Conception and validation of A 3d printed learning model of supra condylar fracture of children.

The supracondylar fracture of the child is a common fracture. Its physiology, physiopathology and treatment use periosteum. As far as we know, there is no 3D printed model of this typical fracture in children with periosteum. The purposes of the research are to present the concept of an educational 3D printed supra condylar model with periosteum of the child and its expert validation. Materials and methods: The basis for the paediatric elbow model was a 3D scan of a four-year-old girl. Once the data had been extracted, the models were constructed using 3D Slicer®, Autodesk fusion 360® and Ultimaker Cura® software's. The Creality 3D Ender 6 SE Printer® used PLA filaments to print bone and TPU for periosteum. Printing took place at the University Hospital and the steps were modelled by hand. 3D printed bones and 3D printed periosteum were manually assembled. Participants: Expert validation with twelve paediatric orthopaedic surgeons took place in three University hospitals of the North of France. Results: Four Lagrange and Rigault 3D printed models of supracondylar fractures with periosteum were obtained with 200 h of design, printing and manual assembly based on a four-year-old elbow. According to the paediatric orthopaedic surgery experts, the size of the model is very good, but the model itself is of little interest compared to the information provided by the reconstruction of a 3D scanner. In total, with 9 out of 12 questions scoring higher than 8/10, the model was considered to be a good model for informing parents and teaching students. Conclusions: This study details the design of the first 3D-printed supra condylar fracture model in children with a full-size physeal and periosteum. The model has been validated by paediatric orthopaedic surgery experts.

Vantris vs. deflux for treatment of paediatric vesicoureteral reflux: Efficacy and obstruction risk.

INTRODUCTION: The aim was to compare the efficacy of polyacrylate polyalcohol copolymer (PPC) injections and dextranomer/hyaluronic acid (Dx/Ha) injections for the endoscopic treatment of vesicoureteral reflux in children. MATERIAL: This retrospective cohort study included 189 young patients who had endoscopic treatment for vesicoureteral reflux from January 2012 to December 2019 in our center. Among them, 101 had PCC injections and 88 had Dx/Ha injections. Indications for treatment were vesicoureteral reflux with breakthrough urinary tract infection or vesicoureteral reflux with renal scarring on dimercaptosuccinic acid (DMSA) renal scan. Endoscopic injection was performed under the ureteral meatus. Early complications, recurrence of febrile urinary tract infection and vesicoureteral reflux after endoscopic injection, ureteral obstruction and reintervention were evaluated and compared between groups. RESULTS: Endoscopic treatment was successful in 90.1% of patients who had PPC injection and in 82% of patients who had Dx/Ha injection. Four patients presented a chronic ureteral obstruction after PPC injection, one with a complete loss of function of the dilated kidney. One patient in the Dx/Ha group presented a postoperative ureteral dilatation after 2 injections. CONCLUSION: Despite a similar success rate after PPC and Dx/Ha injections for endoscopic treatment of VUR, there may be a greater risk of postoperative ureteral obstruction after PPC injections. The benefit of using PPC to prevent febrile UTI and renal scarring in children with low-grade VUR does not seem to outweigh the risk of chronic ureteral obstruction.

Confirmation and further delineation of the SMG9-deficiency syndrome, a rare and severe developmental disorder.

INTRODUCTION: SMG9 deficiency is an extremely rare autosomal recessive condition originally described in three patients from two families harboring homozygous truncating SMG9 variants in a context of severe syndromic developmental disorder. To our knowledge, no additional patient has been described since this first report. METHODS: We performed exome sequencing in a patient exhibiting a syndromic developmental delay and in her unaffected parents and report the phenotypic features. RESULTS: Our patient presented with a syndromic association of severe global developmental delay and diverse malformations, including cleft lip and palate, facial dysmorphic features, brain abnormalities, heart defect, growth retardation, and severe infections. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous. CONCLUSIONS: We confirm that bi-allelic truncating SMG9 variants cause a severe developmental syndrome including brain and heart malformations associated with facial dysmorphic features, severe growth and developmental delay with or without ophthalmological abnormalities, severe feeding difficulties, and life-threatening infections.

High Pressure Balloon Dilatation of Primary Obstructive Megaureter in Children: A Multicenter Study.

Aim of the Study: We described the initial experience of four referral centers in the treatment of primary obstructive megaureter (POM) in children, by high-pressure balloon dilatation (HPBD) of the ureterovesical junction with double JJ stenting. We managed a retrospective multicenter study to assess its effectiveness in long-term. Methods: We reviewed the medical records of all children who underwent HPBD for POM that require surgical treatment from May 2012 to December 2017 in four different institutions. The primary outcome measured was ureterohydronephrosis (UHN) and its degree of improvement after the procedure. Secondary outcomes were postoperative complications and resolution of preoperative symptomatology. Main Results: Forty-two ureters underwent HPBD for POM in 33 children, with a median age of 14.7 months - (range: 3 months -15 years). Ureterohydronephrosis improves in 86% of ureters after one endoscopic treatment. Three cases required a second HPBD. Four patients required surgical treatment for worsening of UHN after endoscopic treatment. The post-operative complication rate was 50% (21 ureters). In 13 cases (61%), they were related to double J stent. The median follow-up was 24 months (2 months -5 years) and all patients were symptom-free. Conclusion: We reported the first multicenter study and the largest series of children treated with HPBD, with an overall success rate of 92%. Endoscopic treatment can be a definitive treatment of POM since it avoided reimplantation in 90% of cases. Complications are mainly due to double J stent.

Diffusion tensor imaging in acute pyelonephritis in children.

BACKGROUND: Diffusion-weighted imaging plays a key role in the imaging of acute pyelonephritis by MRI. However the use of respiratory triggering is challenging and time-consuming in children. Diffusion tensor imaging without respiratory triggering might provide satisfying images of the moving kidneys. OBJECTIVE: To compare mean diffusivity diffusion tensor images obtained with free breathing with diffusion-weighted images obtained with respiratory triggering. MATERIALS AND METHODS: Thirty-one children with suspected acute pyelonephritis underwent axial diffusion tensor imaging acquisition with free breathing and axial and coronal diffusion-weighted imaging acquisitions with respiratory triggering. We compared image quality and detection of nephritis between the two sequences. RESULTS: Diffusion tensor imaging demonstrated agreement with diffusion-weighted imaging in all cases, with no difference in the detection of nephritis areas. The image quality was significantly better with diffusion tensor imaging (P<0.01). CONCLUSION: Diffusion tensor imaging could replace diffusion-weighted imaging for diagnosis of acute pyelonephritis.

Intradetrusor Injections of Botulinum Toxin Type A in Children With Spina Bifida: A Multicenter Study.

OBJECTIVE: To assess the effectiveness of intradetrusor injections of botulinum toxin type A (IDBTX-A) in children with spina bifida. METHODS: All patients aged less than 16 years old who underwent IDBTX-A between 2002 and 2016 at 6 institutions were included in a retrospective study. Our primary endpoint was the success rate of IDBTX-A defined as both clinical improvement (no incontinence episodes between clean intermittent catheterizations [CICs], absence of urgency, and less than 8 CICs per day) and urodynamic improvement (resolution of detrusor overactivity and normal bladder compliance for age) lasting ≥12 weeks. Predictive factors of success were assessed through univariate analysis. RESULTS: Fifty-three patients with a mean age of 8.5 years were included. All patients were under CIC and 88.7% had received anticholinergics with either poor efficacy or bothersome adverse events. The global success rate of the first injection (clinical and urodynamic) was 30%. Patients with closed spinal dysraphism had a significantly better success rate than patients with myelomeningocele (P = .002). The clinical success rate was 66% and was significantly associated with maximum urethral closure pressure (34 cm H2O vs 54.4 cm H2O, P = .02). The urodynamic success rate was 34%. Maximum cystometric capacity (P <.0001) and compliance (P = .01) significantly improved after the first IDBTX-A and maximum detrusor pressure tended to decrease (P = .09) except in the subgroup of patients with poor compliance. After a mean follow-up of 3.7 years, 23 patients (43.4%) required augmentation cystoplasty. Excluding 6 patients who were lost to follow-up, 38.3% of patients were still undergoing botulinum toxin injections at last follow-up. CONCLUSION: In this series, despite the fact that IDBTX-A enabled clinical improvement in 66% patients, urodynamic outcomes were poor resulting in a low global success rate (30%).

Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome.

BACKGROUND: Development of tumours such as adrenocortical carcinomas (ACC), choroid plexus tumours (CPT) or female breast cancers before age 31 or multiple primary cancers belonging to the Li-Fraumeni (LFS) spectrum is, independently of the familial history, highly suggestive of a germline TP53 mutation. The aim of this study was to determine the contribution of de novo and mosaic mutations to LFS. METHODS AND RESULTS: Among 328 unrelated patients harbouring a germline TP53 mutation identified by Sanger sequencing and/or QMPSF, we could show that the mutations had occurred de novo in 40 cases, without detectable parental age effect. Sanger sequencing revealed two mosaic mutations in a child with ACC and in an unaffected father of a child with medulloblastoma. Re-analysis of blood DNA by next-generation sequencing, performed at a depth above 500X, from 108 patients suggestive of LFS without detectable TP53 mutations, allowed us to identify 6 additional cases of mosaic TP53 mutations, in 2/49 children with ACC, 2/21 children with CPT, in 1/31 women with breast cancer before age 31 and in a patient who developed an osteosarcoma at age 12, a breast carcinoma and a breast sarcoma at age 35. CONCLUSIONS: This study performed on a large series of TP53 mutation carriers allows estimating the contribution to LFS of de novo mutations to at least 14% (48/336) and suggests that approximately one-fifth of these de novo mutations occur during embryonic development. Considering the medical impact of TP53 mutation identification, medical laboratories in charge of TP53 testing should ensure the detection of mosaic mutations.

Pyogenic Sacroiliitis in a 13-Month-Old Child: A Case Report and Literature Review.

Pyogenic sacroiliitis is exceptional in very young children. Diagnosis is difficult because clinical examination is misleading. FABER test is rarely helpful in very young children. Inflammatory syndrome is frequent. Bone scintigraphy and MRI are very sensitive for the diagnosis. Joint fluid aspiration and blood cultures are useful to identify the pathogen. Appropriate antibiotic therapy provides rapid regression of symptoms and healing. We report the case of pyogenic sacroiliitis in a 13-month-old child.Clinical, biological, and imaging data of this case were reviewed and reported retrospectively.A 13-month-old girl consulted for decreased weight bearing without fever or trauma. Clinical examination was not helpful. There was an inflammatory syndrome. Bone scintigraphy found a sacroiliitis, confirmed on MRI. Aspiration of the sacroiliac joint was performed. Empiric intravenous biantibiotic therapy was started. Patient rapidly recovered full weight bearing. On the 5th day, clinical examination and biological analysis returned to normal. Intravenous antibiotic therapy was switched for oral. One month later, clinical examination and biological analysis were normal and antibiotic therapy was stopped.Hematogenous osteoarticular infections are common in children but pyogenic sacroiliitis is rare and mainly affects older children. Diagnosis can be difficult because clinical examination is poor. Moreover, limping and decreased weight bearing are very common reasons for consultation. This may delay the diagnosis or refer misdiagnosis. Bone scintigraphy is useful to locate a bone or joint disease responsible for limping. In this observation, bone scintigraphy located the infection at the sacroiliac joint. Given the young age, MRI was performed to confirm the diagnosis. Despite the very young age of the patient, symptoms rapidly disappeared with appropriate antibiotic therapy.We report the case of pyogenic sacroiliitis in a 13-month-old child. It reminds the risk of misdiagnosing pyogenic sacroiliitis in children because it is exceptional and clinical examination is rarely helpful. It also highlights the usefulness of bone scintigraphy and MRI in osteoarticular infections in children.

Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers.

PURPOSE: The aim of the study was to update the description of Li-Fraumeni syndrome (LFS), a remarkable cancer predisposition characterized by extensive clinical heterogeneity. PATIENTS AND METHODS: From 1,730 French patients suggestive of LFS, we identified 415 mutation carriers in 214 families harboring 133 distinct TP53 alterations and updated their clinical presentation. RESULTS: The 322 affected carriers developed 552 tumors, and 43% had developed multiple malignancies. The mean age of first tumor onset was 24.9 years, 41% having developed a tumor by age 18. In childhood, the LFS tumor spectrum was characterized by osteosarcomas, adrenocortical carcinomas (ACC), CNS tumors, and soft tissue sarcomas (STS) observed in 30%, 27%, 26%, and 23% of the patients, respectively. In adults, the tumor distribution was characterized by the predominance of breast carcinomas observed in 79% of the females, and STS observed in 27% of the patients. The TP53 mutation detection rate in children presenting with ACC or choroid plexus carcinomas, and in females with breast cancer before age 31 years, without additional features indicative of LFS, was 45%, 42% and 6%, respectively. The mean age of tumor onset was statistically different (P < .05) between carriers harboring dominant-negative missense mutations (21.3 years) and those with all types of loss of function mutations (28.5 years) or genomic rearrangements (35.8 years). Affected children, except those with ACC, harbored mostly dominant-negative missense mutations. CONCLUSION: The clinical gradient of the germline TP53 mutations, which should be validated by other studies, suggests that it might be appropriate to stratify the clinical management of LFS according to the class of the mutation.

The MDM2 285G-309G haplotype is associated with an earlier age of tumour onset in patients with Li-Fraumeni syndrome.

In the Li-Fraumeni syndrome (LFS) resulting from germline TP53 mutations, the MDM2 SNP309G allele has been shown to be associated with an earlier age of tumour onset, however the significance of this association is controversial. The 285C variation, also located in the MDM2 promoter, has been shown to reduce the strength of Sp1 binding to MDM2 promoter, antagonizing the effect of the 309G variation. In this study, we investigated the interaction of the MDM2 SNP285 and 309 in a large series of 195 LFS patients. Although we observed a lower mean age of tumour onset in patients with MDM2 SNP309 T/G or G/G genotype (23.1 years) than in patients with T/T genotype (27.3 years), the difference was not statistically significant. In contrast, patients with the 285-309 G-G haplotype develop tumours 5 years earlier than patients harbouring other haplotypes (p = 0.044). This result shows that the MDM2 285-309 G-G is a higher risk haplotype in patients with germline TP53 mutations. This study confirms that the MDM2 309G variation is deleterious when its effect is not neutralized by the 285C variation and illustrates the interfering effects of SNPs located within a gene acting as modifier factor in a Mendelian disease.

Idiopathic varicocele in adolescents: risks of the inguinal approach.

INTRODUCTION: The aim of this study was to evaluate the medium-term results and complications of open inguinal varicocelectomy, including vein ligation, intraoperative venography, and antegrade sclerotherapy. MATERIALS AND METHODS: Sixty-four children were treated between 2000 and 2009 for idiopathic varicocele. Fifty children were examined 6 months after surgery. In 2010, 22 patients were recalled for testicular ultrasound scans (US) to evaluate the medium-term results of the technique. RESULTS: The mean age of the children was 12.8 years at first consultation. Of the 50 cases, 35 children were asymptomatic, 13 experienced pain, 3 suffered from discomfort, and 1 had testicular asymmetry. Thirteen children had delayed left testicular growth compared with the right testis. The mean age at surgery was 13.3 years, and follow-up duration was 8.3 months ± 13.9. Thirty-eight patients achieved good results postsurgery; there was varicocele recurrence in 3, testicular hypotrophy in 7, and complete testicular atrophy in 2 patients. CONCLUSION: Naked eye inguinal surgical ligation does not appear to be safe enough to treat young adolescents, with the theoretical risk of a decrease in fertility in the future. In teams which are untrained in microsurgical or laparoscopic varicocelectomy, we suggest referring adolescent patients to a radiologist for embolization.

Drastic effect of germline TP53 missense mutations in Li-Fraumeni patients.

In contrast to other tumor suppressor genes, the majority of TP53 alterations are missense mutations. We have previously reported that in the Li-Fraumeni syndrome (LFS), germline TP53 missense mutations are associated with an earlier age of tumor onset. In a larger series, we observed that mean age of tumor onset in patients harboring dominant negative missense mutations and clearly null mutations was 22.6 and 37.5 years, respectively. To assess the impact of heterozygous germline TP53 mutations in the genetic context of the patients, we developed a new functional assay of the p53 pathway on the basis of induction of DNA damage in Epstein-Barr-virus-immortalized lymphocytes, followed by comparative gene-expression profiling. In wild-type lymphocytes, we identified a core of 173 genes whose expression was induced more than twofold, of which 46 were known p53 target genes. In LFS lymphocytes with canonical missense mutations, the number of induced genes and the level of known p53 target genes induction were strongly reduced as compared with controls and LFS lymphocytes with null mutations. These results show that certain germline missense TP53 mutations, such as those with dominant negative effect, dramatically alter the response to DNA damage. This probably explains why TP53 alterations are predominantly missense mutations.