المؤلفون: Cima, Luca, Bussola, Nicole, Hassell, Lewis A, Kiehl, Tim-Rasmus, Schukow, Casey, Zerbe, Norman, Munari, Enrico, Torresani, Evelin, Barbareschi, Mattia, Cecchini, Matthew J, Cirielli, Vito, Pagliuca, Francesca, Ahsan, Muhammad, Mohanty, Sambit K, Arbitrio, Ernesto, Hughes, Griffin, Mirza, Kamran M

مصطلحات موضوعية: Systematic review

الوصف: Aims Pathology education is a core component of medical training, and its literature is critical for refining educational modalities. We performed a cross-sectional bibliometric analysis to explore publications on pathology education, focusing on new medical education technologies. Methods The analysis identified 64 pathology journals and 53 keywords. Relevant articles were collected using a web application, PaperScraper, developed to accelerate literature search. Citation data were collected from multiple sources. Descriptive statistics, with time period analysis, were performed using Microsoft Excel and visualised with Flourish Studio. Two article groups were further investigated with a bibliometric software, VOSViewer, to establish co-authorship and keyword relationships. Results 8946 citations were retrieved from 905 selected articles. Most articles were published in the last decade (447, 49.4%). The top journals were Archives of Pathology & Laboratory Medicine (184), Human Pathology (122) and the American Journal of Clinical Pathology (117). The highest number of citations was found for Human Pathology (2120), followed by Archives of Pathology & Laboratory Medicine (2098) and American Journal of Clinical Pathology (1142). Authors with different backgrounds had the greatest number of articles and citations. 12 co-authorship, 3 keyword and 8 co-citation clusters were found for the social media/online resources group, 8 co-authorship, 4 keyword and 7 co-citation clusters for the digital pathology/virtual microscopy/mobile technologies group. Conclusions The analysis revealed a significant increase in publications over time. The emergence of digital teaching and learning resources played a major role in this growth. Overall, these findings underscore the transformative potential of technology in pathology education.

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العلاقة: http://jcp.bmj.com/cgi/content/short/77/2/87Test; http://dx.doi.org/10.1136/jcp-2023-209203Test

الإتاحة: https://doi.org/10.1136/jcp-2023-209203Test
http://jcp.bmj.com/cgi/content/short/77/2/87Test

المؤلفون: Bergamini, Marco, Dalla Volta, Alberto, Valcamonico, Francesca, Caramella, Irene, Buffoni, Martina, Munari, Enrico, Fisogni, Simona, Zanotelli, Tiziano, Suardi, Nazareno Roberto, Berruti, Alfredo

المصدر: Case Reports in Oncology ; volume 17, issue 1, page 56-68 ; ISSN 1662-6575

الوصف: Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs.

الإتاحة: https://doi.org/10.1159/000535460Test
https://karger.com/cro/article-pdf/17/1/56/4155230/000535460.pdfTest

المؤلفون: Perrone, Carola, Bozzano, Federica, Dal Bello, Maria Giovanna, Del Zotto, Genny, Antonini, Francesca, Munari, Enrico, Maggi, Enrico, Moretta, Francesca, Farshchi, Alireza Hajabbas, Pariscenti, Gianluca, Tagliamento, Marco, Genova, Carlo, Moretta, Lorenzo, De Maria, Andrea

المصدر: Frontiers in Immunology ; volume 15 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: Background There is little information on the trajectory and developmental fate of Lin - CD34 + DNAM-1 bright CXCR4 + progenitors exiting bone marrow during systemic inflammation. Objective To study Lin - CD34 + DNAM-1 bright CXCR4 + cell circulation in cancer patients, to characterize their entry into involved lung tissue and to characterize their progenies. Methods Flow cytometric analysis of PBMC from 18 patients with lung cancer on samples collected immediately before the first and the second treatment was performed to study Lin - CD34 + DNAM-1 bright CXCR4 + precursors. Precursors were purified (>99%) and cultured in vitro from all patients. Paired PBMC and tissue samples from patients undergoing tumor resection were analyzed by flow cytometry to assess tissue entry and compare phenotype and developmental potential of Lin - CD34 + DNAM-1 bright CXCR4 + cells in both compartments. Results Significant circulation of Lin - CD34 + DNAM-1 bright CXCR4 + precursors was observed 20d after the first treatment. Precursors express CXC3CR1, CXCR3, CXCR1 consistent with travel towards inflamed tissues. Flowcytometric analysis of lung tissue samples showed precursor presence in all patients in tumor and neighboring uninvolved areas. Successful purification and in vitro culture from both blood and lung tissue generates a minor proportion of maturing NK cells (<10%) and a predominant proportion (>85%) of α/β T-progenies with innate-like phenotype expressing NKG2D,NKp30,DNAM-1. Innate-like maturing T-cells in vitro are cytotoxic, can be triggered via NKR/TCR co-stimulation and display broad spectrum Th1,Th2 and Th1/Th17 cytokine production. Conclusion In advanced stage lung cancer CD34 + DNAM-1 bright CXCR4 + inflammatory precursors increase upon treatment, enter involved tissues, generate functional progenies and may thus represent an additional player contributing to immune balance in the highly SDF-1/CXCR4-biased pro-metastatic tumor microenvironment.

الإتاحة: https://doi.org/10.3389/fimmu.2024.1332781Test

المؤلفون: Girolami, Ilaria, Marletta, Stefano, Fiorentino, Vincenzo, Battocchio, Simonetta, Cerbelli, Bruna, Fiamengo, Barbara, Gerosa, Clara, Gianatti, Andrea, Morelli, Luca, Riva, Giulio, Zagami, Maria Giovanna, Fusco, Nicola, Munari, Enrico, L'Imperio, Vincenzo, Pagni, Fabio, Morbini, Patrizia, Martini, Maurizio, Eccher, Albino

المساهمون: Girolami, Ilaria, Marletta, Stefano, Fiorentino, Vincenzo, Battocchio, Simonetta, Cerbelli, Bruna, Fiamengo, Barbara, Gerosa, Clara, Gianatti, Andrea, Morelli, Luca, Riva, Giulio, Zagami, Maria Giovanna, Fusco, Nicola, Munari, Enrico, L'Imperio, Vincenzo, Pagni, Fabio, Morbini, Patrizia, Martini, Maurizio, Eccher, Albino

مصطلحات موضوعية: head and neck squamous cell carcinoma, immunohistochemistry, immunotherapy, programmed death-ligand 1, radio-chemotherapy, systematic review

الوصف: Background: Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. Methods: A systematic search was carried out in electronic databases Pubmed-MEDLINE and Embase to retrieve studies on the comparison of PD-L1 expression before and after conventional therapy. Data were extracted and a quantitative analysis with pooled odds ratios (ORs) was performed when applicable. Results: Of 5688 items, 15 were finally included. Only a minority of studies assessed PD-L1 with the recommended combined positive score (CPS). The results are highly heterogeneous, with some studies reporting an increase in PD-L1 expression and others reporting a decrease. Three studies allowed for quantitative analysis and showed a pooled OR of 0.49 (CI 0.27-0.90). Conclusions: From the present evidence, a clear conclusion towards an increase or decrease in PD-L1 expression after combined therapy cannot be drawn, but even with few studies available, a trend towards an increase in expression in tumor cells at a cutoff of 1% can be noted in patients undergoing platinum-based therapy. Future studies will provide more robust data on the effect of combined therapy on PD-L1 expression.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36836595; info:eu-repo/semantics/altIdentifier/wos/WOS:000940055200001; volume:13; issue:2; firstpage:1; lastpage:12; numberofpages:12; journal:JOURNAL OF PERSONALIZED MEDICINE; https://hdl.handle.net/11380/1317413Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85148937825

الإتاحة: https://doi.org/10.3390/jpm13020363Test
https://hdl.handle.net/11380/1317413Test

المؤلفون: Di Matteo, Sabina, Munari, Enrico, Fiore, Piera Filomena, Santopolo, Silvia, Sampaoli, Camilla, Pelosi, Andrea, Chouaib, Salem, Tumino, Nicola, Vacca, Paola, Mariotti, Francesca Romana, Ebert, Stefan, Machwirth, Markus, Haas, Dorothee, Pezzullo, Marco, Pietra, Gabriella, Grottoli, Melania, Buart, Stephanie, Mortier, Erwan, Maggi, Enrico, Moretta, Lorenzo, Caruana, Ignazio, Azzarone, Bruno

المساهمون: IRCCS Ospedale Pediatrico Bambino Gesù = Bambino Gesù Children’s Hospital, Università degli Studi di Brescia = University of Brescia (UniBs), Institut Gustave Roussy (IGR), Gulf Medical University Ajman, UAE, Immunologie intégrative des tumeurs et immunothérapie des cancers (INTIM), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University Hospital of Würzburg, Università degli studi di Genova = University of Genoa (UniGe), IRCCS Ospedale Policlinico San Martino Genoa, Italy, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)

المصدر: ISSN: 1664-3224.

مصطلحات موضوعية: immunology, melanoma, natural killer cells, IL-15, IL–15 complex, cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology

الوصف: International audience ; Background Melanoma is a lethal skin cancer, and the risk of developing it is increased by exposure to ultraviolet (UV) radiation. The production of cytokines such as interleukin-15 (IL-15), induced by the exposure of skin cells to UV rays, could also promote melanoma development. The aim of this study is to investigate the possible role of Interleukin-15/Interleukin-15 Receptor α (IL-15/IL-15Rα) complexes in melanoma development. Methods The expression of IL-15/IL-15Rα complexes by melanoma cells was evaluated both ex vivo and in vitro by tissue microarray, PCR, and flow cytometry. The presence of the soluble complex (sIL-15/IL-15Rα) in the plasma of metastatic melanoma patients was detected using an ELISA assay. Subsequently, we investigated the impact of natural killer (NK) cell activation after rIL-2 starvation followed by exposure to the sIL-15/IL-15Rα complex. Finally, by analyzing public datasets, we studied the correlation between IL-15 and IL-15Rα expressions and melanoma stage, NK and T-cell markers, and overall survival (OS). Results Analysis of a melanoma tissue microarray shows a significant increase in the number of IL-15 + tumor cells from the benign nevi to metastatic melanoma stages. Metastatic melanoma cell lines express a phorbol-12-myristate-13-acetate (PMA)-cleavable membrane-bound IL-15 (mbIL-15), whereas cultures from primary melanomas express a PMA-resistant isoform. Further analysis revealed that 26% of metastatic patients present with consistently high plasmatic levels of sIL-15/IL-15Rα. When the recombinant soluble human IL-15/IL-15Rα complex is added to briefly starved rIL-2-expanded NK cells, these cells exhibit strongly reduced proliferation and levels of cytotoxic activity against K-562 and NALM-18 target cells. The analysis of public gene expression datasets revealed that high IL-15 and IL-15Rα intra-tumoral production correlates with the high levels of expression of CD5 + and NKp46 + (T and NK markers) and significantly correlates with a better OS in ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37334356; inserm-04119880; https://inserm.hal.science/inserm-04119880Test; https://inserm.hal.science/inserm-04119880/documentTest; https://inserm.hal.science/inserm-04119880/file/fimmu-14-1183668.pdfTest; PUBMED: 37334356; PUBMEDCENTRAL: PMC10272795

الإتاحة: https://doi.org/10.3389/fimmu.2023.1183668Test
https://inserm.hal.science/inserm-04119880Test
https://inserm.hal.science/inserm-04119880/documentTest
https://inserm.hal.science/inserm-04119880/file/fimmu-14-1183668.pdfTest

المؤلفون: Eccher, Albino, Dei Tos, Angelo Paolo, Scarpa, Aldo, L'Imperio, Vincenzo, Munari, Enrico, Troncone, Giancarlo, Naccarato, Antonio Giuseppe, Seminati, Davide, Pagni, Fabio

مصطلحات موضوعية: Best practice

الوصف: Context Despite the reluctance to invest and the challenging estimation of necessary supporting costs, optimising the archives seems to be one of the hottest topics in the future management of the pathology laboratories. Historically, archives were only partially designed to securely store and organise tissue specimens, and tracking systems were often flawed, posing significant risks to patients’ health and legal ramifications for pathologists. Objective The current review explores the available data from the literature on archives’ management in pathology, including comprehensive business plans, structure setup, outfit, inventories, ongoing conservation and functional charges. Data sources Electronic searches in PubMed-MEDLINE and Embase were made to extract pertinent articles from the literature. Works about the archiving process and storage were included and analysed to extract information. Prepublication servers were ignored. Italian Institutional Regional databases for public competitive bidding processes were queried too. Conclusions A new emergent feeling in the pathology laboratory is growing for archives management; the digital pathology era is a great opportunity to apply innovation to tracking systems and samples preservation. The main aim is a critical evaluation of the return of investment in developing automatic and tracked archiving processes for improving not only quality, efficacy and efficiency of the labs but also patients’ healthcare.

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العلاقة: http://jcp.bmj.com/cgi/content/short/76/10/659Test; http://dx.doi.org/10.1136/jcp-2023-209035Test

الإتاحة: https://doi.org/10.1136/jcp-2023-209035Test
http://jcp.bmj.com/cgi/content/short/76/10/659Test

المؤلفون: Marletta, Stefano, Salatiello, Maria, Pantanowitz, Liron, Bellevicine, Claudio, Bongiovanni, Massimo, Bonoldi, Emanuela, De Rezende, Gisele, Fadda, Guido, Incardona, Paolo, Munari, Enrico, Pagni, Fabio, Rossi, Esther Diana, Tallini, Giovanni, Troncone, Giancarlo, Ugolini, Clara, Vigliar, Elena, Eccher, Albino

المصدر: Cytopathology ; volume 34, issue 6, page 581-589 ; ISSN 0956-5507 1365-2303

الوصف: Objective Despite an increase in thyroid fine needle aspiration (FNA) and advances in whole slide imaging (WSI) adoption, digital pathology is still considered inadequate for primary diagnosis of these cases. Herein, we aim to validate the utility of WSI in thyroid FNAs employing the Delphi method strategy. Methods A panel of experts from seven reference cytology centres was recruited. The study consisted of two consecutive rounds: (1) an open‐ended, free‐response questionnaire generating a list of survey items; and (2) a consensus analysis of 80 selected shared WSIs from 80 cases by six investigators answering six morphological questions utilising a 1 to 5 Likert scale. Results High consensus was achieved for all parameters, with an overall average score of 4.27. The broad majority of items (84%) were ranked either 4 or 5 by each physician. Two badly scanned cases were responsible for more than half of the low‐ranked (≤2) values (57%). Good to excellent (≥3) diagnostic confidence was reached in more than 95.2% of cases. For most cases (78%) WSI assessment was not limited by technical issues linked to the image acquisition process. Conclusion This systematic Delphi study indicates broad consensus among participating physicians on the application of DP to thyroid cytopathology, supporting expert opinion that WSI is reliable and safe for primary diagnostic purposes.

الإتاحة: https://doi.org/10.1111/cyt.13279Test

المؤلفون: Aswolinskiy, Witali, Munari, Enrico, Horlings, Hugo M., Mulder, Lennart, Bogina, Giuseppe, Sanders, Joyce, Liu, Yat-Hee, van den Belt-Dusebout, Alexandra W., Tessier, Leslie, Balkenhol, Maschenka, Stegeman, Michelle, Hoven, Jeffrey, Wesseling, Jelle, van der Laak, Jeroen, Lips, Esther H., Ciompi, Francesco

المساهمون: Dutch Cancer Society, HORIZON EUROPE Innovative Europe

المصدر: Breast Cancer Research ; volume 25, issue 1 ; ISSN 1465-542X

الوصف: Background Invasive breast cancer patients are increasingly being treated with neoadjuvant chemotherapy; however, only a fraction of the patients respond to it completely. To prevent overtreatment, there is an urgent need for biomarkers to predict treatment response before administering the therapy. Methods In this retrospective study, we developed hypothesis-driven interpretable biomarkers based on deep learning, to predict the pathological complete response (pCR, i.e., the absence of tumor cells in the surgical resection specimens) to neoadjuvant chemotherapy solely using digital pathology H&E images of pre-treatment breast biopsies. Our approach consists of two steps: First, we use deep learning to characterize aspects of the tumor micro-environment by detecting mitoses and segmenting tissue into several morphology compartments including tumor, lymphocytes and stroma. Second, we derive computational biomarkers from the segmentation and detection output to encode slide-level relationships of components of the tumor microenvironment, such as tumor and mitoses, stroma, and tumor infiltrating lymphocytes (TILs). Results We developed and evaluated our method on slides from n = 721 patients from three European medical centers with triple-negative and Luminal B breast cancers and performed external independent validation on n = 126 patients from a public dataset. We report the predictive value of the investigated biomarkers for predicting pCR with areas under the receiver operating characteristic curve between 0.66 and 0.88 across the tested cohorts. Conclusion The proposed computational biomarkers predict pCR, but will require more evaluation and finetuning for clinical application. Our results further corroborate the potential role of deep learning to automate TILs quantification, and their predictive value in breast cancer neoadjuvant treatment planning, along with automated mitoses quantification. We made our method publicly available to extract segmentation-based biomarkers for research purposes.

الإتاحة: https://doi.org/10.1186/s13058-023-01726-0Test

المؤلفون: Munari, Enrico, Scarpa, Aldo, Cima, Luca, Pozzi, Matteo, Pagni, Fabio, Vasuri, Francesco, Marletta, Stefano, Dei Tos, Angelo Paolo, Eccher, Albino

المساهمون: Università degli Studi di Verona

المصدر: Virchows Archiv ; ISSN 0945-6317 1432-2307

مصطلحات موضوعية: Cell Biology, Molecular Biology, General Medicine, Pathology and Forensic Medicine

الوصف: One of the goals of pathology is to standardize laboratory practices to increase the precision and effectiveness of diagnostic testing, which will ultimately enhance patient care and results. Standardization is crucial in the domains of tissue processing, analysis, and reporting. To enhance diagnostic testing, innovative technologies are also being created and put into use. Furthermore, although problems like algorithm training and data privacy issues still need to be resolved, digital pathology and artificial intelligence are emerging in a structured manner. Overall, for the field of pathology to advance and for patient care to be improved, standard laboratory practices and innovative technologies must be adopted. In this paper, we describe the state-of-the-art of automation in pathology laboratories in order to lead technological progress and evolution. By anticipating laboratory needs and demands, the aim is to inspire innovation tools and processes as positively transformative support for operators, organizations, and patients.

الإتاحة: https://doi.org/10.1007/s00428-023-03637-zTest

المؤلفون: Mariotti, Francesca Romana, Ingegnere, Tiziano, Landolina, Nadine, Vacca, Paola, Munari, Enrico, Moretta, Lorenzo

المساهمون: Fondazione AIRC per la ricerca sul cancro ETS, Ministry of Health, HORIZON EUROPE Marie Sklodowska-Curie Actions

المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: NK cells represent important effectors that play a major role in innate defences against pathogens and display potent cytolytic activity against tumor cells. An array of surface receptors finely regulate their function and inhibitory checkpoints, such as PD-1, can dampen the immune response inducing an immunosuppressive state. Indeed, PD-1 expression in human NK cells correlated with impaired effector function and tumor immune evasion. Importantly, blockade of the PD-1/PD-L1 axis has been shown to reverse NK cell exhaustion and increase their cytotoxicity. Recently, soluble counterparts of checkpoint receptors, such as soluble PD-1 (sPD-1), are rising high interest due to their biological activity and ability to modulate immune responses. It has been widely demonstrated that sPD-1 can modulate T cell effector functions and tumor growth. Tumor-infiltrating T cells are considered the main source of circulating sPD-1. In addition, recently, also stimulated macrophages have been demonstrated to release sPD-1. However, no data are present on the role of sPD-1 in the context of other innate immune cell subsets and therefore this study is aimed to unveil the effect of sPD-1 on human NK cell function. We produced the recombinant sPD-1 protein and demonstrated that it binds PD-L1 and that its presence results in increased NK cell cytotoxicity. Notably, we also identified a pathway regulating endogenous sPD-1 synthesis and release in human NK cells. Secreted endogenous sPD-1, retained its biological function and could modulate NK cell effector function. Overall, these data reveal a pivotal role of sPD-1 in regulating NK-mediated innate immune responses.

الإتاحة: https://doi.org/10.3389/fimmu.2023.1229341Test