Faculty Bibliography

BACKGROUND:Thoracic aortic dissection (AD) is a rare occurrence in childhood and mostly associated with connective tissue disorders or congenital abnormalities. We examined the characteristics associated with AD and predictors of survival. METHODS:The Kids' Inpatient Database (1997-2009) was used to identify thoracic ADs occurring in patients <20-y-old. Clinical characteristics, as well as determinants of survival, were analyzed using standard statistical methods. RESULTS:One hundred sixty-eight cases of thoracic AD were identified during the study period. Overall survival was 83%. Average length of stay was 15.9 ± 16.9 d, with charges 181,867.92 ± $211,985.00. Thoracic dissection tended to affect adolescents aged 15-19 y (67%), males (76%), and Caucasians (56%) most frequently. Most patients were privately insured (64%) and treated at urban teaching centers (86%). Commonly associated diagnoses were hypertension (18%), Marfan syndrome (15%), and aortic valve disorders (8%). When repair was performed, open repair was more frequent (88%) than endovascular repair (6%). Hemorrhage was the most common complication (19%). Multiple determinants of survival were found. Girls (mortality odds ratio: 0.21 [0.05-0.91]) fared better than boys, P = 0.023. Patients with Medicaid (2.84 [1.21-6.69]) had higher mortality versus privately insured, P = 0.014. Income, race, and hospital characteristics, and type of repair were not significant predictors, even on sub-analyses of surgical and nonsurgical groups separately. CONCLUSIONS:Dissection of the thoracic aorta is a rare but significant condition affecting the pediatric population. Most repairs are performed using open technique. Payer status and gender are predictors of survival in these cases.

The gold standard of peripheral nerve repair is nerve autograft when tensionless repair is not possible. Use of nerve autograft has several shortcomings, however. These include limited availability of donor tissue, sacrifice of a functional nerve, and possible neuroma formation. In order to address these deficiencies, researchers have developed a variety of biomaterials available for repair of peripheral nerve gaps. We review the clinical studies published in the English literature detailing outcomes and reconstructive options. Regardless of the material used or the type of nerve repaired, outcomes are generally similar to nerve autograft in gaps less than 3 cm. New biomaterials currently under preclinical evaluation may provide improvements in outcomes.

OBJECTIVES/OBJECTIVE:Other than automobiles, bicycles are connected to more pediatric injuries than any other consumer product. Whereas characterization of injury patterns following motor vehicle accidents has led to safety initiatives and treatment guidelines, knowledge related to bicyclist injuries is lacking. Our purpose is to identify major injury patterns and outcomes associated with pediatric bicycle accidents. METHODS:From January 2000 to December 2012, 1934 consecutive pediatric admissions (≤17 years) at a level I trauma center were retrospectively reviewed for mechanism injury, demographics, and outcomes. Parametric data were analyzed with student's t test and are presented as mean ± standard deviation. Nonparametric data were analyzed with Mann-Whitney-U test and are presented as median (interquartile range). Analysis was performed to recognize injury patterns and outcomes significantly associated with bicycle related accidents. RESULTS:80 pediatric patients were admitted following bicycle related trauma (4% of all pediatric trauma admissions). The cohort was age 11 ± 4 years, ISS 11 ± 10, 48% black, and 81% male. Injury patterns included 21% isolated head, 21% isolated abdominal, 13% isolated extremity, and 34% multiple injuries. 5% were age 0-4 years, 35% were age 5-9 years, 45% were 10-14 years, and 15% were 15-17 years (p < 0.001). 16% required operative intervention (6% abdominal, 9% orthopedic, 1% vascular). Children under age 6 required an abdominal operation 20% of the time. Length of stay was 2 (4) days with a mortality of 2.5%. CONCLUSIONS:Pediatric bicycle accidents more commonly occur in male children aged 10-14 years. Orthopedic injury is the most frequent overall indication for surgery, yet the youngest children more often required an abdominal operation. LEVEL OF EVIDENCE/METHODS:Level III.

Papillary thyroid cancer (PTC) is the most prevalent of all endocrine cancers. In recent studies, the presence of receptors for pituitary-type growth hormone-releasing hormone (pGHRH-R) has been demonstrated in various human cancers, including human prostate, brain, and other cancer lines. Thyroid malignancies, however, have not yet been investigated in this regard. In this study, we found that pGHRH-R and its functional splice variant, SV1, are present in normal thyroid and PTC cells. We also treated seven normal and PTC tumor thyroid cells in vitro with a GHRH antagonist, MIA-602, to compare its anti-proliferation and anti-invasion potential against vehicle-treated cells. We found that treatment with GHRH antagonist increases the expression of SV1 and pGHRH-R in tumor cells compared to tumor cells exposed to vehicle only, a response which may alter the sensitivity of signaling kinases within the cells. GHRH antagonist treatment of tumor cells also reduced activity of the tumor invasion marker, matrix metalloproteinase (MMP)-2, compared to tumor cells exposed to vehicle only. The expression of pGHRH-R and SV1, as well as MMP-2 activity, in normal thyroid cells remained unaffected by GHRH antagonist treatment. Similarly, cell proliferation rates for tumor or normal thyroid cells were not affected by GHRH antagonist treatment. Our findings have important implications for the therapeutic use of GHRH antagonist in cases of aggressive PTC refractory to conventional treatment modalities, and in which protein expression and MMP-2 activity in normal thyroid tissue is left unaltered.

PURPOSE/OBJECTIVE:This study aims to review the incidence and outcomes for children with superficial spreading melanomas (SSM) using population-based data. METHODS:The Surveillance, Epidemiology, and End Results database (1974-2009) was analyzed for all patients less than 20 years of age diagnosed with SSM. RESULTS:Overall, 724 patients were identified. The annual age-adjusted incidence was 1.78 cases per 1,000,000 in 2009. Most patients were adolescents (N = 620, 85.6%), girls (N = 478, 66.0%), and Caucasian (N = 670, 92.5%). Most tumors were located on the trunk (N = 308, 42.5%) or lower extremities (N = 160, 22.1%). Overall and disease-specific survivals were 95.6% and 97.6%, respectively. Lymph node positivity decreased disease-specific survival among patients undergoing lymph node dissection (86% vs. 100% for negative lymph nodes, P = 0.001). CONCLUSIONS:Incidence of SSM increased in the early part of the study, but has remained relatively stable over the past 2 decades. Girls are at higher risk of development of the disease. Outcomes for children with SSM are very favorable.

BACKGROUND:Extracorporeal membrane oxygenation (ECMO) remains a vital therapy for children requiring cardiopulmonary support. METHODS:The Kids' Inpatient Database (KID) was analyzed for ECMO (ICD-9-CM 39.65) patients between 1997 and 2009. RESULTS:Overall, 8005 cases were identified, consisting of neonatal (ECMO <30days of life; 33%), infant (30days to 1year; 46%), young child (1year to 5years; 9.7%), and older child (>5years; 11%) groups. Patients were most commonly male (56%), Caucasian (49%), and insured by Medicaid (46%). ECMO was indicated for respiratory distress syndrome (RDS; 33%), cardiac and circulatory congenital anomalies (CCCA; 22%), congenital diaphragmatic hernia (CDH; 13%), and persistent pulmonary hypertension of the newborn (PPHN; 10%). On multivariate analysis, length of stay (LOS) decreased over the study period, while total charges (TC) increased over time, p<0.001. Survival was higher for boys and those treated in large or urban teaching hospitals, p<0.05. ECMO for CDH, CCCA, and RDS had the highest associated mortality, p<0.001. Neonatal and infant ECMO had no difference in mortality vs. older children. CONCLUSIONS:While LOS for ECMO has decreased over time, TC has increased steadily. Improved survival is found in boys and patients at large or urban teaching hospitals. CDH, CCCA, and RDS portend poor survival outcomes as indicators for ECMO.

BACKGROUND:Severe morbidity and mortality has been reported from chest tube (CT) placement during pediatric extracorporeal membrane oxygenation (ECMO). METHODS:Kids' Inpatient Database (KID) was analyzed for ECMO with CT placed <8days postcannulation (1997-2009). RESULTS:Overall, 5884 patients were identified (213 CT) (56% male, 49% white), with a median (IQR) age at ECMO cannulation 7 (117)days, length of stay (LOS) 26 (35)days, and total charges (TC) 342,116 (409,573) USD. Diagnoses included congenital diaphragmatic hernia (CDH) 16%, meconium aspiration (MA) 2%, pulmonary hypertension (PH) 13%, respiratory distress syndrome (RDS) 41%, and cardiac (C) 29%. Survival was overall 57%, CDH 47%, MA 88%, PH 75%, RDS 57%, and C 52%. There were no differences in survival between CT and non-CT patients compared overall, or by diagnosis, or by age <30days, or by diagnosis and age <30days. Multivariate analysis and propensity score matching for all ages, or <30days of age by diagnosis showed no difference in survival between CT and non-CT patients. CONCLUSION/CONCLUSIONS:Analysis of KID with correlative propensity score matching demonstrates no increased mortality in pediatric ECMO patients requiring CT placement.

The observation that pulmonary inflammatory lesions and bleomycin (BLM)-induced pulmonary fibrosis spontaneously resolve in young mice, whereas remaining irreversible in aged mice suggests that impairment of pulmonary regeneration and repair is associated with aging. Because mesenchymal stem cells (MSCs) may promote repair after injury, we postulated that differences in MSCs from aged mice may underlie postinjury fibrosis in aging. The potential for young-donor MSCs to inhibit BLM-induced pulmonary fibrosis in aged male mice (>22 months) has not been studied. Adipose-derived MSCs (ASCs) from young (4 months) and old (22 months) male mice were infused 1 day after intratracheal BLM administration. At 21-day sacrifice, aged BLM mice demonstrated lung fibrosis by Ashcroft score, collagen content, and α(v)-integrin messenger RNA (mRNA) expression. Lung tissue from aged BLM mice receiving young ASCs exhibited decreased fibrosis, matrix metalloproteinase (MMP)-2 activity, oxidative stress, and markers of apoptosis vs BLM controls. Lung mRNA expression of tumor necrosis factor-alpha was also decreased in aged BLM mice receiving young-donor ASCs vs BLM controls. In contrast, old-donor ASC treatment in aged BLM mice did not reduce fibrosis and related markers. On examination of the cells, young-donor ASCs had decreased mRNA expression of MMP-2, insulin-like growth factor (IGF) receptor, and protein kinase B (AKT) activation compared with old-donor ASCs. These results show that the BLM-induced pulmonary fibrosis in aged mice could be blocked by young-donor ASCs and that the mechanisms involve changes in collagen turnover and markers of inflammation.

Thoracic aortic aneurysm is a rare condition that carries a critical risk of rupture and mortality. These risks are increased during pregnancy because of a progressively hyperdynamic pattern of circulation. Simultaneously, pregnancy-imposed limitations on the use of ionized radiation and intravenous contrast agents may render conventional techniques for imaging and repair confirmation less acceptable. We describe a novel approach to intraoperative management of an endovascular repair for symptomatic thoracic saccular aneurysm in a pregnant patient, based on intravascular ultrasound and transesophageal echocardiography, with maintenance of uterine perfusion. The patient recovered well and proceeded to a normal delivery. Despite a favorable outcome in this case, further studies of perioperative management of aortic disease in pregnancy are needed.

BACKGROUND:Ingested foreign bodies are a frequent presentation in pediatric emergency departments. Although some pass spontaneously through the gastrointestinal tract, the majority of esophageal-ingested foreign bodies (EFB) require removal. MATERIALS AND METHODS/METHODS:Kids' Inpatient Database (1997-2009) was used to identify children (aged <20 y) with EFB (International Classification of Diseases, Ninth Revision, Clinical Modification code 935.1). Multivariate logistic regression analyses were constructed to identify predictors of resource utilization. RESULTS:Overall, 14,767 EFB cases were identified. Most patients were <5 y of age (72%), boys (57%), and non-Caucasian (55%), with a median (interquartile range) length of stay (LOS) of 1 (1) d, and total charges of $11,003 (8503). A total of 11,180 procedures were performed, most commonly esophagoscopy (77%), followed by bronchoscopy (20%), gastroscopy (2%), and rarely surgery (0.8%). By multivariate logistic regression, increased total charges were associated with a diagnosis of esophageal ulceration (odds ratio [OR] = 1.57), esophagoscopy (OR = 1.42), and bronchoscopy (OR = 1.62), all P < 0.001. Total charges also increased with admission to urban nonteaching hospitals (OR = 1.51) versus urban teaching hospitals, P < 0.001. Prolonged LOS (≥1 d) was associated with admission to a hospital in the Midwest (OR = 3.18) and with esophageal ulceration (OR = 2.11) and esophagoscopy (OR = 1.13), P < 0.03. Boys had higher odds of longer hospitalization (OR = 1.21), P < 0.001. Overall hospital mortality was 0.1% (n = 16). CONCLUSIONS:Most EFB occur in children <5 y of age. Esophageal ulceration, esophagoscopy, and bronchoscopy are associated with increased total charges. Esophageal ulceration, esophagoscopy, and boys are associated with an increased LOS. Surgery and hospital mortality are both extremely rare in children with EFB.