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Background: Line‐field confocal optical coherence tomography (LC‐OCT) is an emerging diagnostic tool with imaging depth reaching ~400 μm and a novel three‐dimensional (3D) cube providing cellular resolution. As far as we are aware, there are only a limited number of papers that have reported diagnostic criteria for melanocytic lesions using this technique, and none of them have been multicentric. Objectives: Our aim was to establish the diagnostic criteria for melanocytic lesions using LC‐OCT and identify the most significant architectural and cytologic features associated with malignancy. Methods: A retrospective evaluation of 80 consecutive melanocytic lesions from a prospective multicentric data set spanning three European centres was conducted. We excluded facial, acral and mucosal lesions from the study. Dermoscopic and LC‐OCT images were evaluated by a consensus of four observers. Multivariate logistic regression with backward elimination was employed. Results: The main melanoma diagnostic criteria include detecting >10 pagetoid cells in 3D acquisition, irregular 3D epidermal architecture, disrupted dermoepidermal junction (DEJ) and clefting. Significant risk factors were irregular 3D epidermal architecture, >10 pagetoid cells, dendritic cells at DEJ without underlying inflammation. Novel malignancy criteria in vertical view were DEJ disruption and clefting around atypical melanocyte nests. Exclusive melanoma features were epidermal nests, epidermal consumption, dense dermal nests with atypia. Protective features in the absence of any malignancy indicators were DEJ ring pattern, cobblestone, elongated rete ridges (vertical), well‐defined DEJ and wave pattern (vertical). Conclusions: A series of diagnostic criteria for the identification of melanocytic lesions with LC‐OCT have been established. Validation of these criteria in clinical practice through future studies is essential to further establish their utility. [ABSTRACT FROM AUTHOR]

It is well known that organ transplant recipients are prone to develop non‐melanoma skin cancers, particularly cutaneous squamous cell carcinoma (cSCC). This is explained by the long‐term use of immunosuppressants and thus the decrease of the immunosurveillance that protects from developing malignant tumours. Solid organ transplant recipients (SOTRs) are 65–250 times more likely to develop cSCC compared to the general population (Am J Transplant 2017; 17: 2509). Moreover, in these patients cSCCs follow a more aggressive course. Close follow‐up and regular skin check‐ups by a dermatologist are, therefore, crucial in the management of these patients. When detected early, cSCC can be easily and effectively treated by a simple excision. However, when advanced, outcomes are poor. Immune checkpoints inhibitors (ICIs) have been recently added to our arsenal and represent a breakthrough, having proved to be effective in achieving long‐term responses. We, hereby, present two cases of difficult‐to‐treat cSCCs in renal transplanted patients. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and subtype classification of basal cell carcinoma (BCC) are crucial to reduce morbidity and optimize treatment. Good accuracy in differentiating BCC from clinical imitators has been achieved with existing diagnostic strategies but lower performance in discriminating BCC subtypes. Line‐field confocal optical coherence tomography (LC‐OCT) is a new technology able to combine the technical advantages of reflectance confocal microscopy and OCT. Objectives: To identify and describe LC‐OCT criteria associated with BCC and explore their association with BCC subtypes. Methods: Basal cell carcinoma were imaged with a handheld LC‐OCT device before surgical excision. LC‐OCT images were retrospectively evaluated by three observers for presence/absence of criteria for BCC. Multivariate logistic regression models were used to find independent predictors of BCC subtypes. Results: Eighty‐nine histopathologically proven BCCs were included, of which 66 (74.2%) were pure subtypes [superficial BCC (sBCC): 19/66 (28.8%); nodular BCC (nBCC): 31/66 (47.0%); infiltrative BCC (iBCC): 16/66 (24.2%)]. Lobules, blood vessels and small bright cells within epidermis/lobules were the most frequent criteria for BCC. LC‐OCT criteria independently associated with sBCC were presence of hemispheric lobules, absence of lobule separation from the epidermis, absence of stretching of the stroma; with nBCC were presence of macrolobules, absence of lobule connection to the epidermis; and with iBCC were presence of branched lobules. Conclusions: This was the first study describing the characteristics of BCC under LC‐OCT examination. We proposed morphologic criteria, which could be potentially useful for diagnosis and subtype classification of BCC, as well as for its therapeutic management. Future studies are needed to assess these hypotheses. [ABSTRACT FROM AUTHOR]

Background: Line‐field confocal optical coherence tomography (LC‐OCT) is a non‐invasive optical technique recently developed for skin examination in vivo. It provides real‐time, high‐resolution vertical images with an isotropic resolution of ~1 µm and a penetration depth of ~500 µm. Objectives: Study goals were to qualitatively/quantitatively characterize healthy skin at different body sites using LC‐OCT. Methods: The skin of young healthy volunteers was imaged with a handheld LC‐OCT imaging device. Seven body sites (back of the hand, forehead, cheek, nose, chest, forearm and back) were investigated. An independent qualitative [cutaneous structures' description; visibility of keratinocytes' nuclei and dermal–epidermal junction (DEJ)] and quantitative [stratum corneum (SC)/epidermal thicknesses; height of dermal papillae] assessment of the LC‐OCT images was performed. Results: A total of 88 LC‐OCT images were collected from 29 participants (20 females; nine males; mean age 25.9 years). Keratinocytes' nuclei and DEJ were visible in the totality of images. The different layers of the epidermis and the remaining cutaneous structures/findings were visualized. Body sites‐related variability was detected for SC/epidermal thicknesses and height of dermal papillae. Inter‐observer agreement was excellent (SC thickness), good‐to‐excellent (epidermal thickness) and moderate‐to‐good (papillae). Conclusions: Line‐field confocal‐OCT provides non‐invasive, real‐time imaging of the skin in vivo with deep penetration and high resolution, enabling the visualization of single cells. The histology‐like vertical view provides an easy way to recognize/measure different cutaneous structures/findings. LC‐OCT appears as a promising technique for the examination of physiological/pathological skin. [ABSTRACT FROM AUTHOR]

Purpose of Review: Squamous cell carcinoma (SCC) is the second most common skin cancer, with an increasing incidence. This review highlights this past year's advances regarding the understanding of its pathogenesis, newly introduced diagnostic methods and updates in prevention and treatment., Recent Findings: While the pathogenesis of SCC progression remains unclear, new sequencing techniques are helping to better characterize these tumours at the molecular level. Recently introduced noninvasive imaging techniques are rapidly transforming SCC diagnosis and follow-up. Although nicotinamide has not demonstrated significant benefit in reducing SCC incidence among transplant recipients, larger studies are needed to achieve statistical power. Tirbanibulin, a new field treatment for actinic keratosis is now available and well tolerated for use in areas up to 100 cm2. Surgery remains the cornerstone of SCC treatment and can now be complemented with cemiplimab, when advanced., Summary: Recent years have seen a diagnostic revolution in dermatology, driven by noninvasive imaging and artificial intelligence; however, the physiopathogenesis of SCC progression remains poorly understood. In treatment, immune checkpoint inhibitors have shown good survival outcomes for advanced SCC. Research continues in the neoadjuvant setting and among transplanted patients, with encouraging preliminary results., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Line-field confocal optical coherence tomography (LC-OCT) represents one of the newest non-invasive in vivo skin imaging techniques. Previous studies described morphologic criteria of basal cell carcinoma (BCC) under LC-OCT examination. Preliminary data on LC-OCT diagnostic performance for BCC have recently been published but showed only a modest improvement compared to dermoscopy, possibly due to study limitations., Objectives: The main objective of this study was to find diagnostic performance parameters of LC-OCT for differentiating BCC from its clinical/dermoscopic mimickers and for discriminating among BCC subtypes. An additional objective was to suggest a simple, user-friendly diagnostic algorithm based on the most powerful LC-OCT features in the field of BCC and its imitators., Materials and Methods: Equivocal BCC lesions imaged with an LC-OCT device prior to biopsy/excision were included. Three observers blinded for histopathological diagnosis retrospectively formulated clinical, dermoscopic and LC-OCT diagnoses and evaluated LC-OCT features for each study lesion., Results: A total of 303 lesions (173 BCCs and 130 non-BCCs) from 225 patients were included. For the differentiation of BCC from BCC imitators, the use of LC-OCT increased the diagnostic accuracy compared to clinical examination by 24% and compared to dermoscopy by 12%. For the discrimination of sBCC from other BCC subtypes, LC-OCT increased the diagnostic accuracy compared to clinical examination by 18% and compared to dermoscopy by 12%. The presence of lobule with millefeuille pattern was a significant feature for BCC diagnosis. Lobule shape and location allowed BCC subtype discrimination., Conclusions: The accuracy of BCC diagnosis can be increased by at least 12% with the use of LC-OCT compared to clinical and dermoscopic examinations alone, both in terms of BCC differentiation from clinical/dermoscopic imitators and in terms of BCC-subtype discrimination. A diagnostic algorithm based on significant features for BCC diagnosis is proposed, for which further validation is required., (© 2024 European Academy of Dermatology and Venereology.)

Introduction: UVA-UVB increases skin matrix metalloproteinases and breaks down extracellular proteins and fibrillar type 1 collagen, leading to photodamage. Topical application of nicotinamide prevents UV-induced immunosuppression. Several studies have demonstrated the importance of protection against UV. This study aims to determine the biological effect of a high broad-spectrum UVB-UVA sunscreen containing nicotinamide and panthenol (SSNP) on photodamaged skin using linear confocal optical coherence tomography (LC-OCT), immunohistochemistry, and RNA profiling., Methods: Two areas of severely photodamaged forearm skin (L01 and L02) and one less sun-damaged (naturally protected) area on the inner part of the forearm (L03) were identified in 14 subjects. These areas were imaged using LC-OCT and L01 and L03 were biopsied at baseline. After 4 weeks of treatment with SSNP, L02 was reimaged using LC-OCT, and biopsied. Histology, immunostaining with p21, p53, PCNA, and CPD, and RNA sequencing were performed in all samples., Results: LC-OCT analysis showed that epidermis thickness and the number of keratinocytes is higher in the sun-exposed areas than in the non-exposed areas. Comparing before and after treatment, even though there is a trend towards normalization, the differences were not statistically significant. The expression of p21, PCNA, p53, and CPD increased in severely photodamaged skin compared to less-damaged skin. When comparing before and after treatment, only p21 showed a trend to decrease expression. RNA sequencing analysis identified 1552 significant genes correlating with the progression from non-visibly photodamaged skin to post-treatment and pre-treatment samples; in the analysis comparing pre- and post-treatment samples, 5429 genes were found to be significantly associated. A total of 1115 genes are common in these two analyses. Additionally, nine significant genes from the first analysis and eight from the second are related to collagen. Six of these collagen genes are common in the two analyses. MAPK and cGMP-PKG signalling pathways are upregulated in the progression to photodamage analysis. In the pre- and post-treatment analysis, 32 pathways are downregulated after treatment, the most statistically significant being the ErbB, Hippo, NOD-like receptor, TNF, and NF-kB signalling pathways., Conclusion: This study demonstrates the role of SSNP in collagen generation, highlights the relevance of the cGMP-PKG and MAPK signalling pathways in photodamage, and shows the ability of SSNP to downregulate pathways activated by UV exposure. Additionally, it deepens our understanding of the effect of SSNP on immune-related pathways., Competing Interests: Declarations. Conflict of Interest: All authors declare some conflict of interest since La Roche-Posay funded this study. Moreover, Anne Laure Demessant-Flavigny, Leonor Prieto and Caroline Le Floc’h are L’Oreal Employees. In the last 36 months, existing conflict of interests were: Véronique Del Marmol have grants or contracts from BMS, MSD, Almirall and Sanofia; Josep Malvehy and Susana Puig from Abbvie, Almirall, Amgen, BMS, Biofrontera, Canfield, Cantabria, Fotofinder, GSK, ISDIN, La Roche Posay, Leo Pharma, MSD, MEDA, Novartis, Polychem, Roche and Sun Pharma. Véronique Del Marmol has received consulting fees from BMS, MSD, Sanofi, Merck, Almirall, Abbvie, Leo pharma, Pierre fabre, andNovartis. Josep Malvehy and Susana Puig have received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Roche Posay, Pierre-Fabre, Almirall and ISDIN; Jilliana Monnier from BMS, Pierre Fabre and Novartis; MP from ISDIN; Véronique Del Marmol from BMS, MSD,Sanofi, Sun pharma, Pierre fabre and Novartis. Josep Malvehy and Susana Puig received support for attending meetings and/or travel from Roche Posay, Pierre-Fabre, Almirall and ISDIN; Véronique Del Marmol from BMS, MSD, Pierre Fabre and Novartis; Josep Malvehy and Susana Puig participated on a Data Safety Monitoring Board Advisory Board for Pierre-Fabre, Almirall, SunPharma. Josep Malvehy and Susana Puig have stock options in Athena Tech of Dermavision. Ethical Approval: The study was approved in November 2019 by the Ethics Committee of Hospital Clínic de Barcelona, Spain (Nº HCB20190849). This study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The patients who took part in the study have given written informed consent to the publication of their case details., (© 2024. The Author(s).)

The cutaneous sclerosis, defined as a pathological increase of the elements composing the dermis or hypodermis, results in thickening and hardening of the skin. This cutaneous manifestation is often associated with systemic sclerosis. However, it is also found in other less well-known syndromes that are highly heterogeneous in their clinical presentations. This article reviews the etiologies, clinical presentations, and possible treatments of these rare pathologies., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Extramammary Paget disease (EMPD) is an uncommon adenocarcinoma of apocrine gland-rich areas, presenting significant diagnostic challenges due to its nonspecific clinical appearance and frequent misidentification as benign, inflammatory skin conditions. Traditional diagnostic methods such as biopsy are invasive and uncomfortable, often required repeatedly due to high recurrence rates. Dermoscopy and non-invasive imaging techniques have been used but provide limited diagnostic accuracy due to their constraints in depth penetration and resolution. Recent advancements in imaging technologies, such as line-field confocal optical coherence tomography (LC-OCT), show promise in enhancing diagnostic precision while minimizing invasive procedures. LC-OCT merges high-resolution imaging with deep penetration capabilities, capturing detailed horizontal and vertical skin images akin to histopathology. This study evaluated the diagnostic performance of LC-OCT in detecting EMPD and its recurrence in 17 clinically suspicious anogenital regions, belonging to six patients. Data were collected prospectively at the patient's bedside by an LC-OCT expert with poor training for EMPD, and, then, reviewed retrospectively by an independent LC-OCT expert with adequate training for EMPD and no concerns about time. The prospective examination yielded 64.7% accuracy (11 true results out of 17 total cases), 71.4% sensitivity (10 true positives out of 14 actual positives), and 33.3% specificity (1 true negative out of 3 actual negatives). The retrospective analysis achieved 94.1% accuracy (16 true results out of 17 total cases), 100% sensitivity (14 true positives out of 14 actual positives), and 66.7% specificity (2 true positives out of 3 actual positives), with the only false positive case being a difficult-to-diagnose concomitant presentation of a lichen sclerosus et atrophicus. Despite the need for specialized training, our results suggest that LC-OCT represents a valuable tool for accurately identifying EMPD and improving its management by reducing unnecessary biopsies. Further studies are needed to standardize its clinical application.

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease for which certain risk factors are well known: obesity and smoking (in particular). However, the factors associated with more severe conditions, and therefore potential aggravators of the disease, remain a matter of debate. Our study aims to determine the clinical factors associated with severe HS using several severity scores., Methods: The data were obtained via the ERHS questionnaire from patients exclusively recruited at Erasme Hospital in Brussels. The severity of HS was firstly estimated by the Hurley score, and secondly by a metascore, a system combining the iHS4, HS-PGA, SAHS, and DLQI. Univariable and multivariable analyses were performed., Results: Six hundred and forty-seven patients were included in the Hurley analysis, and 456 patients in the metascore analysis. In multivariable analysis, men have a more severe metascore than women (odds ratio [OR] = 1.89, p = 0.022), smoking was associated with a more severe disease according to metascore, especially in mild cases (OR = 0.76, p = 0.043), and an elevated body mass index was associated with having Hurley stage III disease compared to Hurley I or II disease (OR = 1.09, p = 0.001). A significant association is also shown between blood pressure and Hurley stage (OR = 0.97, p = 0.025). Self-reports of nonsteroidal anti-inflammatory drugs aggravating the disease is also a factor associated with greater severity according to the metascore (OR = 0.12, p = 0.008). Finally, several locations of HS lesions were associated with greater severity, in particular the armpits according to the metascore (OR = 0.29, p < 0.001), and the perianal area according to the Hurley score (OR = 0.15, p < 0.001)., Conclusion: HS seems to be more severe in men; smoking seems to aggravate mild cases of HS, while increased body mass index plays a major role in the transition from Hurley II to Hurley III., (© 2024 S. Karger AG, Basel.)

Squamous cell carcinoma and its precursor lesion actinic keratosis are often found together in areas of skin chronically exposed to sun, otherwise called cancerisation fields. The clinical assessment of cancerisation fields and the correct diagnosis of lesions within these fields is usually challenging for dermatologists. The recent adoption of skin cancer diagnostic imaging techniques, particularly LC-OCT, helps clinicians in guiding treatment decisions of cancerization fields in a non-invasive way. The combination of artificial intelligence and non-invasive skin imaging opens up many possibilities as AI can perform tasks impossible for humans in a reasonable amount of time. In this text we review past examples of the application of AI to dermatological images for actinic keratosis/squamous cell carcinoma diagnosis, and we discuss about the prospects of the application of AI for the characterization and management of cancerization fields.

Introduction: Line-field confocal optical coherence tomography (LC-OCT) is a recently introduced, non-invasive skin imaging technique combining the technical advantages of reflectance confocal microscopy and conventional OCT in terms of isotropic resolution and in-tissue penetration. Several studies have been published so far about the use of LC-OCT in melanocytic and non-melanocytic skin tumors. The aim of this review was to summarize the currently available data on the use of LC-OCT for benign and malignant melanocytic and non-melanocytic skin tumors., Evidence Acquisition: We searched scientific databases for any literature published up to 30 th April 2023 and concerning the use of LC-OCT for melanocytic and non-melanocytic skin tumors. Identified papers were evaluated, and relevant information was extracted., Evidence Synthesis: A total of 29 studies were found including original articles, short reports, and letters to the Editor: 6 applied to melanocytic skin tumors, 22 to non-melanocytic skin tumors and 1 to both. The use of LC-OCT increased the diagnostic accuracy for melanocytic and non-melanocytic skin lesions. The highest diagnostic performance was found for basal cell carcinoma (BCC), but significant improvements in the diagnostic accuracy were also detected for the differentiation of actinic keratosis (AK) from squamous cell carcinoma (SCC) and of melanoma from nevi. The LC-OCT features of other skin tumors were also described and successfully correlated with histopathology., Conclusions: LC-OCT proved to increase the diagnostic accuracy for melanocytic and non-melanocytic skin lesions, thanks to the combination of high resolution/penetration, 3D reconstructions, and integrated dermoscopy. Although BCC seems the most suitable tumors for LC-OCT examination, the device is extremely performant for the differentiation of AK from SCC and the discrimination of melanoma from nevi as well. Additional studies on diagnostic performance and new investigations about the presurgical assessment of tumor margins with LC-OCT and its association with human and artificial intelligence algorithms are in progress.

Background: Line-field confocal optical coherence tomography (LC-OCT) is a new in vivo emerging technique that provides cellular resolution, allows deep imaging (400 μm) and produces real-time images in both the horizontal and vertical plane and in three dimensions. No previous description of different subtypes of melanocytic lesions and their correlation with histopathology and reflectance confocal microscopy has been reported., Aim: To describe the features of melanocytic lesions by LC-OCT and their correlation with histopathology and reflectance confocal microscopy (RCM) findings., Methods: Selected melanocytic benign lesions and melanomas were imaged in vivo with RCM and LC-OCT at the Fundación Hospital Clinic (Barcelona, Spain). A minimum area of 4 × 4 mm (block image) at four depths (stratum granulosum, suprabasal, layer dermoepidermal junction and upper dermis) were acquired with RCM and a minimum of three cubes with LC-OCT. Horizontal, vertical sections and three-dimensional (3D) cubes of LC-OCT were matched with RCM (Vivablock two-dimensional composite mosaic) and histopathology, with ~5 μm lateral resolution accuracy (the same cell nuclei were measured in X, Y and Z) and evaluated by three observers experienced in using RCM and histopathology., Results: In total, 12 melanocytic tumours (2 in situ melanomas, 2 invasive melanomas, 4 atypical naevi, 2 intradermal naevi, 1 compound naevus and 1 junctional naevus) were included. High correlation with 5 μm accuracy between RCM and LC-OCT was observed for each tumour. The 3D images of melanocytic lesions were obtained with cellular resolution and correlated with both RCM and histopathology, allowing an understanding of the architecture and precise correlation at the cellular level with RCM. Similarities between LC-OCT and RCM for the described diagnostic features and architecture (nests of melanocytic cells, ringed and meshwork pattern, and cellular details of tumour cells as dendritic and pagetoid cells) were confirmed. The main advantage of diagnosis by RCM fixed probe was the ability to produce larger scans of the lesion using mosaicing compared with an LC-OCT handheld probe., Conclusion: LC-OCT allows the architectural and cellular description of different types of melanocytic lesions. LC-OCT showed high correlation with histopathology (vertical sections) and RCM (horizontal sections) in melanocytic lesions. Diagnostic criteria for RCM were similar to those for LC-OCT., (© 2022 British Association of Dermatologists.)

Background: Chemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value., Methods: Blood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels - Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC)., Results: 21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. Plasma chemerin concentration were significantly higher in ICU patients than in HC at all time-points analyzed (p<0.0001). Moreover, they were higher in deceased patients compared to survivors (p<0.05). Logistic univariate regression and multivariate analysis demonstrated that chemerin level at day 14 of admission was an independent risk factor for death. Accordingly, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein and tumor necrosis factor α. Finally, IHC analysis revealed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts in advanced acute respiratory distress syndrome (ARDS)., Discussion: Increased plasma chemerin levels are a marker of severity and may predict death of COVID-19 patients. However, multicentric studies are needed, before chemerin can be considered as a biomarker of severity and death used in daily clinical practice. Further studies are also necessary to identify the precise mechanisms of the chemerin/ChemR23 system in ARDS secondary to viral pneumonia., Competing Interests: BB received a financial support from Amgen and Boehringer Ingelheim. These funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article and the decision to submit for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lavis, Morra, Orte Cano, Albayrak, Corbière, Olislagers, Dauby, Del Marmol, Marchant, Decaestecker, Mascart, De Vos, Van de Borne, Salmon, Remmelink, Parmentier, Cardozo and Bondue.)

Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae, but little is known about the eventual persistence of this immune alteration. Herein, we evaluated TLR-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n = 97). In the acute phase, we observed impaired cytokine production by monocytes in the patients with the most severe COVID-19. This capacity was globally restored in convalescent patients. However, we observed increased responsiveness to TLR1/2 ligation in patients who recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. In patients with acute severe COVID-19, we identified a specific transcriptomic and epigenomic state in monocytes that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at activating protein 1 (AP1) and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes, during both the acute and the convalescent phases, in a completely distinct manner. This could have important implications for our understanding of short- and long-term COVID-19-related morbidity.

The new pandemic virus SARS-CoV-2 is characterized by uncontrolled hyper-inflammation in severe cases. As the IL-22/IL-22R1 axis was reported to be involved in inflammation during viral infections, we characterized the expression of IL-22 receptor1, IL-22 and IL-22 binding protein in COVID-19 patients. Blood samples were collected from 19 non-severe and 14 severe patients on the day they presented (D0), at D14, and six months later, and from 6 non-infected controls. The IL-22R1 expression was characterized by flow cytometry. Results were related to HLA-DR expression of myeloid cells, to plasma concentrations of different cytokines and chemokines and NK cells and T lymphocytes functions characterized by their IFN-γ, IL-22, IL-17A, granzyme B and perforin content. The numbers of IL-22R1 + classical, intermediate, and non-classical monocytes and the proportions of IL-22R1 + plasmacytoid DC (pDC), myeloid DC1 and DC2 (mDC1, mDC2) were higher in patients than controls at D0. The proportions of IL-22R1 + classical and intermediate monocytes, and pDC and mDC2 remained high for six months. High proportions of IL-22R1 + non-classical monocytes and mDC2 displayed HLA-DR high expression and were thus activated. Multivariate analysis for all IL-22R1 + myeloid cells discriminated the severity of the disease (AUC=0.9023). However, correlation analysis between IL-22R1 + cell subsets and plasma chemokine concentrations suggested pro-inflammatory effects of some subsets and protective effects of others. The numbers of IL-22R1 + classical monocytes and pDC were positively correlated with pro-inflammatory chemokines MCP-1 and IP-10 in severe infections, whereas IL-22R1 + intermediate monocytes were negatively correlated with IL-6, IFN-α and CRP in non-severe infections. Moreover, in the absence of in vitro stimulation, NK and CD4 + T cells produced IFN-γ and IL-22, and CD4 + and CD8 + T cells produced IL-17A. CD4 + T lymphocytes also expressed IL-22R1, the density of its expression defining two different functional subsets. In conclusion, we provide the first evidence that SARS-CoV-2 infection is characterized by an abnormal expression of IL22R1 on blood myeloid cells and CD4 + T lymphocytes. Our results suggest that the involvement of the IL-22R1/IL-22 axis could be protective at the beginning of SARS-CoV-2 infection but could shift to a detrimental response over time., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Albayrak, Orte Cano, Karimi, Dogahe, Van Praet, Godefroid, Del Marmol, Grimaldi, Bondue, Van Vooren, Mascart and Corbière.)

Background: Surfactant protein D (SP-D) and pulmonary club cell protein 16 (CC-16) are called "pneumoproteins" and are involved in host defense against oxidative stress, inflammation, and viral outbreak. This study aimed to determine the predictive value of these pneumoproteins on the incidence of acute respiratory distress syndrome (ARDS) or death in patients with coronavirus disease-2019 (COVID-19)., Methods: This retrospective study included 87 patients admitted to an emergency department. Blood samples were collected on three time points (days 1, 5, and 14 from hospital admission). SP-D and CC-16 serum levels were determined, and univariate and multivariate analyses considering confounding variables (age, body mass index, tobacco use, dyspnea, hypertension, diabetes mellitus, neutrophil-to-lymphocyte ratio) were performed., Results: Based on the multivariate analysis, SP-D level on D1 was positively and slightly correlated with subsequent development of ARDS, independent of body mass index, dyspnea, and diabetes mellitus. CC-16 level on D1 was modestly and positively correlated with fatal outcome. A rise in SP-D between D1 and D5 and D1 and D14 had a strong negative association with incidence of ARDS. These associations were independent of tobacco use and neutrophil-to-lymphocyte ratio., Conclusions: Overall, our data reveal that increase in SP-D levels is a good prognostic factor for patients with COVID-19, and that initial CC-16 levels correlated with slightly higher risk of death. SP-D and CC-16 may prove useful to predict outcomes in patients with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tiezzi, Morra, Seminerio, Van Muylem, Godefroid, Law-Weng-Sam, Van Praet, Corbière, Orte Cano, Karimi, Del Marmol, Bondue, Benjelloun, Lavis, Mascart, van de Borne and Cardozo.)

Epidermal three-dimensional (3D) topography/quantification has not been completely characterized yet. The recently developed line-field confocal optical coherence tomography (LC-OCT) provides real-time, high-resolution, in-vivo 3D imaging of the skin. This pilot study aimed at quantifying epidermal metrics (epidermal thicknesses, dermal-epidermal junction [DEJ] undulation and keratinocyte number/shape/size) using 3D LC-OCT. For each study participant (8 female, skin-type-II, younger/older volunteers), seven body sites were imaged with LC-OCT. Epidermal metrics were calculated by segmentations and measurements assisted by artificial intelligence (AI) when appropriate. Thicknesses of epidermis/SC, DEJ undulation and keratinocyte nuclei volume varied across body sites. Evidence of keratinocyte maturation was observed in vivo: keratinocyte nuclei being small/spherical near the DEJ and flatter/elliptical near the skin surface. Skin microanatomy can be quantified by combining LC-OCT and AI. This technology could be highly relevant to understand aging processes and conditions linked to epidermal disorders. Future clinical/research applications are to be expected in this scenario., (© 2021 Wiley-VCH GmbH.)