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.

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.

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.

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.

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.

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.

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.

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.

Conservative treatment of stable volar plate injuries of the proximal interphalangeal joint in children and adolescents: a prospective study.

OBJECTIVES: The purpose of this study was to assess a standard conservative management for stable volar plate injuries of the proximal interphalangeal joint in children and adolescents. No study is available regarding this subject for this age group. METHODS: A prospective study was performed on 37 consecutive patients (aged between 9 and 15 years; mean, 13 years) with stable acute volar plate injuries of the proximal interphalangeal joints, including 22 avulsion fractures without dislocation. All patients had a standardized conservative treatment consisting of a dorsal aluminum extension block splinting at a 15-degree flexion for 10 days, followed by a spontaneous mobilization and taping to adjacent fingers for sports only. At follow-up visits, active and passive ranges of motion, swelling of the affected joints, analgesic intake, and pain perception by the patient were recorded. Regular follow-up consisted of standardized assessments at 2, 6, and 12 weeks, with additional consultations if symptoms persisted. RESULTS: Healing was uneventful, and hand therapy was not necessary to regain full range of motion in 32 of 33 children with a regular follow-up. The only flexion contracture observed responded well to splinting. Of the 33 patients, 31 had an excellent outcome and 2 had a good outcome. CONCLUSIONS: Dorsal extension block splinting was an efficient, simple, well-tolerated treatment for stable volar plate injuries of the proximal interphalangeal joint in a preliminary series of patients younger 16 years. Flexion contractures were rare and responded well to dynamic splinting.

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.

The Pediatric Penile Perception Score: an instrument for patient self-assessment and surgeon evaluation after hypospadias repair.

PURPOSE: The aim of this study was to develop and evaluate an instrument that allows assessment and comparison of penile perception of patients, parents and surgeons. MATERIALS AND METHODS: A total of 77 boys 6 to 17 years old who had undergone hypospadias repair were interviewed by a psychologist with a standardized questionnaire concerning penile self-perception with regard to meatus, glans, skin and general appearance. The Pediatric Penile Perception Score was derived from the sum of these 4 items. The results were compared with a control group of age matched boys following inguinal hernia repair. Parents were asked via questionnaire to report the penile appearance of their son using the Pediatric Penile Perception Score. A total of 56 patients accepted standardized photographic documentation, and their pictures were sent for evaluation with the Pediatric Penile Perception Score to 6 blinded urologists. RESULTS: The Pediatric Penile Perception Score allowed us to assess perception of the genitalia by patients, parents and urologists. Statistical analysis of the Pediatric Penile Perception Score assigned by the urologist revealed good interrater reliability (interclass correlation 0.75 to 0.88) and stability (r = 0.59 to 0.83). Intercorrelation of the items "meatus," "glans" and "skin" with "general appearance" was good among the boys, parents and urologists. Patients with hypospadias expressed high satisfaction with the penile appearance, which did not differ significantly from age matched controls. However, parents and urologists were less satisfied with the penile appearance than were the patients themselves. CONCLUSIONS: The Pediatric Penile Perception Score is a reliable instrument to assess penile self-perception in children after hypospadias repair, and for appraisal of the surgical result by parents and uninvolved urologists.

Health-related quality of life and psychological adjustment of children and adolescents with hypospadias.

OBJECTIVE: To assess health-related quality of life (HRQoL) and psychological adjustment of children and adolescents after hypospadias repair and to identify sociodemographic, medical, and psychosocial predictors of outcome. STUDY DESIGN: 77 boys (7-17 years old) who underwent surgery for hypospadias were investigated in a cross-sectional study. Child- and mother-rated HRQoL was evaluated by the TNO-AZL Child Quality of Life Questionnaire, psychological adjustment by the Child Behavior Checklist. Scores were compared with an age-matched control group consisting of 77 boys after hernia repair. RESULTS: Compared with the control subjects, self-reported HRQoL of patients with hypospadias was lower in most dimensions. In contrast, mother-reported HRQoL and psychological adjustment did not differ in the 2 groups. Higher age and "being less ashamed of penile appearance" predicted better self-reported HRQoL, whereas positive penile self-perception, the patient's experience of not having been teased about his penis, and more severe hypospadias contributed to better mother-reported HRQoL. Psychological adjustment was predicted by higher age, Swiss nationality, more severe hypospadias, and the patient's experience of not having been teased about his penis. CONCLUSIONS: In contrast to psychological adjustment, self-reported HRQoL of boys with hypospadias can be diminished. Psychosocial factors are more important predictors than medical variables.

Psychosexual development of children and adolescents with hypospadias.

INTRODUCTION: Hypospadias is the most common malformation of the penis. Despite the common assumption that hypospadias may affect children's psychosexual development, only a few studies report on the patients' psychosexual adjustment during childhood and adolescence. AIM: A comprehensive, cross-sectional investigation of the psychosexual development of boys operated on for hypospadias in comparison to a healthy control group. METHODS: Sixty-eight children and adolescents (7-17 years) operated on for hypospadias were examined by means of a standardized interview assessing penile self-perception, gender-role behavior, sexual experiences, and sexual attitude. Scores were compared to an age-matched control group consisting of 68 boys after hernia repair. Predictive values of medical variables as well as the patients' knowledge of hypospadias were assessed. MAIN OUTCOME MEASURES: The Pediatric Penile Perception Score, the Gender-Role Questionnaire by Ijntema and Cohen-Kettenis, and a self-developed questionnaire on first sexual experiences and sexual attitude comprised the standardized assessment instruments. RESULTS: Boys with hypospadias did not significantly differ from the control subjects with regard to penile self-perception, gender-role behavior, first sexual experiences, and sexual attitude. Younger age and the patient's knowledge of hypospadias predicted a more positive penile self-perception, while a more pronounced masculine gender-role behavior was best predicted by younger age at final surgery. CONCLUSIONS: Boys with corrected hypospadias may show a psychosexual development that is similar to healthy children. Puberty could be a critical time for the patients, however, during which they might require regular urological follow-ups and may benefit from age-appropriate information about their penile condition. Moreover, the later corrective surgery is completed, the more likely the patients may become insecure with regard to gender-role behavior.

Psychosocial adjustment, health-related quality of life, and psychosexual development of boys with hypospadias: a systematic review.

OBJECTIVE: A systematic review of studies on psychosocial adjustment, HRQoL (health-related quality of life), and psychosexual development of boys with hypospadias. METHODS: Research was conducted on several online bibliographic databases. Articles were selected on the basis of predefined criteria. Methodological quality was assessed by two independent reviewers who applied a standardized checklist. When possible, data analyses were performed by calculating effect sizes. RESULTS: Thirteen studies met the criteria for inclusion, whose methodological standard ranged from low to high quality. None of them has focused on HRQoL. Findings with regard to psychosocial and psychosexual adjustment were inconsistent, though they clearly showed that boys with hypospadias suffer from negative genital appraisal and sexual inhibitions. Overall, medical factors exerted a rather small influence. Psychosocial risk factors have hardly been examined so far. CONCLUSIONS: The identification of psychosocial risk factors in methodologically sound studies is necessary to guarantee a comprehensive treatment for boys with hypospadias.

To Cohen and forget? Evaluation of postoperative imaging studies after transtrigonal ureteric reimplantation for vesicoureteric reflux in children.

OBJECTIVES: To determine the clinical significance of routine postoperative voiding cystourethrography (VCUG) and renal functional studies in the postoperative management of children after a transtrigonal ureteric reimplantation. METHODS: A retrospective record review of 126 consecutive patients undergoing transtrigonal ureteric reimplantation. Inclusion criteria included primary reflux and >5 years of follow-up. Follow-up imaging studies consisted of serial renal ultrasounds (US) and one VCUG and intravenous urogram (IVU) each. RESULTS: Of 126 patients, 2 required a reoperation for contralateral reflux and pyelonephritis. In all other patients the results of the VCUG did not alter management. Dilatation seen in IVU was always visible in the renal US as well and always resolved spontaneously. No new dilatation was observed after 1 year of follow-up. CONCLUSIONS: Routine postoperative VCUG and renal functional studies are not warranted in asymptomatic patients after transtrigonal reimplantation. Only in patients with postoperative pyelonephritis did the imaging studies alter the treatment. In the majority of patients, follow-up with an early and 1-year renal US may suffice. Elimination of routine VCUG and functional studies will decrease morbidity and cost after ureteric reimplantation.