[Management of patients with complex ear deformities]. / Prise en charge des patients présentant des déformations complexes du pavillon de l'oreille.

Complex ear reconstruction requires specialized multidisciplinary care. Most patients present with microtia, often associated with hearing disorders. The management of these disorders is a priority, and reconstruction of the external ear remains optional. Nowadays, auricular reconstruction is based on the subcutaneous implantation of either autologous cartilage or an allogeneic implant. Autologous reconstruction requires highly specialized surgical expertise and involves harvesting rib cartilage but carries a lower risk of exposure compared to allogeneic implants. Both techniques yield good results with a high success rate and have a positive impact on the social functioning and daily life of patients.

La reconstruction complexe du pavillon auriculaire nécessite une prise en charge multidisciplinaire spécialisée. La majorité des patients nécessitant ce geste présentent une microtie, souvent associée à des troubles de l'audition. La prise en charge de ceux-ci est prioritaire et la reconstruction du pavillon reste facultative. Aujourd'hui, la reconstruction du pavillon se base sur l'implantation sous-cutanée d'une maquette de cartilage autologue ou d'un implant allogène. La reconstruction autologue demande une expertise chirurgicale hautement spécialisée et nécessite un prélèvement de cartilage costal mais présente un risque d'exposition inférieur par rapport à l'implant allogène. Les deux techniques permettent d'atteindre de bons résultats avec un taux de réussite élevé et un effet positif sur le fonctionnement social et le quotidien des patients.

Artificial Intelligence in the Diagnosis and Management of Appendicitis in Pediatric Departments: A Systematic Review.

INTRODUCTION: Artificial intelligence (AI) is a growing field in medical research that could potentially help in the challenging diagnosis of acute appendicitis (AA) in children. However, usefulness of AI in clinical settings remains unclear. Our aim was to assess the accuracy of AIs in the diagnosis of AA in the pediatric population through a systematic literature review. METHODS: PubMed, Embase, and Web of Science were searched using the following keywords: "pediatric," "artificial intelligence," "standard practices," and "appendicitis," up to September 2023. The risk of bias was assessed using PROBAST. RESULTS: A total of 302 articles were identified and nine articles were included in the final review. Two studies had prospective validation, seven were retrospective, and no randomized control trials were found. All studies developed their own algorithms and had an accuracy greater than 90% or area under the curve >0.9. All studies were rated as a "high risk" concerning their overall risk of bias. CONCLUSION: We analyzed the current status of AI in the diagnosis of appendicitis in children. The application of AI shows promising potential, but the need for more rigor in study design, reporting, and transparency is urgent to facilitate its clinical implementation.

Reflecting the human lip in vitro: Cleft lip skin and mucosa keratinocytes keep their identities.

OBJECTIVES: Cell models have shown great promise as tools for research, potentially providing intriguing alternatives to animal models. However, the original tissue characteristics must be maintained in culture, a fact that is often assumed, but seldom assessed. We aimed to follow the retention of the original tissue identities of cleft lip-derived skin and mucosa keratinocytes in vitro. METHODS: Cleft lip-derived keratinocytes were isolated from discarded tissue along the cleft margins during cheiloplasty. Cell identities were assessed by immunohistochemistry and quantitative real-time PCR for tissue-specific markers and compared with native lip tissue. Moreover, keratinocytes were regularly analyzed for the retention of the original tissue characteristics by the aforementioned methods as well as by differentiation assays. RESULTS: The various anatomical zones of the human lip could be distinguished using a panel of differentiation and functional-based markers. Using these markers, retention of the original tissue identities could be followed and confirmed in the corresponding primary keratinocytes in culture. CONCLUSIONS: Our findings promote patient-derived cells retaining their original identities as astonishing and clinically relevant in vitro tools. Such cells allow a better molecular understanding of various lip-associated pathologies as well as their modeling in vitro, including but not restricted to orofacial clefts.

Postoperative Dysnatremia in Pediatric Patients Undergoing Palatoplasty.

OBJECTIVE: Identifying predisposing factors to dysnatremia to improve perioperative care after cleft surgery. DESIGN: Retrospective case series. Patient data were obtained through the electronic medical records of the hospital. SETTING: Tertiary care university hospital. PATIENTS: The inclusion criterion was the measurement of an abnormal natremia value, defined as Na >150 or <130 mmol/l after a cleft lip or cleft palate repair procedure. The exclusion criterion was natremia between 131 and 149 mmol/l. RESULTS: Natremia measurements were available for 215 patients born between 1995 and 2018. Five patients presented with postoperative dysnatremia. Several predisposing factors to dysnatremia have been identified: drugs, infection, administration of intravenous fluids, and postoperative syndrome of inappropriate antidiuretic hormone secretion. Although the hospital environment contributes to dysnatremia development, the fact that only patients undergoing cleft palate repair develop natremia anomalies suggests that this surgery may be itself a risk factor. CONCLUSION: Children undergoing palatoplasty may be at higher risk to develop postoperative dysnatremia. Early recognition of symptoms and risk factors, postoperative monitoring, and prompt treatment of dysnatremia diminish the risk of neurological complications.

Discovery and characterization of heterogeneous and multipotent fibroblast populations isolated from excised cleft lip tissue.

BACKGROUND: Regularly discarded lip tissue obtained from corrective surgeries to close the cleft lip represents an easily accessible and rich source for the isolation of primary fibroblasts. Primary fibroblasts have been described to show compelling similarities to mesenchymal stem cells (MSCs). Hence, cleft lip and palate (CLP) lip-derived fibroblasts could be thought as an intriguing cell source for personalized regenerative therapies in CLP-affected patients. METHODS: Initially, we thoroughly characterized the fibroblastic nature of the lip-derived mesenchymal outgrowths by molecular and functional assays. Next, we compared their phenotype and genotype to that of bone marrow-mesenchymal stem cells (BM-MSCs) and of human lung-derived fibroblasts WI38, by assessing their morphology, surface marker expression, trilineage differentiation potential, colony-forming (CFU) capacity, and immunomodulation property. Finally, to better decipher the heterogeneity of our CLP cultures, we performed a single cell clonal analysis and tested expanded clones for surface marker expression, as well as osteogenic and CFU potential. RESULTS: We identified intriguingly similar phenotypic and genotypic properties between CLP lip fibroblasts and BM-MSCs, which makes them distinct from WI38. Furthermore, our own data in combination with the complex anatomy of the lip tissue indicated heterogeneity in our CLP cultures. Using a clonal analysis, we discovered single cell-derived clones with increased levels of the MSC markers CD106 and CD146 and clones with variabilities in their commitment to differentiate into bone-forming cells and in their potential to form single cell-derived colonies. However, we were not able to gain clones possessing superior MSC-like capacities when compared to the heterogeneous parental CLP population. Additionally, all clones could still generate contractile forces and retained robust levels of the fibroblast specific marker FSP1, which was not detectable in BM-MSCs. CONCLUSIONS: Our results suggest that we isolate heterogeneous populations of fibroblasts from discarded CLP lip tissue, which show a prominently multipotent character in their entirety avoiding the need for elaborate subpopulation selections in vitro. These findings suggest that CLP lip fibroblasts might be a novel potential cell source for personalized regenerative medicine of clinical benefit for CLP patients.

Final Posttreatment Occlusion in Patients With Unilateral Cleft Lip and Palate.

OBJECTIVE: To evaluate final posttreatment occlusion in patients with complete unilateral cleft lip and palate (cUCLP) by comparing (1) 3 treatment centers, (2) males and females, (3) cleft and noncleft sides, (4) right- and left-sided clefts, and (5) orthodontic treatment with/without orthognathic surgery (OS). DESIGN: Retrospective cohort study. PATIENTS: Blinded posttreatment dental casts of 56 patients (19.4 ± 1.4 years) with cUCLP from 3 centers in Switzerland. MAIN OUTCOME MEASURE: Occlusal assessment using the modified Huddart/Bodenham (MHB) index. RESULTS: Our sample comprised 35 males and 21 females, 46 with left- and 10 with right-sided clefts, of which 32 had undergone OS. The final posttreatment occlusion showed a median MHB score of 0 (interquartile range: -1.0 to 2.0) in the total sample and did not seem to depend on treatment center, sex, or OS. The MHB scores for the anterior buccal and the buccal segments were more negative on the cleft than on the noncleft side (P = .002 and P = .006, respectively). When the cleft was on the left side, the MHB score tended to be more positive in the labial (P = .046) and anterior buccal segments (P = .034). CONCLUSIONS: This study shows a very satisfactory final posttreatment occlusion in patients with cUCLP. The more constricted buccal occlusion on the cleft side emphasizes the attention that should be given in correcting the more medially positioned lesser maxillary segment. The influence of cleft-sidedness should be analyzed further on a sample including more patients with right-sided clefts.

A Living Cell Repository of the Cranio-/Orofacial Region to Advance Research and Promote Personalized Medicine.

The prevalence of congenital anomalies in newborns is estimated to be as high as 6%, many of which involving the cranio-/orofacial region. Such malformations, including several syndromes, are usually identified prenatally, at birth, or rarely later in life. The lack of clinically relevant human cell models of these often very rare conditions, the societal pressure to avoid the use of animal models and the fact that the biological mechanisms between rodents and human are not necessarily identical, makes studying cranio-/orofacial anomalies challenging. To overcome these limitations, we are developing a living cell repository of healthy and diseased cells derived from the cranio-/orofacial region. Ultimately, we aim to make patient-derived cells, which retain the molecular and genetic characteristics of the original anomaly or disease in vitro, available for the scientific community. We report our efforts in establishing a human living cell bank derived from the cranio-/orofacial region of otherwise discarded tissue samples, detail our strategy, processes and quality checks. Such specific cell models have a great potential for discovery and translational research and might lead to a better understanding and management of craniofacial anomalies for the benefit of all affected individuals.

Negative Pressure Wound Therapy in Pediatric Burn Patients: A Systematic Review.

Significance: Negative pressure wound therapy (NPWT) requires the placement of a dressing over a wound, covered with an adhesive film, and applying to these dressing a negative pressure in a controlled fashion. This therapy is a powerful complement to surgical care of wounds. Data are however poor on its use in pediatric burns. Recent Advances: This systematic review, including a total of 466 patients, shows that NPWT as the initial treatment for burned children and after skin grafting has been shown to produce promising results. In the majority of studies, skin graft take rate is close to 100%. This therapy is particularly beneficial in the pediatric population because of less frequent dressing changes and early mobilization. NPWT devices accurately quantify burns water losses and allow tailoring liquid resuscitation. Critical Issues: NPWT is not in the subject of controlled clinical trials in pediatric; most publications are case reports or retrospective reviews. The sporadic complications include bleeding, local infections, and mechanical device issues. Future Directions: NPWT has been used in 2-month up to 18-year-old children with deep second- to third-degree burn of multiple etiologies, from a few days up to several months, on small to 40% total body surface area (%), and in difficult areas. Data gathered provide empirical guidelines on NPWT use in pediatric burns using continuous mode with a pressure of -50 to -75 mmHg for children younger than 2 years, and -75 to -125 mmHg in children over 2 years of age. Prospective randomized studies are needed to provide validated rules.

A Novel Van der Woude Syndrome-Causing IRF6 Variant Is Subject to Incomplete Non-sense-Mediated mRNA Decay Affecting the Phenotype of Keratinocytes.

Van der Woude syndrome (VWS) is a genetic syndrome that leads to typical phenotypic traits, including lower lip pits and cleft lip/palate (CLP). The majority of VWS-affected patients harbor a pathogenic variant in the gene encoding for the transcription factor interferon regulatory factor 6 (IRF6), a crucial regulator of orofacial development, epidermal differentiation and tissue repair. However, most of the underlying mechanisms leading from pathogenic IRF6 gene variants to phenotypes observed in VWS remain poorly understood and elusive. The availability of one VWS individual within our cohort of CLP patients allowed us to identify a novel VWS-causing IRF6 variant and to functionally characterize it. Using VWS patient-derived keratinocytes, we reveal that most of the mutated IRF6_VWS transcripts are subject to a non-sense-mediated mRNA decay mechanism, resulting in IRF6 haploinsufficiency. While moderate levels of IRF6_VWS remain detectable in the VWS keratinocytes, our data illustrate that the IRF6_VWS protein, which lacks part of its protein-binding domain and its whole C-terminus, is noticeably less stable than its wild-type counterpart. Still, it maintains transcription factor function. As we report and characterize a so far undescribed VWS-causing IRF6 variant, our results shed light on the physiological as well as pathological role of IRF6 in keratinocytes. This acquired knowledge is essential for a better understanding of the molecular mechanisms leading to VWS and CLP.

Sella turcica morphometrics in children with unilateral cleft lip and palate.

OBJECTIVE: To use morphometric methods to investigate the size and shape of the sella turcica in children with unilateral cleft lip and palate (UCLP). SETTING AND SAMPLE POPULATION: Fifty-six healthy children with non-syndromic UCLP, from a major paediatric teaching hospital, with lateral cephalograms taken prior to alveolar bone grafting, were compared with an age- and sex-matched control group of healthy children without orofacial clefts, with lateral cephalograms taken prior to orthodontic treatment. MATERIALS AND METHODS: In this cross-sectional study, conventional measurements were performed on the sella turcica to measure width, height and area on lateral cephalograms. Sella shape was also analysed using 11 points defining the sella turcica contours, using geometric morphometrics. Procrustes superimposition was used to register all sella contour tracings to calculate average sella shape. Principal component analysis was applied to the residuals of the point coordinates, and principal components (PCs) of shape were extracted. RESULTS: Statistically significant differences between the UCLP and control groups were found for sella posterior height, midpoint height, maximum height and area, where all of these were smaller in children with UCLP. Principal component analysis revealed that the first two PCs accounted for 84.7% of total shape variance. There was a statistically significant difference in sella shape between children with UCLP and control children. CONCLUSIONS: In children with UCLP, the sella turcica is shorter and with a smaller surface area when compared to matched non-cleft children. Moreover, sella turcica shape, when disregarding size, seems to differ to that of non-cleft children.

Prevalence of bifid uvula in primary school children.

BACKGROUND: A bifid uvula is an anatomic variation that can be predictive of sub-mucous cleft palate, which may cause velopharyngeal insufficiency (VPI). Bifid uvula prevalence in the literature ranges from 0.18% to 10.3%, depending on the population studied. The aim of this study is to determine the prevalence of bifid uvula in the Geneva's school children population. METHODS: A cross-sectional study was conducted in Geneva's primary school children, from September 2014 to June 2015. An examination of the uvula was performed by dentists working for the Scholastic Dental Service, after a specific training in diagnosing bifid uvulas. The dentists recorded their findings on a standardized form. RESULTS: The total number of school children in Geneva in the school year 2014-2015 was 30,375. 23,961 children had their uvula examined, representing 79% of the total population of school children. Among them, a hundred school children had a cleft uvula. One schoolgirl had no uvula. The prevalence of bifid uvula is 0.42%. Sex ratio (M/F) is 0.96. DISCUSSION: This large study, the second in literature for number of patients examined, identified a prevalence of bifid uvula of 0.42%. This result is in agreement with previous studies.

Multiple arteriovenous malformations caused by RASA1 gene mutation presenting during pregnancy - a case report and review of the literature.

Pregnancy can influence the development and progression of congenital arteriovenous malformations (AVM) and thus lead to life-threatening complications for the mother and fetus like high output cardiac failure and premature delivery. The simultaneous presence of a capillary malformation and AVM strongly suggests a RASA1 related disorder. Keywords: Arteriovenous malformations, capillary malformation-arteriovenous malformation, capillaries/abnormalities, port-wine stain, pregnancy, RASA1 protein.

Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation Potential in vitro.

To gain more understanding of the complex molecular processes underlying cleft lip/palate (CLP), we established a unique human cell bank, consisting of keratinocytes and corresponding fibroblasts from individual CLP patients as a new study tool. After their careful characterization, we used such patient-derived cell cultures as well as control keratinocytes for in vitro differentiation and proliferation assays. Foreskin-derived control cells as a group showed significant higher induction of the late differentiation markers Loricrin and Filaggrin than the group of CLP patients-derived keratinocytes. Additionally, we detected great variations between individual CLP keratinocyte cell cultures in regard to their potential to terminally differentiate as assessed by the induction of Loricrin and Filaggrin. Primary patient cell cultures that did not properly differentiate, exhibited high proliferation rates. Moreover, we could correlate the expression levels of transcription factor IRF6 to the ability of individual cell cultures to terminally differentiate. Using clinically relevant, patient-derived cells, our results suggest that some of the genetic predispositions causing CLP might also lead to deficiencies in keratinocyte differentiation manifested in in vitro assays.

[Arteriovenous malformations and its complex management]. / Malformations artérioveineuses : prise en charge complexe.

Congenital arteriovenous malformations (AVM) represent a rare clinical entity. They are present at birth but can remain silent for many years. Due to their potential severity and their complex and specific management, the general practitioner should know when to suspect the presence of an AVM. Anatomic and hemodynamic characteristics of these malformations are well analysed by Doppler ultrasound, which is the first-line diagnostic test. MRI is often used in conjunction with ultrasound to better define the location and extension to neighbouring tissues and organs. Embolisation should be restricted to AVM associated with major functional disability, local complications or systemic cardiac complications in case of high flow volume life-threatening lesions.

Les malformations artérioveineuses (MAV) constituent des affections rares présentes dès la naissance. Il est important que le médecin généraliste puisse évoquer ce diagnostic vu la gravité potentielle de ces lésions et leur prise en charge complexe. Les caractéristiques anatomiques et hémodynamiques des MAV sont analysables en écho-Doppler, ce qui en fait l'examen de première ligne dans cette situation. L'IRM complète souvent le bilan en précisant la localisation exacte et l'extension de la MAV aux organes ou tissus adjacents. L'embolisation de la lésion par l'artère afférente ou par ponction directe au niveau de la MAV demeure exceptionnelle et doit être réservée aux MAV associées à une gêne fonctionnelle majeure, ou des complications locales ou systémiques cardiaques avec menace vitale.

[Velopharyngeal insufficiency in children]. / Insuffisance vélo-pharyngée chez l'enfant.

Velopharyngeal insufficiency (VPI) represents an incomplete closure between the soft palate and the posterior pharyngeal wall. Its etiology can be anatomical (cleft palate), neurologic, or iatrogenic (after adenoidectomy). The evaluation of a VPI begins with a through speech and language assessment and can be complemented by instrumental investigations. VPI treatment relies on its early identification, followed by a specific speech therapy management. Surgery is performed in case of no improvement with speech therapy or in case of an anatomical defect not allowing the child to improve. IVP management requires a multidisciplinary team.

L'insuffisance vélo-pharyngée (IVP) désigne un défaut d'occlusion entre le voile du palais et la paroi postérieure du pharynx. Son étiologie peut être d'ordres anatomique (fente palatine), neurologique ou iatrogène (adénoïdectomie). L'évaluation de l'IVP débute par un bilan phoniatrique et orthophonique détaillé et peut être complétée par des explorations instrumentales. Son traitement repose sur une identification précoce puis une prise en charge et un suivi orthophonique spécifiques. Une chirurgie est réalisée en cas d'absence d'amélioration ou de défaut anatomique ne permettant pas à l'enfant de progresser. L'IVP est une pathologie intéressant plus particulièrement l'enfant et sa prise en charge se fait par une équipe multidisciplinaire.

Skin-Sparing Débridement for Necrotizing Fasciitis in Children.

BACKGROUND: Necrotizing fasciitis is a serious soft-tissue infection associated with sepsis and tissue destruction. Surgical management usually requires extensive débridement of necrotic fascia and overlying skin, with significant aesthetic and functional consequences. The authors review the outcome of all recent cases of necrotizing fasciitis treated with skin-sparing débridement at their institution. METHODS: The authors conducted a retrospective review of all of their cases of necrotizing fasciitis treated with skin-sparing débridement. Medical records were evaluated with a standard form gathering relevant demographic and clinical data. All cases were confirmed as necrotizing fasciitis histologically. RESULTS: Ten patients were admitted with a diagnosis of necrotizing fasciitis. The median age of the patients was 4.9 years (range, 1.7 to 15.1 years). The majority of initial lesions were caused by chickenpox, mostly on the trunk. Interval from admission to surgery was 6 hours (range, 1 to 27.5 hours), with a median hospital stay of 11 days (range, 5 to 43 days). Median fasciectomy was 2.5 percent (range, 1 to 15 percent) of total body surface area, with a median skin excision of 0.25 percent of total body surface area (range, 0.1 to 3 percent). All patients received intravenous amoxicillin/clavulanic acid plus clindamycin. Delayed direct closure was possible for all patients. Median follow-up was 17 months (range, 3 to 79 months). There was no death in this series. CONCLUSION: This surgical management restricts skin excision to the area of definite skin necrosis, limiting skin excision to one-tenth of excised fascia, with long-term favorable cosmetic and functional results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Diagnostic performance of S100B protein serum measurement in detecting intracranial injury in children with mild head trauma.

OBJECTIVE: To assess the accuracy of S100B serum level to detect intracranial injury in children with mild traumatic brain injury. METHODS: A multicenter prospective cohort study was carried out in the paediatric emergency departments of three tertiary hospitals in Switzerland between January 2009 and December 2011. Participants included children aged <16 years with a mild traumatic brain injury (GCS ≥13) for whom a head CT was requested by the attending physician. Venous blood was obtained within 6 h of the trauma in all children for S100B measurement before a head CT was performed. As the S100B value was not available during the acute care period, the patient's management was not altered. The main measures were protein S100B value and the CT result. RESULTS: 20/73 (27.4%) included children had an intracranial injury detected on CT. S100B receiver operating characteristics area under the curve was 0.73 (95% CI 0.60 to 0.86). With a 0.14 µg/L cut-off point, S100B reached an excellent sensitivity of 95% (95% CI 77% to 100%) and 100% (95% CI 81% to 100%) in all children and in children aged >2 years, respectively. The specificity, however, was 34% (95% CI 27% to 36%) and 37% (95% CI 30% to 37%), respectively. CONCLUSIONS: S100B has an excellent sensitivity but poor specificity. It is therefore an accurate tool to help rule out an intracranial injury but cannot be used as the sole marker owing to its specificity. Used with clinical decision rules, S100B may help to reduce the number of unnecessary CT scans.

The Seatbelt Syndrome-Do We Have a Chance?: A Report of 3 Cases With Review of Literature.

The seatbelt syndrome represents an injury pattern seen after motor vehicle accidents. It is secondary to either the misplacement of seatbelts over the abdomen or the misuse of the restraint systems. This syndrome is infrequent in the pediatric population and occurs mostly in school-aged children because recommended lap-shoulder belts and booster seats are often not used in this age group, so that the seatbelt lies over the abdomen. Sudden deceleration bends the child around the lap belt causing injuries to the viscera, head, and spine (Chance fracture), often associated with paraplegia. Because not all patients have an abdominal seatbelt sign, this syndrome can easily not be recognized with potentially life-threatening consequences.We report on 3 patients with the seatbelt syndrome and review the literature regarding prevalence, diagnosis, treatment, and prognosis of the different injuries and discuss the diagnostic challenges of intestinal lesions and their management.Following this accident pattern, in hemodynamically stable patients with a normal abdominal computed tomography scan, close surveillance is warranted to rule out intestinal lesions manifesting with progressive peritoneal irritation. In hemodynamically unstable patients, or if there is evidence of free air on the computed tomography scan, emergency abdominal exploration is required.

Staphylococcus lugdunensis abscesses complicating molluscum contagiosum in two children.

We report the occurrence of Staphylococcus lugdunensis abscesses in two girls with molluscum contagiosum who both required surgical intervention under general anaesthesia. S. lugdunensis is a coagulase-negative Staphylococcus recently recognized as an emerging human pathogen. Because of its ubiquitous nature and the high prevalence of molluscum contagiosum in children, it is likely that this as yet unreported association may be underestimated, thus raising the question as to whether bacterial culture of superinfected mollusca should be obtained more often.