CT-based radiomics can identify physiological modifications of bone structure related to subjects' age and sex.

PURPOSE: Radiomics of vertebral bone structure is a promising technique for identification of osteoporosis. We aimed at assessing the accuracy of machine learning in identifying physiological changes related to subjects' sex and age through analysis of radiomics features from CT images of lumbar vertebrae, and define its generalizability across different scanners. MATERIALS AND METHODS: We annotated spherical volumes-of-interest (VOIs) in the center of the vertebral body for each lumbar vertebra in 233 subjects who had undergone lumbar CT for back pain on 3 different scanners, and we evaluated radiomics features from each VOI. Subjects with history of bone metabolism disorders, cancer, and vertebral fractures were excluded. We performed machine learning classification and regression models to identify subjects' sex and age respectively, and we computed a voting model which combined predictions. RESULTS: The model was trained on 173 subjects and tested on an internal validation dataset of 60. Radiomics was able to identify subjects' sex within single CT scanner (ROC AUC: up to 0.9714), with lower performance on the combined dataset of the 3 scanners (ROC AUC: 0.5545). Higher consistency among different scanners was found in identification of subjects' age (R2 0.568 on all scanners, MAD 7.232 years), with highest results on a single CT scanner (R2 0.667, MAD 3.296 years). CONCLUSION: Radiomics features are able to extract biometric data from lumbar trabecular bone, and determine bone modifications related to subjects' sex and age with great accuracy. However, acquisition from different CT scanners reduces the accuracy of the analysis.

The effect of COVID-19 epidemic on vital signs in hospitalized patients: a pre-post heat-map study from a large teaching hospital.

The Lombardy SARS-CoV-2 outbreak in February 2020 represented the beginning of COVID-19 epidemic in Italy. Hospitals were flooded by thousands of patients with bilateral pneumonia and severe respiratory, and vital sign derangements compared to the standard hospital population. We propose a new visual analysis technique using heat maps to describe the impact of COVID-19 epidemic on vital sign anomalies in hospitalized patients. We conducted an electronic health record study, including all confirmed COVID-19 patients hospitalized from February 21st, 2020 to April 21st, 2020 as cases, and all non-COVID-19 patients hospitalized in the same wards from January 1st, 2018 to December 31st, 2018. All data on temperature, peripheral oxygen saturation, respiratory rate, arterial blood pressure, and heart rate were retrieved. Derangement of vital signs was defined according to predefined thresholds. 470 COVID-19 patients and 9241 controls were included. Cases were older than controls, with a median age of 79 vs 76 years in non survivors (p = < 0.002). Gender was not associated with mortality. Overall mortality in COVID-19 hospitalized patients was 18%, ranging from 1.4% in patients below 65 years to about 30% in patients over 65 years. Heat maps analysis demonstrated that COVID-19 patients had an increased frequency in episodes of compromised respiratory rate, acute desaturation, and fever. COVID-19 epidemic profoundly affected the incidence of severe derangements in vital signs in a large academic hospital. We validated heat maps as a method to analyze the clinical stability of hospitalized patients. This method may help to improve resource allocation according to patient characteristics.

Quantitative chest CT analysis in COVID-19 to predict the need for oxygenation support and intubation.

OBJECTIVE: Lombardy (Italy) was the epicentre of the COVID-19 pandemic in March 2020. The healthcare system suffered from a shortage of ICU beds and oxygenation support devices. In our Institution, most patients received chest CT at admission, only interpreted visually. Given the proven value of quantitative CT analysis (QCT) in the setting of ARDS, we tested QCT as an outcome predictor for COVID-19. METHODS: We performed a single-centre retrospective study on COVID-19 patients hospitalised from January 25, 2020, to April 28, 2020, who received CT at admission prompted by respiratory symptoms such as dyspnea or desaturation. QCT was performed using a semi-automated method (3D Slicer). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient's clinical data including oxygenation support throughout hospitalisation. RESULTS: Two hundred twenty-two patients (163 males, median age 66, IQR 54-6) were included; 75% received oxygenation support (20% intubation rate). Compromised lung volume was the most accurate outcome predictor (logistic regression, p < 0.001). %CL values in the 6-23% range increased risk of oxygenation support; values above 23% were at risk for intubation. %CL showed a negative correlation with PaO2/FiO2 ratio (p < 0.001) and was a risk factor for in-hospital mortality (p < 0.001). CONCLUSIONS: QCT provides new metrics of COVID-19. The compromised lung volume is accurate in predicting the need for oxygenation support and intubation and is a significant risk factor for in-hospital death. QCT may serve as a tool for the triaging process of COVID-19. KEY POINTS: • Quantitative computer-aided analysis of chest CT (QCT) provides new metrics of COVID-19. • The compromised lung volume measured in the - 500, 100 HU interval predicts oxygenation support and intubation and is a risk factor for in-hospital death. • Compromised lung values in the 6-23% range prompt oxygenation therapy; values above 23% increase the need for intubation.

ICU management based on big data.

PURPOSE OF REVIEW: The availability of large datasets and computational power has prompted a revolution in Intensive Care. Data represent a great opportunity for clinical practice, benchmarking, and research. Machine learning algorithms can help predict events in a way the human brain can simply not process. This possibility comes with benefits and risks for the clinician, as finding associations does not mean proving causality. RECENT FINDINGS: Current applications of Data Science still focus on data documentation and visualization, and on basic rules to identify critical lab values. Recently, algorithms have been put in place for prediction of outcomes such as length of stay, mortality, and development of complications. These results have begun being implemented for more efficient allocation of resources and in benchmarking processes, to allow identification of successful practices and margins for improvement. In parallel, machine learning models are increasingly being applied in research to expand medical knowledge. SUMMARY: Data have always been part of the work of intensivists, but the current availability has not been completely exploited. The intensive care community has to embrace and guide the data science revolution in order to decline it in favor of patients' care.

Development of a Natural Language Processing (NLP) model to automatically extract clinical data from electronic health records: results from an Italian comprehensive stroke center.

INTRODUCTION: Data collection often relies on time-consuming manual inputs, with a vast amount of information embedded in unstructured texts such as patients' medical records and clinical notes. Our study aims to develop a pipeline that combines active learning (AL) and NLP techniques to enhance data extraction in an acute ischemic stroke cohort. MATERIALS AND METHODS: Consecutive acute ischemic stroke patients who received reperfusion therapies at IRCCS Humanitas Research Hospital were included. The Italian NLP Bidirectional Encoder Representations from Transformers (BERT) model was trained with AL to automatically extract clinical variables from electronic health text. Simulated active learning performances were evaluated on a set of labels representing patients' comorbidities, comparing Bayesian Uncertainty Sampling by Disagreement (BALD) and random text selection. Prognostic models predicting patients' functional outcomes using Gradient Boosting were trained on manually labelled and semi-automatically extracted data and their performance was compared. RESULTS: The active learning process initially showed null performance until around 20% of texts were labelled, possibly due to root layers freezing in the BERT model, yet overall, active learning improves model learning efficiency across most comorbidities. Prognostic modelling showed no significant difference in performance between models trained on manually labelled versus semi-automatically extracted data, indicating effective prediction capabilities in both settings. CONCLUSIONS: We developed an efficient language model to automate the extraction of clinical data from Italian unstructured health texts in a cohort of ischemic stroke patients. In a preliminary analysis, we demonstrated its potential applicability for enhancing prediction model accuracy.

The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19.

BACKGROUND: COVID-19 clinical course is highly variable and secondary infections contribute to COVID-19 complexity. Early detection of secondary infections is clinically relevant for patient outcome. Procalcitonin (PCT) and C-reactive protein (CRP) are the most used biomarkers of infections. Pentraxin 3 (PTX3) is an acute phase protein with promising performance as early biomarker in infections. In patients with COVID-19, PTX3 plasma concentrations at hospital admission are independent predictor of poor outcome. In this study, we assessed whether PTX3 contributes to early identification of co-infections during the course of COVID-19. METHODS: We analyzed PTX3 levels in patients affected by COVID-19 with (n = 101) or without (n = 179) community or hospital-acquired fungal or bacterial secondary infections (CAIs or HAIs). FINDINGS: PTX3 plasma concentrations at diagnosis of CAI or HAI were significantly higher than those in patients without secondary infections. Compared to PCT and CRP, the increase of PTX3 plasma levels was associated with the highest hazard ratio for CAIs and HAIs (aHR 11.68 and 24.90). In multivariable Cox regression analysis, PTX3 was also the most significant predictor of 28-days mortality or intensive care unit admission of patients with potential co-infections, faring more pronounced than CRP and PCT. INTERPRETATION: PTX3 is a promising predictive biomarker for early identification and risk stratification of patients with COVID-19 and co-infections. FUNDING: Dolce & Gabbana fashion house donation; Ministero della Salute for COVID-19; EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT) and MUR PNRR Italian network of excellence for advanced diagnosis (Project no. PNC-E3-2022-23683266 PNC-HLS-DA); EU MSCA (project CORVOS 860044).

Implementing Artificial Intelligence: Assessing the Cost and Benefits of Algorithmic Decision-Making in Critical Care.

This article provides an overview of the most useful artificial intelligence algorithms developed in critical care, followed by a comprehensive outline of the benefits and limitations. We begin by describing how nurses and physicians might be aided by these new technologies. We then move to the possible changes in clinical guidelines with personalized medicine that will allow tailored therapies and probably will increase the quality of the care provided to patients. Finally, we describe how artificial intelligence models can unleash researchers' minds by proposing new strategies, by increasing the quality of clinical practice, and by questioning current knowledge and understanding.

REVersal of nEuromusculAr bLocking Agents in Patients Undergoing General Anaesthesia (REVEAL Study).

Background: Neuromuscular blocking agent (NMBA) monitoring and reversals are key to avoiding residual curarization and improving patient outcomes. Sugammadex is a NMBA reversal with favorable pharmacological properties. There is a lack of real-world data detailing how the diffusion of sugammadex affects anesthetic monitoring and practice. Methods: We conducted an electronic health record analysis study, including all adult surgical patients undergoing general anesthesia with orotracheal intubation, from January 2016 to December 2019, to describe changes and temporal trends of NMBAs and NMBA reversals administration. Results: From an initial population of 115,046 surgeries, we included 37,882 procedures, with 24,583 (64.9%) treated with spontaneous recovery from neuromuscular block and 13,299 (35.1%) with NMBA reversals. NMBA reversals use doubled over 4 years from 25.5% to 42.5%, mainly driven by sugammadex use, which increased from 17.8% to 38.3%. Rocuronium increased from 58.6% (2016) to 94.5% (2019). Factors associated with NMBA reversal use in the multivariable analysis were severe obesity (OR 3.33 for class II and OR 11.4 for class III obesity, p-value < 0.001), and high ASA score (OR 1.47 for ASA III). Among comorbidities, OSAS, asthma, and other respiratory diseases showed the strongest association with NMBA reversal administration. Conclusions: Unrestricted availability of sugammadex led to a considerable increase in pharmacological NMBA reversal, with rocuronium use also rising. More research is needed to determine how unrestricted and safer NMBA reversal affects anesthesia intraoperative monitoring and practice.

Ursodeoxycholic Acid Does Not Improve COVID-19 Outcome in Hospitalized Patients.

Ursodeoxycholic acid (UDCA) was demonstrated to reduce susceptibility to SARS-CoV-2 infection in vitro and improve infection course in chronic liver diseases. However, real-life evidence is lacking. We analyzed the impact of UDCA on COVID-19 outcomes in patients hospitalized in a tertiary center. Between January 2020 and January 2023, among 3847 patients consecutively hospitalized for COVID19, 57 (=UDCA group) were taking UDCA. The UDCA and the control groups (n = 3790) did not differ concerning comorbidities including diabetes mellitus type 2 (15.8% vs. 12.8%) and neoplasia (12.3% vs. 9.4%). Liver diseases and vaccination rate were more common in the UDCA group (14.0% vs. 2.5% and 54.4% vs. 30.2%, respectively). Overall mortality and CPAP treatment were 22.8 % and 15.7% in the UDCA, and 21.3% and 25.9% in the control group. Mortality was similar (p = 0.243), whereas UDCA was associated with a lower rate of CPAP treatment (OR = 0.76, p < 0.05). Treatment with UDCA was not an independent predictor of survival in patients hospitalized for COVID-19.

Early prediction of SARS-CoV-2 reproductive number from environmental, atmospheric and mobility data: A supervised machine learning approach.

INTRODUCTION: SARS-CoV-2 was declared a pandemic by the WHO on March 11th, 2020. Public protective measures were enforced in every country to limit the diffusion of SARS-CoV-2. Its transmission, mainly by droplets, has been measured by the effective reproduction number (Rt) that counts the number of secondary cases caused in a population by an average infectious individual at time t. Current strategies to calculate Rt reflect the number of secondary cases after several days, due to a delay from symptoms onset to reporting. We propose a complementary Rt estimation using supervised machine learning techniques to predict short term variations with more timely results. MATERIAL AND METHODS: Our primary goal was to predict Rt of the current day in the twelve provinces of Lombardy with the highest possible accuracy, and with no influence of the local testing strategies. We gathered data about mobility, weather, and pollution from different public sources as a proxy of human behavior and public health measures. We built four supervised machine learning algorithms with different strategies: the outcome variable was the daily median Rt values per province obtained from officially adopted algorithms. RESULTS: Data from 243 days for every province were presented to our four models (from February 15th, 2020, to October 14th, 2020). Two models using differential calculation of Rt instead of the raw values showed the highest mean coefficient of determination (0.93 for both) and residuals reported the lowest mean error (-0.03 and 0.01) and standard deviation (0.13 for both) as well. The one with access to the value of Rt of the day before heavily relied on that feature for prediction, while the other one had more distributed weights. DISCUSSION: The model that had not access to the Rt value of the previous day and used Rt differential value as outcome (FDRt) was considered the most robust according to the metrics. Its forecasts were able to predict the trend that Rt values would have developed over different weeks, but it was not particularly accurate in predicting the precise value of Rt. A correlation among mobility, atmospheric, features, pollution and Rt values is plausible, but further testing should be performed.

Outcome prediction during an ICU surge using a purely data-driven approach: A supervised machine learning case-study in critically ill patients from COVID-19 Lombardy outbreak.

PURPOSE: COVID-19 disease frequently affects the lungs leading to bilateral viral pneumonia, progressing in some cases to severe respiratory failure requiring ICU admission and mechanical ventilation. Risk stratification at ICU admission is fundamental for resource allocation and decision making. We assessed performances of three machine learning approaches to predict mortality in COVID-19 patients admitted to ICU using early operative data from the Lombardy ICU Network. METHODS: This is a secondary analysis of prospectively collected data from Lombardy ICU network. A logistic regression, balanced logistic regression and random forest were built to predict survival on two datasets: dataset A included patient demographics, medications before admission and comorbidities, and dataset B included respiratory data the first day in ICU. RESULTS: Models were trained on 1484 patients on four outcomes (7/14/21/28 days) and reached the greatest predictive performance at 28 days (F1-score: 0.75 and AUC: 0.80). Age, number of comorbidities and male gender were strongly associated with mortality. On dataset B, mode of ventilatory assistance at ICU admission and fraction of inspired oxygen were associated with an increase in prediction performances. CONCLUSIONS: Machine learning techniques might be useful in emergency phases to reach good predictive performances maintaining interpretability to gain knowledge on complex situations and enhance patient management and resources.

Artificial intelligence processing electronic health records to identify commonalities and comorbidities cluster at Immuno Center Humanitas.

Background: Comorbidities are common in chronic inflammatory conditions, requiring multidisciplinary treatment approach. Understanding the link between a single disease and its comorbidities is important for appropriate treatment and management. We evaluate the ability of an NLP-based process for knowledge discovery to detect information about pathologies, patients' phenotype, doctors' prescriptions and commonalities in electronic medical records, by extracting information from free narrative text written by clinicians during medical visits, resulting in the extraction of valuable information and enriching real world evidence data from a multidisciplinary setting. Methods: We collected clinical notes from the Allergy Department of Humanitas Research Hospital written in the last 3 years and used it to look for diseases that cluster together as comorbidities associated to the main pathology of our patients, and for the extent of prescription of systemic corticosteroids, thus evaluating the ability of NLP-based tools for knowledge discovery to extract structured information from free text. Results: We found that the 3 most frequent comorbidities to appear in our clusters were asthma, rhinitis, and urticaria, and that 991 (of 2057) patients suffered from at least one of these comorbidities. The clusters which co-occur particularly often are oral allergy syndrome and urticaria (131 patients), angioedema and urticaria (105 patients), rhinitis and asthma (227 patients). With regards to systemic corticosteroid prescription volume by our clinicians, we found it was lower when compared to the therapy the patients followed before coming to our attention, with the exception of two diseases: Chronic obstructive pulmonary disease and Angioedema. Conclusions: This analysis seems to be valid and is confirmed by the data from the literature. This means that NLP tools could have significant role in many other research fields of medicine, as it may help identify other important, and possibly previously neglected clusters of patients with comorbidities and commonalities. Another potential benefit of this approach lies in its potential ability to foster a multidisciplinary approach, using the same drugs to treat pathologies normally treated by physicians in different branches of medicine, thus saving resources and improving the pharmacological management of patients.

An individualized algorithm to predict mortality in COVID-19 pneumonia: a machine learning based study.

Introduction: Identifying SARS-CoV-2 patients at higher risk of mortality is crucial in the management of a pandemic. Artificial intelligence techniques allow one to analyze large amounts of data to find hidden patterns. We aimed to develop and validate a mortality score at admission for COVID-19 based on high-level machine learning. Material and methods: We conducted a retrospective cohort study on hospitalized adult COVID-19 patients between March and December 2020. The primary outcome was in-hospital mortality. A machine learning approach based on vital parameters, laboratory values and demographic features was applied to develop different models. Then, a feature importance analysis was performed to reduce the number of variables included in the model, to develop a risk score with good overall performance, that was finally evaluated in terms of discrimination and calibration capabilities. All results underwent cross-validation. Results: 1,135 consecutive patients (median age 70 years, 64% male) were enrolled, 48 patients were excluded, and the cohort was randomly divided into training (760) and test (327) groups. During hospitalization, 251 (22%) patients died. After feature selection, the best performing classifier was random forest (AUC 0.88 ±0.03). Based on the relative importance of each variable, a pragmatic score was developed, showing good performances (AUC 0.85 ±0.025), and three levels were defined that correlated well with in-hospital mortality. Conclusions: Machine learning techniques were applied in order to develop an accurate in-hospital mortality risk score for COVID-19 based on ten variables. The application of the proposed score has utility in clinical settings to guide the management and prognostication of COVID-19 patients.

A 'Multiomic' Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in Coronavirus Disease 2019.

BACKGROUND AND AIMS: The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. METHODS: Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. RESULTS: We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. CONCLUSION: This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

The antibody response to SARS-CoV-2 infection persists over at least 8 months in symptomatic patients.

BACKGROUND: Persistence of antibodies to SARS-CoV-2 viral infection may depend on several factors and may be related to the severity of disease or to the different symptoms. METHODS: We evaluated the antibody response to SARS-CoV-2 in personnel from 9 healthcare facilities and an international medical school and its association with individuals' characteristics and COVID-19 symptoms in an observational cohort study. We enrolled 4735 subjects (corresponding to 80% of all personnel) for three time points over a period of 8-10 months. For each participant, we determined the rate of antibody increase or decrease over time in relation to 93 features analyzed in univariate and multivariate analyses through a machine learning approach. RESULTS: Here we show in individuals positive for IgG (≥12 AU/mL) at the beginning of the study an increase [p = 0.0002] in antibody response in paucisymptomatic or symptomatic subjects, particularly with loss of taste or smell (anosmia/dysgeusia: OR 2.75, 95% CI 1.753 - 4.301), in a multivariate logistic regression analysis in the first three months. The antibody response persists for at least 8-10 months. CONCLUSIONS: SARS-CoV-2 infection induces a long lasting antibody response that increases in the first months, particularly in individuals with anosmia/dysgeusia. This may be linked to the lingering of SARS-CoV-2 in the olfactory bulb.