Prehospital time and mortality in pediatric trauma.

PURPOSE: The "Golden Hour" of transportation to a hospital has long been accepted as a central principal of trauma care. However, this has not been studied in pediatric populations. We assessed for non-linearity of the relationship between prehospital time and mortality in pediatric trauma patients, redefining the threshold at which reducing this time led to more favorable outcomes. METHODS: We performed an analysis of the 2017-2018 American College of Surgeons Trauma Quality Improvement Program, including trauma patients age < 18 years. We examined the association between prehospital time and odds of in-hospital mortality using linear, polynomial, and restricted cubic spline (RCS) models, ultimately selecting the non-linear RCS model as the best fit. RESULTS: 60,670 patients were included in the study, of whom 1525 died and 3074 experienced complications. Prolonged prehospital time was associated with lower mortality and fewer complications. Both models demonstrated that mortality risk was lowest at 45-60 min, after which time was no longer associated with reduced probability of mortality. CONCLUSIONS: The demonstration of a non-linear relationship between pre-hospital time and patient mortality is a novel finding. We highlight the need to improve prehospital treatment and access to pediatric trauma centers while aiming for hospital transportation within 45 min.

Association Between Congenital Heart Disease-Related Diagnosis Codes and Trauma Surgery Outcomes.

BACKGROUND: Congenital heart disease (CHD) is one the most common congenital anomalies, with a prevalence of 8-10 cases per 1000 live births in the United States. Congenital heart disease has been recognized as a risk factor for poor perioperative and postoperative outcomes in non-cardiac surgery. We aimed to determine if documentation of CHD-related diagnosis codes was associated with similar risks for trauma surgery. METHODS: Data were acquired from the 2010-2019 American College of Surgeons' Trauma Quality Programs Participant Use Files. This study included trauma patients of all ages with one or more surgical procedures and at least one documented non-trauma (comorbidity) International Classification of Diseases code. Patients were stratified based on presence of CHD-related comorbidity codes vs any other comorbidity. Outcomes included mortality, hospital length of stay (LOS), discharge disposition, and in-hospital complications. RESULTS: Using 1:1 propensity score matching, we matched 215 cases with CHD-related comorbid diagnoses to non-CHD controls. Compared to patients with other comorbidities, patients with CHD-related comorbidites were less likely to be discharged home to self-care (odds ratio: 0.44, 95% confidence interval [CI]: 0.25, 078 P = .005) and tended to have prolonged hospital LOS (incidence rate ratio [IRR]: 1.06, 95% CI: 1.001, 1.13, P = .046). CONCLUSIONS: We present the first quantitative multicenter analysis correlating documentation of comorbid CHD-related diagnoses with higher risk of adverse outcomes after trauma surgery. These results support the need to routinely acknowledge and document CHD as comorbidity in trauma admissions that could lead to surgical intervention and for trauma centers to prepare for patients with a possible CHD comorbidity.

Emergency department thoracotomy in children: A Pediatric Trauma Society, Western Trauma Association, and Eastern Association for the Surgery of Trauma systematic review and practice management guideline.

BACKGROUND: The role of emergency department resuscitative thoracotomy (EDT) in traumatically injured children has not been elucidated. We aimed to perform a systematic review and create evidence-based guidelines to answer the following PICO (population, intervention, comparator, and outcome) question: should pediatric patients who present to the emergency department pulseless (with or without signs of life [SOL]) after traumatic injuries (penetrating thoracic, penetrating abdominopelvic, or blunt) undergo EDT (vs. no EDT) to improve survival and neurologically intact survival? METHODS: Using Grading of Recommendations Assessment, Development and Evaluation methodology, a group of 12 pediatric trauma experts from the Pediatric Trauma Society, Western Trauma Association, and Eastern Association for the Surgery of Trauma assembled to perform a systematic review. A consensus conference was conducted, a database was queried, abstracts and manuscripts were reviewed, data extraction was performed, and evidence quality was determined. Evidence tables were generated, and the committee voted on guideline recommendations. RESULTS: Three hundred three articles were identified. Eleven studies met the inclusion criteria and were used for guideline creation, providing 319 pediatric patients who underwent EDT. No data were available on patients who did not undergo EDT. For each PICO, the quality of evidence was very low based on the serious risk of bias and serious or very serious imprecision. CONCLUSION: Based on low-quality data, we make the following recommendations. We conditionally recommend EDT when a child presents pulseless with SOL to the emergency department following penetrating thoracic injury, penetrating abdominopelvic injury and after blunt injury if emergency adjuncts point to a thoracic source. We conditionally recommend against EDT when a pediatric patient presents pulseless without SOL after penetrating thoracic and penetrating abdominopelvic injury. We strongly recommend against EDT in the patient without SOL after blunt injury.

Pediatric emergency resuscitative thoracotomy: A Western Trauma Association, Pediatric Trauma Society, and Eastern Association for the Surgery of Trauma collaborative critical decisions algorithm.

LEVEL OF EVIDENCE: Literature synthesis and expert opinion, Level V.

In-person school attendance and adolescent exposure to injury-related risk behaviors during the COVID-19 pandemic in the United States.

School closures during the COVID-19 pandemic have been reported to influence adolescents' behavioral health and may have altered their exposure to injury risk. We aimed to determine how in-person school attendance of individual adolescents in the United States during the pandemic was correlated with a range of risky health behaviors. We used self-reported data from adolescents 14-18 years old enrolled in grades 9-12 who participated in the 2020 Adolescent Behaviors and Experiences Survey. The exposure of interest was in-person vs remote school attendance in the previous 30 days. Risk behavior outcomes included not wearing a seatbelt when riding in a car; riding with someone who was drinking and driving; suffering intimate partner violence (IPV); forced sexual encounters; suicidal ideation; suicidal planning; electronic bullying; gun carrying; and physical fighting. Based on a multivariable analysis of 5202 students (65% attending school in-person) adjusted for age, sex, race, ethnicity, sexual orientation, parental unemployment, food insecurity, and homelessness, we found that in-person school attendance was associated with increased odds of every risk behavior except suicidal ideation and electronic bullying, with adjusted odds ratios ranging from 1.40 (95% confidence interval [CI]: 1.04, 1.88) for not wearing a seatbelt to 3.43 for IPV (95% CI: 1.97, 5.97). Our analyses demonstrate that in-person school attendance during the COVID-19 pandemic was associated with higher rates of risk behavior among adolescents. Further research is needed explore if this relationship is causal, and how these risks could be mitigated, as most adolescents have now returned to in-person schooling.

Stop the Bleed®: Medical Students as Instructors of the Bleeding Control Basics Course.

BACKGROUND: The Bleeding Control Basics (B-Con) Course was developed to teach lifesaving hemorrhage control techniques to the public. Currently, medical students (MS) without prior clinical experience (CE) may not act as autonomous instructors, limiting the instructor pool. PURPOSE: To assess the bleeding control knowledge of MS (phase I) and compare the knowledge of students taught by a certified instructor vs a medical student (phase II). METHODS: Phase I: 20 MS, 6 with prior CE and 14 without clinical experience (NCE) completed a pre-course and post-course knowledge assessment. Results were assessed by independent sample t-tests. Phase II: 91 first-year MS were taught the B-Con Course by either a third-year MS (n = 45) or certified instructor (n = 46). An analysis of covariance (ANCOVA) was performed to compare scores by instructor type (certified vs MS) using prior CE and pretest scores as confounding variables. RESULTS: In Phase I, the CE group scored higher on the pretest assessment compared to the NCE group (P = .003). All students improved in posttest scoring, and there was no difference in posttest scores between the groups (P = .597). In Phase II, despite no difference in pretest scores between groups, the MS taught learners scored significantly higher on the posttest compared to the certified instructor group (P < .01). Prior CE did not correlate to posttest scores (P = .719). DISCUSSION: Medical students are as effective as certified instructors at conveying the B-Con learning objectives. Based on near-perfect assimilation of content by students, MS should be permitted to teach B-Con Courses.

Outcomes of farm compared to nonfarm pediatric injuries: A propensity-matched analysis.

OBJECTIVES: Pediatric farm-related injuries are rare but tend to be severe relative to other types of pediatric injury and may result in worse clinical outcomes. However, the comparison of farm and nonfarm injuries is confounded by different injury mechanisms, patient characteristics, and treating facilities. Therefore, we used propensity score matching to compare outcomes of pediatric farm and nonfarm injuries in the United States. METHODS: Data were obtained from the 2017-2019 Trauma Quality Program database. Farm as compared to nonfarm injury was defined as the location of an injury and served as the independent variable analyzed in this study. The outcome variables analyzed were in-hospital mortality, hospital length of stay (LOS), and admission to the intensive care unit (ICU). RESULTS: We identified 2,040 farm injuries and 201,865 nonfarm injuries meeting inclusion criteria. In this cohort, the mortality rate was 1%, median LOS was 2 days, and 14% of patients were admitted to the ICU. In the propensity-matched analysis (including 2,039 farm cases matched to 2,039 nonfarm controls), farm as compared to nonfarm injuries were associated with 5% longer LOS (95% CI: 1%, 8%; P = .01), but not mortality or ICU admission. CONCLUSIONS: In a propensity-matched analysis, pediatric farm injuries resulted in prolonged hospital stay compared to nonfarm injuries. Identifying patient- and health care system-level factors contributing to prolonged LOS may help optimize the care of children injured on farms.

Facility Size and Risk Factors for Mortality in Pediatric Trauma.

BACKGROUND: Pediatric trauma outcomes can vary across facilities, yet evidence on the relationship between facility bed size and pediatric trauma outcomes has been mixed. We aimed to identify how facility bed size might modify the impact of patient-level risk factors on mortality in pediatric trauma. We hypothesized that patient-level risk factors would have a stronger association with mortality at smaller trauma centers, and a weaker association with mortality at larger centers. METHODS: We used deidentified data obtained from the 2017-2018 Trauma Quality Programs registry, including patients ages 0-18 years of age who were admitted to the hospital. The primary outcome was in-hospital mortality. Facility bed size was dichotomized as large (>600 beds) vs small/medium (≤600 beds). Sensitivity analyses used 200 and 400 beds as alternative cutoffs. Interaction between facility bed size and patient characteristics was assessed using unadjusted logistic regression, with statistically significant interactions entered in a final, fully adjusted model. RESULTS: The analysis included 171 810 patients (mean age 10 ± 5 years; 65%/35% male/female), including 28% treated in a large hospital and 1.2% who died during the hospitalization. Controlling for trauma center level (or subsetting to pediatric trauma centers only), larger bed size did not reduce mortality risk associated with patient characteristics such as injury mechanism, injury severity, or patient demographics. CONCLUSIONS: Contrary to our hypothesis, greater facility bed size was not associated with reduced mortality risk associated with patient characteristics. Future studies are needed to identify hospital practices or characteristics that can attenuate the excess risk of known patient-level risk factors.

Shelter in Place and an Alarming Increase in Penetrating Trauma in Children and Concerning Decrease in Child Abuse.

BACKGROUND: On March 14, 2020, schools across North Carolina (NC) closed in response to Covid-19, forcing completion of the school year at home. Most pediatric trauma occurs at home with a higher prevalence when children are out of school. We queried the state trauma database to assess if the 2020 "shelter in place" was associated with an increase in pediatric trauma statewide. METHODS: The NC trauma database was queried for injuries in children (age < 18 yrs) from 13 March-1 August 2020, and the corresponding months of 2018 and 2019. The number and type of injuries were compared. We also queried the NC death certificate and child welfare databases. Data were analyzed by standard statistical methods using chi-squared or Kruskal-Wallis test. RESULTS: Total pediatric trauma cases were lower during 2020 (71.6 per 100,000) compared to 2018 (92.4 per 100,000) and 2019 (80 per 100,000) (P < .001); however, average injury severity score (ISS) was higher (P = .001). A significant increase in firearm injuries were seen in 2020 (P = .016), with an increase in mortality (P = .08) and ISS (P = .013). The rate of child abuse trauma decreased in 2020 (P = .005) as did the number of child abuse and neglect reports (P < .001). There were also significant decreases in trauma due to sports, burns, falls, and motor vehicle accidents. CONCLUSION: While overall pediatric trauma decreased during the Covid-19 pandemic, there was an alarming increase in penetrating injuries in children. Child abuse trauma and reports decreased, which is concerning for lower identification of abuse.

Lack of Health Insurance Coverage and Emergency Medical Service Transport for Pediatric Trauma Patients.

INTRODUCTION: Pediatric trauma patients who lack insurance coverage may have less access to transport other than emergency medical services (EMS) or face financial barriers that prevent utilization of these services. We analyzed the association between health insurance coverage and EMS transport while controlling for injury and patient characteristics. MATERIALS AND METHODS: De-identified Trauma Quality Programs registry data were queried for pediatric trauma patients age <18 y. The primary outcome was arrival by EMS (excluding interfacility transfer) versus private transport or walk-in, and the primary exposure was insurance coverage (any versus none). After exact matching on injury and facility characteristics, propensity matching was used to balance demographic covariates and comorbidities between insured and uninsured patients. RESULTS: Of the 130,246 patients analyzed, 9501 (7%) did not have insurance coverage. After matching 9494 uninsured cases to 9494 insured controls, fixed-effects logistic regression found that uninsured patients had 18% greater odds of using EMS transport, compared to insured patients (odds ratio: 1.18; 95% confidence interval: 1.11, 1.26; P < 0.001). Results were similar when comparing uninsured patients to privately insured or publicly insured patients only. CONCLUSIONS: Uninsured pediatric trauma patients have a higher likelihood of using EMS transport compared to insured patients with similar demographic and clinical characteristics, including the exact same score of injury severity. Lack of access to private transport may drive higher EMS utilization in uninsured patients with minor injuries and contribute to higher costs of pediatric trauma care borne by institutions and families.

An in-situ simulation-based educational outreach project for pediatric trauma care in a rural trauma system.

BACKGROUND: Outcome disparities between urban and rural pediatric trauma patients persist, despite regionalization of trauma systems. Rural patients are initially transported to the nearest emergency department (ED), where pediatric care is infrequent. We aim to identify educational intervention targets and increase provider experience via pediatric trauma simulation. METHODS: Prospective study of simulation-based pediatric trauma resuscitation was performed at three community EDs. Level one trauma center providers facilitated simulations, providing educational feedback. Provider performance comfort and skill with tasks essential to initial trauma care were assessed, comparing pre-/postsimulations. Primary outcomes were: 1) improved comfort performing skills, and 2) team performance during resuscitation. RESULTS: Provider comfort with the following improved (p-values <0.05): infant airway, infant IV access, blood administration, infant C-spine immobilization, chest tube placement, obtaining radiographic images, initiating transport, and Broselow tape use. The proportion of tasks needing improvement decreased: 42% to 27% (p-value=0.001). Most common deficiencies were: failure to obtain additional history (75%), beginning secondary survey (58.33%), log rolling/examining the back (66.67%), calling for transport (50%), calculating medication dosages (50%). CONCLUSIONS: Simulation-based education improves provider comfort and performance. Comparison of patient outcomes to evaluate improvement in pediatric trauma care is warranted. LEVEL OF EVIDENCE RATING: IV.

Atropine: A Cure for Persistent Post Laparoscopic Pyloromyotomy Emesis?

BACKGROUND: Atropine has been used as a successful primary medical treatment for hypertrophic pyloric stenosis. Several authors have reported a higher rate of incomplete pyloromyotomy with the laparoscopic approach compared to open. In this study, we evaluated the use of atropine as a medical treatment for infants with emesis persisting greater than 48 hours after a laparoscopic pyloromyotomy. MATERIALS AND METHODS: We performed a retrospective chart review of infants receiving a laparoscopic pyloromyotomy between November 1998 and November 2012. Infants with emesis that persisted beyond 48 hours postoperatively were given 0.01mg/kg of oral atropine 10 minutes prior to feeding. Infants remained inpatient until they tolerated two consecutive feedings without emesis. RESULTS: 965 patients underwent laparoscopic pyloromyotomy; 816 (84.6%) male and 149 (15.4%) female. Twenty-four (2.5%) received oral atropine. The mean length of stay for patients who received atropine was 5.6 ± 2.6 days, an average of 3 additional days. They were discharged home with a one-month supply of oral atropine. Follow up evaluation did not reveal any complications from receiving atropine. The median follow up was 21 days. None returned to the operating room for incomplete pyloromyotomy. There were 17 (1.8%) operative complications in our series; 9 mucosal perforations, 2 duodenal perforations, and 6 conversions to open for equipment failure or poor exposure. There were 4 (0.4%) post-operative complications: 2 episodes of apnea requiring reintubation and 2 incisional hernias that required a second operation. There were no deaths. CONCLUSION: Oral atropine is a viable treatment for persistent emesis after a pyloromyotomy and reduces the need for a second operation due to incomplete pyloromyotomy.

Chest tube placement in children during extracorporeal membrane oxygenation (ECMO).

BACKGROUND: Pleural collections of air and fluid are frequent in infants and children treated with extracorporeal membrane oxygenation (ECMO). In this anticoagulated population, chest tube placement is potentially hazardous, and catastrophic hemorrhage has been reported. We sought to define the risks associated with chest tube placement in a large population of children managed with ECMO. METHODS: The records of 189 consecutive children managed with ECMO at two children's hospitals were reviewed. Demographics, indications for ECMO, and ECMO courses were reviewed. In particular, the occurrence of pleural collections and the frequency and technique of chest tube placement were evaluated. The incidence of complications and mortality were determined. RESULTS: The median age of the subjects was 2days. The overall mortality was 26.5%. A pneumothorax was found in 19 (10.1%), a pleural effusion in 26 (13.8%), and a hemothorax in 2 (1.0%). A chest tube was placed in 27 (19 by a needle-guide wire technique and 8 by cut-down). Major bleeding complications occurred in 6 subjects (22%). CONCLUSIONS: There was a significant incidence of major bleeding complications and death in subjects in whom chest tubes were placed. The placement of a chest tube during ECMO should be done only if it is likely to improve pump flow or promote weaning of support.

Regulation of retinoblastoma protein (Rb) by p21 is critical for adaptation to massive small bowel resection.

BACKGROUND: Adaptation following massive intestinal loss is characterized by increased villus height and crypt depth. Previously, we demonstrated that p21-null mice do not adapt after small bowel resection (SBR). As retinoblastoma protein (Rb) levels are elevated in p21-null crypt cells, we first sought to determine whether Rb is required for normal adaptation. Next, we tested whether Rb expression is responsible for blocked adaptation in p21-nulls. METHODS: Genetically manipulated mice and wild-type (WT) littermates underwent either 50% SBR or sham operation. The intestine was harvested at 3, 7, or 28 days later and intestinal adaptation was evaluated. Enterocytes were isolated and protein levels evaluated by Western blot and quantified by optical density. RESULTS: Rb-null mice demonstrated increased villus height, crypt depth, and proliferative rate at baseline, but there was no further increase following SBR. Deletion of one Rb allele lowered Rb expression and restored resection-induced adaptation responses in p21-null mice. CONCLUSION: Rb is specifically required for resection-induced adaptation. Restoration of adaptation in p21-null mice by lowering Rb expression suggests a crucial mechanistic role for Rb in the regulation of intestinal adaptation by p21.

Dietary bile acid supplementation improves intestinal integrity and survival in a murine model.

PURPOSE: In vitro supplementation of the bile salt, taurodeoxycholic acid (TDCA), has been shown to stimulate proliferation and prevent intestinal apoptosis in IEC-6 cells. We hypothesize that addition of TDCA to a rodent liquid diet will be protective against induced intestinal injury. METHODS: C57Bl6 mice were fed a liquid diet with or without 50-mg/(kg d) TDCA supplementation. After 6 days, the mice were injected with lipopolysaccharide (LPS) (10 mg/kg) to induce intestinal injury. Specimens were obtained 24 hours later and evaluated for intestinal apoptosis, crypt proliferation, and villus length. A separate cohort of animals was injected with LPS (25 mg/kg) and followed 7 days for survival. RESULTS: Mice whose diet was supplemented with TDCA had significantly increased survival. After LPS-induced injury, mice supplemented with TDCA showed decreased intestinal apoptosis by both H&E and caspase-3. They also had increased intestinal proliferation by 5-bromo-2'deoxyuridine staining and increased villus length. CONCLUSIONS: Dietary TDCA supplementation alleviates mucosal damage and improves survival after LPS-induced intestinal injury. Taurodeoxycholic acid is protective of the intestinal mucosa by increasing resistance to injury-induced apoptosis, stimulating enterocyte proliferation, and increasing villus length. Taurodeoxycholic acid supplementation also results in an increased survival benefit. Therefore, bile acid supplementation may potentially protect the intestine from injury or infection.

Extent of small bowel resection does not influence the magnitude of intestinal adaptation in the mouse.

PURPOSE: The magnitude of intestinal adaptation is considered to correlate with the extent of small bowel resection (SBR). However, this association has never been tested in mice. We sought to test the hypothesis that a greater SBR will induce a greater adaptation response. METHODS: C57/B6 mice underwent 50% SBR, 75% SBR, or sham operation and were killed on postoperative day 7. The magnitude of adaptation was compared between 50% SBR and 75% SBR as changes in villus height, crypt depth, as well as rates of apoptosis and proliferation. RESULTS: Seventy-five percent SBR led to decreased survival and increased weight loss compared with 50% SBR. The remnant ileum of both 50% SBR and 75% SBR displayed similar crypt expansion, enhanced villi, and increased apoptotic indices. Proliferation rates increased after 50% and 75% SBR equally. CONCLUSION: Models of resection greater than 50% in mice result in greater morbidity and mortality and do not magnify the adaptation response to massive SBR. The use of more extreme resection models does not appear to provide added benefit for investigating mechanisms of intestinal adaptation.

Growth factors: possible roles for clinical management of the short bowel syndrome.

The structural and functional changes during intestinal adaptation are necessary to compensate for the sudden loss of digestive and absorptive capacity after massive intestinal resection. When the adaptive response is inadequate, short bowel syndrome (SBS) ensues and patients are left with the requirement for parenteral nutrition and its associated morbidities. Several hormones have been studied as potential enhancers of the adaptation process. The effects of growth hormone, insulin-like growth factor-1, epidermal growth factor, and glucagon-like peptide 2 on adaptation have been studied extensively in animal models. In addition, growth hormone and glucagon-like peptide 2 have shown promise for the treatment of SBS in clinical trials in human beings. Several lesser studied hormones, including leptin, corticosteroids, thyroxine, testosterone, and estradiol, are also discussed.

Murine functional liver mass is reduced following partial small bowel resection.

INTRODUCTION: Liver mass is regulated in precise proportion to body mass in health and is restored by regeneration following acute injury. Despite extensive experimental analyses, the mechanisms involved in this regulation have not been fully elucidated. Previous investigations suggest that signals from the bowel may play an important role. The purpose of the studies reported here was to determine the effect of proximal partial small bowel resection on liver mass in a murine model. METHODS: Mice were subjected to a 50% proximal small bowel resection or sham surgery followed by primary anastomosis, then sacrificed at serial times for determination of liver:body mass ratio and analyses of liver tissue. RESULTS: Liver:body weight ratio was significantly decreased 72 h after small bowel resection, and this decrease correlated with reduced functional liver mass as assessed by determination of total hepatic tissue protein and alanine transaminase (ALT) activity. Liver from bowel-resected animals demonstrated increased expression of LC3-II, a marker of autophagy, and also of pro-apoptotic Bax compared to anti-apoptotic Bcl-2. CONCLUSION: These data support a role for signals from the intestine in liver mass regulation, and they have potential implications regarding the pathogenesis of liver injury following small bowel resection.

p21(waf1/cip1) deficiency does not perturb the intestinal crypt stem cell population after massive small bowel resection.

BACKGROUND: After small bowel resection (SBR), adaptation is initiated in intestinal crypts where stem cells reside. Prior studies revealed SBR-induced enterocyte proliferation requires the expression of p21(waf1/cip1). As deficient expression of p21(waf1/cip1) has been shown to result in reduced numbers of hematopoietic stem cells. We sought to test the hypothesis that p21(waf1/cip1)deficiency similarly perturbs the intestinal stem cell population after SBR. METHODS: Control (n = 21; C57Bl/6) and p21(waf1/cip1)-null mice (n = 30) underwent 50% proximal SBR or sham operation. After 3 days, the ileum was harvested and the crypt stem cell population evaluated by counting crypt base columnar cells on histologic sections, determining the expression of Musashi-1 and Lgr5, and profiling the transcriptional expression of 84 known stem cell genes. RESULTS: There were no significant differences in crypt base columnar cells, expression of Musashi-1 or Lgr5, or in stem cell gene expression after SBR in control mice. Furthermore, there were no differences in these markers between controls and p21(waf1/cip1)-null mice. CONCLUSION: In contrast with bone marrow stem cells, the stem cell population of the gut is unaffected by deficient expression of p21(waf1/cip1). Additional mechanisms for the role of p21(waf1/cip1) in small bowel proliferation and adaptation after massive SBR must be considered.

Intestinal resection induces angiogenesis within adapting intestinal villi.

PURPOSE: Adaptive growth of the intestinal mucosa in response to massive gut loss is fundamental for autonomy from parenteral nutrition. Although angiogenesis is essential for cellular proliferation in other tissues, its relevance to intestinal adaptation is unknown. We tested the hypothesis that resection-induced adaptation is associated with new blood vessel growth. METHODS: Male C57Bl/6 mice underwent either a 50% small bowel resection or a sham (transection and reanastomosis) operation. After 1, 3, or 7 days, capillary density within the intestinal villi was measured using confocal microscopy. A messenger RNA reverse-transcriptase polymerase chain reaction (RT-PCR) array was used to determine angiogenic gene expression during adaptation. RESULTS: Mice that underwent small bowel resection had a significantly increased capillary density compared to sham-operated mice at postoperative day 7. This morphological alteration was preceded by significant alterations in 5 candidate genes at postoperative day 3. CONCLUSION: New vessel blood growth is observed in the adapting intestine after massive small bowel loss. This response appears to follow rather than initiate the adaptive alterations in mucosal morphology that are characteristic of adaptation. A better understanding of this progress and the signaling factors involved may improve therapeutic options for children with short gut syndrome.