Orbital exenteration reconstruction using a superficial temporalis muscle flap: The "Carpaccio flap", an innovative approach.

INTRODUCTION: Malignant orbital diseases may lead surgeons to practice an orbital exenteration associated with chemotherapy and/or radiotherapy to ensure curative treatment. That radical procedure makes physicians consider reconstructive filling in order to allow prothesis wearing and reduce esthetic and social after-effects. We first describe the clinical case of a 6-year-old patient who presented an orbital rhabdomyosarcoma and underwent an orbital exenteration with immediate reconstruction by a superficial temporal pedicled on the middle temporalis muscle flap. TECHNICAL NOTE: Through that case-report, we propose an original temporal flap to repair ipsilateral midface defects which may reduce donor site side effects and allow furthers corrections. DISCUSSION: In pediatrics cases, our Carpaccio flap was an available regional tool to rehabilitate an irradiated orbital socket with an appropriate bulking and vascularization effect after subtotal exenteration. Furthermore, we prescribe that flap as a posterior orbital filling, when eyelid and conjunctiva are spared, to prepare orbital prosthesis implementation. A mild sunken temporal fossa appears with our procedure but by preserving the deep layer of the temporalis muscle, autologous reconstruction such as lipofilling are permitted in post-radiotherapy condition to enhance esthetic sequelae.

GLUT2 expression by glial fibrillary acidic protein-positive tanycytes is required for promoting feeding-response to fasting.

Feeding behavior is a complex process that depends on the ability of the brain to integrate hormonal and nutritional signals, such as glucose. One glucosensing mechanism relies on the glucose transporter 2 (GLUT2) in the hypothalamus, especially in radial glia-like cells called tanycytes. Here, we analyzed whether a GLUT2-dependent glucosensing mechanism is required for the normal regulation of feeding behavior in GFAP-positive tanycytes. Genetic inactivation of Glut2 in GFAP-expressing tanycytes was performed using Cre/Lox technology. The efficiency of GFAP-tanycyte targeting was analyzed in the anteroposterior and dorsoventral axes by evaluating GFP fluorescence. Feeding behavior, hormonal levels, neuronal activity using c-Fos, and neuropeptide expression were also analyzed in the fasting-to-refeeding transition. In basal conditions, Glut2-inactivated mice had normal food intake and meal patterns. Implementation of a preceeding fasting period led to decreased total food intake and a delay in meal initiation during refeeding. Additionally, Glut2 inactivation increased the number of c-Fos-positive cells in the ventromedial nucleus in response to fasting and a deregulation of Pomc expression in the fasting-to-refeeding transition. Thus, a GLUT2-dependent glucose-sensing mechanism in GFAP-tanycytes is required to control food consumption and promote meal initiation after a fasting period.

Impact of radiotherapy schedule on survival of patients treated with immune-checkpoint inhibitors for advanced melanoma and non-small cell lung cancer.

PURPOSE: Preclinical and clinical data suggest a potential benefit in the addition of radiotherapy (RT) to immune-checkpoint inhibitors (ICI) during the treatment of advanced cancers. Nevertheless, the ideal patients for this approach and the optimal RT regimen is still debated. MATERIAL AND METHODS: The aim of this study was to determine the effect RT schedule has on survival for advanced non-small cell lung cancer and melanoma patients (pts) treated with ICI (anti-PD1 or anti-CTLA4) and concomitant RT. RESULTS: A total of 58 pts were identified, of which 26 received RT concomitantly with ICI while the remaining 32 pts were treated with RT at the time of progression under ICI. The RT parameters associated with outcome include dose per fraction, biological effective dose, RT to all targets and lung irradiation. Independent predictors of improved progression-free survival were lung irradiation, melanoma histology, oligometastatic status (<6 metastasis), presence of liver metastasis, PNN<7000/mm3 and normal LDH. Independent predictors of improved overall survival were melanoma histology and normal LDH. Among pts who were irradiated at progression, 68.7% had an overall clinical benefit and had a median extension of ICI use by 2.3 months (range: 0-29.1), among which 2 presented with an abscopal effect. CONCLUSIONS: The irradiation of lung metastases may increase survival in patients under ICI. RT at progression could prolong the use of ICI, and neutrophilia and LDH should be considered during patient selection of this combined RT/ICI approach.

[EASYSCAN: French pilot study for securing drug administration by barcode reading]. / EASYSCAN : étude pilote française pour la sécurisation de l'administration des médicaments par lecture code-barres.

OBJECTIVES: Medication errors are common at the time of administration. To prevent them, technologies allowing consistency check by bar code technology at bedside have been developed. Our study focuses on the evaluation of a BarCode Medication Administration (BCMA) called EASYSCAN with Electronic Medication Administration Record (e-MAR) to verify both patient's identity and medication to be administrated. METHODS: A prospective observational study was conducted during seven weeks in a French medicine ward. The performance of the system was evaluated by the success rate of BCMA and by the average time for administration with and without EASYSCAN. A satisfaction questionnaire about BCMA was proposed to nurses. RESULTS: We observed 182 administrations including 87 (48%) with EASYSCAN. The verification of the patient's identity was successful in 77% of administrations and 65% of the drugs were scanned successfully. The main causes of check failures were the lack of datamatrix on the drug (81%), error messages (14%) and the lack of system functionality (5%). The average time for administration per patient was significantly increased: 4.68min/patient with versus 2.87min/patient without EASYSCAN. CONCLUSIONS: The study shows the EASYSCAN's performance in its first version. Material and software evolutions and an increase of nurses'pratices will be necessary to continue the experimentation of this system still unpublished in France.

[Suicidality in the perinatal period: Descriptive study on factors associated with suicidal ideation among women hospitalized in the perinatal period at the specialized hospital center]. / Suicidalité en période périnatale : quels sont les facteurs associés ?

OBJECTIVES: Suicide is the leading cause of maternal mortality in high-resource countries. The onset of suicidal ideation is a major risk factor for suicide attempts. Suicidality has a major impact on the mother-baby relationship and on child development. The main objective of the study was to identify factors associated with the occurrence of perinatal suicidal ideation in women requiring hospitalization. The secondary objectives of the study were to describe the socio-demographic and clinical characteristics of this specific population, to specify the follow-up procedures at hospital discharge and to develop a semi-directed interview framework for psychiatric evaluation of perinatal patients admitted to a psychiatric hospital in order to better identify those at risk of suicide and improve overall management, particularly in terms of referral to existing perinatal care services. METHODS: Descriptive and retrospective study carried out at the Specialized Hospital Center of women hospitalized in the perinatal period between 2014 and 2019. The inclusion criteria were: inpatient pregnant or postpartum within one year of delivery, 16 to 43 years. A keyword search was performed to retrieve the computerized records. All records matching the inclusion criteria were included. We studied the occurrence of suicidal ideation according to the main known clinical and socio-demographic risk factors. RESULTS: The sample included 25 pregnant patients and 57 post-partum patients. The presence of a psychiatric history increased the risk of suicidal ideation by 4.38 (P<0.03). The association between the occurrence of a stressful life event and the risk of suicidal ideation onset was close to significant (P<0.10). One third of the patients had been admitted for a reason related to suicidality. Less than one-third of the patients had been referred to existing perinatal services. CONCLUSIONS: Suicidality in the perinatal period has a major impact on the dyad as well as on the whole family. The search for suicidal ideas must be systematic during psychiatric interviews, a fortiori when a psychiatric history has been authenticated. Every patient hospitalized in adult psychiatry should be referred to specialized outpatient perinatal psychiatry services. Prevention involves raising awareness and training of all health professionals, networking, but also informing the general public.

Cleft palate lateral synechia syndrome in two patients and literature review.

Cleft palate lateral synechia (CPLS) syndrome is an extremely rare congenital malformation syndrome of unknown origin, characterized by the association of cleft palate and one or more intraoral lateral synechiae (OMIM # 119550). Fewer than 20 cases have been described to date. The clinical and histological findings and results of genetic investigations for two additional cases of CPLS are presented herein, in order to better delineate this syndrome, within the context of the relevant literature. The first case presented with a U-shaped cleft palate, bilateral synechiae, and Pierre Robin sequence, requiring early sectioning of the synechiae because of severe feeding problems. The second case presented with a V-shaped cleft palate and a single synechia, running from the left border of the cleft to the floor of the mouth, and was without feeding difficulties. In both cases, histopathological examination of the synechiae revealed an aspect of mucous membranes macroscopically, while staining of sections indicated lymphocyte infiltrates and parakeratosis with stratified squamous epithelium, associated with vessel and connective tissue abnormalities. Sequencing of candidate genes did not identify a genetic cause. Accurate clinical descriptions, histopathological diagnosis, and genetic investigations of patients with synechiae are lacking in the literature. Better characterization of future cases of CPLS will give new insights into its developmental causes.

[Rhinopoiesis after traumatic total amputation in childhood in an 11-year-old child]. / Rhinopoïese après amputation traumatique totale dans l'enfance chez un enfant de 11 ans.

Fortunately, traumatic total amputations of the nose are rare, especially in children. Their reconstructions generally require several operative steps, most often associating cartilaginous grafts (rib and/or concha), a free radial antebrachial flap for mucosal reconstruction and a frontal flap for the skin covering. These are therefore long and complex procedures requiring a trained surgical team and maximum patient adherence to their treatment plan. The clinical case described is that of an 11-year-old child presenting a sub-total amputation of the nose and having undergone reconstruction with skin expansion of the frontal flap due to a horizontal frontal scar of unknown origin and a particularly low hair implantation.

Protuberant fibro-osseous lesion of the temporal bone: report of four cases and review of the literature.

'Bullough lesions', also referred to as protuberant fibro-osseous lesions (PFOL), are rare temporal bone lesions initially described in 1999. Since only 12 cases have been reported, several key issues, such as their origin and recommended management strategies, remain unresolved. This article reports the largest cohort included in the literature to date, comprising four patients with PFOL. PFOL appears to be characterized by female and right-side predominance. These lesions were consistently located regarding the mastoid, generally diagnosed in early adulthood, without functional symptoms, and were always fibro-osseous. Invasive/malignant features were not found on imaging or histology. The main differential diagnosis was malignant low-grade parosteal osteosarcoma. Clinical examination and computed tomography images provided strong elements supporting the diagnosis of PFOL. Biopsy allowed molecular biology investigations (MDM2 and CDK4 amplification), in order to rule out low-grade parosteal osteosarcoma.

Dynamic orthognathic surgical procedure (DOSP) in asymmetric maxillomandibular dysmorphism secondary to unilateral micrognathia: Outcomes of 12 consecutive cases.

This study aimed to evaluate the outcomes following a dynamic orthognathic surgical procedure performed at the end of growth to treat asymmetric maxillomandibular deformities linked to unilateral micrognathia when conventional orthognathic surgery was not feasible. The dynamic orthognathic surgical procedure (DOSP) combined concomitant mandibular distraction osteogenesis with contralateral poorly stabilized sagittal split osteotomy and Le Fort I osteotomy. Cephalometric studies were retrospectively conducted on pre- and postoperative lateral and frontal cephalographs, and maxillomandibular movements were calculated. Outcome scores were computed by both experts and laypersons based on photographic analyses. There was a significant postoperative increase in height of the micrognathic ramus in all patients (n = 12; p = 0.002). The angle between the occlusal cant and horizontal reference plane decreased significantly in all of the patients, as did the angle between the midline sagittal plane and mandibular tilt (p < 0.001). Postoperative outcome scores showed significant improvements in all cases, according to both expert and layperson groups. This procedure allows correction of maxillomandibular asymmetries linked to micrognathia. However, it cannot resolve all the factors participating in facial asymmetry, such as those originating in the oculo-auriculo-ventricular spectrum or complex tumor sequelae, and second-step procedures may be required.

Speech outcome after intravelar veloplasty.

OBJECTIVE: Cleft lip and palate is the main craniofacial malformation in France. Many surgical techniques had been described to restore cleft palate. In this study, we evaluate phonation in a homogeneous series of patient with isolated unilateral non-syndromic cleft lip and palate before (and after) alveolar cleft closure, operated according to our surgical protocol. METHODS: We included retrospectively 71 patients with isolated non-syndromic unilateral cleft lip and palate (UCLP), operated in our department from 2009 to 2013. All patients underwent the same surgical protocol: modified Millard cheilorhinoplasty (from 5 to 9-month-old); direct hard palatal closure (from 12 to 20-month-old); alveolar cleft closure with cancellous iliac bone graft (from 4 to 6-year-old). The phonation and clinical statute were evaluated before and after alveolar cleft closure. Fistula rate and speech evaluation were recorded. RESULTS: The rate of oronasal fistula was 12.7%. About phonation, 76% and 86% of patients were competent or borderline competent respectively before and after gingivoperiostoplasty. CONCLUSION: This surgical protocol provided speech results in patients with isolated unilateral non-syndromic cleft lip and palate. The gingivoperiostoplasty improved the speech intelligibility.

Early mandibular morphological differences in patients with FGFR2 and FGFR3-related syndromic craniosynostoses: A 3D comparative study.

Syndromic craniosynostoses are defined by the premature fusion of one or more cranial and facial sutures, leading to skull vault deformation, and midfacial retrusion. More recently, mandibular shape modifications have been described in FGFR-related craniosynostoses, which represent almost 75% of the syndromic craniosynostoses. Here, further characterisation of the mandibular phenotype in FGFR-related craniosynostoses is provided in order to confirm mandibular shape modifications, as this could contribute to a better understanding of the involvement of the FGFR pathway in craniofacial development. The aim of our study was to analyse early mandibular morphology in a cohort of patients with FGFR2- (Crouzon and Apert) and FGFR3- (Muenke and Crouzonodermoskeletal) related syndromic craniosynostoses. We used a comparative geometric morphometric approach based on 3D imaging. Thirty-one anatomical landmarks and eleven curves with sliding semi-landmarks were defined to model the shape of the mandible. In total, 40 patients (12 with Crouzon, 12 with Apert, 12 with Muenke and 4 with Crouzonodermoskeletal syndromes) and 40 age and sex-matched controls were included (mean age: 13.7 months ±11.9). Mandibular shape differed significantly between controls and each patient group based on geometric morphometrics. Mandibular shape in FGFR2-craniosynostoses was characterized by open gonial angle, short ramus height, and high and prominent symphysis. Short ramus height appeared more pronounced in Apert than in Crouzon syndrome. Additionally, narrow inter-condylar and inter-gonial distances were observed in Crouzon syndrome. Mandibular shape in FGFR3-craniosynostoses was characterized by high and prominent symphysis and narrow inter-gonial distance. In addition, narrow condylar processes affected patients with Crouzonodermoskeletal syndrome. Statistical analysis of variance showed significant clustering of Apert and Crouzon, Crouzon and Muenke, and Apert and Muenke patients (p < 0.05). Our results confirm distinct mandibular shapes at early ages in FGFR2- (Crouzon and Apert syndromes) and FGFR3-related syndromic craniosynostoses (Muenke and Crouzonodermoskeletal syndromes) and reinforce the hypothesis of genotype-phenotype correspondence concerning mandibular morphology.

Sagittal split ramus osteotomy-related biomechanical properties.

Sagittal split ramus osteotomy (SSRO) is one of the most common maxillofacial operations, and the technique relies on a directed fracture involving different biomechanical variables. The aim of this study was to find out the biomechanical characteristics involved during each step of sagittal split osteotomy. We sampled eight fully dentate human mandibles and used the right side for hardness tests and the left side for a traction-to-fracture test within an unfinished SSRO. Right sides were sampled in five parts underlying the corticotomy course and tested with a hardness testing automatic machine. The mean hardness measures ranked to 21.5HV (Hardness Vickers Unit): 17.8HV; 27.4HV; 22.7HV; 28.7HV; for the lingual, diagonal, vestibular, full ramus, and full body samples, respectively. Left sides were cut using Epker's technique, and split with an electromechanical testing machine. The higher values reached before fracture in the traction-to-fracture tests ranked to 99.1N/6.7mm; 137.2N/10.8mm; 36.2N/4.2mm; 93.0N/7.3mm; 74.0N/8.1mm; 78.1N/4.5mm; 90.9N/10.6mm; and 64.7N/4.1mm, respectively, for specimens I, II, III, IV, V, VI, VII and VIII. This study provides to our knowledge the first biomechanical characteristics of SSRO and proposes a reproducible method for evaluation.

Virtual versus traditional classroom on facial traumatology learning: Evaluation of medical student's knowledge acquisition and satisfaction.

INTRODUCTION: The high rate of absenteeism in the courses led us to offer virtual classrooms to better meet the expectations of students who may have geographical constraints. The objectives of this study were: to compare student's knowledge acquisition and satisfaction between virtual and traditional face-to-face classroom and to determine potential factors that may correlate with the level of knowledge acquisition following both type of courses. METHODS: Our study included fifth-year medical students attending the course of facial traumatology, who voluntarily participated either in virtual or traditional classroom. Students' knowledge acquisition was evaluated through a multiple-choice questions test. A second questionnaire aimed to determine factors potentially correlated with students' knowledge acquisition and to evaluate their satisfaction. Results of questionnaire no 1 were compared between virtual and traditional classroom. Additionally, a correlation study was performed between the results of questionnaire no 1 and the factors listed in questionnaire no 2. RESULTS: One hundred thirty-six students participated to the course (virtual: 64, traditional: 72). Knowledge acquisition and concentration level didn't significantly differ between the two groups. Knowledge acquisition was positively correlated with the intensity of study of the course topic prior to the class only in traditional classroom (P<10-2). The main listed advantage of the virtual classroom was its flexibility particularly for students with geographical constraints (15/28). CONCLUSION: Considering there is no noticeable difference in knowledge acquisition between virtual and traditional classroom, we will continue virtual classroom in parallel with traditional classroom and extend it to the other courses of our field.

Maxillary shape at the end of puberty in operated unilateral cleft lip and palate: A geometric morphometric assessment using computer tomography.

INTRODUCTION: Cleft lip and palate (CLP) surgery interferes with maxillary growth and contributes to transversal and sagittal growth impairment. Our retrospective descriptive study aimed to evaluate maxillary bone shape in a homogenous unilateral CLP patient group using geometric morphometrics based on CT-scan data. MATERIAL AND METHODS: We included all patients with available CT-scans at the end of pubertal growth and operated on at Smile House of Milan, according to the standard protocol, involving two surgical steps: (1) primary closure of the lip and soft palate at 6 months of age and (2) early secondary gingivoalveoloplasty (GAP) associated with hard palate repair at 18-36 months. Shape differences between CLP and an age-matched control group were characterized using geometric morphometrics based on 15 3D landmarks. RESULTS: We included 16 unilateral CLP patients and 20 age-matched controls. Principal component and canonical variate analyses showed that the maxillary shape in CLP was significantly different from controls but that this difference was limited. Linear and angular measurements confirmed these differences. CONCLUSION: Early secondary GAP results in satisfactory maxillary shape, with significant but limited differences relative to controls.

Association of combined PD-L1 expression and tumour-infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma.

BACKGROUND: Recent advances obtained with immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) protein have significantly improved the outcome of patients with metastatic melanoma. The PD-L1 expression in tumour cells as detected by immunohistochemistry is a predictive biomarker in some solid tumours, but appears insufficient as prognostic or predictive factor of response to ICIs in metastatic melanomas. OBJECTIVES: We investigated whether the presence and the features of pretreatment CD8+ tumour-infiltrating T lymphocytes (TILs) could be a complementary prognostic or predictive biomarker in patients with metastatic melanoma. METHODS: In this retrospective study, we evaluated the association of PD-L1 expression ≥5% of tumour cells combined with TIL features (CD8, CD28, Ki67) with the overall survival (OS) among 51 patients treated with ICIs and 54 patients treated with other treatment options (non-ICIs). RESULTS: PD-L1 positivity was observed in 33% and 39% of primary melanomas and matched metastases, respectively, with, however, poor concordance between the primary and the matched metastatic site (κ = 0.283). No significant association was noted between PD-L1 expression and CD8+ TIL profile analysed as single markers and OS or response to immunotherapy. Instead, their combined analysis in primary melanoma samples showed that the PD-L1-/CD8+ status was significantly associated with prolonged OS in the whole population (P = 0.04) and in the subgroup treated with non-ICIs (P = 0.009). Conversely, the PD-L1+/CD8+ status was a good prognostic factor in patients treated with ICIs (P = 0.022), whereas was significantly associated with poor prognosis in patients treated with non-ICIs (P = 0.014). While the expression of CD28 was not related to outcome, the Ki67 expression was significantly associated with poor OS in the subgroup CD8+ TIL+/PD-L1- (P = 0.02). CONCLUSIONS: The pretreatment combination of PD-L1 expression with the level of CD8+ TILs could better assess OS and predict therapeutic response of patients with metastatic melanoma treated by either immunotherapy or other treatment regimens.

The use of three-dimensional reconstructions of CT scans to evaluate anomalies of hyoid bone in Pierre Robin sequence: A retrospective study.

AIM: The aim of the study was to investigate hyoid bone anomalies in patients with Pierre Robin sequence (PRS) compared to the control group, using computed tomography (CT) examination and three-dimensional reconstruction of the hyoid bone and mandible. METHODS: A retrospective study was performed of patients between birth and 12 months old with isolated PRS (i-PRS) and syndromic PRS (ni-PRS), who had undergone CT examination, and whose results were compared to the control group of the same age. DICOM data was processed to highlight bone tissue. The mandible and hyoid bones were the main targets of the three-dimensional reconstruction. The study outcomes were the analysis of hyoid bone ossification, volume, and position (distance between hyoid and mandibular symphysis). Univariate and multivariate statistical analyses were performed with α=0.05 as level of significance. RESULTS: The study sample included 29 i-PRS and 21 ni-PRS patients, while 43 infants in the control group. Hyoid ossification was present in 26/50 (52%) PRS patients (14 i-PRS; 12 ni-PRS) but in 31/43 controls (72%). Statistical analysis showed that absence of hyoid ossification was significantly associated with the diagnosis of PRS (P<0.05). Only ni-PRS patients showed a significant reduction of the distance between hyoid and mandible compared to the control group (P<0.001). Hyoid volume was significantly lower only in the ni-PRS group than in controls (P<0.001). CONCLUSION: I-PRS and ni-PRS patients differ both etiologically and clinically. Ni-PRS patients confirmed their worst clinical condition than i-PRS with severe anomalies of hyoid development, helping for their ontogeny classification.

[Secondary surgeries in craniosynostosis and faciocraniosynostosis]. / Chirurgie secondaire des craniosténoses et faciocraniosténoses.

Secondary surgeries for single craniosynostosis surgeries are mainly esthetic refinements rather than functional indications. However, cranioplasties for bone defects correction or insufficient corrections may be undertaken. Management of syndromic craniosynostoses usually requires multiple surgical interventions, the sequence of which might vary per the genetic mutation. It is commonplace to start with posterior vault expansion before age 6 months, then treat cerebellar tonsillar herniation by the age of twelve months, and delay fronto-facial monobloc advancement until at least 18-24 months of age. Ventricular shunting is preferably avoided or delayed. Failure to respect these guidelines can significantly complicate the subsequent management. Primary fronto-orbital advancement or early facial osteotomy type Le Fort3, may compromise the subsequent fronto-facial monobloc advancement. However, this salvage secondary monobloc may be undertaken in some instances despite previous anterior osteotomies with a higher morbidity.

[Secondary nasal surgery with cleft palates]. / Les rhinoseptoplasties secondaires des fentes labiopalatines.

Residual nasal deformity in patients with cleft palate remains the main demand of these patients. Performing primary nasal surgery has significantly improved the results. However, it is still often necessary to improve the nasal morphology. Respect of tissues during primary surgery is essential and allows easier secondary corrections. Anatomical reconstruction greatly facilitates the treatment of secondary deformities. Do not hesitate in case of major labionasales sequelae, to make revision, according to the rules of primary surgery, of the entire lip and nose.

Shoe microclimate: An objective characterisation and subjective evaluation.

Shoe microclimate (temperature and humidity) has been suggested to contribute to perceptions of foot thermal comfort. However, limited data is available for perceptual responses in relation to shoe microclimate development both over time and within different areas of the shoe. This study evaluates perceptions of foot thermal comfort for two running shoes different in terms of air permeability in relation to temporal and spatial characteristics of shoe microclimate. The temporal characteristics of shoe microclimate development were similar for both shoes assessed. However, higher temperatures and humidity were observed for the less permeable shoe. Changes to shoe microclimate over time and differences between shoes were perceivable by the users. This study provides the most detailed assessment of shoe microclimate in relation to foot thermal comfort to date, providing relevant information for footwear design and evaluation.