A neurophysiological profiling of the heartbeat-evoked potential in severe acquired brain injuries: A focus on unconsciousness.

Unconsciousness in severe acquired brain injury (sABI) patients occurs with different cognitive and neural profiles. Perturbational approaches, which enable the estimation of proxies for brain reorganization, have added a new avenue for investigating the non-behavioural diagnosis of consciousness. In this prospective observational study, we conducted a comparative analysis of the topological patterns of heartbeat-evoked potentials (HEP) between patients experiencing a prolonged disorder of consciousness (pDoC) and patients emerging from a minimally consciousness state (eMCS). A total of 219 sABI patients were enrolled, each undergoing a synchronous EEG-ECG resting-state recording, together with a standardized consciousness diagnosis. A number of graph metrics were computed before/after the HEP (Before/After) using the R-peak on the ECG signal. The peak value of the global field power of the HEP was found to be significantly higher in eMCS patients with no difference in latency. Power spectrum was not able to discriminate consciousness neither Before nor After. Node assortativity and global efficiency were found to vary with different trends at unconsciousness. Lastly, the Perturbational Complexity Index of the HEP was found to be significantly higher in eMCS patients compared with pDoC. Given that cortical elaboration of peripheral inputs may serve as a non-behavioural determinant of consciousness, we have devised a low-cost and translatable technique capable of estimating causal proxies of brain functionality with an endogenous, non-invasive stimulus. Thus, we present an effective means to enhance consciousness assessment by incorporating the interaction between the autonomic nervous system (ANS) and central nervous system (CNS) into the loop.

Neural coding of autonomic functions in different states of consciousness.

Detecting signs of residual neural activity in patients with altered states of consciousness is a crucial issue for the customization of neurorehabilitation treatments and clinical decision-making. With this large observational prospective study, we propose an innovative approach to detect residual signs of consciousness via the assessment of the amount of autonomic information coded within the brain. The latter was estimated by computing the mutual information (MI) between preprocessed EEG and ECG signals, to be then compared across consciousness groups, together with the absolute power and an international qualitative labeling. One-hundred seventy-four patients (73 females, 42%) were included in the study (median age of 65 years [IQR = 20], MCS +: 29, MCS -: 23, UWS: 29). Electroencephalography (EEG) information content was found to be mostly related to the coding of electrocardiography (ECG) activity, i.e., with higher MI (p < 0.05), in Unresponsive Wakefulness Syndrome and Minimally Consciousness State minus (MCS -). EEG-ECG MI, besides clearly discriminating patients in an MCS - and +, significantly differed between lesioned areas (sides) in a subgroup of unilateral hemorrhagic patients. Crucially, such an accessible and non-invasive measure of residual consciousness signs was robust across electrodes and patient groups. Consequently, exiting from a strictly neuro-centric consciousness detection approach may be the key to provide complementary insights for the objective assessment of patients' consciousness levels and for the patient-specific planning of rehabilitative interventions.

Multiplexing Biosensor for the Detection of Extracellular Vesicles as Biomarkers of Tissue Damage and Recovery after Ischemic Stroke.

The inflammatory, reparative and regenerative mechanisms activated in ischemic stroke patients immediately after the event cooperate in the response to injury, in the restoration of functions and in brain remodeling even weeks after the event and can be sustained by the rehabilitation treatment. Nonetheless, patients' response to treatments is difficult to predict because of the lack of specific measurable markers of recovery, which could be complementary to clinical scales in the evaluation of patients. Considering that Extracellular Vesicles (EVs) are carriers of multiple molecules involved in the response to stroke injury, in the present study, we have identified a panel of EV-associated molecules that (i) confirm the crucial involvement of EVs in the processes that follow ischemic stroke, (ii) could possibly profile ischemic stroke patients at the beginning of the rehabilitation program, (iii) could be used in predicting patients' response to treatment. By means of a multiplexing Surface Plasmon Resonance imaging biosensor, subacute ischemic stroke patients were proven to have increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) and translocator protein (TSPO) on the surface of small EVs in blood. Besides, microglia EVs and endothelial EVs were shown to be significantly involved in the intercellular communications that occur more than 10 days after ischemic stroke, thus being potential tools for the profiling of patients in the subacute phase after ischemic stroke and in the prediction of their recovery.

Effects of COVID-19 pandemic on intensive rehabilitation after severe acquired brain injuries.

PURPOSE: COVID-19 pandemic has affected most components of health systems including rehabilitation. The study aims to compare demographic and clinical data of patients admitted to an intensive rehabilitation unit (IRU) after severe acquired brain injuries (sABIs), before and during the pandemic. MATERIALS AND METHODS: In this observational retrospective study, all patients admitted to the IRU between 2017 and 2020 were included. Demographics were collected, as well as data from the clinical and functional assessment at admission and discharge from the IRU. Patients were grouped in years starting from March 2017, and the 2020/21 cohort was compared to those admitted between March 2017/18, 2018/19, and 2019/20. Lastly, the pooled cohort March 2017 to March 2020 was compared with the COVID-19 year alone. RESULTS: This study included 251 patients (F: 96 (38%): median age 68 years [IQR = 19.25], median time post-onset at admission: 42 days, [IQR = 23]). In comparison with the pre-pandemic years, a significant increase of hemorrhagic strokes (p < 0.001) and a decrease of traumatic brain injuries (p = 0.048), a reduction of the number of patients with a prolonged disorder of consciousness admitted to the IRU (p < 0.001) and a lower length of stay (p < 0.001) were observed in 2020/21. CONCLUSIONS: These differences in the case mix of sABI patients admitted to IRU may be considered another side-effect of the pandemic. Facing this health emergency, rehabilitation specialists need to adapt readily to the changing clinical and functional needs of patients' addressing the IRUs.

Effects of control strategies on gait in robot-assisted post-stroke lower limb rehabilitation: a systematic review.

BACKGROUND: Stroke related motor function deficits affect patients' likelihood of returning to professional activities, limit their participation in society and functionality in daily living. Hence, robot-aided gait rehabilitation needs to be fruitful and effective from a motor learning perspective. For this reason, optimal human-robot interaction strategies are necessary to foster neuroplastic shaping during therapy. Therefore, we performed a systematic search on the effects of different control algorithms on quantitative objective gait parameters of post-acute stroke patients. METHODS: We conducted a systematic search on four electronic databases using the Population Intervention Comparison and Outcome format. The heterogeneity of performance assessment, study designs and patients' numerosity prevented the possibility to conduct a rigorous meta-analysis, thus, the results were presented through narrative synthesis. RESULTS: A total of 31 studies (out of 1036) met the inclusion criteria, without applying any temporal constraints. No controller preference with respect to gait parameters improvements was found. However, preferred solutions were encountered in the implementation of force control strategies mostly on rigid devices in therapeutic scenarios. Conversely, soft devices, which were all position-controlled, were found to be more commonly used in assistive scenarios. The effect of different controllers on gait could not be evaluated since conspicuous heterogeneity was found for both performance metrics and study designs. CONCLUSIONS: Overall, due to the impossibility of performing a meta-analysis, this systematic review calls for an outcome standardisation in the evaluation of robot-aided gait rehabilitation. This could allow for the comparison of adaptive and human-dependent controllers with conventional ones, identifying the most suitable control strategies for specific pathologic gait patterns. This latter aspect could bolster individualized and personalized choices of control strategies during the therapeutic or assistive path.

Machine learning methods for functional recovery prediction and prognosis in post-stroke rehabilitation: a systematic review.

BACKGROUND: Rehabilitation medicine is facing a new development phase thanks to a recent wave of rigorous clinical trials aimed at improving the scientific evidence of protocols. This phenomenon, combined with new trends in personalised medical therapies, is expected to change clinical practice dramatically. The emerging field of Rehabilomics is only possible if methodologies are based on biomedical data collection and analysis. In this framework, the objective of this work is to develop a systematic review of machine learning algorithms as solutions to predict motor functional recovery of post-stroke patients after treatment. METHODS: We conducted a comprehensive search of five electronic databases using the Patient, Intervention, Comparison and Outcome (PICO) format. We extracted health conditions, population characteristics, outcome assessed, the method for feature extraction and selection, the algorithm used, and the validation approach. The methodological quality of included studies was assessed using the prediction model risk of bias assessment tool (PROBAST). A qualitative description of the characteristics of the included studies as well as a narrative data synthesis was performed. RESULTS: A total of 19 primary studies were included. The predictors most frequently used belonged to the areas of demographic characteristics and stroke assessment through clinical examination. Regarding the methods, linear and logistic regressions were the most frequently used and cross-validation was the preferred validation approach. CONCLUSIONS: We identified several methodological limitations: small sample sizes, a limited number of external validation approaches, and high heterogeneity among input and output variables. Although these elements prevented a quantitative comparison across models, we defined the most frequently used models given a specific outcome, providing useful indications for the application of more complex machine learning algorithms in rehabilitation medicine.

Cross-validation of predictive models for functional recovery after post-stroke rehabilitation.

BACKGROUND: Rehabilitation treatments and services are essential for the recovery of post-stroke patients' functions; however, the increasing number of available therapies and the lack of consensus among outcome measures compromises the possibility to determine an appropriate level of evidence. Machine learning techniques for prognostic applications offer accurate and interpretable predictions, supporting the clinical decision for personalised treatment. The aim of this study is to develop and cross-validate predictive models for the functional prognosis of patients, highlighting the contributions of each predictor. METHODS: A dataset of 278 post-stroke patients was used for the prediction of the class transition, obtained from the modified Barthel Index. Four classification algorithms were cross-validated and compared. On the best performing model on the validation set, an analysis of predictors contribution was conducted. RESULTS: The Random Forest obtained the best overall results on the accuracy (76.2%), balanced accuracy (74.3%), sensitivity (0.80), and specificity (0.68). The combination of all the classification results on the test set, by weighted voting, reached 80.2% accuracy. The predictors analysis applied on the Support Vector Machine, showed that a good trunk control and communication level, and the absence of bedsores retain the major contribution in the prediction of a good functional outcome. CONCLUSIONS: Despite a more comprehensive assessment of the patients is needed, this work paves the way for the implementation of solutions for clinical decision support in the rehabilitation of post-stroke patients. Indeed, offering good prognostic accuracies for class transition and patient-wise view of the predictors contributions, it might help in a personalised optimisation of the patients' rehabilitation path.

Brain microstate spatio-temporal dynamics as a candidate endotype of consciousness.

Consciousness can be defined as a phenomenological experience continuously evolving. Current research showed how conscious mental activity can be subdivided into a series of atomic brain states converging to a discrete spatiotemporal pattern of global neuronal firing. Using the high temporal resolution of EEG recordings in patients with a severe Acquired Brain Injury (sABI) admitted to an Intensive Rehabilitation Unit (IRU), we detected a novel endotype of consciousness from the spatiotemporal brain dynamics identified via microstate analysis. Also, we investigated whether microstate features were associated with common neurophysiological alterations. Finally, the prognostic information comprised in such descriptors was analysed in a sub-cohort of patients with prolonged Disorder of Consciousness (pDoC). Occurrence of frontally-oriented microstates (C microstate), likelihood of maintaining such brain state or transitioning to the C topography and complexity were found to be indicators of consciousness presence and levels. Features of left-right asymmetric microstates and transitions toward them were found to be negatively correlated with antero-posterior brain reorganization and EEG symmetry. Substantial differences in microstates' sequence complexity and presence of C topography were found between groups of patients with alpha dominant background, cortical reactivity and antero-posterior gradient. Also, transitioning from left-right to antero-posterior microstates was found to be an independent predictor of consciousness recovery, stronger than consciousness levels at IRU's admission. In conclusions, global brain dynamics measured with scale-free estimators can be considered an indicator of consciousness presence and a candidate marker of short-term recovery in patients with a pDoC.

Low-density EEG-based Functional Connectivity Discriminates Minimally Conscious State plus from minus.

OBJECTIVE: Within the continuum of consciousness, patients in a Minimally Conscious State (MCS) may exhibit high-level behavioral responses (MCS+) or may not (MCS-). The evaluation of residual consciousness and related classification is crucial to propose tailored rehabilitation and pharmacological treatments, considering the inherent differences among groups in diagnosis and prognosis. Currently, differential diagnosis relies on behavioral assessments posing a relevant risk of misdiagnosis. In this context, EEG offers a non-invasive approach to model the brain as a complex network. The search for discriminating features could reveal whether behavioral responses in post-comatose patients have a defined physiological background. Additionally, it is essential to determine whether the standard behavioral assessment for quantifying responsiveness holds physiological significance. METHODS: In this prospective observational study, we investigated whether low-density EEG-based graph metrics could discriminate MCS+/- patients by enrolling 57 MCS patients (MCS-: 30; males: 28). At admission to intensive rehabilitation, 30 min resting-state closed-eyes EEG recordings were performed together with consciousness diagnosis following international guidelines. After EEG preprocessing, graphs' metrics were estimated using different connectivity measures, at multiple connection densities and frequency bands (α,θ,δ). Metrics were also provided to cross-validated Machine Learning (ML) models with outcome MCS+/-. RESULTS: A lower level of brain activity integration was found in the MCS- group in the α band. Instead, in the δ band MCS- group presented an higher level of clustering (weighted clustering coefficient) respect to MCS+. The best-performing solution in discriminating MCS+/- through the use of ML was an Elastic-Net regularized logistic regression with a cross-validation accuracy of 79% (sensitivity and specificity of 74% and 85% respectively). CONCLUSION: Despite tackling the MCS+/- differential diagnosis is highly challenging, a daily-routine low-density EEG might allow to differentiate across these differently responsive brain networks. SIGNIFICANCE: Graph-theoretical features are shown to discriminate between these two neurophysiologically similar conditions, and may thus support the clinical diagnosis.

Quantitative EEG and prognosis for recovery in post-stroke patients: The effect of lesion laterality.

OBJECTIVE: There is emerging confidence that quantitative EEG (qEEG) has the potential to inform clinical decision-making and guide individualized rehabilitation after stroke, but consensus on the best EEG biomarkers is needed for translation to clinical practice. This study investigates the spatial qEEG spectral and symmetry distribution in patients with a left/right hemispheric stroke, to evaluate their side-specific prognostic power in post-acute rehabilitation outcome. METHODS: Resting-state 19-channel EEG recordings were collected with clinical information on admission to intensive inpatient rehabilitation (within 30 days post stroke), and six months post stroke. After preprocessing, spectral (Delta-to-Alpha Ratio, DAR) and symmetry (pairwise and hemispheric Brain Symmetry Index) features were extracted. Patients were divided into Affected Right and Left (AR/AL) groups, according to the location of their lesion. Within each group, DAR was compared between homologous electrode pairs and the pairwise difference between pairs was compared across pairs in the scalp. Then, the prognostic power of qEEG admission metrics was evaluated by performing correlations between admission metrics and discharge mBI values. RESULTS: Fifty-two patients with hemorrhagic or ischemic stroke (20 females, 38.5 %, median age 76 years [IQR = 22]) were included in the study. DAR was significantly higher in the affected hemisphere for both AR and AL groups, and, a higher frontal (to posterior) asymmetry was found independent of the side of the lesion. DAR was found to be a prognostic marker of 6-months modified Barthel Index (mBI) only for the AL group, while hemispheric asymmetry did not correlate with follow-up outcomes in either group. DISCUSSION: While the presence of EEG abnormalities in the affected hemisphere of a stroke is well recognized, we have shown that the extent of DAR abnormalities seen correlates with disability at 6 months post stroke, but only for left hemispheric lesions. Routine prognostic evaluation, in addition to motor and functional scales, can add information concerning neuro-prognostication and reveal neurophysiological abnormalities to be assessed during rehabilitation.

Can Respiration Complexity Help the Diagnosis of Disorders of Consciousness in Rehabilitation?

BACKGROUND: Autonomic Nervous System (ANS) activity, as cardiac, respiratory and electrodermal activity, has been shown to provide specific information on different consciousness states. Respiration rates (RRs) are considered indicators of ANS activity and breathing patterns are currently already included in the evaluation of patients in critical care. OBJECTIVE: The aim of this work was to derive a proxy of autonomic functions via the RR variability and compare its diagnostic capability with known neurophysiological biomarkers of consciousness. METHODS: In a cohort of sub-acute patients with brain injury during post-acute rehabilitation, polygraphy (ECG, EEG) recordings were collected. The EEG was labeled via descriptors based on American Clinical Neurophysiology Society terminology and the respiration variability was extracted by computing the Approximate Entropy (ApEN) of the ECG-derived respiration signal. Competing logistic regressions were applied to evaluate the improvement in model performances introduced by the RR ApEN. RESULTS: Higher RR complexity was significantly associated with higher consciousness levels and improved diagnostic models' performances in contrast to the ones built with only electroencephalographic descriptors. CONCLUSIONS: Adding a quantitative, instrumentally based complexity measure of RR variability to multimodal consciousness assessment protocols may improve diagnostic accuracy based only on electroencephalographic descriptors. Overall, this study promotes the integration of biomarkers derived from the central and the autonomous nervous system for the most comprehensive diagnosis of consciousness in a rehabilitation setting.

EEG fractal dimensions predict high-level behavioral responses in minimally conscious patients.

Objective.Brain-injured patients may enter a state of minimal or inconsistent awareness termed minimally conscious state (MCS). Such patient may (MCS+) or may not (MCS-) exhibit high-level behavioral responses, and the two groups retain two inherently different rehabilitative paths and expected outcomes. We hypothesized that brain complexity may be treated as a proxy of high-level cognition and thus could be used as a neural correlate of consciousness.Approach.In this prospective observational study, 68 MCS patients (MCS-: 30; women: 31) were included (median [IQR] age 69 [20]; time post-onset 83 [28]). At admission to intensive rehabilitation, 30 min resting-state closed-eyes recordings were performed together with consciousness diagnosis following international guidelines. The width of the multifractal singularity spectrum (MSS) was computed for each channel time series and entered nested cross-validated interpretable machine learning models targeting the differential diagnosis of MCS±.Main results.Frontal MSS widths (p< 0.05), as well as the ones deriving from the left centro-temporal network (C3:p= 0.018, T3:p= 0.017; T5:p= 0.003) were found to be significantly higher in the MCS+ cohort. The best performing solution was found to be the K-nearest neighbor model with an aggregated test accuracy of 75.5% (median [IQR] AuROC for 100 executions 0.88 [0.02]). Coherently, the electrodes with highest Shapley values were found to be Fz and Cz, with four out the first five ranked features belonging to the fronto-central network.Significance.MCS+ is a frequent condition associated with a notably better prognosis than the MCS-. High fractality in the left centro-temporal network results coherent with neurological networks involved in the language function, proper of MCS+ patients. Using EEG-based interpretable algorithm to complement differential diagnosis of consciousness may improve rehabilitation pathways and communications with caregivers.

Machine learning based estimation of dynamic balance and gait adaptability in persons with neurological diseases using inertial sensors.

Poor dynamic balance and impaired gait adaptation to different contexts are hallmarks of people with neurological disorders (PwND), leading to difficulties in daily life and increased fall risk. Frequent assessment of dynamic balance and gait adaptability is therefore essential for monitoring the evolution of these impairments and/or the long-term effects of rehabilitation. The modified dynamic gait index (mDGI) is a validated clinical test specifically devoted to evaluating gait facets in clinical settings under a physiotherapist's supervision. The need of a clinical environment, consequently, limits the number of assessments. Wearable sensors are increasingly used to measure balance and locomotion in real-world contexts and may permit an increase in monitoring frequency. This study aims to provide a preliminary test of this opportunity by using nested cross-validated machine learning regressors to predict the mDGI scores of 95 PwND via inertial signals collected from short steady-state walking bouts derived from the 6-minute walk test. Four different models were compared, one for each pathology (multiple sclerosis, Parkinson's disease, and stroke) and one for the pooled multipathological cohort. Model explanations were computed on the best-performing solution; the model trained on the multipathological cohort yielded a median (interquartile range) absolute test error of 3.58 (5.38) points. In total, 76% of the predictions were within the mDGI's minimal detectable change of 5 points. These results confirm that steady-state walking measurements provide information about dynamic balance and gait adaptability and can help clinicians identify important features to improve upon during rehabilitation. Future developments will include training of the method using short steady-state walking bouts in real-world settings, analysing the feasibility of this solution to intensify performance monitoring, providing prompt detection of worsening/improvements, and complementing clinical assessments.

The Consciousness Domain Index: External Validation and Prognostic Relevance of a Data-Driven Assessment.

The prognosis of neurological outcomes in patients with prolonged Disorders of Consciousness (pDoC) has improved in the last decades. Currently, the level of consciousness at admission to post-acute rehabilitation is diagnosed by the Coma Recovery Scale-Revised (CRS-R) and this assessment is also part of the used prognostic markers. The consciousness disorder diagnosis is based on scores of single CRS-R sub-scales, each of which can independently assign or not a specific level of consciousness to a patient in a univariate fashion. In this work, a multidomain indicator of consciousness based on CRS-R sub-scales, the Consciousness-Domain-Index (CDI), was derived by unsupervised learning techniques. The CDI was computed and internally validated on one dataset (N=190) and then externally validated on another dataset (N=86). Then, the CDI effectiveness as a short-term prognostic marker was assessed by supervised Elastic-Net logistic regression. The prediction accuracy of the neurological prognosis was compared with models trained on the level of consciousness at admission based on clinical state assessments. CDI-based prediction of emergence from a pDoC improved the clinical assessment-based one by 5.3% and 3.7%, respectively for the two datasets. This result confirms that the data-driven assessment of consciousness levels based on multidimensional scoring of the CRS-R sub-scales improve short-term neurological prognosis with respect to the classical univariately-derived level of consciousness at admission.

Heart rate variability for the evaluation of patients with disorders of consciousness.

OBJECTIVE: Clinical responsiveness of patients with a Disorder of Consciousness (DoC) correlates to sympathetic/parasympathetic homeostatic balance. Heart Rate Variability (HRV) metrics result in non-invasive proxies of modulation capabilities of visceral states. In this work, our aim was to evaluate whether HRV measures could improve the differential diagnosis between Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) with respect to multivariate models based on standard clinical electroencephalography (EEG) labeling only in a rehabilitation setting. METHODS: A prospective observational study was performed consecutively enrolling 82 DoC patients. Polygraphic recordings were performed. HRV-metrics and EEG descriptors derived from the American Clinical Neurophysiology Society's Standardized Critical Care terminology were included. Descriptors entered univariate and then multivariate logistic regressions with the target set to the UWS/MCS diagnosis. RESULTS: HRV measures resulted significantly different between UWS and MCS patients, with higher values being associated with better consciousness levels. Specifically, adding HRV-related metrics to ACNS EEG descriptors increased the Nagelkerke R2 from 0.350 (only EEG descriptors) to 0.565 (HRV-EEG combination) with the outcome set to the consciousness diagnosis. CONCLUSIONS: HRV changes across the lowest states of consciousness. Rapid changes in heart rate, occurring in better consciousness levels, confirm the mutual correlation between visceral state functioning patterns and consciousness alterations. SIGNIFICANCE: Quantitative analysis of heart rate in patients with a DoC paves the way for the implementation of low-cost pipelines supporting medical decisions within multimodal consciousness assessments.

Predicting outcome of patients with prolonged disorders of consciousness using machine learning models based on medical complexity.

Patients with severe acquired brain injury and prolonged disorders of consciousness (pDoC) are characterized by high clinical complexity and high risk to develop medical complications. The present multi-center longitudinal study aimed at investigating the impact of medical complications on the prediction of clinical outcome by means of machine learning models. Patients with pDoC were consecutively enrolled at admission in 23 intensive neurorehabilitation units (IRU) and followed-up at 6 months from onset via the Glasgow Outcome Scale-Extended (GOSE). Demographic and clinical data at study entry and medical complications developed within 3 months from admission were collected. Machine learning models were developed, targeting neurological outcomes at 6 months from brain injury using data collected at admission. Then, after concatenating predictions of such models to the medical complications collected within 3 months, a cascade model was developed. One hundred seventy six patients with pDoC (M: 123, median age 60.2 years) were included in the analysis. At admission, the best performing solution (k-Nearest Neighbors regression, KNN) resulted in a median validation error of 0.59 points [IQR 0.14] and a classification accuracy of dichotomized GOS-E of 88.6%. Coherently, at 3 months, the best model resulted in a median validation error of 0.49 points [IQR 0.11] and a classification accuracy of 92.6%. Interpreting the admission KNN showed how the negative effect of older age is strengthened when patients' communication levels are high and ameliorated when no communication is present. The model trained at 3 months showed appropriate adaptation of the admission prediction according to the severity of the developed medical complexity in the first 3 months. In this work, we developed and cross-validated an interpretable decision support tool capable of distinguishing patients which will reach sufficient independence levels at 6 months (GOS-E > 4). Furthermore, we provide an updated prediction at 3 months, keeping in consideration the rehabilitative path and the risen medical complexity.

Consciousness-Domain Index: a data-driven clustering-based consciousness labeling.

Assessing consciousness results in one of the most complex neurological diagnosis. Even more complex and uncertain is prognosticating on consciousness recovery. Currently, consciousness is assessed by using a six-items scale, the Coma Recovery Scale-Revised. Namely, scores on the sub-items can individually assign or not a specific level of consciousness to a patient. In our work, by using solely the six sub-items of the CRS-R, we implemented a clustering algorithm labeling patients with the Consciousness-Domains Index (CDI) starting from a dataset of 190 patients with a Disorder of Consciousness (DoC). Then, the CDI is compared with the clinical state at admission and at six months via univariate analysis. The number of clusters best dividing the groups resulted equal to two and the most influencing sub-items resulted the visual and motor one. The CDI closely resembles the clinical state at admission (CSA) (Cohen's k=0.85). On the other hand, when comparing CDI and CSA, a net improvement was found in the prognostic power of the neurological outcome at six months, targeted as presence/absence of a DoC ( ). Data-driven techniques pave the way for automated and model-based search of prognostic factors, together with the use of such prognostic factors in multivariate prognostic models. Future works will address the external validation of the CDI, together with the inclusion of the CDI in a multivariate supervised model, in order to assess the true potential of such novel index. Clinical Relevance- A completely data-driven index was derived from a clustering of CRS-R sub-items. It correlates with the neurological outcome at six months better than the state of consciousness at admission.

Predicting SARS-CoV-2 infection duration at hospital admission:a deep learning solution.

COVID-19 cases are increasing around the globe with almost 5 million of deaths. We propose here a deep learning model capable of predicting the duration of the infection by means of information available at hospital admission. A total of 222 patients were enrolled in our observational study. Anagraphical and anamnestic data, COVID-19 signs and symptoms, COVID-19 therapy, hematochemical test results, and prior therapies administered to patients are used as predictors. A set of 55 features, all of which can be taken in the first hours of the patient's hospitalization, was considered. Different solutions were compared achieving the best performance with a sequential convolutional neural network-based model merged in an ensemble with two different meta-learners linked in cascade. We obtained a median absolute error of 2.7 days (IQR = 3.0) in predicting the duration of the infection; the error was equally distributed in the infection duration range. This tool could preemptively give an outlook of the COVID-19 patients' expected path and the associated hospitalization effort. The proposed solution could be viable in tackling the huge burden and the logistics complexity of hospitals or rehabilitation centers during the pandemic waves. With data taken ad admission, entering a PCA-based feature selection, a k-fold cross-validated CNN-based model was implemented. After external texting, a median absolute error of 2.7 days [IQR = 3 days].

Study and validation of an explainable machine learning-based mortality prediction following emergency surgery in the elderly: A prospective observational study.

INTRODUCTION: The heterogeneity of procedures and the variety of comorbidities of the patients undergoing surgery in an emergency setting makes perioperative risk stratification, planning, and risk mitigation crucial. In this optic, Machine Learning has the capability of deriving data-driven predictions based on multivariate interactions of thousands of instances. Our aim was to cross-validate and test interpretable models for the prediction of post-operative mortality after any surgery in an emergency setting on elderly patients. METHODS: This study is a secondary analysis derived from the FRAILESEL study, a multi-center (N = 29 emergency care units), nationwide, observational prospective study with data collected between 06-2017 and 06-2018 investigating perioperative outcomes of elderly patients (age≥65 years) undergoing emergency surgery. Demographic and clinical data, medical and surgical history, preoperative risk factors, frailty, biochemical blood examination, vital parameters, and operative details were collected and the primary outcome was set to the 30-day mortality. RESULTS: Of the 2570 included patients (50.66% males, median age 77 [IQR = 13] years) 238 (9.26%) were in the non-survivors group. The best performing solution (MultiLayer Perceptron) resulted in a test accuracy of 94.9% (sensitivity = 92.0%, specificity = 95.2%). Model explanations showed how non-chronic cardiac-related comorbidities reduced activities of daily living, low consciousness levels, high creatinine and low saturation increase the risk of death following surgery. CONCLUSIONS: In this prospective observational study, a robustly cross-validated model resulted in better predictive performance than existing tools and scores in literature. By using only preoperative features and by deriving patient-specific explanations, the model provides crucial information during shared decision-making processes required for risk mitigation procedures.

EEG-based methods for recovery prognosis of patients with disorders of consciousness: A systematic review.

OBJECTIVE: Disorders of consciousness (DoC) are acquired conditions of severely altered consciousness. Electroencephalography (EEG)-derived biomarkers have been studied as clinical predictors of consciousness recovery. Therefore, this study aimed to systematically review the methods, features, and models used to derive prognostic EEG markers in patients with DoC in a rehabilitation setting. METHODS: We conducted a systematic literature search of EEG-based strategies for consciousness recovery prognosis in five electronic databases. RESULTS: The search resulted in 2964 papers. After screening, 15 studies were included in the review. Our analyses revealed that simpler experimental settings and similar filtering cut-off frequencies are preferred. The results of studies were categorised by extracting qualitative and quantitative features. The quantitative features were further classified into evoked/event-related potentials, spectral measures, entropy measures, and graph-theory measures. Despite the variety of methods, features from all categories, including qualitative ones, exhibited significant correlations with DoC prognosis. Moreover, no agreement was found on the optimal set of EEG-based features for the multivariate prognosis of patients with DoC, which limits the computational methods applied for outcome prediction and correlation analysis to classical ones. Nevertheless, alpha power, reactivity, and higher complexity metrics were often found to be predictive of consciousness recovery. CONCLUSIONS: This study's findings confirm the essential role of qualitative EEG and suggest an important role for quantitative EEG. Their joint use could compensate for their reciprocal limitations. SIGNIFICANCE: This study emphasises the need for further efforts toward guidelines on standardised EEG analysis pipeline, given the already proven role of EEG markers in the recovery prognosis of patients with DoC.