Golf cart injuries have similar severity to all-terrain vehicle injuries in children: a multicenter comparison over a 5-year period.

Background: Golf carts (GCs) and all-terrain vehicles (ATVs) are popular forms of personal transport. Although ATVs are considered adventurous and dangerous, GCs are perceived to be safer. Anecdotal experience suggests increasing numbers of both GC and ATV injuries, as well as high severity of GC injuries in children. This multicenter study examined GC and ATV injuries and compared their injury patterns, resource utilization, and outcomes. Methods: Pediatric trauma centers in Florida submitted trauma registry patients age <16 years from January 2016 to June 2021. Patients with GC or ATV mechanisms were identified. Temporal trends were evaluated. Injury patterns, resource utilization, and outcomes for GCs and ATVs were compared. Intensive care unit admission and immediate surgery needs were compared using multivariable logistic regression. Results: We identified 179 GC and 496 ATV injuries from 10 trauma centers. GC and ATV injuries both increased during the study period (R2 0.4286, 0.5946, respectively). GC patients were younger (median 11 vs 12 years, p=0.003) and had more intracranial injuries (34% vs 19%, p<0.0001). Overall Injury Severity Score (5 vs 5, p=0.27), intensive care unit (ICU) admission (20% vs 16%, p=0.24), immediate surgery (11% vs 11%, p=0.96), and mortality (1.7% vs 1.4%, p=0.72) were similar for GCs and ATVs, respectively. The risk of ICU admission (OR 1.19, 95% CI 0.74 to 1.93, p=0.47) and immediate surgery (OR 1.04, 95% CI 0.58 to 1.84, p=0.90) remained similar on multivariable logistic regression. Conclusions: During the study period, GC and ATV injuries increased. Despite their innocuous perception, GCs had a similar injury burden to ATVs. Heightened safety measures for GCs should be considered. Level of evidence: III, prognostic/epidemiological.

Social determinants of health in pediatric trauma: Associations with injury mechanisms and outcomes in the context of the COVID-19 pandemic.

BACKGROUND: Relationships between social determinants of health and pediatric trauma mechanisms and outcomes are unclear in context of COVID-19. METHODS: Children <16 years old injured between 2016 and 2021 from ten pediatric trauma centers in Florida were included. Patients were stratified by high vs. low Social Vulnerability Index (SVI). Injury mechanisms studied were child abuse, ATV/golf carts, and firearms. Mechanism incidence trends and mortality were evaluated by interrupted time series and multivariable logistic regression. RESULTS: Of 19,319 children, 68% and 32% had high and low SVI, respectively. Child abuse increased across SVI strata and did not change with COVID. ATV/golf cart injuries increased after COVID among children with low SVI. Firearm injuries increased after COVID among children with high SVI. Mortality was predicted by injury mechanism, but was not independently associated with SVI, race, or COVID. CONCLUSION: Social vulnerability influences pediatric trauma mechanisms and COVID effects. Child abuse and firearm injuries should be targeted for prevention.

Risk of Injury-Related Readmission Varies by Initial Presenting-Hospital Type Among Children at High Risk for Physical Abuse.

OBJECTIVES: Children experiencing physical abuse may initially present to hospitals with underappreciated minor injuries, only to experience more severe injuries in the future. The objectives of this study were to 1) describe young children presenting with high-risk diagnoses for physical abuse, 2) characterize the hospitals to which they initially presented, and 3) evaluate associations of initial presenting-hospital type with subsequent admission for injury. METHODS: Patients aged younger than 6 years from the 2009-2014 Florida Agency for Healthcare Administration database with high-risk diagnoses (codes previously associated with >70% risk of child physical abuse) were included. Patients were categorized by the hospital type to which they initially presented: community hospital, adult/combined trauma center, or pediatric trauma center. Primary outcome was subsequent injury-related hospital admission within 1 year. Association of initial presenting-hospital type with outcome was evaluated with multivariable logistic regression, adjusting for demographics, socioeconomic status, preexisting comorbidities, and injury severity. RESULTS: A total of 8626 high-risk children met inclusion criteria. Sixty-eight percent of high-risk children initially presented to community hospitals. At 1 year, 3% of high-risk children had experienced subsequent injury-related admission. On multivariable analysis, initial presentation to a community hospital was associated with higher risk of subsequent injury-related admission (odds ratio, 4.03 vs level 1/pediatric trauma center; 95% confidence interval, 1.83-8.86). Initial presentation to a level 2 adult or combined adult/pediatric trauma center was also associated with higher risk for subsequent injury-related admission (odds ratio, 3.19; 95% confidence interval, 1.40-7.27). CONCLUSIONS: Most children at high risk for physical abuse initially present to community hospitals, not dedicated trauma centers. Children initially evaluated in high-level pediatric trauma centers had lower risk of subsequent injury-related admission. This unexplained variability suggests stronger collaboration is needed between community hospitals and regional pediatric trauma centers at the time of initial presentation to recognize and protect vulnerable children.

Advances in pulmonary management and weaning from ECLS.

ECMO for neonatal and pediatric respiratory failure provides gas exchange to allow lung recovery from reversible pulmonary ailments. This is a comprehensive discussion on the various strategies and advances utilized by pediatric ECLS specialists today. ECMO patients require continual monitoring, serial gasses and radiographs, near-infrared spectroscopy (NIRS - to monitor oxygen delivery to regional tissue beds), and more quality ECLS directed care. As the foundation to lung recovery, good EMCO closely monitors ECLS flow rates, sweep gasses, and membrane lung function. Mixed venous oxygen saturation (Sv02) greater than 65% indicates good oxygen delivery and sweep gas adjustments maintain PaCO2 of 40-45 mm Hg. Lung recovery ventilatory settings do not fully rest the lungs but maintain normal or nontoxic pressure and oxygen levels. Neonatal recovery settings are PIP (cm H20) of 15-20, PEEP of 5-10, ventilator rate of 12-20 and an inspiratory time of 0.5-1 s, and FiO2 of 0.3-0.5. Pediatric recovery settings are PIP (cm H20) < 25, PEEP of 5-15, ventilator rate of 10-20 and an inspiratory time of 0.8-1 s, and FiO2 of <0.5. Some studies demonstrate a higher recovery PEEP level decreases duration of ECMO, but do not demonstrate a mortality difference. Multiple adjunctive therapies such as surfactant, routine pulmonary clearance and respiratory physiotherapy, iNO, prone positioning, bronchoscopy, POCUS, CT imaging, and extubation or "awake ECLS" can significantly affect pulmonary recovery. Patience is necessary as lung recovery may take weeks or even months on the nontoxic settings. On these settings, dynamic recovery will be revealed by improvement in tidal volume, minute ventilation and radiographic pulmonary aeration, prompting discussion about weaning. When this pulmonary compliance recovery becomes evident, decreasing ECLS flow while also decreasing circuit FiO2 and/or sweep gas are common components to ECMO weaning strategies.

The International Classification of Disease Critical Care Severity Score demonstrates that pediatric burden of injury is similar to that of adults: Validation using the National Trauma Databank☆.

BACKGROUND/PURPOSE: Resource-based severity of injury (SOI) measures, such as the International Classification of Disease (ICD) Critical Care Severity Score (ICASS), may characterize traumatic burden better than standard mortality-based measures. The purpose of this study was to validate the ICASS in a representative national-level trauma cohort and compare SOI measures between children and adults. METHODS: The National Trauma Databank was used to derive (2008-12) and validate (2013-15) ICASS and ICD Injury Severity Scores (ICISS, standard mortality-based SOI measure). SOI metrics and outcomes were compared between pediatric, adult, and elderly age groups. Logistic regression modeling evaluated predictors of critical care resource utilization. RESULTS: Derivation and validation cohorts consisted of 3.90 and 1.97 million patients, respectively. ICASS strongly predicted actual critical care utilization (OR 1.04, 95% CI 1.04-1.04, p<0.0001). Mean ICASS was 24.4 for children and 33.0 for adults (ratio 0.74), indicating predicted critical care utilization in children was three-quarters that of adults. In contrast, predicted pediatric mortality was less than half that of adults. CONCLUSIONS: Mortality-based SOI measures underestimate pediatric burden of injury. This study validates ICASS and demonstrates that pediatric resource-based SOI is more similar to that of adults. ICASS is easily calculated without a trauma registry and complements mortality-based measures. Level of evidence III, retrospective comparative study.

The effort and outcomes of the Pediatric Surgery match process: Are we interviewing too many?

PURPOSE: Increasing numbers of programs participating in the pediatric surgery match has resulted in economic and logistical issues for candidates, General Surgery residencies, and Pediatric Surgery training programs (PSTP). We sought to determine the ideal number of interviews conducted by programs based on resultant rank order lists (ROL) of matched candidates. METHODS: PSTPs received 4 online surveys regarding interview practices (2011-2012, 2014), and matched candidate ROL (2008-2010, 2012, 2014). Program directors (PD) also provided estimates regarding minimum candidate interview numbers necessary for an effective match (2011-2012, 2014). Kruskal-Wallis equality-of-populations rank tests compared ROL and interview numbers conducted. Quartile regression predicted ROL based on the interview numbers. Wilcoxon signed rank-sum tests compared the interview numbers to the minimal interview number using a matched pair. p Values<0.05 were significant. RESULTS: Survey response rates ranged from 85-100%. Median ROL of matched candidates (2-3.5) did not differ between programs (p=0.09) and the lowest matched ROL for any year was 10-12. Interview numbers did not affect the final candidate ROL (p=0.22). While PDs thought the minimum median interview number should be 20, the number actually conducted was significantly higher (p<0.001). CONCLUSION: These data suggest that PSTPs interview excessive numbers of candidates. Programs and applicants should evaluate mechanisms to reduce interviews to limit costs and effort associated with the match.

Gene alterations and intestinal mucosal changes following growth factor and omega-3 exposure in a rat model of inflammatory bowel disease.

BACKGROUND: We have previously shown that there is synergism between Hepatocyte Growth Factor (HGF) and Omega-3 (OM-3) enriched feeds using an immunologic model of inflammatory bowel disease (IBD). This combination decreased inflammation and cytokine levels and increased microvascular density and mucosal mass. This study evaluates the gene alterations that occurred using this same model. METHODS: Twenty adult female transgenic HLA-B27 rats were divided into four groups: Group 1: (Regular feeds, IV saline); Group 2: (OM-3 feeds, IV saline); Group 3: (Regular feeds, IV HGF 150 µg/kg/day); Group 4: (OM-3 feeds, IV HGF 150 µg/kg/day). Rats were sacrificed 14 days after pump placement. Bowel was harvested and RNA extracted. Microarray gene chips were used. Statistical analysis was done by analysis of variance using Partek Genomics Suite. Results were significant if fold change was more than 2 or less than -2, with P<0.05. RESULTS: In the ileum, HGF up- or down-regulated 34 genes, while OM-3 affected 60 genes. Together 68 genes were affected. Families with a synergistic effect included Solute Carrier Proteins, ATP Binding Cassette Proteins, and Matrix Metalloproteinases. In the colon, 23 genes were affected by HGF, while 66 genes were affected with OM-3. Combined exposure affected 32 genes, including a synergistic effect on solute carrier proteins, aquaporins, and immunologic factors. CONCLUSIONS: There is a synergistic gene alteration effect of exposure of two (HGF and Omega-3 enriched feeds) agents on bowel mucosa. Of most interest was the synergistic effect on the solute carrier protein family, a previously identified gene family up-regulated in response to intestinal failure.

Hepatocyte growth factor and omega-3-enriched feeds have a synergistic effect on mucosal mass in an animal model of inflammatory bowel disease.

BACKGROUND: Hepatocyte growth factor (HGF) decreases intestinal inflammation and cytokine levels in an animal model of inflammatory bowel disease (IBD). Luminal omega-3 (OM-3) is anti-angiogenic, reduces inflammation, and may decrease symptoms in patients with Crohn's disease. This study evaluates the synergism of HGF and OM-3. METHODS: Twenty adult female transgenic HLA-B27 rats were divided into 4 groups: group 1: regular feeds, IV saline; group 2: OM-3-enriched feeds, IV saline; group 3: regular feeds, IV HGF (150 µg/kg per day); and group 4: OM-3-enriched feeds, IV HGF(150 µg/kg per day). Rats were killed at 14 days after pump placement. Small and large bowel mucosa was harvested, and DNA and protein were extracted and quantified. Statistical analysis was done by analysis of variance with post-hoc Tukey's HSD test. RESULTS: Content of protein and DNA in the ileum were significantly increased by supplementation of HGF (P < .001, P < .01, respectively) alone. OM-3 significantly increased protein content but not DNA (P = .02, P = 0.3, respectively). Combined, they had a synergistic effect greater than either supplement alone (P = .0001, P = .002, respectively). In the colon, HGF and OM-3 did not significantly increase protein or DNA content individually or together. CONCLUSIONS: This is the first demonstration of the synergistic effect of a growth factor (HGF) and a dietary supplement (OM-3) in an immunologic model of IBD.

Chronology of the effect of massive small bowel resection and hepatocyte growth factor (HGF) on intestinal adaptation.

BACKGROUND: We previously demonstrated that hepatocyte growth factor (HGF) increases mucosal protein and DNA content at single time points during intestinal adaptation in rats. This study evaluates mucosal changes after massive small bowel resection (MSBR) and with the addition of IV HGF measured over the timeframe of intestinal adaptation. METHODS: Sixty adult female Sprague-Dawley rats were divided into three groups and underwent massive small bowel resection (MSBR), MSBR+HGF (intravenous 150 mg/kg/d), or sham operation (control). Five animals per group were sacrificed at 7, 14, 21, and 28 d. Ileal mucosa was harvested and DNA and protein extracted. DNA content (ug/mg mucosa) was measured at 260 nm and protein content (ug/mg mucosa) was measured using the Bradford assay. MIB-5 immunohistochemical staining was done to confirm that the increased DNA content was due to proliferation. Statistical analysis was by ANOVA with post-hoc Tukey's HSD test. RESULTS: At 7 and 14 d, protein concentration was increased following HGF administration in comparison to MSBR alone and in control rats (P<0.05 and P<0.03, respectively). Mucosal DNA content in the MSBR-HGF rats was significantly increased over MSBR and control groups at 21 and 28 d (P<0.02 and P<0.004, respectively). MIB-5 immunohistochemical staining correlated with mucosal DNA content at 21 and 28 d (P<0.0005 and P<0.002, respectively). CONCLUSIONS: The mucosal response to MSBR for the period 7-14 d after surgery demonstrates that protein content is increased due to an emphasis on hypertrophy, whereas at 21-28 d hyperplasia is the primary change as demonstrated by the increase in DNA content. This response was enhanced by HGF. This is the first demonstration correlating the bimodal gene response during intestinal adaptation to the bimodal mucosal response. Also, this is the first demonstration of a biphasic response by the mucosa to HGF during intestinal adaptation.

The effect of hepatocyte growth factor on gene transcription during intestinal adaptation.

PURPOSE: Previously, we investigated the physiologic effects of hepatocyte growth factor (HGF) on intestinal adaptation using a massive small bowel resection (MSBR) rat model. To correlate these altered physiologic changes with gene alterations, we used microarray technology at 7, 14, and 21 days after MSBR. METHODS: Forty-five adult female rats were divided into 3 groups and underwent 70% MSBR, MSBR + HGF (intravenous 150 µg/kg per day), or sham operation (control). Five animals per group were killed at each time point. Ileal mucosa was harvested and RNA extracted. Rat Gene Chips and Expression Console software (Affymetrix, Santa Clara, CA) were used. Statistical analysis was done by analysis of variance using Partek Genomics Suite (Partek, Inc, St Louis, MO). Results were significant if fold change was more than 2 or less than -2, with P < .05. RESULTS: Compared with the control group, MSBR group had significant increases in up-regulated and down-regulated genes. The MSBR-HGF group had further increases in up-regulated and down-regulated genes compared with the MSBR group. At 7 days, 6 cellular hypertrophy families had 30 genes up-regulated, and HGF up-regulated an additional 14 genes. At 21 days, 5 hyperplasia gene families had 32 up-regulated genes. Hepatocyte growth factor up-regulated an additional 16 genes. CONCLUSIONS: Microarray analysis of intestinal adaptation identified an early emphasis on hypertrophy and later emphasis on hyperplasia. This is the first demonstration that the effect of HGF on intestinal adaptation is recruitment of more genes rather than an increase in the fold change of already up-regulated genes.

Early experience with single-incision thoracoscopic surgery in the pediatric population.

INTRODUCTION: Single-incision pediatric endosurgery is gaining popularity in children. We have recently applied the single-incision approach for thoracoscopic procedures. We report our initial experience with single-incision thoracoscopic surgery in the pediatric population. METHODS: A retrospective chart review of the first 10 single-incision thoracoscopic operations done at our institution was conducted. The patients' mean age and weight and the median operative time, postoperative length of stay, and time until discontinuation of chest tubes were determined. RESULTS: The 10 procedures were performed in eight patients (two patients each had bilateral procedures). The procedures performed included wedge resection and mechanical pleurodesis for spontaneous pneumothorax (n = 7), wedge biopsies for lymphoma (n = 1) and chronic granulomatous disease (n = 1), and resection of an apical extrapulmonary neuroblastoma (n = 1). All of the procedures were completed without intraoperative complication or significant blood loss. In each case, multiple trocars and/or unsheathed instruments were passed through a single small incision, which was subsequently used for the chest tube(s). The mean patient age was 13.5 years (range 3-18 years). The mean weight was 47 kilograms (range 16-63 kg). The median operative time was 64 minutes (range 50-201 minutes). The median postoperative length of stay was 7 days (range 3-19 days). The median time until chest tube removal was 3 days (range 2-15 days). The mean follow-up was 7 months (range 3-12 months). One patient developed a recurrent pneumothorax and persistent air leak after having undergone a wedge resection and pleurodesis for a spontaneous pneumothorax and required a reoperation. CONCLUSION: Single-incision thoracoscopic surgery is a feasible alternative to the traditional multiple-incision approach in the pediatric population. The in-line positioning of the camera and instruments often proves to be an advantage rather than a hindrance.

Dose variation of hepatocyte growth factor and its effects on an animal model of TPN-induced liver injury.

BACKGROUND: Total parenteral nutrition (TPN) induced liver failure is the leading indication for transplantation in children. Our previous research demonstrated the benefit of a specific intravenous dose of hepatocyte growth factor (HGF) in the amelioration of TPN-induced liver injury. This study was designed to ascertain the optimum concentration of HGF in an animal model of TPN-induced liver injury. MATERIALS AND METHODS: Twenty adult female Sprague-Dawley rats underwent 70% small bowel resection and placement of venous catheters connected to subcutaneous osmotic minipumps. Four groups (n=5 each) based on the contents of the osmotic pump were utilized as follows: group 1 (control): saline; group 2: HGF 75 mcg/kg/d; group 3: HGF 150 mcg/kg/d; and group 4: HGF 250 mcg/kg/d. Each rat received 14 d of TPN without enteral nutrition. After sacrifice, the liver was harvested. Hepatic inflammation was evaluated using antibodies for TNF-α and IL-6. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technique. RESULTS: All concentrations induced statistically significantly less IL-6 and TNF- α expression compared to the control animals. Increased efficacy was demonstrated with increasing dose concentration up to 150 mcg/kg/d but not 250 mcg/kg/d. Apoptotic activity was decreased statistically significantly for all dose concentrations compared with the controls, as well as to increases in dose concentration. CONCLUSIONS: Increasing concentrations of HGF were directly correlated with increased modulation of inflammatory response and apoptotic index in this animal model for TPN-induced liver injury, up to 150 mcg/kg/d. Further increases were significant with respect to apoptotic index only. Further investigations are warranted to determine if HGF may be useful to minimize TPN-induced liver injury in children.

A comparison of laparoscopic and open Nissen fundoplication and gastrostomy placement in the neonatal intensive care unit population.

INTRODUCTION: The aim of this study was to compare outcomes after laparoscopic and open techniques for Nissen fundoplication and gastrostomy placement in the neonatal intensive care unit (NICU) population. METHODS: The medical records for NICU inpatients who underwent laparoscopic and open Nissen fundoplication and gastrostomy placement from August 2002 to August 2008 were reviewed after Institutional Review Board approval. Each technique was compared with regard to operative time, estimated blood loss, postoperative 24-hour narcotic requirements, time to goal feeds, and complication rates. Analysis of variance was used to determine statistical significance. Data are quoted as mean +/- SEM. RESULTS: Fifty-seven NICU patients underwent fundoplication and gastrostomy placement (25 laparoscopic and 32 open). The time to goal feeds was significantly shorter for the laparoscopic group (4.3 +/- 0.4 vs 6.1 +/- 0.6 days, P = .04). The 24-hour postoperative narcotic requirement was significantly lower in the laparoscopic group (0.24 +/- 0.05 vs 0.55 +/- 0.08 mg/kg, P = .007). Operation times (111 +/- 5 [open] vs 113 +/- 5 minutes, P = .76) and estimated blood loss (13 +/- 2 [open] vs 11 +/- 1 mL, P = .33) were comparable for both groups. CONCLUSION: Laparoscopic and open techniques for Nissen fundoplication with gastrostomy placement are safe and appropriate treatment methods with equivalent operating times for the treatment of gastroesophageal reflux in the NICU population.

Growth factor modulation of hepatic inflammation: a novel approach to the management of total parenteral nutrition-associated liver disease.

PURPOSE: Dependence on total parenteral nutrition in intestinal failure or short bowel syndrome patients can lead to many complications. The most significant complication is progressive liver injury leading to liver failure. This study assesses the potential of hepatocyte growth factor (HGF) in modulating the hepatic response in a rat cholestatic liver injury model. METHODS: Female Sprague-Dawley rats were divided into 3 groups: control (n = 5), chronic liver injury (alpha-naphtylisocyocyanate [ANIT] every 3.5 days at 75 mg/kg; n = 5), and chronic liver injury plus HGF (ANIT + HGF at 250 microg kg(-1) d(-1); n = 5). The rats initially underwent massive (80%) small bowel resections. Seven days later, they were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic minipump for continuous intravenous saline or HGF. Intraperitoneal saline or ANIT injections were subsequently administered every 3.5 days to create a chronic cholestatic model. After 14 days, the animals were euthanized, and liver biopsies were obtained. The liver biopsies were evaluated by histology, immunofluorescence staining for interleukin-6 and tumor necrosis factor alpha, and assessment of apoptosis by terminal dUTP-transferase-mediated nick end labeling (TUNEL) technique. RESULTS: In this chronic liver injury model, HGF did not effect the grade of inflammation. However, HGF did induce retention of the ductal structures and avoided ductal proliferation, damage, and evidence of primary sclerosing cholangitis (P < .05). Hepatocyte growth factor induced less interleukin-6 (P < .011) and tumor necrosis factor alpha (P < .01) expression. Apoptotic activity was also significantly less in the HGF group (P < .01). CONCLUSION: Hepatocyte growth factor preserved the hepatic ductal system, modulated the hepatic inflammatory response, and reduced the apoptotic index in this chronic cholestatic liver injury model. It may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury.

Growth factor manipulation of intestinal angiogenesis: a possible new paradigm in the management of inflammatory bowel disease.

BACKGROUND: Using the transgenic HLA-B27 rat model of inflammatory bowel disease (IBD), we have previously demonstrated hepatocyte growth factor's (HGF) potential to ameliorate diarrhea and decrease bowel injury. This study was designed to assess the effect of HGF on the neovascularization and inflammation in IBD. MATERIALS AND METHODS: Female transgenic HLA-B27 rats were divided into two groups: group 1, saline (control, n = 6); group 2, HGF (150 mug/kg/d, n = 9). Treatments were delivered into the jugular vein via a 14-d subcutaneously placed osmotic mini-pump. Intestinal microvascular density (MVD), histologic inflammatory score, inflammatory cell infiltration, and cytokine expression (tumor necrosis factor-alpha {TNF-alpha}, interferon-gamma {IFN-gamma}, and interleuken-2 {IL-2}) were assessed. Analysis of variance (ANOVA) was used to determine statistical significance. RESULTS: Administration of HGF resulted in variable but significant alterations in ileal and colonic histology compared with control animals. Compared with group 1, inflammatory cell infiltration was significantly reduced in group 2 (7.7 +/- 1.2 versus 13.3 +/- 2.1 SEM, P < 0.05). Enzyme linked immunosorbent assays (ELISA) demonstrated significantly less expression of ileal IFN-gamma, ileal IL-2 and colonic IL-2 in group 2 (P < 0.05) (Fig. 1). Of importance is that Group 2 exhibited significantly greater MVD in the ileum and colon, both P < 0.05 (Figs. 2 and 3). CONCLUSION: HGF stimulates neovascularization while modulating the intestinal inflammatory response. This is the first demonstration in which a growth factor (HGF) stimulates nonpathologic angiogenesis in an animal model of IBD. HGF administration may be beneficial in the clinical management of IBD.

Neonatal outcomes associated with intestinal abnormalities diagnosed by fetal ultrasound.

PURPOSE: Intestinal abnormalities are sometimes seen during antenatal testing; however, the postnatal importance of these findings has not been well established. We evaluated whether abnormal intestinal appearance on fetal ultrasound (US) was ultimately related to neonatal outcome. METHODS: Fetal US examinations from 2003 to 2006 were evaluated. Hyperechogenic bowel was defined as having the echogenicity comparable to bone, and dilated bowel was identified based on the sonographer's assessment. Persistence or resolution of US findings on subsequent US examinations and eventual outcomes were assessed. Cases were categorized as hyperechogenic or dilated and then subgrouped based on whether the US finding resolved. RESULTS: Sixty-eight fetuses had either hyperechogenic (n = 48) or dilated bowel (n = 20) on antenatal US. In 56 cases, complete data were available for analysis. Of 44 liveborn infants, 11 (25.0%) had an abdominal abnormality, and 33 (75.0%) were normal at birth. Compared to those with dilated bowel, fetuses with hyperechogenic bowel had a higher rate of prenatal demise (20.8% vs 10%) but a lower rate of abnormality at birth (10.3% vs 53.3%). Hyperechogenic bowel resolved on subsequent US more frequently than dilated bowel (65.5% vs 20.0%). In both groups, all fetuses with sonographic resolution were normal at birth. Of 9 fetuses that had persistently hyperechogenic bowel, 3 (33.3%) were born with an abnormality, and all were found to have meconium peritonitis or meconium ileus. In the 12 cases where dilated bowel did not resolve, 8 (66.7%) were eventually born with an abnormality, most commonly intestinal atresia. CONCLUSIONS: Hyperechogenic and dilated bowel are associated with a significant rate of fetal demise. Hyperechogenicity is more common than dilation and is more likely to be transient. Dilated bowel is more often associated with neonatal abnormality than hyperechogenic bowel. Persistence of fetal US findings predicts a higher likelihood of abnormality in the neonate.

Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model: a potential approach to the management and treatment of cholestatic liver disease.

BACKGROUND/PURPOSE: The major side effect of total parenteral nutrition is liver injury leading to liver failure. This study was designed to assess specific growth factors in modulating the hepatic response in an ANIT-induced liver-injury model. METHODS: Sprague-Dawley rats were divided into four groups: control (n = 5), liver-injury control (alpha-naphthylisothiocyanate [ANIT], 100 mg/kg, n = 8), ANIT + epidermal growth factor (EGF, 150 mug/kg per day, n = 10), and ANIT + hepatocyte growth factor (HGF, 250 mug/kg per day, n = 9). Rats were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic mini-pump for 7 days of continuous intravenous saline (liver injury control), EGF, or HGF. Seven and 14 days later, liver biopsies were obtained and evaluated for interleukin (IL)-6 and tumor necrosis factor alpha expression by immunofluorescent staining, and for apoptosis, by the terminal transferase dUTP nick end labeling (TUNEL) technique. All animals were euthanized at 14 days. RESULTS: Epidermal growth factor (P < .025) and HGF (P < .001) groups induced less IL-6 expression at day 14 compared to liver-injury controls. In addition, the interval decrease in IL-6 expression between days 7 and 14 was greater in EGF (P < .001) and HGF (P < .001) groups compared to liver-injury controls. At day 14, HGF also demonstrated decreased tumor necrosis factor alpha expression (P < .005). Apoptotic activity was significantly less for the EGF (P < .011) and HGF (P < .0012) groups. CONCLUSION: Epidermal growth factor and HGF modulated the hepatic inflammatory response and apoptotic index in this established liver-injury model and may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury.