Search

Hepatic gene therapy by delivering non-integrating therapeutic vectors in newborns remains challenging due to the risk of dilution and loss of efficacy in the growing liver. Previously we reported on hepatocyte transfection in piglets by intraportal injection of naked DNA vectors. Here, we established delivery of naked DNA vectors to target periportal hepatocytes in weaned pigs by hydrodynamic retrograde intrabiliary injection (HRII). The surgical procedure involved laparotomy and transient isolation of the liver. For vector delivery, a catheter was placed within the common bile duct by enterotomy. Under optimal conditions, no histological abnormalities were observed in liver tissue upon pressurized injections. The transfection of hepatocytes in all tested liver samples was observed with vectors expressing luciferase from a liver-specific promoter. However, vector copy number and luciferase expression were low compared to hydrodynamic intraportal injection. A 10-fold higher number of vector genomes and luciferase expression was observed in pigs using a non-integrating naked DNA vector with the potential for replication. In summary, the HRII application was less efficient (i.e., lower luciferase activity and vector copy numbers) than the intraportal delivery method but was significantly less distressful for the piglets and has the potential for injection (or re-injection) of vector DNA by endoscopic retrograde cholangiopancreatography.

Conjoined twins are a rare developmental anomaly with a reported prevalence of 1.47 per 100,000 births. We present an uncommon case of a parasitic ischiopagus tetrapus with a parasitic ischiopagus partial twin joined to the complete fetus at the level of the ischium diagnosed in utero by fetal MRI. The correct prenatal diagnosis led to birth by caesarean section. Prenatal MRI findings are presented and corroborated by postnatal imaging delineating the full extent and associated anomalies of this rare malformation. Differential diagnosis of duplicated lower extremities is discussed.

BACKGROUND & AIMS Hirschsprung's disease (HSCR) is a congenital intestinal motility disorder defined by the absence of enteric neuronal cells (ganglia) in the distal gut. The development of HSCR-associated enterocolitis remains a life-threatening complication. Absence of enteric ganglia implicates innervation of acetylcholine-secreting (cholinergic) nerve fibers. Cholinergic signals have been reported to control excessive inflammation, but the impact on HSCR-associated enterocolitis is unknown. METHODS We enrolled 44 HSCR patients in a prospective multicenter study and grouped them according to their degree of colonic mucosal acetylcholinesterase-positive innervation into low-fiber and high-fiber patient groups. The fiber phenotype was correlated with the tissue cytokine profile as well as immune cell frequencies using Luminex analysis and fluorescence-activated cell sorting analysis of colonic tissue and immune cells. Using confocal immunofluorescence microscopy, macrophages were identified in close proximity to nerve fibers and characterized by RNA-seq analysis. Microbial dysbiosis was analyzed in colonic tissue using 16S-rDNA gene sequencing. Finally, the fiber phenotype was correlated with postoperative enterocolitis manifestation. RESULTS The presence of mucosal nerve fiber innervation correlated with reduced T-helper 17 cytokines and cell frequencies. In high-fiber tissue, macrophages co-localized with nerve fibers and expressed significantly less interleukin 23 than macrophages from low-fiber tissue. HSCR patients lacking mucosal nerve fibers showed microbial dysbiosis and had a higher incidence of postoperative enterocolitis. CONCLUSIONS The mucosal fiber phenotype might serve as a prognostic marker for enterocolitis development in HSCR patients and may offer an approach to personalized patient care and new therapeutic options.

The purpose of this single-centre randomized controlled trial was to assess the non-inferiority of buddy taping versus splint immobilization of extra-articular paediatric finger fractures. Secondary fracture displacement was the primary outcome; patient comfort, cost and range of finger motion were secondary outcomes. Ninety-nine children were randomly assigned to taping or splinting. Sixty-nine fractures were undisplaced; 31 were displaced and required reduction before taping or splinting. Secondary displacement occurred in one patient in the taping and three in the splinting group. The risk difference was below the predefined non-inferiority level of 5%. All secondary displacements occurred in the 31 displaced fractures after reduction and were in little fingers. Patient comfort was significantly higher and cost lower in the taping group. We conclude from this study the non-inferiority of buddy taping versus splint immobilization of extra-articular paediatric finger fractures in general. We advise treatment may need to be individualized for patients with displaced fractures because we cannot make any absolute conclusions for these fractures. Level of evidence: I.

Beta-blockers are a highly promising treatment modality for complicated infantile hemangiomas (IH). However, data on propranolol as first-line treatment, objective outcome measures and impact on hemodynamics in young infants is limited. We retrospectively evaluated a homogenous group of infants with proliferating complicated IH treated with propranolol (2mg/kg/day). Outcome was assessed by blinded evaluation of clinical photographs by visual analogue scale (VAS), ultrasound examination and ophthalmological review (if appropriate). Tolerance and hemodynamic variables were recorded over time, including a 2-day in-patient observation at the initiation of therapy. Twenty-five infants (median age 3.6 (1.5-9.1) months) were included in the study. The median follow-up-time was 14 (9-20) months and 14 patients completed treatment at a median age of 14.3 (11.4-22.1) months, after a duration of 10.5 (7.5-16) months. In all patients, there was significant fading of colour (with a VAS of −9 (−6 to −9) after 7months) and significant decrease in size of the IH (with a VAS of −8 (−3 to −10) after 7months). Median thickness of the lesions assessed by ultrasound at baseline and after 1month was 14 (7-28) mm and 10 (5-23) mm, respectively (p < 0.01). In children with periocular involvement, astigmatism and amblyopia resolved rapidly within 8weeks. The overall tolerance of propranolol was good, and no relevant hemodynamic changes were noted. Conclusion: Our report supports the excellent effect and good tolerance of this novel therapy, and we propose the use of propranolol as first-line treatment for IH

INTRODUCTION Acute compartment syndrome (ACS) can lead to irreversible damage if fasciotomy is not performed in a timely manner. Needle manometry is a tool to confirm suspected ACS. The threshold for compartment pressures that can be tolerated has been debated. The aim of this study is to assess the normal compartment pressures in noninjured forearms of children. Further, we sought to quantify the maximum tolerable compartment pressures in fractured forearms of children, thus establishing a baseline and providing guidance in evidence-based decision making to evaluate children with suspected ACS. METHODS This prospective study included children up to the age of 16 years with forearm fractures that needed reduction with or without osteosynthesis. Between June 2009 and March 2013, 41 children were included. Mean age was 9.25 years (range, 4 to 15.4 y). We used needle manometry to measure the pressures in the superficial and deep volar as well as in the dorsal compartments (DCs) on both the forearms. The mean pressures between compartments in healthy versus injured arms were analyzed using a 1-sided, paired t test. RESULTS On the injured side, the mean compartment pressure was 19.12 mm Hg (range, 3 to 49 mm Hg) in the deep volar compartment, 15.56 mm Hg (range, 5 to 37 mmHg) in the DC, and 14.8 mm Hg (range, 2 to 35 mm Hg) in the superficial volar compartment. On the noninjured side, the mean compartment pressure was 12.9 mm Hg (range, 6 to 31 mm Hg) in the DC, 10.22 mm Hg (range, 3 to 22 mm Hg) in the deep volar compartment, and 9.66 mm Hg (range, 3 to 21 mm Hg) in the superficial volar compartment. We measured an absolute compartment pressure of >30 mm Hg in 15 patients on the fractured side. Three of them had an absolute compartment pressure of >45 mm Hg. Only 1 had ACS. This patient underwent fasciotomy and was excluded for further analysis. On follow-up (mean, 24.84 mo), no patient was found to have any sequelae of ACS. DISCUSSION This is the first study to report