[Modeling T2 high severe asthma using human induced pluripotent stem cells (hiPSC)]. / Modélisation de l'asthme sévère par la technologie des cellules humaines souches pluripotentes induites (hiPSC).

Severe asthma patients with persistent airflow obstruction are characterized by functional obstruction due to mucus plugs containing mucins, fibrin, and eosinophil derived Charcot- Leyden crystals. The molecular mechanisms underlying this endotype are not clearly understood. Developing new models is crucial to respiratory research insofar as critical differences exist between human and rodent airway epithelium. We (and other teams) have shown that it is possible to reconstitute in vitro a complex and functional airway epithelium displaying all the features described in vivo from human-induced pluripotent stem cells (hiPSC). Our aim is to establish a human in vitro model of severe asthma that will recapitulate airway epithelium remodeling and mucus plugs.

Post-traumatic stress disorder in hospital doctors after the COVID-19 pandemic.

BACKGROUND: Prior studies showed that during the coronavirus disease 2019 (COVID-19) pandemic healthcare workers had a higher risk of developing post-traumatic stress disorder (PTSD) symptoms. However, studies conducted among doctors several years after the beginning of the COVID-19 pandemic are scarce. AIMS: To evaluate the prevalence of PTSD among hospital doctors and to describe potential explanatory factors. METHODS: The Protec-Cov study was an observational, cross-sectional, multicentre study, which used an anonymous online questionnaire to evaluate PTSD in doctors from six hospitals in France between December 2021 and March 2022. The presence of PTSD was assessed using the Post-traumatic Stress Disorder Checklist Scale (PCLS) questionnaire with a cut-off of 44. RESULTS: Among the 307 doctors included, 18% presented a PCLS ≥44. The multivariate analysis showed that factors associated with a PCLS ≥44 were having a higher workload than before the COVID-19 pandemic (odds ratio [OR] = 4.75; 95% confidence interval [CI] 1.68-13.38), not feeling recognized within the professional environment (OR = 2.83; 95% CI 1.26-6.33), and feeling isolated because of the lockdown (OR = 4.2; 95% CI 1.97-8.95). Approximately 30% of hospital doctors (n = 91) felt a need for psychological support but only 31% of them (n = 28) received support. CONCLUSIONS: Based on our findings, a high prevalence of PTSD was observed among hospital doctors 2 years after the beginning of the COVID-19 pandemic. This study supports an early diagnosis of PTSD in this category of healthcare workers and warrants further study.

Un entre en la inter-consulta de Salud Mental. Algunas reflexiones y puntos de encuentro posibles / An entry into the Mental Health inter-consultation. Some reflections and possible meeting points

El presente trabajo intentará reflexionar acerca de la práctica de Interconsulta de Salud Mental, en una sala de pediatría general, dentro del H.I.A.E.P. Sor María Ludovica, ubicado en la ciudad de La Plata, Buenos Aires. Dicha práctica se enmarca como rotación curricular del programa de residentes de psicología y tiene una duración de nueve meses. El objetivo del mismo es tensionar las concepciones de la interconsulta desde el discurso médico y desde el discurso psicoanalítico, en pos de precisar y tender puentes de diálogo e intercambio posibles entre las disciplinas

[The morbidity and mortality review meetings in radiotherapy departments: Procedure, implementation and prospects of the "Proust" French national project]. / Revue de morbidité et mortalité en radiothérapie : procédure, implémentation et perspectives du projet national français « Proust ¼.

Radiation-induced acute and late toxicity depends on several parameters. The type, severity and duration of morbidity are mainly related to irradiated volume, total dose and its fractionation and the intrinsic radiosensitivity of the patients. The follow-up of these toxicities is essential. However, unlike many specialties, morbidity and mortality reviews procedures are not developed as part of quality governance programs in radiation therapy departments for the monitoring of toxicity which sometimes hinder the patients' quality of life. One French survey published within the framework of the project entitled Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (Proust), conclude that there was a lack of knowledge of morbidity and mortality reviews and considerable confusion between these reviews and other quality processes without perspective for the local morbidity and mortality reviews development in a large number of the participated centers. In this article, we will discuss the procedure of the "ideal morbidity and mortality reviews" and its implementation through a monocentric experience started in 2015. Thus, the Proust project is a unique opportunity to implement and standardize a national morbidity and mortality reviews implementation in radiation therapy departments by involving the French regions.

[Production of innervated bronchial epithelium from a blood sample]. / Fabrication d'un épithélium bronchique innervé à partir d'une prise de sang.

Asthma is a frequent respiratory disease, with severe asthma occurring in 3 to 5% of cases. Chronic inflammation of the bronchial epithelium is essential to its pathophysiology. When activated by the bronchial environment, the peripheral sensory nervous system contributes to inflammation of the airways. However, due to a lack of reliable models, the mechanisms of action remain largely unknown. Using induced pluripotent stem cells reprogrammed from blood cells, we have set up a model of bronchial epithelium innervated by sensory neurons. This model will ensure better understanding of the mechanisms of action underlying neurogenic inflammation.

"African" acral keratoderma: Further evidence for a single entity. A retrospective study of 42 patients.

BACKGROUND: Several phenotypes of non-inflammatory palmar and plantar keratoderma (PPK) have been described in patients of Sub-Saharan African descent. They include keratosis punctata of the palmar creases, marginal keratoderma, also known as acrokeratoelastoidosis or focal acral hyperkeratosis, knuckle pads, other forms of diffuse hyperkeratosis, the very rare "mosaic acral keratosis", and ainhum. A previous survey has shown that these various forms of PPK are particularly frequent in patients of Sub-Saharan African descent and that they commonly occur concurrently, suggesting that they could form part of a single entity called "African" Acral Keratoderma (AAK). AIM: To assess the validity of the concept of AAK and clarify its main characteristics. METHODS: A retrospective, descriptive, monocenter study was carried out on patients with AAK seen at our institution between 2009 and 2020. RESULTS: There were 42 patients (median age 38 years, range: 12-69 years), all of Sub-Saharan African descent. The male-female sex ratio was 0.3. Thirty-three (78%) had diffuse keratoderma, 25 (59%) had marginal keratoderma on their hands and/or feet, 20 (48%) had knuckle pads, 20 (48%) had keratosis punctata of the palmar creases, 3 had ainhum, and 2 had mosaic acral keratoderma. Mixed forms were seen in 76% of the patients (n = 32). Familial histories were reported by 17 patients (40%). Treatment was topical in over 90% of patients and systemic in 9 patients (21%). Ainhum was managed surgically. CONCLUSION: This retrospective study provides additional evidence for the concept of AAK. A genetic origin is suggested by the familial aggregation of cases.

Keloid disease: Review with clinical atlas. Part I: Definitions, history, epidemiology, clinics and diagnosis.

Keloids are chronic progressive dermal pseudo-tumors that can grow considerably in volume and surface area but do not invade other tissues. They are usually triggered by dermal injury or inflammation, but they are not scars in the normal sense of the word, since they enlarge and progress over decades. The phenomenon usually referred to as "hypertrophic scars" represents a kind of keloidal process that does not extend beyond the initial site of injury and spontaneously regresses in 12-24 months. The multiplication of keloids and hypertrophic scars in a single patient is known as keloid disease. Keloid disease is due to a familial predisposition (autosomal dominant) that preferentially affects people of non-European ancestry, especially those of sub-Saharan African descent. Keloid disease has a deep impact on quality of life, not only because of disfiguring lesions, but also because of the frequency of associated intense neurogenic pruritus and pain, as well as recurrent bouts of suppuration. Diagnosis relies primarily on a good knowledge of the clinical characteristics of keloids, thus warranting the inclusion of a clinical atlas in the first part of the review. The second part will deal with the pathology, pathophysiology and treatment of keloid disease.

Identification of actions to be taken by managers to facilitate the return to work of cancer survivors: Consensus between managers and cancer survivors.

BACKGROUND: Managers are considered to be main stakeholders in the return to work (RTW) of cancer survivors. However, the perspectives of cancer survivors and managers differ on what managerial actions should be taken during the RTW of cancer survivors. This difference might put effective collaboration and successful RTW at risk. Therefore, this study aims to reach consensus among managers and cancer survivors on the managerial actions to be taken during the four different RTW phases of cancer survivors (i.e., Disclosure, Treatment, RTW plan, Actual RTW). METHODS: The Technique for Research of Information by Animation of a Group of Experts (TRIAGE) was implemented with managers and cancer survivors (hereafter referred to as "experts"). An initial list of 24 actions was derived from a previous study. Firstly, for each action, fifteen experts were asked to indicate individually how important this action is per RTW phase (Likert scale from 1 - "Not important at all" to 6 - "Very important"). Consensus was reached when ≥ 80% (i.e., ≥ twelve experts) of the experts rated that action ≥5. Secondly, for each phase of the RTW process, the 15 actions with the highest percentage were discussed with eight experts during the collective consultation, except for the actions that already reached consensus. After discussion, the experts voted whether each action was important ("yes" / "no") and consensus required ≥ 87.5% (i.e., ≥ seven experts) of the experts to consider an action as important. RESULTS: Twenty-five managerial actions were finally retained for at least one of the RTW phases, e.g., Disclosure: "respect privacy" and "radiate a positive attitude", Treatment: "show appreciation" and "allow sufficient sick leave", RTW Plan: "tailor" and "communicate", and Actual RTW: "support practically" and "balance interest". CONCLUSION: Cancer survivors and managers reached consensus on the importance of 25 managerial actions, distributed into each phase of the RTW process. These actions should be considered an interplay of managerial actions by different stakeholders on the part of the employer (e.g., direct supervisor, HR-manager), and should be a responsibility that is shared by these stakeholders. The collective implementation of these actions within the company will help cancer survivors feel fully supported.

New KCNN4 Variants Associated With Anemia: Stomatocytosis Without Erythrocyte Dehydration.

The K+ channel activated by the Ca2+, KCNN4, has been shown to contribute to red blood cell dehydration in the rare hereditary hemolytic anemia, the dehydrated hereditary stomatocytosis. We report two de novo mutations on KCNN4, We reported two de novo mutations on KCNN4, V222L and H340N, characterized at the molecular, cellular and clinical levels. Whereas both mutations were shown to increase the calcium sensitivity of the K+ channel, leading to channel opening for lower calcium concentrations compared to WT KCNN4 channel, there was no obvious red blood cell dehydration in patients carrying one or the other mutation. The clinical phenotype was greatly different between carriers of the mutated gene ranging from severe anemia for one patient to a single episode of anemia for the other patient or no documented sign of anemia for the parents who also carried the mutation. These data compared to already published KCNN4 mutations question the role of KCNN4 gain-of-function mutations in hydration status and viability of red blood cells in bloodstream.

Neutrophilic dermatoses.

Neutrophilic dermatoses (ND) are a group of inflammatory skin conditions characterized by a neutrophilic infiltrate on histopathology with no evidence of infection. ND are classified based upon the localization of neutrophils within the skin and clinical features. Recent findings suggest that ND are due to two main mechanisms: i) a polyclonal hereditary activation of the innate immune system (polygenic or monogenic); or ii) a clonal somatic activation of myeloid cells such as encountered in myelodysplastic syndrome or VEXAS syndrome. ND belong to internal medicine as a great number of patients with ND suffer from an underlying condition (such as hematological malignancy, inflammatory bowel disease, auto-immune and auto-inflammatory diseases). ND are diagnoses of exclusion and physicians should always consider differential diagnoses, particularly skin infections. Here, we review the pathophysiology and classification of the main ND (i.e., subcorneal pustular dermatosis (Sneddon-Wilkinson Disease) and Intercellular IgA dermatoses, aseptic pustulosis of the folds, Sweet syndrome, neutrophilic eccrine hidradenitis, pyoderma gangrenosum, erythema elevatum diutinum, neutrophilic urticarial dermatosis and neutrophilic panniculitis), their clinical and histopathological features, and we highlight the investigations that are useful to identify ND-associated diseases and to exclude the differential diagnoses.

A statistical methodology to select covariates in high-dimensional data under dependence. Application to the classification of genetic profiles in oncology.

We propose a new methodology for selecting and ranking covariates associated with a variable of interest in a context of high-dimensional data under dependence but few observations. The methodology successively intertwines the clustering of covariates, decorrelation of covariates using Factor Latent Analysis, selection using aggregation of adapted methods and finally ranking. A simulation study shows the interest of the decorrelation inside the different clusters of covariates. We first apply our method to transcriptomic data of 37 patients with advanced non-small-cell lung cancer who have received chemotherapy, to select the transcriptomic covariates that explain the survival outcome of the treatment. Secondly, we apply our method to 79 breast tumor samples to define patient profiles for a new metastatic biomarker and associated gene network in order to personalize the treatments.

Blaschko-linear lichen planus of the face: A retrospective study of 6 cases and a literature review.

INTRODUCTION AND METHODS: Different clinical and histological variants of lichen planus (LP) exist, such as lichen planopilaris, pigmentosus, linear, or atrophic LP. Recently, some cases came to our attention of hyperpigmented and atrophic linear lesions of the face with lichenoid histology, suggesting a combination of these different variants. We carried out a single-center, retrospective descriptive study of 6 similar cases selected from our database and compared them with a literature review. RESULTS: There were 4 males and 2 females of mean age 42 years. Each had linear lesions located on one side of the face. All lesions were initially itchy; they appeared hyperpigmented in all patients and atrophic in 5 cases. Biopsies indicated lichen planopilaris in 5 patients, with deep peri-eccrine involvement in 4 of them. Only 2 of the 6 patients had extra-facial lesions. DISCUSSION AND LITERATURE REVIEW: We found 24 cases in the literature having similar clinical and histological aspects. Men aged around 37 years seemed particularly affected. An atrophic course was noticed in 10 patients. Such a clinicopathological picture may suggest differential diagnoses like lichen striatus, lupus erythematosus, lichen sclerosus atrophicus, or Moulin's linear atrophoderma. Early histopathological examination could be of precious assistance in allowing the initiation of effective treatment immediately as of the initial inflammatory phase, thereby limiting the risk of cosmetic sequelae such as atrophy or residual pigmentation. CONCLUSION: We describe a form of facial lichen planus that is highly particular in terms of its follicular tropism, its blaschkoid distribution, its pigmented character, and its atrophic progression.

[Dose optimization in 3D pulsed dose rate brachytherapy for patients with locally advanced cervical cancer: A French multicenter phase II trial]. / Optimisation de la curiethérapie utérovaginale de débit pulsé des cancers du col utérin localement évolués : résultats finaux du PHRC Tridicol.

PURPOSE: We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers. MATERIAL AND METHODS: Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy. RESULTS: The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications. CONCLUSION: HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

Interest of awake surgery for ruptured cerebral arteriovenous malformations close to speech areas - Surgical note.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are rare, with incidence of 1.12-1.42 cases per 100,000 person-years (Ozpinar et al., 2017). Few studies report applications of awake surgery. The goal of this report was to assess the interest of awake surgery in complete resection of cortical AVMs located close to eloquent speech areas, enabling detection of real functional cortical reorganization due to the AVM and parenchymal hematoma. CASE REPORT: A 38-year-old right-handed patient was admitted to the University Hospital of Besançon for dysphasia due to a ruptured left temporal arteriovenous malformation. The patient underwent asleep-awake-asleep surgery. Intraoperative cortical mapping revealed the presence of functional language areas in uncommon locations compared to known neuro-functional anatomy. DISCUSSION: In this patient, speech areas were redistributed, probably due to neuroplasticity after cerebral hemorrhage, leading to a new cortical architecture, which would have been unrecognized based on preoperative radiological imaging alone. CONCLUSION: We report the interest of awake surgery to achieve complete safe resection of ruptured AVMs located close to eloquent speech areas, using intraoperative cortical mapping.

Role of radiotherapy in the treatment of primary vaginal cancer: Recommendations of the French society for radiation oncology.

Primary vaginal cancers are rare tumours, for which external beam radiotherapy and brachytherapy are major treatment tools. Given the complexity of brachytherapy techniques, the treatment should be performed in specialised centres. We present the recommendations of the French society for radiation oncology on the indications and techniques for external beam radiotherapy and brachytherapy for primary vaginal cancer.