The holistic perspective of the INCISIVE project : artificial intelligence in screening mammography

Finding new ways to cost-effectively facilitate population screening and improve cancer diagnoses at an early stage supported by data-driven AI models provides unprecedented opportunities to reduce cancer related mortality. This work presents the INCISIVE project initiative towards enhancing AI solutions for health imaging by unifying, harmonizing, and securely sharing scattered cancer-related data to ensure large datasets which are critically needed to develop and evaluate trustworthy AI models. The adopted solutions of the INCISIVE project have been outlined in terms of data collection, harmonization, data sharing, and federated data storage in compliance with legal, ethical, and FAIR principles. Experiences and examples feature breast cancer data integration and mammography collection, indicating the current progress, challenges, and future directions

Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations.

The B cell receptor immunoglobulin (BcR IG) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n=488) i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL) as well as provisional entities (n=76) according to the World Health Organization classification. The most striking IG gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different IG gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ IG sequence dataset with a large dataset of IG sequences (MZ-related or not; n=65,837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia but also rheumatoid factors and non-malignant spleen MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms, may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments.This work was supported in part by H2020 “AEGLE, An analytics framework for integrated and personalized healthcare services in Europe”, by the European Union (EU); H2020 No. 692298 project “MEDGENET, Medical Genomics and Epigenomics Network” by the EU; grant AZV 15-30015A from the Ministry of Health of the Czech Republic, and the project CEITEC2020 LQ1601 from the Ministry of Education, Youth, and Sports of the Czech Republic; Bloodwise Research Grant (15019); the Swedish Cancer Society, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Karolinska Institutet, Stockholm, the Lion’s Cancer Research Foundation, Uppsala, the Marcus Borgström Foundation and Selander’s Foundation, Uppsala

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Immunogenetic analysis of the T cell receptor repertoire of cytotoxic T lymphocytes with high throughput sequence

Introduction: Mono-, oligo- and poly- clonal expansions of CD3+CD8+CD57+ T-LGL may be either idiopathic or develop within the clinical context of several conditions e.g. autoimmunity, viral infections, post-transplant and in hematologic malignancies. Whether this heterogeneity reflects a dynamic process of cytotoxic T-cell responses against auto- and exoantigens remains to be established. Aim: The limited analytical depth of Sanger-based analysis has hindered firm conclusions from being drawn regarding the pathogenesis of these entities. In order to overcome these limitations and obtain insight into the role of antigenic drive in T-LGL lymphoproliferations, we here exploited high-throughput next generation sequencing (NGS) to interrogate the TRB gene repertoire. In the era of high throughput sequencing, our perceptions about immune responses will be revised. However, the absence of standardized experimental procedure and dedicated bioinformatics pipeline, special designed for immunogenetics data doesn’t ensure the repeatability of our results. Material and Methods: Included in the study were (i) a father and a son with T-LGL leukemia, the first case of intra-family occurrence; a single blood sample from the father and 2 samples from the son spanning 5 years were analyzed; and, (ii) a patient with T-LGL leukemia of donor cell origin developing after allogeneic hematopoietic cell transplantation (allo-HCT) for Philadelphia-positive acute lymphoblastic leukemia: and (iii) 13 well characterized Chronic Idiopathic Neutropenia (CIN) cases. TRBV-TRBJ-TRBD rearrangements were amplified on gDNA or/and cDNA and subjected to paired end NGS, covering the CDR3 twice/sequence. To increase the consistency of results, raw NGS reads were analyzed by a purpose-built bioinformatics algorithm, performing: (i) quality filtering, (ii) merging of filtered in paired reads and (iii) quality filter of stitched sequences. Filtered-in sequences were submitted to IMGT/HighV-QUEST, and metadata was processed by an in-house dedicated bioinformatics pipeline. Results: Major findings in all cases included: (i) pronounced skewing of the TRBV repertoire; (ii) existence of more than one immunodominant clonotype; (iii) persisting clonotypes in different timepoints albeit with fluctuating frequencies (clonal drift); and, (iv) shared (‘public’)clonotypes between cases and the public databases, further suggest a limited number of antigens implicated in pathogenesis of T-LGL cases.Conclusions: The borders between polyclonal versus oligoclonal versus monoclonal T-LGL lymphoproliferations are not sharply demarcated, but rather the transition from a polyclonal cytotoxic response to the development of T-LGL leukemia is a gradual process. Repertoire restrictions, public clonotypes and clonal drift strongly indicate selection by restricted (perhaps also shared) antigens in T-LGL leukemia ontogeny and evolution.Εισαγωγή: Οι λεμφοϋπερπλασίες CD3+CD8+CD57+ μεγάλων Τ λεμφοκυττάρων με κοκκία (T-LGL) αναπτύσσονται σε ευρύ νοσολογικό ετερογενές φάσμα διαφόρων κλινικών οντοτήτων και χαρακτηρίζονται από επικάλυψη κλινικών συμπτωμάτων αλλά και εργαστηριακών ευρημάτων. Η ανοσογενετική ανάλυση των γονιδίων της β αλυσίδας του Τ κυτταρικού υποδοχέα των κυτταροτοξικών Τ λεμφοκυττάρων των οντοτήτων αυτών αναδεικνύει ενδείξεις περί αντιγονικής εμπλοκής στην οντογένεση και πιθανώς εξέλιξη της νόσου. Σκοπός: Οι εγγενείς αδυναμίες της αλληλούχησης χαμηλής κλίμακας δεν μας επέτρεπαν την εξαγωγή ασφαλών συμπερασμάτων σχετικά με την παθογένεια των οντοτήτων. Η εφαρμογή μεθόδων αλληλούχησης υψηλής απόδοσης προσφέρει μία πληρέστερη εικόνα του ρεπερτορίου του Τ κυτταρικού υποδοχέα που θα ανασκευάσει τις απόψεις περί της σύστασης των άνοσων αποκρίσεων. Παρόλα αυτά, η έλλειψη προτυποιημένης πειραματικής διαδικασίας αλλά και βιοπληροφορικής ανάλυσης ειδικής για ανοσογενετικά δεδομένα δεν εξασφαλίζουν την επαναληψιμότητα των αποτελεσμάτων μας και την οριστική εξαγωγή συμπερασμάτων. Υλικά και μέθοδοι: Στην παρούσα μελέτη επιχειρήθηκε η προτυποποίηση της πειραματικής προσέγγισης αλλά και της βιοπληροφορικής ανάλυσης ανοσογενετικών δεδομένων τα οποία προκύπτουν με μεθόδους αλληλούχησης επόμενης γενιάς. Το προτυποποιημένο πειραματικό πρωτόκολλο εφαρμόσθηκε στη συνέχεια σε δείγματα (i) πατέρα και υιού με οικογενή T-LGL λευχαιμία (ii) ενός ασθενή με Ph+ALL που ανέπτυξε T-LGL λευχαιμία από τα κύτταρα του δότη μετά από αλλογενή μεταμόσχευση αιμοποιητικών κυττάρων (allo-HCT) και σε (iii) σε ασθενείς με Χρόνια Ιδιοπαθή Ουδετεροπενία (CIN), προκειμένου να αναζητηθούν περαιτέρω ανοσογενετικές μοριακές ενδείξεις για το ρόλο της επιλογής από αντιγόνο στις T-LGL λεμφοϋπερπλασίες. Αναδιατάξεις TRBV-TRBD-TRDJ ενισχύθηκαν από γενωμικό DNA ή/και cDNA με το πρωτόκολλο Biomed-2. Τα προϊόντα PCR υποβλήθηκαν σε paired-end πρωτόκολλο NGS (MiSeq Illumina). Η επεξεργασία των αλληλουχιών πραγματοποιήθηκε με εξειδικευμένο αλγόριθμο βιοπληροφορικής που περιλάμβανε: (i) ποιοτικά φίλτρα, (ii) σύνθεση των paired-end αλληλουχιών, (iii) προετοιμασία των συντεθειμένων αλληλουχιών για το εργαλείο IMGT/HighV-QUEST, και (iv) ομαδοποίηση και ερμηνεία των αποτελεσμάτων.Αποτελέσματα: Η ανάλυση των δεδομένων και στις τρεις περιπτώσεις κλινικών οντοτήτων επιβεβαιώνει : (i.) την επιλεκτικότητα του ρεπερτορίου, (ii.) την παρουσία δημόσιων κλωνότυπων και (iii.) τη διαχρονική παραμονή των εκπτυγμένων κλωνότυπων, δεδομένα που υπαινίσσονται ισχυρά επιλογή από περιορισμένο αριθμό αντιγόνων στην ανάπτυξη και πιθανώς εξέλιξη της T-LGL ανά περίπτωση. Συμπεράσματα: Τα όρια μεταξύ πολύ-, όλιγο-, μονο-, κλωνικότητας δεν είναι σαφώς οριοθετημένα. Η μετάβαση από μία πολυκλωνική κατάσταση σε μονοκλωνική εξαλλαγή των κυτταροτοξικών Τ λεμφοκυττάρων είναι μία δυναμική, πολυπαραγοντική διαδικασία, με το μικροπεριβάλλον να διαδραματίζει βασικό ρόλο. Η ανοσογενετική μελέτη των κυτταροτοξικών Τ λεμφοκυττάρων με μεθόδους αλληλούχησης υψηλής απόδοσης θα οδηγήσει στην αναθεώρηση των απόψεων περί σύστασης των άνοσων αποκρίσεων και θα προσφέρει ισχυρές ενδείξεις για την εμπλοκή αντιγόνου στη λεμφωματογένεση. Η φύση των αντιγόνων αυτών παραμένει να διευκρινιστεί

The Clinical Utility of ABO and RHD Systems as Potential Indicators of Health Status, a Preliminary Study in Greek Population

Objective: The objective of this study is to further highlight the differences between different ABO blood groups and Rhesus types with health biomarkers. Methods: In total 150 active healthy blood donors participated in our study comprising of 80 males from 19–61 years and 70 females aged from 21 to 64. Participants carrying blood group A were 55 individuals, blood group B 32, blood group O 51, and blood group AB 12, RHD+ 132, and RHD- 18. All the volunteer regular blood donors were selected recognizing them as a healthy population excluding drug and supplements intake. Their blood samples were analyzed just before blood donation for biochemical, hematological, and antioxidant markers. Statistical computations were performed using the SPSS tool, specifically, the one-way ANOVA test, Chi-square statistics, and logistic regression were used as statistical models. Results: O blood donors presented better iron absorption and the worst lipid profile. Indeed, a significant trend of high atheromatic index values revealed an increased risk for hyperlipidemia, in contrast with blood group A presenting a better lipid profile with lower atheromatic index values. There was also a gender related association for blood group A compared with O that was further highlighted using binary logistic regression. Conclusion: In this study, a significant difference was observed among the ABO blood groups in several of the examined biochemical and hematological biomarkers. O blood group appeared different behavior in comparison to all the tested blood groups and furthermore the RHD-group presented a better lipid profile in comparison to the RHD+ group. In order to obtain a more comprehensive view of the correlation between the ABO blood group and biochemical markers, further studies are required

Experiences of cancer survivors in Europe : has anything changed? Can artificial intelligence offer a solution?

INTRODUCTION: Cancer is a major global health issue. Despite technological advancements in oncology, challenges remain in many aspects related to cancer management. This study constitutes one part of the user requirement definition of INCISIVE EU H2020 project, which has been designed to explore the full potential of artificial intelligence (AI) based technologies in cancer imaging. The study aimed to explore cancer survivors’ experiences of cancer care in five European countries. METHODS: A qualitative study employing semi-structured interviews was conducted. A purposive sampling strategy was used to recruit participants across the five validation countries of INCISIVE project: Greece, Cyprus, Spain, Italy, and Serbia. Forty cancer survivors were interviewed between November 2020 and March 2021. Data was analysed thematically using the framework approach and coded using NVivo12 software. RESULTS: The analysis yielded several gaps within the cancer care pathway which reflected on the participants experiences. Five key themes were revealed; (1) perceived challenges during the cancer journey, (2) the importance of accurate and prompt diagnosis, (3) perceived need for improving cancer diagnosis, (4) absence of well-established/designated support services within the pathway and (5) suggestions to improve cancer care pathway. CONCLUSION: Cancer survivors experienced significant burdens pertaining to cancer diagnosis and treatment. Our findings underscored some main gaps within the cancer care pathway which contributed to the challenges articulated by the participants including lack of resources and delays in diagnostic and treatment intervals. Additionally, several suggestions were provided by the cancer survivors which could be considered towards the improvement of the current state of care, some of which can be optimised using new technologies involving AI such as the one proposed by INCISIVE

The Potential Impact of Blood System on Dietary Habits and Smoking

The ‘Blood-Type’ diet advises individuals to eat according to their ABO blood group to improve their health and decrease the risk of chronic diseases. However, the food preferences of individuals with different blood groups have not been examined. The aim of our study was to investigate, in healthy regular blood donors (rBDs), the associations of smoke, alcohol, caffeine, vitamin and fat intake with their different blood groups and if ABO groups could be a potential predictor tool for disease prevention. A total of 329 volunteers were divided into four groups according to their ABO types: Group 1 (A) comprised 141 rBDs; Group 2 (B), 65 rBDs; Group 3 (O), 96 rBDs; and Group 4, 27 rBDs. Additionally, they were divided into two groups according to their rhesus types and their preferences for smoke, too. Dietary intake was assessed using 3-day food recall and the Food Processor computer program for nutrient analysis. Alcohol, caffeine, sugar and Vitamin D consumption were significantly (p < 0.05) higher in the O group. The A group presented statistically significantly (p < 0.05) greater preferences for cholesterol intake and a higher trend for smoking (25%) habits compared with all the other groups, whereas Group B preferred more fatty foods. The blood group AB appeared to be the most controlled food intake group. Regarding the rhesus comparisons, alcohol; caffeine; and Vitamin C, D, E and K consumptions were significantly (p < 0.05) higher in rhesus-positive individuals than their rhesus-negative counterparts. For the non-smoker group, compared with the smokers, a higher consumption of Vitamin D and fibers was found. In conclusion, in the present study, statistically significant correlations of the ABO and rhesus system with some dietary parameters were found, indicating a consequent influence of these preferences on the progression of different diseases