Artificial intelligence-based diagnosis in fetal pathology using external ear shapes.

OBJECTIVE: Here we trained an automatic phenotype assessment tool to recognize syndromic ears in two syndromes in fetuses-=CHARGE and Mandibulo-Facial Dysostosis Guion Almeida type (MFDGA)-versus controls. METHOD: We trained an automatic model on all profile pictures of children diagnosed with genetically confirmed MFDGA and CHARGE syndromes, and a cohort of control patients, collected from 1981 to 2023 in Necker Hospital (Paris) with a visible external ear. The model consisted in extracting landmarks from photographs of external ears, in applying geometric morphometry methods, and in a classification step using machine learning. The approach was then tested on photographs of two groups of fetuses: controls and fetuses with CHARGE and MFDGA syndromes. RESULTS: The training set contained a total of 1489 ear photographs from 526 children. The validation set contained a total of 51 ear photographs from 51 fetuses. The overall accuracy was 72.6% (58.3%-84.1%, p < 0.001), and 76.4%, 74.9%, and 86.2% respectively for CHARGE, control and MFDGA fetuses. The area under the curves were 86.8%, 87.5%, and 90.3% respectively for CHARGE, controls, and MFDGA fetuses. CONCLUSION: We report the first automatic fetal ear phenotyping model, with satisfactory classification performances. Further validations are required before using this approach as a diagnostic tool.

An automatic facial landmarking for children with rare diseases.

Two to three thousand syndromes modify facial features: their screening requires the eye of an expert in dysmorphology. A widely used tool in shape characterization is geometric morphometrics based on landmarks, which are precise and reproducible anatomical points. Landmark positioning is user dependent and time consuming. Many automatic landmarking tools are currently available but do not work for children, because they have mainly been trained using photographic databases of healthy adults. Here, we developed a method for building an automatic landmarking pipeline for frontal and lateral facial photographs as well as photographs of external ears. We evaluated the algorithm on patients diagnosed with Treacher Collins (TC) syndrome as it is the most frequent mandibulofacial dysostosis in humans and is clinically recognizable although highly variable in severity. We extracted photographs from the photographic database of the maxillofacial surgery and plastic surgery department of Hôpital Necker-Enfants Malades in Paris, France with the diagnosis of TC syndrome. The control group was built from children admitted for craniofacial trauma or skin lesions. After testing two methods of object detection by bounding boxes, a Haar Cascade-based tool and a Faster Region-based Convolutional Neural Network (Faster R-CNN)-based tool, we evaluated three different automatic annotation algorithms: the patch-based active appearance model (AAM), the holistic AAM, and the constrained local model (CLM). The final error corresponding to the distance between the points placed by automatic annotation and those placed by manual annotation was reported. We included, respectively, 1664, 2044, and 1375 manually annotated frontal, profile, and ear photographs. Object recognition was optimized with the Faster R-CNN-based detector. The best annotation model was the patch-based AAM (p < 0.001 for frontal faces, p = 0.082 for profile faces and p < 0.001 for ears). This automatic annotation model resulted in the same classification performance as manually annotated data. Pretraining on public photographs did not improve the performance of the model. We defined a pipeline to create automatic annotation models adapted to faces with congenital anomalies, an essential prerequisite for research in dysmorphology.

Orbital shape in intentional skull deformations and adult sagittal craniosynostoses.

Intentional cranial deformations are the result of external mechanical forces exerted on the skull vault that modify the morphology of various craniofacial structures such as the skull base, the orbits and the zygoma. In this controlled study, we investigated the 3D shape of the orbital inner mould and the orbital volume in various types of intentional deformations and in adult non-operated scaphocephaly - the most common type of craniosynostosis - using dedicated morphometric methods. CT scans were performed on 32 adult skulls with intentional deformations, 21 adult skull with scaphocephaly and 17 non-deformed adult skulls from the collections of the Muséum national d'Histoire naturelle in Paris, France. The intentional deformations group included six skulls with Toulouse deformations, eight skulls with circumferential deformations and 18 skulls with antero-posterior deformations. Mean shape models were generated based on a semi-automatic segmentation technique. Orbits were then aligned and compared qualitatively and quantitatively using colour-coded distance maps and by computing the mean absolute distance, the Hausdorff distance, and the Dice similarity coefficient. Orbital symmetry was assessed after mirroring, superimposition and Dice similarity coefficient computation. We showed that orbital shapes were significantly and symmetrically modified in intentional deformations and scaphocephaly compared with non-deformed control skulls. Antero-posterior and circumferential deformations demonstrated a similar and severe orbital deformation pattern resulting in significant smaller orbital volumes. Scaphocephaly and Toulouse deformations had similar deformation patterns but had no effect on orbital volumes. This study showed that intentional deformations and scaphocephaly significantly interact with orbital growth. Our approach was nevertheless not sufficient to identify specific modifications caused by the different types of skull deformations or by scaphocephaly.

Description of the Pedicled Osteo-Muscular Flap of Split Temporal Muscle.

Background: Reconstruction of the head and neck is dominated by free flaps, and for bone reconstruction by fibula and scapula flaps. However, this choice is sometimes difficult to make in patients who cannot tolerate an extensive and lengthy surgical procedure. In addition, vascular micro-anastomoses are sometimes complicated in patients who have been previously irradiated. Pedicle flaps remain an option and can sometimes be considered as first choice for head and neck reconstruction. Purpose: In this study, we describe the feasibility of a split temporal muscle pedicled flap with coronal harvesting for a reconstruction that can reach the midline. Study design sample covariates: Ten fresh-frozen human cadaver heads were dissected, and the length of the split flap was noted, followed by the length of the non-split flap. Results: The mean length was 155.7 mm (± 20.0) for the split flap, from the point of rotation to the tip of the coronoid process. These results coincide with the tragus-midline distance, which makes it possible to consider reconstruction of the midline, especially the maxilla and the mandible, which has not yet been described in the literature. Conclusions and relevance: This technique would then allow a supply of pedicled vascularized bone for loco-regional reconstruction.

Humanitarian Facial Recognition for Rare Craniofacial Malformations.

Children with congenital disorders are unfortunate collateral victims of wars and natural disasters. Improved diagnosis could help organize targeted medical support campaigns. Patient identification is a key issue in the management of life-threatening conditions in extreme situations, such as in oncology or for diabetes, and can be challenging when diagnosis requires biological or radiological investigations. Dysmorphology is a central element of diagnosis for craniofacial malformations, with high sensibility and specificity. Massive amounts of public data, including facial pictures circulate daily on news channels and social media, offering unique possibilities for automatic diagnosis based on facial recognition. Furthermore, AI-based algorithms assessing facial features are currently being developed to decrease diagnostic delays. Here, as a case study, we used a facial recognition algorithm trained on a large photographic database to assess an online picture of a family of refugees. Our aim was to evaluate the relevance of using an academic tool on a journalistic picture and discuss its potential application to large-scale screening in humanitarian perspectives. This group picture featured one child with signs of Apert syndrome, a rare condition with risks of severe complications in cases of delayed management. We report the successful automatic screening of Apert syndrome on this low-resolution picture, suggesting that AI-based facial recognition could be used on public data in crisis conditions to localize at-risk patients.

Distractor position and distraction amplitude in fronto-facial monobloc advancement : A case series.

Fronto-facial monobloc advancement with internal distraction (FFMBA) is a central procedure in the management of faciocraniosynostoses. In techniques with internal distraction, two sets of devices are generally positioned: bilateral fronto-orbital and temporo-zygomatic distractors, using a temporal tongue and groove osteotomy design. It is believed that distractors must be positioned as parallel as possible in the horizontal and sagittal planes to avoid mechanical conflicts between the sliding bone fragments of the tongue and groove during distraction, and thus optimize the advancement amplitude. Several approaches involving surgical planification and guides for distractor positioning have thus been proposed to monitor distractor placement. To explore the need for surgical planification in distractor placement, the parallelism of the position of the 4 distractors was assessed in 19 FFMBA procedures and we correlated a set of 10 distractor angles with the degree of advancement. We report that the horizontal cut of the tongue and groove can be used as a landmark for the positioning of the lower, temporo-zygomatic, distractor in fronto-facial monobloc advancement. Other parameters (relative position of the two homolateral and the two contralateral distractors and the orientations of the vertical and horizontal cuts of the tongue and groove) do not interfere with distraction, other things being equal. Our results indicate that distractor orientation is not a critical issue in fronto-facial monobloc advancement when devices are positioned as parallel as possible based on visual monitoring.

Genetic determinism and hemispheric influence in hair whorl formation.

BACKGROUND: The mechanisms determining the laterality and the rotation direction of hair whorls are unknown. Here we report observations on twins investigating the genetic bases of whorl pattern formation. Knowing that vortex phenomena may depend on geographic effects, we also provide comparative data on whorls from children born in the Northern hemisphere (France) versus children born in the Southern hemisphere (Chile). MATERIAL AND METHODS: We retrospectively included children from three populations: (1) Northern hemisphere general population, (2) Southern hemisphere general population, and (3) same-sex Northern hemisphere twins. We recorded whorl rotation direction (clockwise, counterclockwise), whorl position (left, right, central) and twinning type. Univariate logistic models were used to screen for associations between rotation direction and whorl position. For twins, the variable of interest was binary, i.e. same rotation direction (reference class) or opposite directions for each twin pair. For controls, all single combinations were included as virtual twins, and compared to real twins. Odds ratios (OR) were compared for both hemispheres, for real twins and virtual (control) twins. RESULTS: Seventy-four (37 pairs) twins and 50 children from the general population of each hemisphere were included. The OR for opposite rotation directions between two twins was ≠1 (p = 0.017), meaning that whorls rotated preferentially in the same direction in twins. ORs were <1 for Northern and Southern hemispheres, meaning that whorls rotated preferentially in the same direction in simulated twins. OR for the Northern hemisphere (0.04 [0.03; 0.05]) was less than the OR for the Southern hemisphere (0.28 [0.24; 0.32]) with no confidence interval superimposition, indicating than counterclockwise whorls were more frequent in the Southern hemisphere (p < 0.001). CONCLUSIONS: We suggest that hair whorl formation is a genetically determined developmental process that can be influenced by extrinsic environmental factors. Our results furthermore underline the general importance of studies focused on limit phenomena that can provide insights on general developmental mechanisms. We plead for large-scale epidemiological assessments of hair whorls in several Northern and Southern hemisphere populations to confirm these surprising findings suggesting significant modulations of craniofacial development by geographic effects.

Next generation phenotyping for diagnosis and phenotype-genotype correlations in Kabuki syndrome.

The field of dysmorphology has been changed by the use Artificial Intelligence (AI) and the development of Next Generation Phenotyping (NGP). The aim of this study was to propose a new NGP model for predicting KS (Kabuki Syndrome) on 2D facial photographs and distinguish KS1 (KS type 1, KMT2D-related) from KS2 (KS type 2, KDM6A-related). We included retrospectively and prospectively, from 1998 to 2023, all frontal and lateral pictures of patients with a molecular confirmation of KS. After automatic preprocessing, we extracted geometric and textural features. After incorporation of age, gender, and ethnicity, we used XGboost (eXtreme Gradient Boosting), a supervised machine learning classifier. The model was tested on an independent validation set. Finally, we compared the performances of our model with DeepGestalt (Face2Gene). The study included 1448 frontal and lateral facial photographs from 6 centers, corresponding to 634 patients (527 controls, 107 KS); 82 (78%) of KS patients had a variation in the KMT2D gene (KS1) and 23 (22%) in the KDM6A gene (KS2). We were able to distinguish KS from controls in the independent validation group with an accuracy of 95.8% (78.9-99.9%, p < 0.001) and distinguish KS1 from KS2 with an empirical Area Under the Curve (AUC) of 0.805 (0.729-0.880, p < 0.001). We report an automatic detection model for KS with high performances (AUC 0.993 and accuracy 95.8%). We were able to distinguish patients with KS1 from KS2, with an AUC of 0.805. These results outperform the current commercial AI-based solutions and expert clinicians.

Gonadotropin administration to mimic mini-puberty in hypogonadotropic males: pump or injections?

Objective: Newborns with congenital hypogonadotropic hypogonadism (CHH) have an impaired postnatal activation of the gonadotropic axis. Substitutive therapy with recombinant gonadotropins can be proposed to mimic physiological male mini-puberty during the first months of life. The aim of this study was to compare the clinical and biological efficacy of two treatment modalities of gonadotropins administration during mini-puberty in CHH neonates. Design: Multicenter retrospective analytical epidemiological study comparing two treatments, pump vs injection, between 2004 and 2019. Methods: Clinical (penile size, testis size, testicular descent) and biological parameters (serum concentrations of testosterone, anti-Müllerian hormone (AMH) and Inhibin B) were compared between the two groups by multivariate analyses. Results: Thirty-five patients were included. A significantly higher increase in penile length and testosterone level was observed in the injection group compared to the pump group (+0.16 ± 0.02 mm vs +0.10 ± 0.02 mm per day, P = 0.002; and +0.04 ± 0.007 ng/mL vs +0.01 ± 0.008 ng/mL per day, P = 0.001). In both groups, significant increases in penile length and width, testosterone, AMH, and Inhibin B levels were observed, as well as improved testicular descent (odds ratio of not being in a scrotal position at the end of treatment = 0.97 (0.96; 0.99)). Conclusions: Early postnatal administration of recombinant gonadotropins in CHH boys is effective in stimulating penile growth, Sertoli cell proliferation, and testicular descent, with both treatment modalities.

Hemifacial myohyperplasia is due to somatic muscular PIK3CA gain-of-function mutations and responds to pharmacological inhibition.

Hemifacial myohyperplasia (HFMH) is a rare cause of facial asymmetry exclusively involving facial muscles. The underlying cause and the mechanism of disease progression are unknown. Here, we identified a somatic gain-of-function mutation of PIK3CA in five pediatric patients with HFMH. To understand the physiopathology of muscle hypertrophy in this context, we created a mouse model carrying specifically a PIK3CA mutation in skeletal muscles. PIK3CA gain-of-function mutation led to striated muscle cell hypertrophy, mitochondria dysfunction, and hypoglycemia with low circulating insulin levels. Alpelisib treatment, an approved PIK3CA inhibitor, was able to prevent and reduce muscle hypertrophy in the mouse model with correction of endocrine anomalies. Based on these findings, we treated the five HFMH patients. All patients demonstrated clinical, esthetical, and radiological improvement with proof of target engagement. In conclusion, we show that HFMH is due to somatic alteration of PIK3CA and is accessible to pharmacological intervention.

AI-based diagnosis in mandibulofacial dysostosis with microcephaly using external ear shapes.

Introduction: Mandibulo-Facial Dysostosis with Microcephaly (MFDM) is a rare disease with a broad spectrum of symptoms, characterized by zygomatic and mandibular hypoplasia, microcephaly, and ear abnormalities. Here, we aimed at describing the external ear phenotype of MFDM patients, and train an Artificial Intelligence (AI)-based model to differentiate MFDM ears from non-syndromic control ears (binary classification), and from ears of the main differential diagnoses of this condition (multi-class classification): Treacher Collins (TC), Nager (NAFD) and CHARGE syndromes. Methods: The training set contained 1,592 ear photographs, corresponding to 550 patients. We extracted 48 patients completely independent of the training set, with only one photograph per ear per patient. After a CNN-(Convolutional Neural Network) based ear detection, the images were automatically landmarked. Generalized Procrustes Analysis was then performed, along with a dimension reduction using PCA (Principal Component Analysis). The principal components were used as inputs in an eXtreme Gradient Boosting (XGBoost) model, optimized using a 5-fold cross-validation. Finally, the model was tested on an independent validation set. Results: We trained the model on 1,592 ear photographs, corresponding to 1,296 control ears, 105 MFDM, 33 NAFD, 70 TC and 88 CHARGE syndrome ears. The model detected MFDM with an accuracy of 0.969 [0.838-0.999] (p < 0.001) and an AUC (Area Under the Curve) of 0.975 within controls (binary classification). Balanced accuracies were 0.811 [0.648-0.920] (p = 0.002) in a first multiclass design (MFDM vs. controls and differential diagnoses) and 0.813 [0.544-0.960] (p = 0.003) in a second multiclass design (MFDM vs. differential diagnoses). Conclusion: This is the first AI-based syndrome detection model in dysmorphology based on the external ear, opening promising clinical applications both for local care and referral, and for expert centers.

Criteria for early and late velopharyngoplasty in 61 children with cleft palate.

BACKGROUND: Velopharyngeal insufficiency persists in 15 to 30% of children with cleft palate, despite early velar surgery. Pharyngoplasty using a superior pedicle flap is the most common secondary surgery to treat velopharyngeal insufficiency. This study aims to identify the criteria leading to indicate velopharyngoplasty in 3 groups of age. MATERIALS AND METHODS: we conducted a retrospective single center study in the reference center for cleft palate in Paris from 2013 to 2016. We included 61 children with non-syndromic cleft operated on with a velopharyngoplasty for velopharyngeal insufficiency. Pre-operative speech and surgical assessments, as well as the operative reports of the children, were analyzed retrospectively using multivariate models. RESULTS: We included 61 patients. The only criteria factor for an early velopharyngoplasty was the Pittsburgh Weighted Speech Scale (PWSS) score (OR 1.20, CI 95% 1.07 to 1.4 ; P=.006). Criteria for a late velopharyngoplasty were a degradation of the velopharyngeal function (OR 16.07, CI 95% 1.7 to 518.7 ; P=.041) and lost of follow-up (OR 5.78, CI 95% 3.9 to 4320 ; P=.017). CONCLUSION: Criteria for early and late velopharyngoplasty were identified, and we demonstrated the insufficiency of Borel-Maisonny classification for scientific clinical study.

Scaphocephaly and increased intra-cranial pressure in non-operated adults: A controlled anthropological study on 21 skulls.

AIM AND SCOPE: The prevalence of increased intra-cranial pressure (ICP) in patients with scaphocephaly is controversial. Here, based on anthropological material, we aimed to determine whether adults with non-operated sagittal synostosis show indirect signs of increased ICP. MATERIALS AND METHODS: Thirty-eight dry skulls (21 skulls with sagittal craniosynostosis and 17 controls) were selected from the collections of the National Museum of Natural History (Paris, France). All skulls registered as 'fused sagittal suture' or 'scaphocephaly' in the registry of the Museum were included. All had total fusion of the sagittal suture. Controls were selected within skulls of similar origin (France), without visible craniofacial anomalies. The 38 skulls were CT-scanned using a standard medical CT-scan with a protocol dedicated to dry bone imaging. Eight radiological signs associated with raised ICP were assessed: (1) calvaria and (2) skull base thinning, (3) dorsum sellae erosion, (4) sella turcica lengthening, (5) copper beaten skull, (6) suture diastasis, (7) persistent metopic suture, and (8) small frontal sinus. Scaphocephaly was assessed based on head circumference, cranial index, intra-cranial volume, fronto-nasal angle, and inter-zygomatic distance. Linear and non-linear logistic models were used to compare groups. RESULTS: 19/21 skulls with sagittal synostosis were significantly scaphocephalic. None of the criteria for ICP were significantly different in skulls with scaphocephaly relative to controls. Nevertheless, 5 individual skulls with scaphocephaly had ≥ 3 signs in favor of a history of raised ICP. We do not report the significant prevalence of indirect signs of raised ICP in adults with scaphocephaly. These results do not allow ruling out a history of early raised ICP or of minor prolonged raised ICP. Even though our findings support the fact that scaphocephaly is not significantly associated with prolonged raised ICP, individual cases (5/21) with clear signs in favor of a history of brain compression indicate that scaphocephaly correction should be considered as a functional procedure until the production of clear evidence. Cognitive assessments of non-operated adult patients with scaphocephaly could contribute to tackle this recurring question in craniofacial surgery.

Intentional craniofacial remodelling in Europe in the XIXth century: Quantitative evidence of soft tissue modifications from Toulouse, France.

Intentional skull deformations have been practiced by every human population, from the prehistoric times until the XXth century. In Europe, they were specifically prevalent in the region of Toulouse, France. The soft-tissue modifications due to such practices are not well characterized in the literature due to the rarity of photographic data. Most studies on skull deformations are thus based on skeletal remains. Here we performed a controlled geometric morphometric assessment of 31 frontal pictures and 70 lateral pictures of individuals from Toulouse with intentional deformations extracted from two XIXth century historical French photographic archives. We also measured the forces exerted on the skull vault by the traditional deformation device from Toulouse using a 3D-printed skull and pressure sensors. We showed that individuals with Toulouse deformations have distinctive facial features, caused by moderate forces exerted on the skull vault. Our results exhibit and quantify for the first time the real face of intentional skull deformations, which are a ubiquitous and distinctive feature of the human species.

Growth charts in FGFR2- and FGFR3-related faciocraniosynostoses.

Objective: Faciocraniosynostoses (FCS) are malformations affecting the development of the bones of the skull and face, due to the premature closure of one or more craniofacial sutures, mostly secondary to activating Fibroblast Growth Factor Receptor (FGFR) 1-3 mutations. Gain-of-function FGFR3 mutations are also responsible for various conditions referred to as osteochondrodysplasia (OCD), characterized by structural and functional abnormalities of growth plate cartilages. We hypothesized that patients with FGFR-related faciocraniosynostoses may present extra-cranial growth anomalies. Study design: We retrospectively collected height and weight data from a cohort of 70 patients. Included patients were admitted for FGFR-related FCS between 2000 and 2021 at the Craniofacial Unit of Necker - Enfants Malades University Hospital in Paris, France. Results: We showed that FGFR-related faciocraniosynostoses had significantly reduced heights and weights relative to controls, and that two specific time periods (1-3 years and > 8 years of age) were associated with lower height and weight values. Four patients had received growth hormone treatment but remained below normal values for growth in height and weight. Conclusions: Patients with FGFR-related faciocraniosynostoses have clinically significant extra-cranial anomalies which are not currently investigated and managed in usual protocols; these patients could benefit from a systematic pre-pubertal endocrine assessment. More generally, our results extend the scope of extracranial anomalies in FGFR-related faciocraniosynostoses and support the hypothesis that all conditions with activating FGFR mutations affect both membranous ossification and long bones.

Management of sagittal craniosynostosis: morphological comparison of eight surgical techniques.

The aim of this study was to carry out a retrospective multicentre study comparing the morphological outcome of 8 techniques used for the management of sagittal synostosis versus a large cohort of control patients. Computed tomographic (CT) images were obtained from children CT-scanned for non-craniosynostosis related events (n = 241) and SS patients at preoperative and postoperative follow-up stages (n = 101). No significant difference in morphological outcomes was observed between the techniques considered in this study. However, the majority of techniques showed a tendency for relapse. Further, the more invasive procedures at older ages seem to lead to larger intracranial volume compared to less invasive techniques at younger ages. This study can be a first step towards future multicentre studies, comparing surgical results and offering a possibility for objective benchmarking of outcomes between methods and centres.

Injuries and child abuse increase during the pandemic over 12942 emergency admissions.

INTRODUCTION: A strict lockdown was decided from 17/03/2020 to 11/05/2020 in France in order to tackle the first wave of the COVID19 pandemic. In the Great Paris region, several areas are severely affected by overcrowding, creating difficult conditions for children and their families during a period of nearly two months. The objective was to assess the effects of the 2020 spring lockdown on injuries, child abuse and neglect. MATERIAL AND METHODS: The central medical data warehouse was screened for all pediatric admissions at emergency and critical care departments of 20 hospitals, in a cohort of 12942 children. Specific keywords were used to screen for both injuries and child abuse and neglect. RESULTS: We found head and neck trauma (1.2% in 2020 vs. 0.7% in 2019, p<0.001), burns (0.6% in 2020 vs. 0.1% in 2019, p < 0.001), lacerations (0.5% in 2020 vs. 0.3% in 2019, p<0.001), fractures (0.5% in 2020 vs. 0.3% in 2019, p<0.017), dog bites (0.1% in 2020 vs. 0.0% in 2019, p<0.001), and child abuse and neglect (18 cases during the 2020 lockdown vs. 24 cases in 2019, p=0.005) were significantly more prevalent during this period than during the same control period in 2019. CONCLUSIONS: These results indicate that specific prevention measures are crucial if strict lockdowns are to be decided in the future.

Tocilizumab versus Rituximab in Patients with Moderate to Severe Steroid-resistant Graves' Orbitopathy.

INTRODUCTION: To describe the efficacy of tocilizumab in patients with Graves' orbitopathy resistant or dependent to steroids and compare to rituximab treated patients. PATIENTS AND METHODS: Graves's orbitopathy response was considered as decrease of at least 2 points of the CAS. RESULTS: Twenty-one patients were included, 7 patients were treated with tocilizumab and 14 with rituximab. The primary was achieved in all 7 patients (100%) on tocilizumab and 9 out of 14 patients on (64%) rituximab (p = .17). Mean change in CAS was consistent with a decrease of 3.3 ± 0.5 points in patients on tocilizumab versus 2.5 ± 1.9 in patients on rituximab (p = .07). One patient on tocilizumab (14%) and 4 patients (29%) on rituximab experienced significant relapse during the follow-up. The difference in relapse-free survival was not significant in patients on tocilizumab (10.8 ± 4 months) compared with rituximab (17.88 ± 3.66). CONCLUSION: We showed a significant improvement in the CAS, visual acuity, diplopia, and proptosis with both tocilizumab and rituximab.

Association between sex and survival in patients with head and neck spindle cell carcinoma.

BACKGROUND: Head and neck spindle cell carcinoma (HNSpCC) is a rare histological variant associated with worse outcomes. Our objective was to identify clinicopathological factors associated with survival in patients with HNSpCC compared to patients with conventional head and neck squamous cell carcinoma (HNSCC). METHODS: Using clinical data from the Surveillance, Epidemiology, and End Results database, we performed a survival analysis in patients with HNSpCC or HNSCC between 2004 and 2016. RESULTS: A total of 458 HNSpCC and 77 104 HNSCC were identified, including 17% and 16% female, respectively. Five-year disease-specific survival (DSS) was 63.90% and 73.90% in patients with HNSpCC and HNSCC, respectively. Sex (hazard ratio [HR] for females = 2.816; CI: 1.139-6.965; p = 0.025) was significantly associated with DSS in HNSpCC while no association was observed between sex and DSS in HNSCC. CONCLUSION: HNSpCC in women is a specific subgroup of HNSCC, which is associated with a poor prognosis.

Computational diagnostic methods on 2D photographs: A review of the literature.

Here we provide a literature review of all the methods reported to date for analyzing 2D pictures for diagnostic purposes. Pubmed was used to screen the MEDLINE database using MeSH (Medical Subject Heading) terms and keyworks. The different recognition steps and the main results were reported. All human studies involving 2D facial photographs used to diagnose one or several conditions in healthy populations or in patients were included. We included 1515 articles and 27 publications were finally retained. 67% of the articles aimed at diagnosing one particular syndrome versus healthy controls and 33% aimed at performing multi-class syndrome recognition. Data volume varied from 15 to 17,106 patient pictures. Manual or automatic landmarks were one of the most commonly used tools in order to extract morphological information from images, in 22/27 (81%) publications. Geometrical features were extracted from landmarks based on Procrustes superimposition in 4/27 (15%). Textural features were extracted in 19/27 (70%) publications. Features were then classified using machine learning methods in 89% of publications, while deep learning methods were used in 11%. Facial recognition tools were generally successful in identifying rare conditions in dysmorphic patients, with comparable or higher recognition accuracy than clinical experts.