Non-Radiographic Severity Measurement of Pectus Excavatum.

BACKGROUND: To avoid the radiation exposure of CT imaging and the expense of CT or MRI studies, we sought to develop a non-radiographic severity measurement of pectus excavatum based on 3D photogrammetric imaging. METHODS: Over 28 mo, ten consecutive patient volunteers with pectus excavatum underwent 3D stereophotogrammetric imaging. The surface width to surface depth ratio (Surface Lengths Pectus Index), the chest deformity's surface area to total chest surface area (Pectus Surface Area Ratio), and the chest deformity's volume to total chest volume (Pectus Volume Ratio) were calculated. Simple linear regression analysis compared the Surface Lengths Pectus Index, Pectus Surface Area Ratio, and Pectus Volume Ratio calculations each to the corresponding known CT pectus index. RESULTS: The correlation between CT pectus index versus Surface Lengths Pectus Index yielded an R-squared value of 0.7637 and a P value of 0.0013. A CT pectus index of 3.4 or greater (eight patients) corresponded to a Surface Lengths Pectus Index of 1.86 or greater (six patients). The CT pectus index versus Pectus Surface Area Ratio (R-squared = 0.4627, P = 0.0305) and the CT pectus index versus the Pectus Volume Ratio (R-squared = 0.3048, P = 0.0990) demonstrated less correlation. CONCLUSION: Surface Lengths Pectus Index corresponds to the CT pectus index and may be adequate to determine severity of pectus excavatum in some patients.

Mesenchymal change and drug resistance in neuroblastoma.

BACKGROUND: Metastatic initiation has many phenotypic similarities to epithelial-to-mesenchymal transition, including loss of cell-cell adhesion, increased invasiveness, and increased cell mobility. We have previously demonstrated that drug resistance is associated with a metastatic phenotype in neuroblastoma (NB). The purpose of this project was to determine if the development of doxorubicin resistance is associated with characteristics of mesenchymal change in human NB cells. MATERIALS AND METHODS: Total RNA was isolated from wild type (WT) and doxorubicin-resistant (DoxR) human NB cell lines (SK-N-SH and SK-N-BE(2)C) and analyzed using the Illumina Human HT-12 version 4 Expression BeadChip. Differentially expressed genes (DEGs) were identified. Volcano plots and heat maps were generated. Genes of interest with a fold change in expression >1.5 and an adjusted P < 0.1 were analyzed. Immunofluorescence (IF) and Western blot analysis confirmed microarray results of interest. Matrigel invasion assay and migration wounding assays were performed. RESULTS: Volcano plots and heat maps visually demonstrated a similar pattern of DEGs in the SK-N-SH and SK-N-BE(2)C DoxR cell lines relative to their parental WT lines. Venn diagramming revealed 1594 DEGs common to both DoxR cell lines relative to their parental cell lines. Network analysis pointed to several significantly upregulated epithelial-to-mesenchymal transition pathways, through TGF-beta pathways via RhoA, PI3K, and ILK and via SMADs, as well as via notch signaling pathways. DoxR cell lines displayed a more invasive phenotype than respective WT cell lines. CONCLUSIONS: Human SK-N-SH and SK-N-BE(2)C NB cells display characteristics of mesenchymal change via multiple pathways in the transition to a drug-resistant state.

The use and timing of angioembolization in pediatric blunt liver and spleen injury.

BACKGROUND: Nonoperative management (NOM) is the standard of care for the management of blunt liver and spleen injuries (BLSI) in the stable pediatric patient. Angiography with embolization (AE) is used as an adjunctive therapy in the management of adult BLSI patients, but it is rarely used in the pediatric population. In this planned secondary analysis, we describe the current utilization patterns of AE in the management of pediatric BLSI. METHODS: After obtaining IRB approval at each center, cohort data was collected prospectively for children admitted with BLSI confirmed on CT at 10 Level I pediatric trauma centers (PTCs) throughout the United States from April 2013 to January 2016. All patients who underwent angiography with or without embolization for a BLSI were included in this analysis. Data collected included patient demographics, injury details, organ injured and grade of injury, CT finding specifics such as contrast blush, complications, failure of NOM, time to angiography and techniques for embolization. RESULTS: Data were collected for 1004 pediatric patients treated for BLSI over the study period, 30 (3.0%) of which underwent angiography with or without embolization for BLSI. Ten of the patients who underwent angiography for BLSI failed NOM. For patients with embolized splenic injuries, splenic salvage was 100%. Four of the nine patients undergoing embolization of the liver ultimately required an operative intervention, but only one patient required hepatorrhaphy and no patient required hepatectomy after AE. Few angiography studies were obtained early during hospitalization for BLSI, with only one patient undergoing angiography within 1 hour of arrival at the PTC, and 7 within 3 hours. CONCLUSION: Angioembolization is rarely used in the management of BLSI in pediatric trauma patients with blunt abdominal trauma and is generally used in a delayed fashion. However, when implemented, angioembolization is associated with 100% splenic salvage for splenic injuries. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

The utility of surgical lung biopsy in immunocompromised children.

OBJECTIVE: To determine the utility of lung biopsy in immunocompromised pediatric patients with suspected infectious lung disease and to evaluate the risks and benefits of biopsy in the era of minimally invasive thoracic surgery. STUDY DESIGN: We reviewed charts for 50 immunocompromised patients who underwent surgical lung biopsy between January 2000 and July 2011 at a free-standing, tertiary care, urban children's hospital. The primary outcome variable was "benefit from biopsy," defined as change in therapy based on biopsy results. The secondary outcome variable was survival to discharge. The χ(2) analysis was used for categorical variables and Student t test for continuous variables. RESULTS: Biopsy provided a definitive histopathologic or microbiologic diagnosis in 25 patients (50%), the most common diagnosis being fungal infection (22%). Diagnostic and nondiagnostic biopsy results yielded benefit in 25 surviving patients (50%) for whom the biopsy results were used to tailor treatment. Taking more than one biopsy specimen did not improve diagnostic yield. Six patients (12%) had a major morbidity including reinsertion of chest tube after initial chest tube removal (3), prolonged air leak (1), and a new requirement for mechanical ventilation postoperatively (2). Two patients died postoperatively, but the mortalities were not clearly related to surgery. Underlying diagnoses included hematologic malignancy (64%), primary immunodeficiency (12%), organ transplant recipient (12%), and solid malignancy (10%). Twelve patients (24%) had undergone stem cell transplantation. CONCLUSION: Lung biopsy in immunocompromised pediatric patients alters therapy in 50% of cases, but predictably carries identifiable morbidities. This study is limited by its retrospective nature.

Lower incidence of blunt cerebrovascular injury among young, properly restrained children: An ATOMAC multicenter study.

BACKGROUND: Motor vehicle collision (MVC) remains a leading cause of injury and death among children, but the proper use of child safety seats and restraints has lowered the risks associated with motor vehicle travel. Blunt cerebrovascular injury (BCVI) is rare but significant among children involved in MVC. This study reviewed the incidence of BCVI after MVC causing blunt injury to the head, face, or neck, comparing those that were properly restrained with those that were not. METHODS: A prospective, multi-institutional observational study of children younger than 15 years who sustained blunt trauma to the head, face, or neck (Abbreviated Injury Scale score >0) and presented at one of six level I pediatric trauma centers from 2017 to 2020 was conducted. Diagnosis of BCVI was made either by imaging or neurological symptoms at 2-week follow-up. Restraint status among those involved in MVC was compared for each age group. RESULTS: A total of 2,284 patients were enrolled at the 6 trauma centers. Of these, 521 (22.8%) were involved in an MVC. In this cohort, after excluding patients with missing data, 10 of 371 (2.7%) were diagnosed with a BCVI. For children younger than 12 years, none who were properly restrained suffered a BCVI (0 of 75 children), while 7 of 221 (3.2%) improperly restrained children suffered a BCVI. For children between 12 and 15 years of age, the incidence of BCVI was 2 of 36 (5.5%) for children in seat belts compared with 1 of 36 (2.8%) for unrestrained children. CONCLUSION: In this large multicenter prospectively screened pediatric cohort, the incidence of BCVI among properly restrained children under 12 years after MVC was infrequent, while the incidence was 3.2% among those without proper restraint. This effect was not seen among children older than 12 years. Restraint status in young children may be an important factor in BCVI screening. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Diagnostic accuracy of screening tools for pediatric blunt cerebrovascular injury: An ATOMAC multicenter study.

BACKGROUND: Blunt cerebrovascular injury (BCVI) is rare but significant among children. There are three sets of BCVI screening criteria validated for adults (Denver, Memphis, and Eastern Association for the Surgery of Trauma criteria) and two that have been validated for use in pediatrics (Utah score and McGovern score), all of which were developed using retrospective, single-center data sets. The purpose of this study was to determine the diagnostic accuracy of each set of screening criteria in children using a prospective, multicenter pediatric data set. METHODS: A prospective, multi-institutional observational study of children younger than 15 years who sustained blunt trauma to the head, face, or neck and presented at one of six level I pediatric trauma centers from 2017 to 2020 was conducted. All patients were screened for BCVI using the Memphis criteria, but criteria for all five were collected for analysis. Patients underwent computed tomography angiography of the head or neck if the Memphis criteria were met at presentation or neurological abnormalities were detected at 2-week follow-up. RESULTS: A total of 2,284 patients at the 6 trauma centers met the inclusion criteria. After excluding cases with incomplete data, 1,461 cases had computed tomography angiography and/or 2-week clinical follow-up and were analyzed, including 24 cases (1.6%) with BCVI. Sensitivity, specificity, positive predictive value, and negative predictive value for each set of criteria were respectively 75.0, 87.5, 9.1, and 99.5 for Denver; 91.7, 71.1, 5.0, and 99.8 for Memphis; 79.2, 82.7, 7.1, and 99.6 for Eastern Association for the Surgery of Trauma; 45.8, 95.8, 15.5, and 99.1 for Utah; and 75.0, 89.5, 10.7, and 99.5 for McGovern. CONCLUSION: In this large multicenter pediatric cohort, the Memphis criteria demonstrated the highest sensitivity at 91.7% and would have missed the fewest BCVI, while the Utah score had the highest specificity at 95.8% but would have missed more than half of the injuries. Development of a tool, which narrows the Memphis criteria while maintaining its sensitivity, is needed for application in pediatric patients. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level II.

Hemodilution in pediatric trauma: Defining the expected hemoglobin changes in patients with liver and/or spleen injury: An ATOMAC+ secondary analysis.

BACKGROUND: Many children with blunt liver and/or spleen injury (BLSI) never bleed intraperitoneally. Despite this, decreases in hemoglobin are common. This study examines initial and follow up measured hemoglobin values for children with BLSI with and without evidence of intra-abdominal bleeding. METHODS: Children ≤18 years of age with BLSI between April 2013 and January 2016 were identified from the prospective ATOMAC+ cohort. Initial and follow up hemoglobin levels were analyzed for 4 groups with BLSI: (1) Non bleeding; (2) Bleeding, non transfused (3) Bleeding, transfused, and (4) Bleeding resulting in non operative management (NOM) failure. RESULTS: Of 1007 patients enrolled, 767 were included in one or more of four study cohorts. Of 131 non bleeding patients, the mean decrease in hemoglobin was 0.83 g/dL (+/-1.35) after a median of 6.3 [5.1,7.0] hours, (p = 0.001). Follow-up hemoglobin levels in patients with and without successful NOM were not different. For patients with an initial hemoglobin >9.25 g/dL, the odds ratio (OR) for NOM failure was 14.2 times less, while the OR for transfusion was 11.4 times less (p = 0.001). CONCLUSION: Decreases in hemoglobin are expected after trauma, even if not bleeding. A hemoglobin decrease of 2.15 g/dL [0.8 + 1.35] would still be within one standard deviation of a non bleeding patient. An initial low hemoglobin correlates with failure of NOM as well as transfusion, thereby providing useful information. By contrast, subsequent hemoglobin levels do not appear to guide the need for transfusion, nor correlate with failure of NOM. These results support initial hemoglobin measurement but suggest a lack of utility for routine rechecking of hemoglobin. LEVEL OF EVIDENCE: Level II Prognostic Study.

Pediatric appendicitis in the time of the COVID-19 pandemic: A retrospective chart review.

Aim: Conduct a time trend analysis that describes 2 groups of patients admitted to a large tertiary children's hospital that presented with appendicitis and determine if there was an increase in complicated appendicitis when compared between 2 time periods before and during the early coronavirus disease 2019 (COVID-19) pandemic of 2020. Methods: We conducted a retrospective analysis of all children presenting to a single-center site with appendicitis between March 23 and August 31, 2020, in the Central Texas region. We compared 507 patients presenting with appendicitis from the non-COVID-19 era in 2019 with n = 249 to patients presenting during the COVID time period with n = 258. All patients with appendicitis within those time periods were reviewed with analysis of various characteristics in regard to presentation, diagnosis of uncomplicated versus complicated appendicitis, and management outcomes. Results: There were no significant demographic differences or change in the number of appendicitis cases noted between the 2 time periods of comparison. There was no significant difference in rates of complicated appendicitis or presentation time following symptom onset between the 2 eras. There was no significant difference in intraoperative or postoperative complications. There was a statistically significant increase in the use of computed tomography (CT) scans (P-value = 0.004) with patients 1.81 times more likely to have a CT scan in the pandemic era after adjusting for patient-level factors. The effect of severe acute respiratory syndrome coronavirus 2 status on outcomes was not part of the data analysis. Conclusion: Our study is the largest to date examining appendicitis complications in the era of COVID. In the time of the COVID-19 pandemic, we found no delay in presentation in children presenting to the emergency department and no increase in complicated appendicitis. We did identify an increase in the use of CT scans for definitive diagnosis of appendicitis noted in the pandemic era. Although COVID-19 status was not studied, the finding of increased CT use for a definitive diagnosis of appendicitis was a distinctive finding of this study showing a change in practice in pediatric emergency medicine.

Predictors of swimming pool supervision for caregivers of toddlers.

BACKGROUND: In the U.S., drowning is a leading cause of death for toddlers. One important layer of protection against submersion injuries and fatalities is parent or caregiver supervision. The aims of this study are to explore current supervisory behavior of caregivers, determine how caregivers view com-mon supervision distractions, like cell phones and grilling, and identify what factors shape the quality of supervision that is given when swimming with their toddler at a swimming pool. METHODS: This cross-sectional study used the MTurk online platform to survey 650 caregivers of toddlers (1-4 yrs old) about their supervision behavior, their drowning knowledge, their perceptions of arm's reach supervision, the water competency of their toddler, and other background information. Regression analysis was used to identify factors that predicted report-ed supervision behavior. RESULTS: The average supervision behavior score for caregivers indicated an attitude between neutral and disagreement with allowing distractions for themselves while supervising their toddler in a swimming pool. High water safety knowledge and positive perceptions of arm's reach supervision were the biggest predictors of attentive supervision behavior. Having a home pool, higher education level, and believing their toddler had greater water competency were predictive of less attentive supervision behavior. CONCLUSIONS: Results suggest that supervision behavior while toddlers are in a swimming pool may be inade-quate. Low water safety knowledge and attitudes about what constitutes quality supervision are related to pool supervision behavior and changing these may reduce drowning risk. Caregivers should be encouraged to not reduce supervision as their toddlers gain water competency and if they have a home pool.

Early vasopressor administration in pediatric blunt liver and spleen injury: An ATOMAC+ study.

BACKGROUND: No prior studies have examined the outcomes of early vasopressor use in children sustaining blunt liver or spleen injury (BLSI). METHODS: A planned secondary analysis of vasopressor use from a 10-center, prospective study of 1004 children with BLSI. Inverse probability of treatment weighting (IPTW) was used to compare patients given vasopressors <48 h after injury to controls based on pretreatment factors. A logistic regression was utilized to assess survival associated with vasopressor initiation factors on mortality and nonoperative management (NOM) failure. RESULTS: Of 1004 patients with BLSI, 128 patients were hypotensive in the Pediatric Trauma Center Emergency Department (ED); 65 total patients received vasopressors. Hypotension treated with vasopressors was associated with a sevenfold increase in mortality (AOR = 7.6 [p < 0.01]). When excluding patients first given vasopressors for cardiac arrest, the risk of mortality increased to 11-fold (AOR = 11.4 [p = 0.01]). All deaths in patients receiving vasopressors occurred when started within the first 12 h after injury. Vasopressor administration at any time was not associated with NOM failure. CONCLUSION: After propensity matching, early vasopressor use for hypotension in the ED was associated with an increased risk of death, but did not increase the risk of failure of NOM. LEVEL OF EVIDENCE: Level III prognostic and epidemiological, prospective.

Child abuse and the pediatric surgeon: A position statement from the Trauma Committee, the Board of Governors and the Membership of the American Pediatric Surgical Association.

BACKGROUND: The pediatric surgeon is in a unique position to assess, stabilize, and manage a victim of child physical abuse (formerly nonaccidental trauma [NAT]) in the setting of a formal trauma system. METHODS: The American Pediatric Surgical Association (APSA) endorses the concept of child physical abuse as a traumatic disease that justifies the resource utilization of a trauma system to appropriately evaluate and manage this patient population including evaluation by pediatric surgeons. RESULTS: APSA recommends the implementation of a standardized tool to screen for child physical abuse at all state designated trauma or ACS verified trauma and children's surgery hospitals. APSA encourages the admission of a suspected child abuse patient to a surgical trauma service because of the potential for polytrauma and increased severity of injury and to provide reliable coordination of services. Nevertheless, APSA recognizes the need for pediatric surgeons to participate in a multidisciplinary team including child abuse pediatricians, social work, and Child Protective Services (CPS) to coordinate the screening, evaluation, and management of patients with suspected child physical abuse. Finally, APSA recognizes that if a pediatric surgeon suspects abuse, a report to CPS for further investigation is mandated by law. CONCLUSION: APSA supports data accrual on abuse screening and diagnosis into a trauma registry, the NTDB and the Pediatric ACS TQIP® for benchmarking purposes and quality improvement.

Occupational exposure to methyl iodide.

Little is known about the effects of methyl iodide (MI) on the skin after short-term accidental cutaneous exposure because this type of exposure to MI has rarely been reported. In the present case, asymptomatic vesicles developed within 24 hours of exposure, an acute hemorrhagic eruption developed several days later, and an erythematous edematous eruption and large bullae developed several days after the hemorrhagic eruption. This sequence of findings was remarkably similar to the most recently reported case of short-term accidental MI exposure, and we believe that the findings described and the time course of the findings may be a reproducible phenomenon following this type of cutaneous exposure to MI.

Endoloop as the first line tool for appendiceal stump closure in children with appendicitis.

PURPOSE: The objective of this study is to compare outcomes for pediatric patients undergoing laparoscopic appendectomy (LA) performed either (1) using an endostapler (ES) to divide the appendix and mesoappendix or (2) using endoloops (ELs) to close the appendiceal stump and electrocautery to divide the mesoappendix. METHODS: We conducted a retrospective chart review of all patients who underwent LA for suspected appendicitis 4 years at a free standing children's hospital. The use of EL and ES was compared separately in patients with perforated and nonperforated appendicitis. We compared patient characteristics and outcomes. RESULTS: There were no significant differences in rate of postoperative abscess, rate of subsequent small bowel obstruction requiring operation or rate of intraperitoneal hematoma between the ES and EL groups for both nonperforated and perforated appendectomy cases. Superficial wound infection was more common in the nonperforated EL group (17/309, 5.5%) than in the nonperforated ES group (2/235, 0.9%; p = 0.007). Operative time for the EL technique (52.2 ± 15.8 minutes; p = 0.047) was shorter than for the ES technique (58 ± 23.2 minutes) for patients with perforated appendicitis. CONCLUSION: EL stump closure and mesoappendix cauterization during LA is safe and effective in children with appendicitis, including perforated appendicitis.

The positive and negative predictive value of transabdominal color Doppler ultrasound for diagnosing ovarian torsion in pediatric patients.

PURPOSE: The purposes of this study were to (1) determine the positive and negative predictive value (NPV) of transabdominal color Doppler ultrasound (CDU) for diagnosing ovarian torsion (OT) in pediatric patients and 2) identify predictors of a false-positive CDU result for OT. METHODS: An IRB-approved retrospective chart review was performed on all female patients who underwent transabdominal CDU evaluation of the ovaries (664 CDUs in 605 patients) for acute abdominal pain. CDU reports were categorized as positive for OT if the report stated "cannot rule out torsion" or "positive for torsion." RESULTS: There were 47 false-positive ultrasounds, 3 false negatives, 11 true positives, and 603 true negatives for OT. Sensitivity was 78.6%, specificity 92.3%, positive predictive value (PPV) 19.0%, and NPV 99.5%. False-positive CDU when compared to true positives were more common in older patients (p=0.004) and were more commonly read as "cannot rule out torsion" (p<0.001). Ovarian cysts were larger in true-positive CDU than in false-positive CDU (p<0.001). However, cyst presence/absence did not predict a true positive result. CONCLUSION: Transabdominal CDU has a low PPV and a high NPV for ovarian torsion in pediatric patients. False-positive results are more common in older patients and associated with small ovarian cysts.

Current diagnosis and management of urachal remnants.

PURPOSE: The purposes of this study are to review our experience with patients who were found to have urachal remnants. We discuss their diagnosis and management and we also evaluate post-operative complications in our cohort of patients with this entity. METHODS: We performed a retrospective review of all patients diagnosed with a urachal remnant (UR) between January 2006 and December 2010. Patient variables included age, gender, presenting symptoms and signs, diagnostic modality, and type of urachal remnant. Operative management, post-operative complications, and non-operative follow-up were abstracted. RESULTS: We identified 103 pediatric patients with either a urachal cyst (n = 38), urachal diverticulum (n = 13), urachal sinus (n = 11), patent urachus (n = 21), or a non-specific atretic urachal remnant (n = 20). Seventy-eight patients had symptomatic URs. Thirty-four symptomatic patients underwent surgical excision of the UR and 44 symptomatic patients were observed. Eighteen URs were incidentally diagnosed in asymptomatic patients, none of whom underwent surgical excision. In 7 patients symptoms could not be determined from the records. No patients with non-specific atretic remnants were operated upon. Nineteen of the observed patients were reimaged subsequently. In fifteen (78.9%) of these patients, the URs had resolved spontaneously. None of the patients who were observed required subsequent excision of the UR. Post-operative complications occurred in 14.7% of patients in whom URs were excised. CONCLUSION: Review of our patients diagnosed with URs indicates there is a subset of patients in whom spontaneous resolution could be expected. Complications are not uncommon after surgical excision.

Fate of the uterus in 46XX cloacal exstrophy patients.

PURPOSE: Genetically female cloacal exstrophy (46XX CE) patients develop complications later in life due to their abnormal uterine anatomy, resulting in various invasive gynecologic procedures. Furthermore, they have difficulty becoming pregnant, and if they do conceive, they are unlikely to carry the pregnancy to term. We performed this review to determine the rate of gynecological complications, the fate of the uterus, and the rate of pregnancy in 46XX cloacal exstrophy patients. METHODS: All charts for 46XX CE patients treated by us were reviewed following IRB approval. Patient age at last follow-up, surgical management of the uterus, uterine complications, and pregnancies were recorded. RESULTS: The charts of all 16 of our 46XX CE patients who survived past the neonatal period were reviewed. Two patients underwent hemi-hysterectomy (HH): 1 for an atretic hemi-uterus at birth, another for abnormal uterine insertion at 3 years. A third patient initially had HH for hydrometrocolpos leading to ureteral and colonic obstruction at 14 years but she required a completion hysterectomy a year later. Four patients underwent total hysterectomy (TH) at the outset: 2 neonates for a diminutive uterus with extreme disparity in the halves, another for uterine prolapse at 1 month of age, and a fourth for hematometrocolpos at 16 years of age. Six patients reached adulthood without requiring gynecologic intervention; one of these six is now being managed at another institution. Two patients are prepubertal and one was lost to follow-up. The only patient in the series who became pregnant miscarried at 11 weeks gestation. CONCLUSION: Out of 13 post-pubertal patients 6 have retained the entire uterus and another 2 had a hemi-hysterectomy. One patient who became pregnant miscarried at 11 weeks gestation. We believe it is appropriate to avoid ablative genital surgery as far as possible and for these patients to become pregnant after detailed discussion with physicians experienced in the care of 46XX CE patients.

The implications of missed opportunities to diagnose appendicitis in children.

OBJECTIVES: The purpose of this study was to determine the fraction of children with acute appendicitis who had recent false-negative diagnoses and to analyze the association of a missed diagnosis of appendicitis with patient outcome. METHODS: The records of all 816 patients who underwent appendectomy for suspected appendicitis at a free-standing children's hospital between 2007 and 2010 were reviewed. A patient admitted or evaluated in the emergency department (ED), discharged without a diagnosis of appendicitis, and then readmitted with histopathologically confirmed appendicitis within 3 days was considered to have a "missed diagnosis." Outcomes for this missed group were compared to those of the remainder of the appendectomy cohort. RESULTS: Thirty-nine patients with appendicitis (4.8%) were missed at initial presentation. The most common initial discharge diagnoses were acute gastroenteritis (43.6%), constipation (10.3%), and emesis (10.3%). The median duration from the initial evaluation to the appendicitis admission was 28.3 hours (interquartile range [IQR] = 17.0 to 39.6 hours). A missed diagnosis was associated with a longer median hospitalization (5.8 days [IQR = 4.0 to 8.1 days] vs. 2.5 days [IQR = 1.8 to 4.6 days]; p < 0.001), higher rate of perforation (74.4% vs. 29.0%; p < 0.001), higher complication rate (28.2% vs. 10.4%; p = 0.002), and higher rate of reintervention (20.5% vs. 6.2%; p = 0.003). CONCLUSIONS: Of children diagnosed with appendicitis, 4.8% may have had a missed opportunity for earlier diagnosis. These false-negative diagnoses are associated with higher rates of perforation, postoperative complications, and need for postoperative interventions, as well as longer hospitalizations.

Midkine Mediates Intercellular Crosstalk between Drug-Resistant and Drug-Sensitive Neuroblastoma Cells In Vitro and In Vivo.

Resistance to cytotoxic agents has long been known to be a major limitation in the treatment of human cancers. Although many mechanisms of drug resistance have been identified, chemotherapies targeting known mechanisms have failed to lead to effective reversal of drug resistance, suggesting that alternative mechanisms remain undiscovered. Previous work identified midkine (MK) as a novel putative survival molecule responsible for cytoprotective signaling between drug-resistant and drug-sensitive neuroblastoma, osteosarcoma and breast carcinoma cells in vitro. In the present study, we provide further in vitro and in vivo studies supporting the role of MK in neuroblastoma cytoprotection. MK overexpressing wild type neuroblastoma cells exhibit a cytoprotective effect on wild type cells when grown in a co-culture system, similar to that seen with doxorubicin resistant cells. siRNA knockdown of MK expression in doxorubicin resistant neuroblastoma and osteosarcoma cells ameliorates this protective effect. Overexpression of MK in wild type neuroblastoma cells leads to acquired drug resistance to doxorubicin and to the related drug etoposide. Mouse studies injecting various ratios of doxorubicin resistant or MK transfected cells with GFP transfected wild type cells confirm this cytoprotective effect in vivo. These findings provide additional evidence for the existence of intercellular cytoprotective signals mediated by MK which contribute to chemotherapy resistance in neuroblastoma.

Delayed repeated enema and operative findings after unsuccessful primary enema for intussusception.

INTRODUCTION: The purpose of this study was (1) to evaluate the role for and the potential morbidity associated with delayed repeated enema (DRE) and (2) to compare surgical findings for patients undergoing operative exploration after failed primary enema and DRE reduction attempts for intussusception. METHODS: After obtaining approval from the Internal Review Board, we completed a retrospective review of all patients treated for intussusception at a large, tertiary care pediatric hospital. We evaluated the success of primary reduction enema, DRE, and compared surgical findings after failed enema reduction. RESULTS: A total of 135 intussusceptions underwent an attempt at enema reduction following diagnosis. Of these, 83 (61.5%) intussusceptions were reduced with primary enema. Thirty-four patients (25.2%) proceeded directly to surgical exploration after a failed primary enema and 4 more patients were explored after successful reduction due to suspicion for a pathologic lead point. Thirty-four of these operations were therapeutic. In this, four patients had a negative exploration; eight patients required a bowel resection due to necrotic bowel, perforation, or persistence of an irreducible intussusception. Eighteen patients underwent a DRE after a failed primary enema. Two DREs revealed the intussusception had completely reduced before the study, and 11 DREs were successful in reducing persistent intussusceptions. Five patients underwent operative exploration after a failed DRE and were all found to have a persistent intussusception which was successfully reduced intraoperatively. There were no negative laparotomies, pathologic lead points, or instances of necrotic bowel or perforation in patients explored following unsuccessful DRE and no bowel resections were required. CONCLUSIONS: The use of DRE in select patients with persistence of an intussusception may result in successful subsequent reduction with no apparent increase in morbidity. A DRE may lead to improved outcomes for patients with intussusception through avoidance of unnecessary surgical reductions and negative explorations.