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Introduction: Blunt abdominal trauma is a common problem in children. Computed tomography (CT) is the gold standard for imaging in pediatric blunt abdominal trauma, however up to 50% of CTs are normal and CT carries a risk of radiation-induced cancer. Contrast enhanced ultrasound (CEUS) may allow accurate detection of abdominal organ injuries while eliminating exposure to ionizing radiation., Methods: Children aged 7-18years with a CT-diagnosed abdominal solid organ injury underwent grayscale/power Doppler ultrasound (conventional US) and CEUS within 48h of injury. Two blinded radiologists underwent a brief training in CEUS and then interpreted the CEUS images without patient interaction. Conventional US and CEUS images were compared to CT for the presence of injury and, if present, the injury grade. Patients were monitored for contrast-related adverse reactions., Results: Twenty one injured organs were identified by CT in eighteen children. Conventional US identified the injuries with a sensitivity of 45.2%, which increased to 85.7% using CEUS. The specificity of conventional US was 96.4% and increased to 98.6% using CEUS. The positive predictive value increased from 79.2% to 94.7% and the negative predictive value from 85.3% to 95.8%. Two patients had injuries that were missed by both radiologists on CEUS. In a 100kg, 17year old female, a grade III liver injury was not seen by either radiologist on CEUS. Her accompanying grade I kidney injury was not seen by one of the radiologist on CEUS. The second patient, a 16year old female, had a grade III splenic injury that was missed by both radiologists on CEUS. She also had an adjacent grade II kidney injury that was seen by both. Injuries, when noted, were graded within 1 grade of CT 33/35 times with CEUS. There were no adverse reactions to the contrast., Conclusion: CEUS is a promising imaging modality that can detect most abdominal solid organ injuries in children while eliminating exposure to ionizing radiation. A multicenter trial is warranted before widespread use can be recommended., Level of Evidence: Level II; Diagnostic Prospective Study., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Although a few techniques for lengthening intestine by mechanical stretch have been described, they are relatively complex, and the majority involve placement of an intraluminal device. Ideally, techniques applicable to humans would be easy to perform and extraluminal to avoid the potential for mucosal injury. This study of distraction enterogenesis used an extraluminal, radially self-expanding shape-memory polymer cylinder and a simple operative approach to both elongate intestine and grow new tissue., Methods: Young Sprague Dawley rats (250-350 g) underwent Roux-en-Y isolation of a small intestinal limb and were divided in three groups: no further manipulation (Control 1, C1); placement of a nonexpanding device (Control 2, C2); or placement of a radially expanding device by the limb (Experimental, Exp). For C2 and Exp animals, the blind end of the limb was wrapped around the radially expanding cylindrical device with the limb-end sutured back to the limb-side. Bowel length was measured at operation and at necropsy (14 days) both in-situ and ex-vivo under standard tension (6g weight). Change in length is shown as mean ± standard deviation. A blinded gastrointestinal pathologist reviewed histology and recorded multiple measures of intestinal adaptation. The DNA to protein ratio was quantified as a surrogate for cellular proliferation. Changes in length, histologic measures, and DNA:protein were compared using analysis of variance, with significance set at P<0.05., Results: The length of the Roux limb in situ increased significantly in Exp animals (n=8, 29.0 ± 5.8mm) compared with C1 animals (n=5, -11.2 ± 9.0mm, P<0.01). The length of the Roux limb ex vivo under standard tension increased in the Exp group (25.8 ± 4.2mm) compared with the C2 group (n=6, -4.3 ± 6.0, P<0.01). There were no differences in histologic measures of bowel adaptation between the groups, namely villous height and width, crypt depth, crypt density, and crypt fission rate (all P ≥ 0.08). Muscularis mucosal thickness was also not different (P=0.25). There was no difference in DNA:protein between groups (P=0.47)., Conclusion: An extraluminally placed, radially expanding shape-memory polymer cylinder successfully lengthened intestine, without damaging mucosa. Lack of difference in muscularis thickness and a constant DNA:protein ratio suggests that this process may be related to actual growth rather than mere stretch. This study demonstrated a simple approach that warrants further study aiming at potential clinical applicability., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We sought to study the impact of trans-amniotic stem cell therapy (TRASCET) in the Chiari-II malformation in experimental spina bifida., Methods: Sprague-Dawley fetuses (n=62) exposed to retinoic acid were divided into three groups at term (21-22 days gestation): untreated isolated spina bifida (n=21), isolated spina bifida treated with intra-amniotic injection of concentrated, syngeneic, labeled amniotic fluid mesenchymal stem cells (afMSCs) on gestational day 17 (n=28), and normal controls (n=13). Analyses included measurements of brainstem and cerebellar placement on high resolution MRI and histology. Statistical comparisons included ANOVA., Results: In parallel to the expected induced coverage of the spina bifida in the afMSC-treated group (P<0.001), there were statistically significant differences in brainstem displacement across the groups (P<0.001), with the highest caudal displacement in the untreated group. Significant differences in cerebellar displacement were also noted, albeit less pronounced. Pairwise comparisons were statistically significant, with P=0.014 between treated and normal controls in caudal brainstem displacement and P<0.001 for all other comparisons. Labeled afMSCs were identified in 71% of treated fetuses., Conclusions: Induced coverage of spina bifida by TRASCET minimizes the Chiari-II malformation in the retinoic acid rodent model, further suggesting it as a practical alternative for the prenatal management of spina bifida., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We sought to determine whether simple intra-amniotic delivery of concentrated amniotic mesenchymal stem cells (afMSCs) may elicit prenatal coverage of experimental spina bifida., Methods: Time-dated pregnant Sprague-Dawley dams (n=24) exposed to retinoic acid for the induction of fetal neural tube defects were divided in three groups. Group I had no further manipulations. Groups II and III received volume-matched intra-amniotic injections of either saline (Group II) or a suspension of syngeneic afMSCs labeled with green fluorescent protein (Group III) in all fetuses (n=202) on gestational day 17 (term=21-22 days). Animals were killed before term. Statistical comparisons were by ANOVA (P<0.05)., Results: Of 165 fetuses viable at euthanasia, a spina bifida was present in 58% (96/165), with no significant differences in defect dimension across the groups (P=0.19). However, variable degrees of coverage of the defect by a rudimentary skin confirmed histologically were only present in Group III (P<0.001), in which donor afMSCs were documented, with no differences between Groups I and II (P=0.98)., Conclusions: Amniotic mesenchymal stem cells can induce partial or complete coverage of experimental spina bifida after concentrated intra-amniotic injection. Trans-amniotic stem cell therapy (TRASCET) may become a practical option in the prenatal management of spina bifida., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We sought to test a novel, extraluminal method of intestinal lengthening that precludes violation of the intestinal wall., Methods: Sprague-Dawley rats (n=45) with size-matched bowel segments isolated by Roux-en-Y reconstruction were divided into three groups. Group 1 (n=14) had no further manipulations. In Groups 2 (n=12) and 3 (n=19), the isolated segment was wrapped around a length-matched device in a helicoidal fashion. In Group 2, the device consisted of plain polyurethane tubing. In Group 3, it consisted of a gradually expanding hygroscopic hydrogel (12.5mm final diameter). Euthanasia was performed at 8-21 days. Statistical analysis was by two-way ANOVA (P<0.05)., Results: Overall survival was 87% (39/45). There was a statistically significant increase in bowel length in Group 3 compared to the other two groups (P<0.001). This increase correlated with the number of helicoidal coils (P=0.018), but not with post-operative time (P>0.50). There were no significant differences in total DNA/protein ratio across the groups (P=0.65). Histologically, there was an apparent increase in the goblet cell density in Group 3., Conclusions: Measured extraluminal helicoidal stretch (Helixtretch) is tolerated by the intestine. Helixtretch induces bowel lengthening in a rodent model. Further analysis of this novel, minimally invasive alternative for intestinal augmentation is warranted., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Mesenchymal stem cells (MSCs) are particularly valuable for structural tissue replacement. We compared the response to hypoxia among human MSCs derived from four different clinically relevant sources as an adjunct to translational developments., Methods: Immunophenotypically indistinguishable human MSC lineages derived from bone marrow (bmMSCs), adipose tissue (adMSCs), amniotic fluid (afMSCs), and umbilical cord blood (cbMSCs) were submitted to either room air or 1% O2, under otherwise standard culture conditions. Cell expansion and quantitative RT-PCR data were obtained at different time points. Statistical analysis was by two-way mixed model and the F-test (P<0.05)., Results: The effect of hypoxia on expansion kinetics was dependent on cell source. Only prenatal sources of MSCs - afMSCs (P=0.002) and cbMSCs (P<0.001) - proliferated significantly faster under hypoxia than normoxia. Increased HIF1-alpha expression correlated consistently with increased cell expansion only among afMSCs. There were no significant variabilities in Survivin, Oct-4, and VEGF expressions., Conclusions: Mesenchymal stem cell tolerance to hypoxia in vitro varies with cell source. Prenatal cells, particularly those derived from amniotic fluid, are more robust than their postnatal counterparts. HIF1-alpha may play a role in the amniotic fluid-derived cells' enhanced response. These findings should inform the choice of mesenchymal stem cells for prospective regenerative strategies., (Copyright © 2014 Elsevier Inc. All rights reserved.)