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Pancreatic ductal adenocarcinoma is associated with a poor prognosis and there are few treatment options. The development of immunotherapy in pancreatic ductal adenocarcinoma has been difficult, and immune checkpoint inhibitors are only effective in a very small subset of patients. Most obstacles for treatment have been related to intertumoural and intratumoural heterogeneity, the composition of tumour stroma, and crosstalk with cancer cells. Improved molecular characterisation of pancreatic ductal adenocarcinoma and a better understanding of its microenvironment have paved the way for novel immunotherapy strategies, including the identification of predictive biomarkers, the development of rational combinations to optimise effectiveness, and the targeting of new mechanisms. Future immunotherapy strategies should consider individual characteristics to move beyond the traditional immune targets and circumvent the resistance to therapies that have been developed so far.

Syndromic primary hyperparathyroidism has several features in common: younger age at diagnosis when compared with sporadic primary hyperparathyroidism, often synchronous or metachronous multi-glandular involvement, higher possibility of recurrence, association with other endocrine or extra-endocrine disorders, and suggestive family background with autosomal dominant inheritance. Hyperparathyroidism in multiple endocrine neoplasia type 1 is the most common syndromic hyperparathyroidism. It is often asymptomatic in adolescents and young adults, but may be responsible for recurrent lithiasis and/or bone loss. Hyperparathyroidism-jaw tumor syndrome is less frequent, but often immediately symptomatic, with higher blood calcium levels, and is sometimes associated with an atypic parathyroid tumor or parathyroid carcinoma. Hyperparathyroidism in multiple endocrine neoplasia type 2A is not at the forefront of the clinical picture, rarely revealing the disease, and often manifests with few symptoms. Multiple endocrine neoplasia type 4 is a more recently described entity, in which hyperparathyroidism seems to occur later and be less severe than in previous syndromes. In all cases, the indications and modalities of surgical treatment should be discussed in an expert center. The risk of recurrence after surgery, particularly high in multiple endocrine neoplasia type 1, requires long-term monitoring.

Le syringo-fibroadénome eccrine (SFAE) est une tumeur annexielle rare dérivée des cellules de l’acrosyringium des glandes sudoripares eccrines, initialement décrit par Mascaro en 1993. Les présentations cliniques sont multiples: un nodule isolé, de multiples papules, voire un placard érythémateux.

•Rapid antimicrobial testing (RAST) can be used routinely to rapidly detect resistant Gram-negative strains isolated from blood cultures.•RAST significantly increases the number of patients with effective antibiotic therapy on the day of positive blood culture.•RAST occasions antibiotic de-escalation on the day of positive blood culture.

Cancer patients at advanced stages experience a severe depletion of skeletal muscle compartment together with a decrease in muscle function, known as cancer cachexia. Cachexia contributes to reducing quality of life, treatment efficiency, and lifespan of cancer patients. However, the systemic nature of the syndrome is poorly documented. Here, we hypothesize that glucocorticoids would be important systemic mediators of cancer cachexia. To explore the role of glucocorticoids during cancer cachexia, biomolecular analyses were performed on several tissues (adrenal glands, blood, hypothalamus, liver, and skeletal muscle) collected from ApcMin/+male mice, a mouse model of intestine and colon cancer, aged of 13 and 23 weeks, and compared with wild type age‐matched C57BL/6J littermates. Twenty‐three‐week‐old Apcmice recapitulated important features of cancer cachexia including body weight loss (−16%, P< 0.0001), muscle atrophy (gastrocnemiusmuscle: −53%, P< 0.0001), and weakness (−50% in tibialis anteriormuscle force, P< 0.0001), increased expression of atrogens (7‐fold increase in MuRF1 transcript level, P< 0.0001) and down‐regulation of Akt–mTOR pathway (3.3‐fold increase in 4EBP1 protein content, P< 0.0001), together with a marked transcriptional rewiring of hepatic metabolism toward an increased expression of gluconeogenic genes (Pcx: +90%, Pck1: +85%), and decreased expression of glycolytic (Slc2a2: −40%, Gk: −30%, Pklr: −60%), ketogenic (Hmgcs2: −55%, Bdh1: −80%), lipolytic/fatty oxidation (Lipe: −50%, Mgll: −60%, Cpt2: −60%, Hadh: −30%), and lipogenic (Acly: −30%, Acacb: −70%, Fasn: −45%) genes. The hypothalamic pituitary–adrenal axis was activated, as evidenced by the increase in the transcript levels of genes encoding corticotropin‐releasing hormone in the hypothalamus (2‐fold increase, P< 0.01), adrenocorticotropic hormone receptor (3.4‐fold increase, P< 0.001), and steroid biosynthesis enzymes (Cyp21a1, P< 0.0001, and Cyp11b1, P< 0.01) in the adrenal glands, as well as by the increase in corticosterone level in the serum (+73%, P< 0.05), skeletal muscle (+17%, P< 0.001), and liver (+24%, P< 0.05) of cachectic 23‐week‐old Apcmice. A comparative transcriptional analysis with dexamethasone‐treated C57BL/6J mice indicated that the activation of the hypothalamic–pituitary–adrenal axis in 23‐week‐old ApcMin/+mice was significantly associated with the transcription of glucocorticoid‐responsive genes in skeletal muscle (P< 0.05) and liver (P< 0.001). The transcriptional regulation of glucocorticoid‐responsive genes was also observed in the gastrocnemiusmuscle of Lewis lung carcinoma tumour‐bearing mice and in KPCmice (tibialis anteriormuscle and liver). These findings highlight the role of the hypothalamic–pituitary–adrenal‐glucocorticoid pathway in the transcriptional regulation of skeletal muscle catabolism and hepatic metabolism during cancer cachexia. They also provide the paradigm for the design of new therapeutic strategies.

Les cystopathies chroniques inflammatoires et douloureuses sont des pathologies impactant lourdement la qualité de vie des patients qui en sont atteints. Bien qu’avec des physiopathologies différentes, les cystopathies chroniques ont en commun une altération de la couche, faisant interface entre l’urine et l’urothélium, rendant appropriée l’utilisation d’agents topiques.

The potential role of CLEC12B, a gene predominantly expressed by skin melanocytes discovered through transcriptomic analysis, in melanoma is unknown. In this study, we show that CLEC12B expression is lower in melanoma and melanoma metastases than in melanocytes and benign melanocytic lesions and that its decrease correlates with poor prognosis. We further show that CLEC12B recruits SHP2 phosphatase through its immunoreceptor tyrosine-based inhibition motif domain, inactivates signal transducer and activator of transcription 1/3/5, increases p53/p21/p27 expression/activity, and modulates melanoma cell proliferation. The growth of human melanoma cells overexpressing CLEC12B in nude mice after subcutaneous injection is significantly decreased compared with that in the vehicle control group and is associated with decreased signal transducer and activator of transcription 3 phosphorylation and increased p53 levels in the tumors. Reducing the level of CLEC12B had the opposite effect. We show that CLEC12Brepresses the activation of the signal transducer and activator of transcription pathway and negatively regulates the cell cycle, providing a proliferative asset to melanoma cells.

La folliculite pustuleuse à éosinophiles (FPE) ou maladie d’Ofuji est une dermatose chronique rare, évoluant par poussées. Le traitement est mal codifié, reposant en première intention sur l’indométacine et les dermocorticoïdes (DCT). Nous rapportons le cas d’une FPE résistante, traitée efficacement par dupilumab.

La fiabilité d'une mesure fait référence à sa reproductibilité lorsqu'elle est répétée de manière aléatoire sur le même sujet. Le coefficient de corrélation intra-classe de concordance à deux voies (ICC2a) est un paramètre clé pour quantifier la fiabilité inter-observateurs. De nombreuses solutions ont été essayées pour améliorer son intervalle de confiance (IC) mais les IC asymptotiques restent très libéraux ou non-informatifs et ne sont pas munis de méthodes dédiées au calcul de taille d’échantillon suffisant. Ce travail propose un nouvel IC asymptotique de l'ICC2a muni de formules simples pour le calcul de taille d’échantillon avec des recommandations pour le design des études de fiabilité inter-juge.

Le complexe de Carney(CNC), syndrome génétique rare, principalement dû à des variants pathogènes de PRKAR1A, présente un large spectre de manifestations : lésions cutanées, myxomes cardiaques, dysplasie micro-nodulaire pigmentée surrénalienne... Des tumeurs du sein bénignes y sont associées, mais l’association avec des carcinomes n’a jamais été étudiée.

En France, un dépistage génétique est recommandé en cas d’hyperparathyroïdie primaire (HPT1) isolée sporadique avant l’âge de 50 ans ou familiale. Cinq pour cent des HPT1 seraient génétiques, pourtant il n’y a pas de grandes études confirmant cette prévalence, particulièrement en cas d’HPT1 isolée.

Context.Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of the twenty predisposing genes described to date.

L’analyse élémentaire des perturbations chimiques d’origine anthropique bénéficie aux études archéologiques. Pour la première fois, une fouille archéologique menée par le musée du quai Branly et l’université Versailles St-Quentin a appliqué ces techniques biomédicales au sol archéologique afin de mettre à jour la topographie précise de pratiques magico-religieuses.

Durant la première vague de l’épidémie à SARS-CoV-2/COVID-19, un nombre élevé et inattendu de cas de pseudo-engelures des extrémités a été rapportés sans qu’il soit clairement démontré une relation entre les deux phénomènes ; un lien direct ou indirect avec le virus est encore discuté. Grâce à sa haute résolution 3D et ses capacités de contraste très élevées dans les tissus mous, la nano-imagerie par contraste de phase à rayon X synchrotron pourrait aider à comprendre le lien entre ces deux phénomènes, au contraire des études histologiques qui sont limitées à la 2D et à une résolution donnée. Le but de cette étude était d’étudier des pseudo-engelures COVID-19 en imagerie cutanée par rayonnement synchrotron.

Metabolic flexibility is one of the key hallmarks of cancer and metabolites are the final products of this adaptation, reflecting the tumors’ aberrant changes. However, the metabolic plasticity of pancreatic neuroendocrine tumors (pNET) is still unknown. pNETs are heterogeneous which makes their diagnosis and therapeutic management difficult. We aimed to assess the metabolomic profile of pNETs patients to understand metabolic deregulation and identify novel biomarkers.

L’hyperplasie macronodulaire des surrénales (HMBS) évolue lentement. Sa vitesse de progression n’a jamais été étudiée. L’inactivation d’ARMC5 entraîne in vitro une diminution de la production de cortisol par cellule faisant suggérer que « l’effet masse » lié à la perte d’apoptose participerait à l’hypercortisolisme.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer. Management of advanced MCC is mainly based on immune-checkpoint inhibitors (ICI). The high failure rate warrants investigation of new therapeutic targets. The recent identification of BRCA1or BRCA2 (BRCA1/2)mutations in some MCC raises the issue of the use of poly-(ADP-Ribose)-polymerase inhibitors (PARPi) in selected advanced cases.

Introduction : Les réunions de concertation pluridisciplinaires (RCP) de pelvi-périnéologie ont vocation à se généraliser en France avec dorénavant une obligation légale de validation des dossiers avant toute promontofixation ou pose de bandelette sous-uréthrale. L’accès à ces réunions reste cependant inégal sur le territoire. Le but de cette étude était de réaliser un état des lieux de la mise en place de ces RCP en France.

Nous rapportons un cas de morphées généralisées immuno-induites et cortico-dépendantes améliorées sous tocilizumab.

De par leur mécanisme d’action, les inhibiteurs de point de contrôle immunitaires (ICI) s’associent surtout à des toxicités d’origine immunologique, notamment dermatologiques. Nous rapportons le cas d’un patient présentant une toxidermie lichénoïde (TL) de présentation zostériforme au nivolumab (NIVO), dans un contexte de mélanome (M) traité en situation adjuvante.

Les lymphomes B centro-folliculaires cutanés primitifs (LBCF-CP) sont des proliférations cutanées de centrocytes et centroblastes, de phénotype centre germinatif, ne s’accompagnant d’aucune localisation extra-cutanée au diagnostic.

A clinical study was performed to determine the in vivo mass loss of both lozenges in 16 healthy volunteers. In vitro, mass loss over time was measured for both formulations and correlated to the release of CPC and benzocaine. In vivo, the oral mass loss profiles of both lozenges were similar, with a mean difference between the two curves, up to the first point greater than 85% of 3.2%, and a f2 similarity factor of 69%. In vitro, the mass loss of both lozenges was similar and a strong correlation between mass loss and release of CPC and benzocaine was observed, indicating that the active ingredients were homogeneously dispersed within the lozenges. Based on the results, it was possible to establish a link between the in vitro and in vivo drug release and mass losses using an in vitro–in vivo correlation (IVIVC). In vivo release profiles of benzocaine and CPC were calculated and found to be similar for the sugar-free and sugared lozenges; more than 85% of the active ingredients were released in 186 and 209 s, respectively. These results suggest that in vitro mass loss and corresponding drug release is an adequate surrogate for bioequivalence studies, waiving their need for lozenges with excipient changes, and that the clinical risk–benefit profile of sugar-free CPC/benzocaine (1.4 mg/10 mg) lozenges is unlikely to differ from sugared lozenges.

Pigmentation of the human skin is a complex process regulated by many genes. However, only a few have a profound impact on melanogenesis. Transcriptome analysis of pigmented skin compared with analysis of vitiligo skin devoid of melanocytes allowed us to unravel CLEC12Bas a melanocytic gene. We showed that CLEC12B, a C-type lectin receptor, is highly expressed in melanocytes and that its expression is decreased in dark skin compared with that in white skin. CLEC12B directly recruits and activates SHP1 and SHP2 through its immunoreceptor tyrosine-based inhibitory motif domain and promotes CRE-binding protein degradation, leading to the downregulation of the downstream MITF pathway. CLEC12B ultimately controls melanin production and pigmentation in vitro and in a model of reconstructed human epidermis. The identification of CLEC12B in melanocytes shows that C-type lectin receptors exert function beyond immunity and inflammation. It also provides insights into the understanding of melanocyte biology and regulation of melanogenesis.