Efficacy and safety of propranolol as first-line treatment for infantile hemangiomas

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 I

Cholinergic Signaling Attenuates Pro-Inflammatory Interleukin-8 Response in Colonic Epithelial Cells.

Infants affected by Hirschsprung disease (HSCR), a neurodevelopmental congenital disorder, lack ganglia of the intrinsic enteric nervous system (aganglionosis) in a variable length of the colon, and are prone to developing severe Hirschsprung-associated enterocolitis (HAEC). HSCR patients typically show abnormal dense innervation of extrinsic cholinergic nerve fibers throughout the aganglionic rectosigmoid. Cholinergic signaling has been reported to reduce inflammatory response. Consequently, a sparse extrinsic cholinergic innervation in the mucosa of the rectosigmoid correlates with increased inflammatory immune cell frequencies and higher incidence of HAEC in HSCR patients. However, whether cholinergic signals influence the pro-inflammatory immune response of intestinal epithelial cells (IEC) is unknown. Here, we analyzed colonic IEC isolated from 43 HSCR patients with either a low or high mucosal cholinergic innervation density (fiber-low versus fiber-high) as well as from control tissue. Compared to fiber-high samples, IEC purified from fiber-low rectosigmoid expressed significantly higher levels of IL-8 but not TNF-α, IL-10, TGF-β1, Muc-2 or tight junction proteins. IEC from fiber-low rectosigmoid showed higher IL-8 protein concentrations in cell lysates as well as prominent IL-8 immunoreactivity compared to IEC from fiber-high tissue. Using the human colonic IEC cell line SW480 we demonstrated that cholinergic signals suppress lipopolysaccharide-induced IL-8 secretion via the alpha 7 nicotinic acetylcholine receptor (a7nAChR). In conclusion, we showed for the first time that the presence of a dense mucosal cholinergic innervation is associated with decreased secretion of IEC-derived pro-inflammatory IL-8 in the rectosigmoid of HSCR patients likely dependent on a7nAChR activation. Owing to the association between IL-8 and enterocolitis-prone, fiber-low HSCR patients, targeted therapies against IL-8 might be a promising immunotherapy candidate for HAEC treatment

Delivery of non-viral naked DNA vectors to liver in small weaned pigs by hydrodynamic retrograde intrabiliary injection

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

Buddy taping versus splint immobilization for paediatric finger fractures: a randomized controlled trial

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

In utero and postnatal imaging findings of parasitic conjoined twins (ischiopagus parasiticus tetrapus)

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

Primary reconstruction of fingernail injuries in children with split-thickness nail bed grafts

INTRODUCTION: Failure to detect and treat partial or complete avulsions of the nail bed may lead to severe nail deformity that predisposes to repeat injuries and is cosmetically inacceptable. Treatment of these injuries with split-thickness nail bed grafts (STNBGs) is controversial and no pediatric series has been published. METHODS: A retrospective, single center case series of nine fingers with complex nail bed injuries that were reconstructed primarily with STNBGs was performed. Surgical outcome and patient satisfaction were assessed. RESULTS: For six nail bed reconstructions, the nail bed graft was harvested from the injured finger, and for the remaining three from the great toe. Harvesting of the great toe's nail bed could be performed without removal of the nail plate by only lifting it up distally. Insufficient vascularization required primary flap coverage in six cases with three Moberg flaps, two palmar V-Y flaps, and one thenar flap. No flap was lost and all nail bed grafts had a 100% take. Only one patient required reoperation due to a hook- and split-nail deformity. All other patients were satisfied or very satisfied and the surgical outcome was least satisfactory in all but two patients. CONCLUSIONS: Primary reconstruction of complex nail bed injuries with STNBGs usually gives good cosmetic and functional results in children and prevents secondary nail growth disturbances reliably

Influencing factors and outcomes of Multisource-Feedback in Postgraduate Medical Training - A Focus Group Study

Background: Multisource-Feedback (MSF) is a form of workplace-based assessment appropriate for postgraduate training. Here, feedback is given by raters via questionnaires and then summed up by a supervisor in a facilitating conversation, in which learning goals are formulated. While there has been publishedmuch on the MSF questionnaire itself, only little is known on the other factors of the MSF process. Thus, our research question is: Which factors influence MSF which aims to improve postgraduate training and what are the expected and unexpected outcomes?Summary of Work: We implemented MSF in the surgical unit of a paediatric university hospital in Switzerland and conducted focus group interviews with participants from all stakeholder groups: trainees, raters, and supervisors. The transcripts of all interviews were analysed using a thematic analysis approach as described by Braun and Clarke [Braun 2006].Summary of Results:We identified the following factors and outcomes: Supporting factors: Clear communication of goal of MSF; self-assessment and narrative comments on the questionnaires to set learning goals; training of raters; continuity and preparation of raters; timing of MSF during rotations; clear role of supervisor; clear structure of the facilitating conversation. Outcomes: Residents perceived that the multiperspective feedback supported the improvement of their professional development; Teamwork and interdisciplinarity were perceived as helpful and were enhanced by MSF; Raters raised their commitment on the training of residents.Discussion and Conclusions:Some of our results confirm other studies, other results have not yet been described in detail such as a helpful structure of the supervision conversation, timing of the MSF assessments during clinical rotations and impact on teamwork and sharedresponsibility. Further analysis is planned to better understand the relationships between the extracted factors and to derive recommendations on how the potential of MSF can be exploited further.Take-home Messages: When implementing MSF, factors already described in the literature as well as our findings regarding influencing factors and outcomes can be helpful to make best use of it