procedure information, cause of wounds, and reimbursement. chi(2) test and linear regression were performed using GraphPad Prism (GraphPad Software Inc, San Diego, CA).Overall, 7620 children (age 0-18 years) received wound care through PAWS from 2001 to 2007. There were no differences in patient age, race, and sex during this time period. Between 2001 and 2007, the percentage of patients seen as outpatients increased from 51% to 68% (P.05), and the average number of visits per patient decreased from 3.9 to 2.4 (P = .05). In, 2007, 46% of the children required only 1 visit. In 2007, 74% of the visits were for management of wound and soft tissue infections, compared with only 9% in 2001 (P.05). The contribution margin of a PAWS visit and total contribution margin in 2007 were $1052 and $4.0 million, respectively.The creation of PAWS has allowed for the transition in management of most pediatric skin and soft tissue wounds and infections to an independent ambulatory setting, alleviating the need for operating room resources, while functioning at a profitable cost margin for the hospital.

Background Although the accumulation of hydrophobic bile acid (e.g., glycine conjugated chenodeoxycholic acid, GCDC) is considered to be an important factor contributing to cholestatic liver dysfunction, its pathogenesis is poorly understood. The purpose of this study was to examine the effect of the bile salt GCDC on the regulation of iNOS expression, a key immune modulator during liver inflammation. Materials and methods GCDC significantly decreased cytokine-stimulated iNOS promoter activity, and both iNOS mRNA and protein expression. GCDC decreased iNOS promoter activity by preventing IκB degradation and inhibiting NF-κB DNA-binding activity. To explore the role of iNOS in bile salt induced apoptosis, we also examined the effect of NO on caspase-3 activity. Results GCDC strongly induced caspase-3 activity, and this increase was abrogated by both exogenous NO exposure and endogenous NO synthesis. Furthermore, adenoviral iNOS (AdiNOS) pre-treatment decreased acute cholestatic-induced liver injury in a rat bile duct ligation model. Conclusions These findings indicate a novel signaling pathway where potentially toxic bile salts down-regulate hepatic iNOS expression. This blockade of the iNOS mediated antiapoptotic phenotype may have important implications in certain liver disorders.

Fluorous tin oxide (C6F13CH2CH2)2SnO is readily synthesized, exhibits spectra that are generally similar to dibutyltin oxide and appears to exist as an oligomer or polymer. The fluorous tin oxide can be used catalytically to effect the selective monotosylation of 1,2-diols with TsCl/Et3N, and it can be readily recovered and reused.

Whilst temporary vacuum-assisted wound management has become a mainstay in the treatment of patients with severe abdominal trauma in extremis, the use of this technique in the management of exsanguinating injuries and resultant physiologic decompensation in other body cavities is ill defined. Concerns over potential cardiac and pulmonary compromise secondary to packing along with the lethal nature of penetrating injuries to the thorax has limited extension of these practices to the management of this body region. Many patients with central vascular injuries secondary to penetrating trauma either expire prior to hospital arrival or arrive haemodynamically unstable and require emergency department thoracotomy. To our knowledge, there are no reports of the use of damage control sternotomy with temporary substernal and intrathoracic packing for traumatic thoracic injuries. We report our experience treating an adolescent patient who sustained a central venous injury and bilateral lung lacerations with a damage control sternotomy approach. A 15-year-old girl presented to the emergency department after sustaining multiple stab wounds to the neck, chest and back. On arrival to the emergency department, she was tachycardic (HR = 120) and hypothermic (T = 34.5 8C) but normotensive (SBP = 113) and neurologically intact (GCS = 15). Exam findings included a 3 cm laceration extending from zone 2 to zone 1 of her right neck, a 2 cm infraclavicular sucking wound to the left chest with associated crepitus and a 5 cm laceration to the posterior left shoulder. Standard ATLS resuscitation was performed and a left tube thoracostomy was placed with resultant rush of air and 500 ml of bloody drainage. A subsequent chest X-ray demonstrated a large right haemothorax. After placement of a right tube thoracostomy and immediate drainage of over 1000 ml of blood, the patient began to cough, resulting in massive bleeding from her neck wound and haemodynamic instability. Direct pressure was applied to the neck to temporarily control bleeding. Subsequent Accepted 1 March 2010

Objective To identify clinical factors associated with pulmonary hypertension and mortality in patients with congenital diaphragmatic hernia (CDH). Study design A prospective cohort of neonates with a diaphragm defect identified at one of seven collaborating medical centers was studied. Echocardiograms were performed at one month and three months of age and analyzed at a central core by two cardiologists independently. Degree of pulmonary hypertension and survival were tested for association with clinical variables using Fischers exact test, chi-square and regression analysis. Results 220 patients met inclusion criteria. Worse pulmonary hypertension measured at one month of life was associated with higher mortality. Other factors associated with mortality were need for extracorporeal membrane oxygenation (ECMO), patients inborn at the treating center and patients with a prenatal diagnosis of CDH. Interestingly, patients with right sided CDH did not have worse outcomes. Conclusions Severity of pulmonary hypertension is associated with mortality in CDH. Other factors associated with mortality were birth weight, gestational age at birth, inborn status and need for ECMO.

Background: Low dose CO is non-toxic and has been shown to possess potent anti-inflammatory properties. We hypothesize that CO would decrease cytokine-stimulated iNOS induction in rat hepatocytes. Methods: Primary hepatocytes from Sprague-Dawley rats were exposed to combinations of cytokines (TNFα, IL-1, IFγ) in the presence or absence of CO pre- and co- treatment at 250 ppm. Protein was harvested for Western blotting at 0, 1 and 6 hours after treatment. Greiss reaction was used to quantify NO production and crystal violet staining was used to measure cell viability. Experiments were performed 2–3 times each and t-test was used to assess significance between groups. Results: CO exposure at 250 ppm did not decrease hepatocyte viability measured by crystal violet staining at 24 hours. Pretreatment with CO resulted in a statistically significant decrease in cytokine mixture (TNFα 500 U/ml, IL-1 200 U/ml, IFγ 100 U/ml) stimulated hepatocyte NO production measured by Greiss reaction (37.8 ± 7.4 to 20.8 ± 5.7 μM, p < 0.05). Western blot 6 hours after stimulation resulted in a similar decrease in iNOS protein in the CO exposed hepatocytes. Pretreatment with CO up-regulated mitogen activated protein kinase phosphatase-1 (MKP-1) protein and decreased TNFα induced c-Jun N-terminal kinase (JNK) activation measured by Western blot. Conclusions: CO pretreatment decreased cytokine stimulated hepatocyte iNOS protein synthesis and NO production. A possible mechanism for this effect is the up-regulation of MKP-1 protein and subsequent decrease in cytokine stimulated JNK activation. The study provides a new mechanism for the anti-inflammatory effects of CO and validates the importance of JNK activation in pro-inflammatory signaling.

Introduction: Stress response genes, such as heme oxygenase-1 (HO-1) and heat shock protein 70 (HSP70), are known to be involved in ischemia/reperfusion (I/R) injury and have beneficial effects against oxidative stress. Carbon monoxide (CO), the byproduct of heme degradation by HO-1, has been shown to provide protection against I/R injury. This study was designed to examine whether donor pretreatment with CO has beneficial effects on hepatic cold I/R injury. Methods: Orthotopic syngenic LEW rat liver transplantation (OLT) was performed after 18 hrs preservation in cold UW. Donor rats were exposed to a non-toxic dose of CO (250 ppm) in a CO chamber for 24 hrs before harvesting. Controls donors were maintained in room air. Hepatic I/R injury was evaluated by serum AST levels and histopathology. Expression of HSP70 protein in donor liver was investigated before harvest. After OLT, expression of TNF-α and ICAM-1 mRNA, iNOS protein, and cleaved caspase-3 were measured. Results (Table) : TABLE—ABSTRACT 107 . AST (IU/L) 24 h Neutrophil (/mm 2 ) 48 h TNF-α (fold increase) 1 h iNOS (band denity) 3 h Caspase-3 (band denity) 3 h Air 5547 ± 979 87.1 ± 15.2 14.7 ± 5.3 26.3 ± 5.3 3.8 ± 0.3 CO 1981 ± 381 ∗ 23.6 ± 8.6 ∗ 4.8 ± 1.5 ∗ 7.5 ± 2.1 ∗ 2.8 ± 0.1 ∗ Mean ± SD, n = 2–6 animals per group, ∗ P CO-inhalation for 24 hrs significantly increased HSP70 expression in the donor liver. After OLT, donor CO pretreatment markedly attenuated hepatic I/R injury assessed by low AST levels, reduced necrosis, and decreased neutrophil infiltration. Hepatic expression of TNF-α and ICAM-1 mRNA, and iNOS protein was significantly reduced in CO-treated group. Additionally, cleaved caspase-3 expressing apoptotic cells were significantly decreased with donor CO-inhalation. Conclusion: These results demonstrate that donor CO pretreatment leads to attenuation of hepatic cold I/R injury through the inhibition of iNOS induction, pro-inflammatory responses, and pro-apoptotic reactions. The protective effect of donor CO pretreatment is in part mediated by HSP70 induction in the donor liver. Thus, low-dose CO inhalation would be a novel therapeutic strategy to combat hepatic cold I/R injury.