Towards Explainable and Trustworthy AI for Decision Support in Medicine: An Overview of Methods and Good Practices

Artificial Intelligence (AI) is defined as intelligence exhibited by machines, such as electronic computers. It can involve reasoning, problem solving, learning and knowledge representation, which are mostly in focus in the medical domain. Other forms of intelligence, including autonomous behavior, are also parts of AI. Data driven methods for decision support have been employed in the medical domain for some time. Machine learning (ML) is used for a wide range of complex tasks across many sectors of the industry. However, a broader spectrum of AI, including deep learning (DL) as well as autonomous agents, have been recently gaining more focus and have risen expectation for solving numerous problems in the medical domain. A barrier towards AI adoption, or rather a concern, is trust in AI, which is often hindered by issues like lack of understanding of a black-box model function, or lack of credibility related to reporting of results. Explainability and interpretability are prerequisites for the development of AI-based systems that are lawful, ethical and robust. In this respect, this paper presents an overview of concepts, best practices, and success stories, and opens the discussion for multidisciplinary work towards establishing trustworthy AI

Commonly Used Severity Scores Are Not Good Predictors of Mortality in Sepsis from Severe Leptospirosis: A Series of Ten Patients

Introduction. Severe leptospirosis, also known as Weil's disease, can cause multiorgan failure with high mortality. Scoring systems for disease severity have not been validated for leptospirosis, and there is no documented method to predict mortality. Methods. This is a case series on 10 patients admitted to ICU for multiorgan failure from severe leptospirosis. Data were collected retrospectively, with approval from the Institution Ethics Committee. Results. Ten patients with severe leptospirosis were admitted in the Patras University Hospital ICU in a four-year period. Although, based on SOFA scores, predicted mortality was over 80%, seven of 10 patients survived and were discharged from the hospital in good condition. There was no association between SAPS II or SOFA scores and mortality, but survivors had significantly lower APACHE II scores compared to nonsurvivors. Conclusion. Commonly used severity scores do not seem to be useful in predicting mortality in severe leptospirosis. Early ICU admission and resuscitation based on a goal-directed therapy protocol are recommended and may reduce mortality. However, this study is limited by retrospective data collection and small sample size. Data from large prospective studies are needed to validate our findings

BigO: A public health decision support system for measuring obesogenic behaviors of children in relation to their local environment

Obesity is a complex disease and its prevalence depends on multiple factors related to the local socioeconomic, cultural and urban context of individuals. Many obesity prevention strategies and policies, however, are horizontal measures that do not depend on context-specific evidence. In this paper we present an overview of BigO (http://bigoprogram.eu), a system designed to collect objective behavioral data from children and adolescent populations as well as their environment in order to support public health authorities in formulating effective, context-specific policies and interventions addressing childhood obesity. We present an overview of the data acquisition, indicator extraction, data exploration and analysis components of the BigO system, as well as an account of its preliminary pilot application in 33 schools and 2 clinics in four European countries, involving over 4,200 participants.Comment: Accepted version to be published in 2020, 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Montreal, Canad

Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series

<p>Abstract</p> <p>Introduction</p> <p>Tetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial.</p> <p>Case presentations</p> <p>Three Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition.</p> <p>Conclusion</p> <p>In comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports) without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases.</p

Influence of ultra-low dose Aprotinin on thoracic surgical operations: a prospective randomized trial

<p>Abstract</p> <p>Background</p> <p>The blood saving effect of aprotinin has been well documented in cardiac surgery. In thoracic surgery, very few recent studies, using rather high doses of aprotinin, have shown a similar result. In a randomized prospective trial, we have tested the influence of aprotinin using an ultra-low dose drug regime.</p> <p>Methods</p> <p>Fifty-nine patients, mean age 58 ± 13.25 years (mean ± SD) undergoing general thoracic procedures were randomized into placebo (Group A) and treatment group (Group B). The group B (n = 29) received 500.000 IU of aprotinin after induction to anesthesia and a repeat dose immediately after chest closure. A detailed protocol with several laboratory parameters was recorded. Patients were transfused when perioperative Ht was less than 26%.</p> <p>Results</p> <p>The two groups were similar in terms of age, gender, diagnosis, pathology, co-morbidity and operations performed. The mean drainage of the first and second postoperative day in group B was significantly reduced (412.6 ± 199.2 vs. 764.3 ± 213.9 ml, p < 0.000, and 248.3 ± 178.5 vs. 455.0 ± 274.6, p < 0.001). Similarly, the need for fresh frozen plasma transfusion was lower in group B, p < 0.035. Both the operation time and the hospital stay were also less for group B but without reaching statistical significance (84.6 ± 35.2 vs 101.2 ± 52.45 min. and 5.8 ± 1.6 vs 7.2 ± 3.6 days respectively, p < 0.064). The overall transfusion rate did not differ significantly. No side effects of aprotinin were noted.</p> <p>Conclusion</p> <p>The perioperative ultra-low dose aprotinin administration was associated with a reduction of total blood losses and blood product requirements. We therefore consider the use of aprotinin safe and effective in major thoracic surgery.</p

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

Multilevel modeling and analysis of biosignals of cardiac atrial activity in atrial fibrillation

Atrial Fibrillation (AF) is one of the most common atrial arrhythmias. The initiation and perpetuation of AF is related to atrial remodeling affecting the electrical and structural characteristics of the atria. The diagnosis and understanding of the pathophysiological mechanisms is succeeded using invasive or not techniques. P-wave morphology, as recorded by the surface electrocardiogram (ECG), depends on the origin of the sinus rhythm (SR) and the atrial conduction routes, whereas, the its analysis in patients with history of AF, during SR, has revealed differences compared with the signals derived from healthy individuals. To better understand the pathophysiology of AF there is a need to link different levels of analysis, in order to interpret macroscopic observations, through a surface electrocardiogram, with changes occurring at the cell and tissue levels. Towards this direction, computational modeling can be used as it is a reproducible and non-invasive method of analyzing the electrical activity of the heart.The goal of this present thesis was the beat-to-beat analysis of the P-waves in patients with a history of paroxysmal AF (pAF) during SR and the detection of differences with the corresponding waves from healthy volunteers, with the ultimate goal to differentiate these groups. In addition, an attempt was made to interpret these differences through microscopic simulations in order to investigate the different atrial activation patterns in those groups.In more detail, for the macroscopic analysis of AF, ECG data from patients with a history of pAF and from healthy volunteers were analyzed. The beat-to-beat morphological characteristics of P-waves, during SR, were analyzed in both time and time-frequency domain, with the ultimate goal to study the changes that may occur in patients with pAF and which can be used as the basis for distinguishing between pathological and healthy individuals. The results of macroscopic analysis revealed the existence of a secondary P-wave morphology, while the proportion of the beats where the P-wave follows the secondary morphology is higher in patients with a history of pAF. In addition, the time-frequency analysis of the P-waves, which follow the main morphology, led to the development of a classifier that can accurately distinguish (93.75%) signals derived pAF and healthy volunteers during SR. The proposed methodology is available to the clinical practitioner to predict AF occurrence and to perform further analyzes.The difference in the percentage of the P-wave following the main morphology and their spectral characteristics implies greater electrical instability of the atrial substrate in patients with pAF and different conduction patterns. This observation has led to the hypothesis that the multiple P-wave morphologies may be the result of a transient shift in the stimulus origin, possibly within the broader anatomical region of the sinus, and that it is the atrial electrical remodeling that contributes to more frequent P-waves following a secondary morphology in patients with pAF. In order to confirm the research hypothesis it was necessary to use computational models and conduct simulations of the electrical propagation in the atria. After an extensive bibliographic review, which revealed the lack of studies investigating this case, a two-dimensional geometric model describing the atrial tissue was designed. The electrophysiological characteristics of the atria were adapted to describe both healthy and electrically remodeled tissue. The results show that in electrically remodeled tissue, the displacement of the excitation site within the sinus resulted in significant changes in atrial activation time compared to healthy tissue, and the greater the spatial extent of the remodeling the greater the differences in the completion of the electrophysiological processes. It also revealed the importance of heart rate frequency in changing the timing of electrical activation of the atria.In conclusion, it was found that beat-to-beat P-wave analysis, during SR, can predict the existence of pAF, while computational modeling enables the interpretation of the results of macroscopic analysis. These results underline the need to link the macroscopic findings to the suspected microscopic electrical activity in order to better understand the pathophysiology of AF. This thesis is a step towards computational medicine in cardiology. In the future, a larger sample of signals should be used to improve the performance of the classifier, while it is necessary to use a detailed three-dimensional model of human atria to investigate the reproducibility of the results. Finally, an additional area of research is the investigation of the conditions leading to the transient modification of the stimulus origin within the sinus.Η κολπική μαρμαρυγή (ΚΜ) είναι η συνηθέστερη καρδιακή αρρυθμία. Η έναρξη και η διατήρηση της ΚΜ σχετίζεται με φαινόμενα κολπικής αναδιαμόρφωσης, που αναφέρονται στην τροποποίηση των ηλεκτρικών και δομικών χαρακτηριστικών των κόλπων. Η διάγνωση και κατανόηση των παθοφυσιολογικών μηχανισμών γίνεται με επεμβατικές και μη μεθόδους. Η μορφολογία ενός κύματος Ρ, όπως αυτό καταγράφεται από το επιφανειακό ηλεκτροκαρδιογράφημα (ΗΚΓ), εξαρτάται από τη θέση έναρξης του ερεθίσματος και από την ακολουθούμενη αγώγιμη οδό, ενώ η σε βάθος ανάλυση του σε ασθενείς με ιστορικό ΚΜ κατά τη διάρκεια του φλεβοκομβικού ρυθμού, έχει αποκαλύψει διαφορές σε σύγκριση με τα αντίστοιχα κύματα από υγιείς εθελοντές. Για την καλύτερη κατανόηση της παθοφυσιολογίας της ΚΜ παρουσιάζεται η ανάγκη σύνδεσης διαφορετικών επιπέδων ανάλυσης, με σκοπό την ερμηνεία των μακροσκοπικών παρατηρήσεων, μέσω ενός ηλεκτροκαρδιογραφήματος επιφανείας, με τις αλλαγές που συντελούνται στο επίπεδο του κυττάρου και του ιστού. Η υπολογιστική μοντελοποίηση μπορεί να χρησιμοποιηθεί προς αυτή την κατεύθυνση καθώς αποτελεί μία αναπαραγώγιμη και μη επεμβατική μέθοδο ανάλυσης της ηλεκτρικής δραστηριότητας της καρδιάς.Ο σκοπός της παρούσας διατριβής υπήρξε η σε βάθος ανάλυση των κυμάτων Ρ, από παλμό σε παλμό, σε ασθενείς με ιστορικό παροξυσμικής ΚΜ (ΠΚΜ) κατά τη διάρκεια του φλεβοκομβικού ρυθμού και η ανίχνευση διαφορών με τα αντίστοιχα κύματα υγιών εθελοντών, με απώτερο στόχο την διερεύνηση της ικανότητας της μεθόδου να διαχωρίζει τις ομάδες αυτές. Επιπλέον έγινε προσπάθεια οι διαφορές αυτές να ερμηνευθούν μέσω διενέργειας προσομοιώσεων σε μικροσκοπικό επίπεδο, ώστε να διερευνηθεί ο διαφορετικός τρόπος ενεργοποίησης των κόλπων στις δύο υπό μελέτη ομάδες.Πιο αναλυτικά, στην μακροσκοπική μελέτη της ΚΜ χρησιμοποιήθηκαν δεδομένα ΗΚΓ από ασθενείς με ιστορικό ΠΚΜ και από υγιείς εθελοντές. Τα μορφολογικά χαρακτηριστικά των κυμάτων Ρ, από παλμό σε παλμό, κατά τη διάρκεια του φλεβόκομβου, αναλύθηκαν τόσο στο πεδίο του χρόνου όσο και στο χρονοφασματικό επίπεδο, με απώτερο στόχο την διερεύνηση αλλαγών που μπορεί να εμφανιστούν σε ασθενείς με ΠΚΜ και τα οποία μπορεί να αποτελέσουν τη βάση για τη διάκριση μεταξύ παθολογικών και υγιών ατόμων. Τα αποτελέσματα της μακροσκοπικής ανάλυσης αποκάλυψαν την ύπαρξη μίας δευτερεύουσας μορφολογίας κυμάτων Ρ, ενώ το ποσοστό των παλμών όπου το κύμα Ρ ακολουθεί τη δευτερεύουσα μορφολογία είναι υψηλότερο στους ασθενείς με ιστορικό ΠΚΜ. Επιπλέον η χρονοφασματική ανάλυση των κυμάτων Ρ, τα οποία ακολουθούν την κύρια μορφολογία, οδήγησε στην δημιουργία ενός ταξινομητή ο οποίος είναι δυνατό να διακρίνει, με μεγάλη ακρίβεια (93.75%), τα σήματα ασθενών με ΠΚΜ από τα υγιή σήματα, κατά τη διάρκεια φλεβοκομβικού ρυθμού. Η προτεινόμενη μεθοδολογία είναι διαθέσιμη στον κλινικό ιατρό για τη πρόβλεψη της εμφάνισης ΚΜ και τη διενέργεια περαιτέρω αναλύσεων.Η διαφορά στο ποσοστό της κύριας μορφολογίας του κύματος Ρ και των χρονοφασματικών τους χαρακτηριστικών υποδηλώνει μεγαλύτερη ηλεκτρική αστάθεια του κολπικού υποστρώματος σε ασθενείς με ΠΚΜ και διαφορετικούς τρόπους αγωγής στους κόλπους. Η παρατήρηση αυτή οδήγησε στην υπόθεση ότι οι πολλαπλές μορφολογίες του κύματος Ρ σε ένα ΗΚΓ, μπορεί να είναι αποτέλεσμα της τυχαίας αλλαγής της θέσης έναρξης του ερεθίσματος, πιθανώς εντός της ευρύτερης ανατομικής περιοχής του φλεβόκομβου, και ότι η ηλεκτρική αναδιαμόρφωση των κόλπων είναι αυτή η οποία συμβάλλει ώστε συχνότερα να καταγράφονται κύματα Ρ που ακολουθούν τη δευτερεύουσα μορφολογία στους ασθενείς με ΠΚΜ. Για την επιβεβαίωση της ερευνητικής υπόθεσης κρίθηκε απαραίτητη η χρήση υπολογιστικών μοντέλων και η διενέργεια προσομοιώσεων της ηλεκτρικής διάδοσης στους κόλπους. Μετά από μία εκτενή βιβλιογραφική ανασκόπηση, η οποία αποκάλυψε την απουσία μελετών που να ερευνούν τη συγκεκριμένη υπόθεση, σχεδιάστηκε μία δισδιάστατη γεωμετρική δομή που περιγράφει τον κολπικό ιστό. Τα ηλεκτροφυσιολογικά χαρακτηριστικά των κόλπων προσαρμόστηκαν κατάλληλα ώστε να περιγράψουν τόσο τον υγιή όσο και τον ηλεκτρικά αναδιαμορφωμένο ιστό. Τα αποτελέσματα δείχνουν ότι σε ηλεκτρικά αναδιαμορφωμένο ιστό, η μετατόπιση της θέσης διέγερσης, εντός της περιοχής του φλεβόκομβου, οδήγησε σε σημαντικές αλλαγές στον χρόνο ενεργοποίησης των κόλπων, σε σύγκριση με τον υγιή ιστό, ενώ όσο μεγαλύτερη ήταν η χωρική έκταση της αναδιαμόρφωσης τόσο μεγαλύτερες οι αλλαγές στου χρόνους ολοκλήρωσης των ηλεκτροφυσιολογικών διαδικασιών. Επίσης αποκαλύφθηκε η σημασία της συχνότητας του καρδιακού ρυθμού στην μεταβολή των χρόνων ηλεκτρικής ενεργοποίησης των κόλπων. Συμπερασματικά, βρέθηκε ότι η ανάλυση των κυμάτων Ρ, από παλμό σε παλμό, κατά τη διάρκεια φλεβοκομβικού ρυθμού, είναι δυνατό να προβλέψει την ύπαρξη ΠΚΜ, ενώ η υπολογιστική μοντελοποίηση παρέχει τη δυνατότητα ερμηνείας των αποτελεσμάτων της μακροσκοπικής ανάλυσης. Τα ευρήματα αυτά υπογραμμίζουν την ανάγκη σύνδεσης των μακροσκοπικών ευρημάτων της ανάλυσης στην υποφαινόμενη ηλεκτρική δραστηριότητα των κόλπων σε μικροσκοπικό επίπεδο, με σκοπό την καλύτερη κατανόηση της παθοφυσιολογιάς της ΚΜ. Η παρούσα διατριβή αποτελεί ένα βήμα προς την κατεύθυνση της υπολογιστικής ιατρικής στην καρδιολογία. Στο μέλλον, μεγαλύτερο δείγμα σημάτων πρέπει να χρησιμοποιηθεί για την βελτίωση της απόδοσης του ταξινομητή, ενώ είναι απαραίτητη η χρήση ενός λεπτομερούς τρισδιάστατου μοντέλου των ανθρώπινων κόλπων για να διερευνηθεί η αναπαραγωγιμότητα των αποτελεσμάτων σε μικροσκοπικό επίπεδο. Τέλος, ένα επιπλέον πεδίο έρευνας είναι η διερεύνηση των συνθηκών που οδηγούν στην μετατόπιση της θέσης έναρξης του ερεθίσματος, εντός του φλεβόκομβου

REVIEW Open Access Airway trauma: a review on epidemiology, mechanisms of injury, diagnosis and treatment

Airway injuries are life threatening conditions. A very little number of patients suffering air injuries are transferred live at the hospital. The diagnosis requires a high index of suspicion based on the presence of non-specific for these injuries symptoms and signs and a thorough knowledge of the mechanisms of injury. Bronchoscopy and chest computed tomography with MPR and 3D reconstruction of the airway represent the procedures of choice for the definitive diagnosis. Endotracheal intubation under bronchoscopic guidance is the key point to gain airway control and appropriate ventilation. Primary repair with direct suture or resection and an end to end anastomosis is the treatment of choice for patients suffering from tracheobronchial injuries (TBI). The surgical approach to the injured airway depends on its location. Selected patients, mainly with iatrogenic injuries, can be treated conservatively as long as the injury is small (&lt;2 cm), a secure and patent airway and adequate ventilation are achieved, and there are no signs of sepsis. Patients with delayed presentation airway injuries should be referred for surgical treatment. Intraoperative evaluation of the viability of the lung parenchyma beyond the site of stenosis/obstruction is mandatory to avoid unnecessary lung resection