FLight Biofabrication Supports Maturation of Articular Cartilage with Anisotropic Properties.

Tissue engineering approaches that recapitulate cartilage biomechanical properties are emerging as promising methods to restore the function of injured or degenerated tissue. However, despite significant progress in this research area, the generation of engineered cartilage constructs akin to native counterparts still represents an unmet challenge. In particular, the inability to accurately reproduce cartilage zonal architecture with different collagen fibril orientations is a significant limitation. The arrangement of the extracellular matrix (ECM) plays a fundamental role in determining the mechanical and biological functions of the tissue. In this study, it is shown that a novel light-based approach, Filamented Light (FLight) biofabrication, can be used to generate highly porous, 3D cell-instructive anisotropic constructs that lead to directional collagen deposition. Using a photoclick-based photoresin optimized for cartilage tissue engineering, a significantly improved maturation of the cartilaginous tissues with zonal architecture and remarkable native-like mechanical properties is demonstrated.

Paediatric fractures of carpal bones other than the scaphoid.

OBJECTIVES: Fractures of carpal bones other than the scaphoid are rare in children. The aim of this study was to analyze results and identify risk factors for an unfavorable outcome. MATERIAL AND METHODS: Children and adolescents up to the age of 16 years who sustained a carpal fracture other than in the scaphoid between 2004 and 2021 were reviewed in this single-center retrospective study. RESULTS: In a series of 209 children and adolescents with carpal fractures, 22 had fractures other than the scaphoid. Mean age was 13 years (range 8-16) years, with a total of 41 fractures, with highest incidences for the capitate (10), trapezium (6), triquetrum (4) and pisiform (4). Twenty-nine of these 41 fractures were missed on initial X-ray. Non-displaced fractures were treated with a short arm spica cast including the thumb. Four patients were operated on for displacement fracture or carpometacarpal subluxation. All fractures united, and patients returned to full activities. At the final consultation at a median 14 months (range 6-89) post-injury, all patients with non-displaced fractures were free of symptoms, with excellent Mayo Wrist Scores (MWS). However, three patients with operated trapezium fractures developed early radiological signs of osteoarthritis, two of them with residual pain and MWS rated only good. CONCLUSION: Non-displaced pediatric carpal fractures treated by forearm cast have excellent prognosis. Fractures of the trapezium with displacement or first carpometacarpal subluxation incur a risk of osteoarthritis despite anatomical reduction and internal fixation.

PIK3CA Mutational Analysis in Patients With Macrodactyly.

BACKGROUND: Somatic mosaicism for PIK3CA mutations causes various types of growth disorders, which have been summarized under the term PROS (PIK3CA related overgrowth spectrum). Targeted therapy with PI3K inhibitors seems to be a promising alternative for severe PROS cases. Therefore, PIK3CA testing may become more relevant in the future. METHODS: We report on 14 PROS patients, who had surgery for macrodactyly in the majority of cases. Clinical data were retrieved from the patient's records. Macroscopic and microscopic findings were retrospectively reviewed. Mutational analysis was performed on formalin-fixed paraffin-embedded (FFPE) material. RESULTS: Patient age ranged from 7 months to 35 years. Five patients showed additional anomalies. One patient had CLOVES syndrome. The majority of the specimens were ray resections characterized by hypertrophic fat tissue. Overall, microscopy was subtle. The abnormal adipose tissue showed lobules exhibiting at least focally fibrous septa. In each case, we could detect a PIK3CA mutation. CONCLUSION: Histology of affected fat tissue in PROS patients is overall nonspecific. Therefore, mutational analysis represents the key to the diagnosis, especially in unclear clinical cases. We demonstrated that FFPE material is suitable for PIK3CA testing, which can be considered as basis for targeted therapy with PI3K inhibitors.

Etiology of Carpal Tunnel Syndrome in a Large Cohort of Children.

(1) Background: Carpal tunnel syndrome (CTS), a compressive mononeuropathy of the median nerve at the wrist, is rare in childhood and occurs most frequently due to secondary causes. (2) Methods: Medical history, electrodiagnostic findings, and imaging data of patients with CTS from two pediatric neuromuscular centers were analyzed retrospectively. The etiology of CTS was investigated and compared with the literature. (3) Results: We report on a cohort of 38 CTS patients (n = 22 females, n = 29 bilateral, mean age at diagnosis 9.8 years). Electrodiagnostic studies of all patients revealed slowing of the antidromic sensory or orthodromic mixed nerve conduction velocities across the carpal tunnel or lack of the sensory nerve action potential and/or prolonged distal motor latencies. Median nerve ultrasound was diagnostic for CTS and confirmed tumorous and vascular malformations. Etiology was secondary in most patients (n = 29; 76%), and mucopolysaccharidosis was the most frequent underlying condition (n = 14; 37%). Idiopathic CTS was rare in this pediatric cohort (n = 9; 24%). (4) Conclusion: Since CTS in childhood is predominantly caused by an underlying disorder, a thorough evaluation and search for a causative condition is recommended in this age group.

Laparoscopic Ureteroureterostomy vs. Common Sheath Ureteral Reimplantation in Children With Duplex Kidney Anomalies.

Purpose: Laparoscopic ureteroureterostomy (LUU) has been proposed as an alternative to common sheath ureteral reimplantation (CSUR) in children with symptomatic duplex kidneys. However, data is limited for LUU in the pediatric population. The aim of this study was to analyze our experience with LUU and to compare the results with those after CSUR to assess whether a less invasive surgical approach could be a valid alternative. Patients and methods: The data of all children with duplex kidneys who underwent either LUU or CSUR at our center from 2006 to 2018 were reviewed retrospectively. After parental counseling, the option of LUU was provided as an alternative to CSUR for unilateral procedures and in the absence of vesicoureteral reflux to the receiving ureter. Baseline characteristics, indication for surgery, hospitalization and operative times, and intraoperative, post-operative, and late complications were analyzed. Preoperative and 1-year post-operative sonographies were reviewed by a pediatric radiologist. Increasing renal pelvic diameter (Δ >5 mm) was regarded as a sign of ureteral obstruction. Results: Forty children were included in this study, with 16 children receiving LUU and 24 children receiving CSUR. The children had a mean age of 2.7 years (7 months-9.8 years) and were followed up in our outpatient clinic for an average of 3.9 years (3 months-10.6 years) after surgery. The median hospital stay was 2 days shorter after LUU. Initially, a considerably longer time was needed for LUU, but after more experience was gained, similar operative times were observed for both procedures. Complications were encountered in both groups. After LUU, two patients developed anastomotic leakage: one was managed conservatively, and one required temporary nephrostomy. In the CSUR group, one patient developed vesicoureteral obstruction during follow-up and required reoperation with LUU. The occurrence of post-operative urinary tract infections was similar in both groups. No complications related to the ureteral stump after LUU arose. Conclusion: LUU is a safe and efficacious treatment option for children with duplex kidney anomalies and can be used as an alternative to CSUR. All children receiving LUU showed a non-obstructive, patent anastomosis and no signs for stenotic compromise of the receiving ureter.

Non-operative treatment versus suture refixation of the nail plate in paediatric fingernail avulsion injuries.

The study compared a non-operative treatment, consisting of ointment dressing only, with the standard surgical nail plate refixation for simple fingernail avulsion injuries in children. A non-inferiority hypothesis was tested in a single-centre, prospective cohort study. The quality of the new nail was the primary outcome and was assessed with the Nail Appearance Score. The secondary outcome was patient and parental satisfaction, which was assessed with the Patients' and Parental Nail Satisfaction Score. Fifty-one patients were enrolled; 39 (76%) chose the non-operative treatment and 12 (24%) the standard operative therapy. Comparison of the two groups confirmed the non-inferiority hypothesis with a risk difference for the new nail of -0.02 with a 95% confidence interval of (-0.05, 0.01). The outcome was excellent in all fingers with no significant differences regarding either the primary or secondary outcome. In view of associated risks and costs for surgery, we recommend ointment dressings for such injuries.Level of evidence: II.

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.

Nonarticular Base and Shaft Fractures of Children's Fingers: Are Follow-up X-rays Needed? Retrospective Study of Conservatively Treated Proximal and Middle Phalangeal Fractures.

BACKGROUND: Phalangeal fractures of the hand are common in children, and most extra-articular fractures can be treated with nonoperative management. Minimally or nondisplaced fractures may simply be immobilized, whereas displaced fractures need closed reduction before immobilization. Although few of these fractures displace secondarily, most schemes currently recommend follow-up x-rays after initial diagnosis. Our primary objective was to identify subgroups of finger fractures that are stable, thus requiring no radiographic monitoring. METHODS: This study was designed as a retrospective, single-center analysis of conservatively treated pediatric finger fractures of the proximal and middle phalanges. We included patients up to 16 years with base or shaft fractures of the index to little fingers who underwent nonoperative treatment and standardized follow-up controls in our pediatric hand surgery outpatients' clinic between 2010 and 2016. Fracture angular deformity in x-rays taken at diagnosis and after 1 and 3 weeks were reassessed blinded, and a statistical analysis was conducted to identify fracture types that are prone to secondary angular deformity. RESULTS: A total of 478 patients were eligible; 113 were lost due to missing final radiographic controls. Overall, 365 patients were analyzed; they had a mean age of 9.7 years (range, 1 to 16), and 33.4% required a primary closed reduction. A secondary angular deformity occurred in 2.2% (8/365) of all finger fractures. No secondary angulation occurred in primary minimally and nondisplaced fractures, but 6.6% (8/122) of the reduced fractures showed a subsequent loss of reduction. CONCLUSIONS: Minimally angulated (<10 degrees) and nondisplaced metaphyseal and diaphyseal fractures of proximal and middle phalanges of the index to little fingers are stable and therefore do not need radiographic follow-ups. However, initially angulated fractures requiring closed reduction bear a risk of subsequent loss of reduction. LEVEL OF EVIDENCE: Level III-retrospective study.

Retroauricular full-thickness skin grafts in syndactyly repair: outcome and comparison with inguinal full-thickness skin grafts: retrospective (cross-sectional) study.

OBJECTIVE: Most surgeons recommend the use of full-thickness skin grafts for syndactyly repair. Common donor sites include the groin and elbow, but only one publication has previously mentioned retroauricular skin. No publication has compared the results for full-thickness skin grafts between retroauricular and other donor sites. This study aims at comparing functional and aesthetic outcomes and parents' satisfaction with retroauricular vs inguinal full-thickness skin grafts. METHODS: Eleven children with retroauricular and 15 with inguinal full-thickness skin grafts were included in this retrospective study. Examination included the Patient and Observer Scar Assessment Scale, parent satisfaction, and a colour match measurement. RESULTS: Both pigmentation match and parents' overall impression of the donor site were significantly better for retroauricular than for inguinal full-thickness skin grafts. CONCLUSION: Due to the excellent pigmentation match and the inconspicuousness of the donor site, this study recommends the use of retroauricular full-thickness skin grafts for syndactyly repair.

Compartment Pressures in Children With Normal and Fractured Forearms: A Preliminary Report.

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 normal compartment pressure measurements in noninjured forearms and in fractured forearms without clinical suspicion of ACS in children.The mean compartment pressure measured in the deep volar compartment (DVC) in healthy children was 10.22 mm Hg (range, 3 to 22 mm Hg) and therefore slightly higher than in adults. Some children with fractures tolerated absolute compartment pressures >30 mm Hg without clinical signs of ACS. Fasciotomy in children under close observation could eventually be delayed despite surpassing the accepted pressure limits for adults. LEVEL OF EVIDENCE: Level I-prognostic.

Appraisal of adult genitalia after hypospadias repair: Do laypersons mind the difference?

INTRODUCTION: Men with corrected hypospadias often suffer from sexual inhibition and fear of being ridiculed by others because of their penile appearance. However, no investigation has thus far been made of the perception of hypospadias-affected surgically repaired genitals by laypersons unacquainted with hypospadias. Therefore, the aim of this study was to find out whether laypersons notice a difference between genitals of men with corrected hypospadias in comparison with circumcised genitals. Furthermore, the most relevant predictors of laypersons' perception of hypospadias-affected genitals were examined. STUDY DESIGN: A cross-sectional study was performed in which a questionnaire with 10 standardized photographs of non-erect hypospadias-affected genitals and 10 circumcised genitals was presented to laypersons unacquainted with hypospadias to measure how they rated these genitals. Laypersons were 105 women and 70 men of three different age groups (age ranges 16-20, 25-30, and 40-45 years). Furthermore, laypersons were asked about demographic characteristics, their sexuality and their genital self-perception. RESULTS: The results showed that genitals with distal forms of hypospadias were rated similarly to circumcised genitals. In contrast, genitals with more proximal types were perceived as significantly less positive than circumcised genitals. However, the effect size was small. Higher age, being in an intimate relationship, higher socio-economic status, and a higher sexual interest predicted a better layperson's perception of hypospadias-affected genitals. DISCUSSION: These findings do not support the fear of some men with corrected hypospadias of being ridiculed by others because of their penile appearance. The results indicate that laypersons do not notice a difference between corrected distal types of hypospadias (which represent the majority of hypospadias) and circumcised genitals. Although the findings showed that laypersons perceive more proximal forms of hypospadias less positively than circumcised genitals, the difference does not appear to be clinically relevant as the effect size was small. A major strength of this study is its comprehensive study design. However, the low response rate of hypospadias patients and control individuals for photo documentation and of laypersons who rated these photosets is a limitation of the study. Therefore, generalization from the results must be made carefully. CONCLUSIONS: The results are relevant for patient counseling. Knowing that the penile appearance would not trouble laypersons may prevent the development of a negative genital self-perception and feelings of shame. The findings also suggest that hypospadias-affected genitals seem to be rated more positively when laypersons know more about the "normal" variation of penile appearance (e.g. with increasing sexual experience at a higher age).

What is a Good Looking Penis? How Women Rate the Penile Appearance of Men with Surgically Corrected Hypospadias.

INTRODUCTION: Some men with corrected hypospadias perceive their penile appearance to be abnormal, although health professionals consider these results satisfactory. AIM: The aim of this study was to investigate how relevant women consider single aspects of penile appearance to be. Moreover, we studied whether women perceive hypospadias-affected surgically repaired genitals (HASRGs) to be as normal-looking as circumcised genitals and identified the most relevant predictors that influence whether a penis is perceived as normal. METHODS: In this cross-sectional study, 105 women in different age groups (age range: 16-20, 25-30, and 40-45 years) completed a standardized questionnaire. MAIN OUTCOME MEASURES: Participants had to rate the importance of eight penile aspects and to indicate how normal they found the appearance of standardized photos of 10 HASRGs and of 10 circumcised genitals. Furthermore, they were asked about demographic characteristics and their sexuality. RESULTS: Results showed that women considered the position and shape of the meatus as the least important penile aspect. Furthermore, results showed that HASRGs with distal hypospadias were perceived to be as normal-looking as circumcised genitals, whereas genitals with more proximal hypospadias were perceived as significantly less normal. However, the difference need not be considered clinically relevant, as the effect size was small. Observer-related predictors of a more positive perception of HASRGs were higher age, higher sexual interest, and perceiving the general cosmetic penile appearance as more important and penile length as less important. CONCLUSIONS: Overall, women were found to consider the "position and shape of the meatus" as the least important penile aspect. These findings may stimulate reflections regarding the relevance of surgical correction of the meatus in minor forms of hypospadias. In addition, this study indicates that women perceived genitals of men with distal operated hypospadias (which represents the majority of hypospadias) to be as normal as nonaffected, circumcised genitals.

The influence of stromal cells on the pigmentation of tissue-engineered dermo-epidermal skin grafts.

It has been shown in vitro that melanocyte proliferation and function in palmoplantar skin is regulated by mesenchymal factors derived from fibroblasts. In this study, we investigated in vivo the influence of mesenchymal-epithelial interactions in human tissue-engineered skin substitutes reconstructed from palmar- and nonpalmoplantar-derived fibroblasts. Tissue-engineered dermo-epidermal analogs based on collagen type I hydrogels were populated with either human palmar or nonpalmoplantar fibroblasts and seeded with human nonpalmoplantar-derived melanocytes and keratinocytes. These skin substitutes were transplanted onto full-thickness skin wounds of immunoincompetent rats. Four weeks after transplantation the development of skin color was measured and grafts were excised and analyzed with regard to epidermal characteristics, in particular melanocyte number and function. Skin substitutes containing palmar-derived fibroblasts in comparison to nonpalmoplantar-derived fibroblasts showed (a) a significantly lighter pigmentation; (b) a reduced amount of epidermal melanin granules; and (c) a distinct melanosome expression. However, the number of melanocytes in the basal layer remained similar in both transplantation groups. These findings demonstrate that human palmar fibroblasts regulate the function of melanocytes in human pigmented dermo-epidermal skin substitutes after transplantation, whereas the number of melanocytes remains constant. This underscores the influence of site-specific stromal cells and their importance when constructing skin substitutes for clinical application.

Ureteral obstruction following injection of dextranomer/hyaluronic acid copolymer: an infrequent but relevant complication.

PURPOSE: To report our experience with ureteral obstruction after injection of dextranomer/hyaluronic acid copolymer (Dx/Ha) to treat vesicoureteral reflux, and analyze its possible causes, management and outcome. MATERIALS AND METHODS: Retrospective review of patients undergoing injection of Dx/Ha. The charts of patients with clinically relevant ureteral obstruction were evaluated for indications, prior interventions, technique of injection and volume injected. Video recordings obtained during injection were analyzed to detect possible technical errors. RESULTS: Fifty-four patients (87 ureters) were treated with Dx/Ha injection in a 5-year period. Five ureters (5.7%) in five patients (9.3%) developed significant ureteral obstruction requiring intervention. Manifestations of obstruction included pain in two patients, urinary tract infections in one and loss of function in one. Increased serum creatinine was observed in a patient with a transplanted kidney. Four obstructions resolved spontaneously (two after percutaneous nephrostomy, two after placement of a ureteral stent) and one required reimplantation. Review of the videos did not reveal any deviation from the usual technique. The volumes injected in the obstructed cases (0.7-1.2 ml) were in the usual range. CONCLUSIONS: In this series, the incidence of post Dx/Ha ureteral obstruction was higher than previously reported. Although 4/5 cases resolved spontaneously, they required drainage to relieve symptoms or to improve renal function. Surgeons need to be aware of this complication and include its possible occurrence in the informed consent obtained prior to injection.

Repeated Botulinum-A toxin injection in the treatment of neuropathic bladder dysfunction and poor bladder compliance in children with myelomeningocele.

AIMS: To evaluate the efficacy of intradetrusor injection of Botulinum-A toxin (BoNT/A) in children with neuropathic bladder dysfunction and poor bladder compliance, due to meningomyelocele. METHODS: We retrospectively reviewed the charts of 11 children (mean age 6.7 ± 5.3 years) with neuropathic bladder and poor bladder compliance (mean 7 ml/cmH(2) O) treated with intradetrusor injection of BoNT/A. After urodynamic evaluation a standardized injection was performed. The authors describe their results in 11 children after the first (5×) or repeated (6×) BoNT/A injections. Re-evaluation was performed 3 and 12 months after each injection. RESULTS: Three months after injection detrusor pressure decreased by 17% and bladder capacity increased by 33%. In all but 1 patient bladder compliance stayed poor. Twelve months after treatment patients still had an effect but the values were already reverting towards preoperative levels. With repeated injections we achieved a similar effect on capacity and detrusor pressure as after the first injection. Overall, bladder compliance normalized (>20 cmH(2) O) in only 1 patient. CONCLUSIONS: The results confirmed the positive temporary effect of BoNT/A on detrusor pressure and bladder capacity in children with myelomeningocele, even after repeated injections. Nevertheless, bladder compliance stayed severely pathological. Whether an earlier treatment may prevent poor bladder compliance is a yet unanswered question.