Patients with Disorder of Consciousness (DoC) entering Intensive Rehabilitation Units after a severe Acquired Brain Injury have a highly variable evolution of the state of consciousness which is a ...complex aspect to predict. Besides clinical factors, electroencephalography has clearly shown its potential into the identification of prognostic biomarkers of consciousness recovery. In this retrospective study, with a dataset of 271 patients with DoC, we proposed three different Elastic-Net regressors trained on different datasets to predict the Coma Recovery Scale-Revised value at discharge based on data collected at admission. One dataset was completely EEG-based, one solely clinical data-based and the last was composed by the union of the two. Each model was optimized, validated and tested with a robust nested cross-validation pipeline. The best models resulted in a median absolute test error of 4.54 IQR = 4.56, 3.39 IQR = 4.36, 3.16 IQR = 4.13 for respectively the EEG, clinical and hybrid model. Furthermore, the hybrid model for what concerns overcoming an unresponsive wakefulness state and exiting a DoC results in an AUC of 0.91 and 0.88 respectively. Small but useful improvements are added by the EEG dataset to the clinical model for what concerns overcoming an unresponsive wakefulness state. Data-driven techniques and namely, machine learning models are hereby shown to be capable of supporting the complex decision-making process the practitioners must face.
This study describes a dynamic non-linear mathematical approach for modeling the course of disease in acquired brain injury (ABI) patients. Data from a multicentric study were used to evaluate the ...reliability of the Michaelis-Menten (MM) model applied to well-known clinical variables that assess the outcome of ABI patients. The sample consisted of 156 ABI patients admitted to eight neurorehabilitation subacute units and evaluated at baseline (T0), 4 months after the event (T1) and at discharge (T2). The MM model was used to characterize the trend of the first Principal Component Analysis (PCA) dimension (represented by the variables: feeding modality, RLAS, ERBI-A, Tracheostomy, CRS-r and ERBI-B) in order to predict the most plausible outcome, in terms of positive or negative Glasgow outcome score (GOS) at discharge. Exploring the evolution of the PCA dimension 1 over time, after day 86 the MM model better differentiated between the time course for individuals with a positive and negative GOS (accuracy: 85%; sensitivity: 90.6%; specificity: 62.5%). The non-linear dynamic mathematical model can be used to provide more comprehensive trajectories of the clinical evolution of ABI patients during the rehabilitation period. Our model can be used to address patients for interventions designed for a specific outcome trajectory.
Comparison studies on recovery outcomes in ischemic (IS) and hemorrhagic strokes (HS) have yielded mixed results. In this retrospective observational study of consecutive IS and HS patients, we aimed ...at evaluating functional outcomes at discharge from an intensive rehabilitation hospital, comparing IS vs. HS, analyzing possible predictors. Modified Rankin Scale (mRS) at discharge was the main outcome. Out of the 229 patients included (mean age 72.9 ± 13.9 years, 48% males), 81 had HS (35%). Compared with IS (
= 148), HS patients were significantly younger (75 ± 12.5 vs. 68.8 ± 15.4 years,
= 0.002), required longer hospitalizations both in acute (23.9 ± 36.7 vs. 35.2 ± 29.9 days,
= 0.019) and rehabilitation hospitals (41.5 ± 31.8 vs. 77.2 ± 51.6 days,
= 0.001), and had more severe initial clinical deficit (mean number of neurological impairments: 2.0 ± 1.1 vs. 2.6 ± 1.4,
= 0.001) and mRS scores at admission (
= 0.046). At discharge, functional status change, expressed as mRS, was not significantly different between IS and HS (
= 0.01,
= 0.902), nor was the discharge destination (
= 0.428). Age and clinical severity were predictors of functional outcome in both stroke types. On admission in an intensive rehabilitation hospital, HS patients presented a worse functional and clinical status compared to IS. Despite this initial gap, the two stroke types showed an overlapped trajectory of functional recovery, with age and initial stroke severity as the main prognostic factors.
•Predictors of successful decannulation are a current focus of clinical research.•Two independent machine learning model were cross-validated on 327 patients.•Decannulation was predicted (AUC = 0.85) ...by a machine learning models ensemble.•Early/late decannulation (90 days threshold) can be discriminated with an AUC = 0.82.•Clinical decision can be supported with non-instrumental features taken at admission.
From a rehabilitation perspective, removal of tracheostomy in patients with severe acquired brain injuries (sABI) is a crucial step. Predictive parameters for a successful decannulation are currently still a focus of the research for sABI patients, especially for those presenting a disorder of consciousness. For this reason, we adopted a data-driven approach predicting decannulation probability and timing using ensemble learning models in patients in intensive rehabilitation units.
327 patients, 186 of which were successfully decannulated during their intensive rehabilitative stay, were recruited in a non-concurrent retrospective study. Decannulation probability and timing were predicted using data available within one week from admission at the rehabilitation unit. Two predictive models were trained and cross-validated independently, with the first being an ensemble of a Support Vector Machine and Random Forests and the second an Adaptive Boosting with a Support Vector Regression as weak learner. Confusion matrix, accuracy and AUC were considered as evaluation metrics for the classifier and median absolute error was considered for the regressor. To quantify the advantages in the clinical practice of using the latter prediction, we compared timing estimation with a timing guess (median) calculated on available data. The comparison was based on a Wilcoxon signed rank test.
Decannulation probability was successfully predicted with an accuracy of 84.8% (AUC = 0.85) and timing with a median absolute error of 25.7 days IQR = 25.6. This resulted in a significant improvement with respect to the weaning time guess (p<0.05) with an effect size of 71.7%. Furthermore, dichotomizing the regression prediction with a threshold (3 months from the event), resulted in a prediction accuracy of 77.5% (AUC = 0.82) on the test set.
A model capable of providing a prediction on decannulation probability and timing was developed and cross-validated, built on data taken at admission to the intensive rehabilitation unit. Translated in clinical practice, this information can support the clinical decision process and provide a mean to improve both in-hospital and domiciliary care organization.
Decompressive craniectomy (DC) is a life-saving procedure conducted to treat refractory intracranial hypertension. Although DC reduces mortality of severe Acquired Brain Injury (sABI) survivors, it ...has been associated with severe long-term disability. This observational study compares functional outcomes at discharge from an Intensive Rehabilitative Unit (IRU) between sABI patients with and without DC.
sABI patients undergoing DC before entering the Don Gnocchi Foundation IRU were compared with a group of sABI patients who did not undergo DC (No-DC group), after matching it by age, sex, aetiology, time post-onset, and clinical status. Inclusion criteria were: diagnosis of sABI, age 18+, time from the event <90 days.
A total of 87 (DC: 47) patients were included (median age: 60.5 IQR = 17.47). The two groups did not differ for admission clinical features except for the tracheostomy presence (more frequent in DC, p < 0.001). No significant differences were also found at discharge. DC group presented a significantly longer length-of-stay than No-DC group (p < 0.001) and a longer time to tracheostomy removal (p = 0.036). DC was not found to influence outcomes as consciousness improvement, tracheostomy removal, oral intake and functional independence.
sABI patients with DC improved after rehabilitation as much as No-DC patients did but they required a longer stay.
Implications for Rehabilitation
Decompressive craniectomy (DC) is practiced during the acute phase after hemorrhagic, ischemic, traumatic severe brain injury as a life-saving procedure to treat refractory intracranial hypertension
DC has been associated with follow-up severe long-term disability, but no study yet addressed whether DC may affect intensive rehabilitation outcomes.
Undergoing a DC is not a negative prognostic factor for achieving rehabilitation goals after a severe acquired brain injury
DC must be taken into account when customizing rehabilitation pathway especially because these patients required a longer time to reach the outcomes.
Objectives
Critical illness polyneuropathy and myopathy (CIPNM) frequently affects critical patients and can occur after severe acquired brain injuries (sABI) influencing the functional recovery. We ...aimed to assess how the concomitance between CIPNM and sABI might influence the rehabilitative outcomes in terms of functional autonomy, oral feeding recovery and endotracheal tube weaning.
Materials and Methods
Adult patients with sABI admitted to an intensive rehabilitation unit and underwent an electromyography examination within seven days after admission were included. Assessed rehabilitative outcomes at discharge were decannulation success and its timing, functional autonomy measured by the Functional Independence Measure (FIM) and the Glasgow outcome scale expanded (GOS‐E) and oral feeding recovery assessed by the Functional Oral Intake Scale (FOIS) score.
Results
Among the 224 included patients (81 (36%) females, age (medianIQR): 68.7321.66 years), 119 (53.1%) presented CIPNM at admission. Albeit the change of rehabilitative outcomes between admission and discharge was significant in all the sABI patients (P < .001 for ΔFOIS, ΔFIM and ΔGOS‐E), those with a concomitant CIPNM achieved significantly lower scores as evaluated by Mann‐Whitney tests (P < .001 for ΔFIM Δ and GOS‐E; P < .005 for ΔFOIS). The CIPNM absence was associated with a higher probability to achieve functional autonomy (GOS‐E > 4) (OR:4.57 (1.49/14.06); P < .01) and oral feeding recovery (FOIS ≥ 4) (OR:2.07 (1.07/3.99); P = .03) at discharge. CIPNM presence did not influence decannulation success but a longer time to cannula weaning was required (P < .01 in the log‐rank test).
Conclusions
CIPMN significantly affects the rehabilitative outcomes after a sABI and should be taken into account for better rehabilitative handling.
Background
Gender differences in stroke functional recovery after rehabilitation are poorly investigated. Our aim was to compare functional outcomes at discharge from an intensive rehabilitation ...hospital after stroke in men and women, and to analyze their prognostic factors.
Methods
Retrospective observational study of consecutive stroke patients discharged from an intensive neurological rehabilitation hospital, from January 2018 to June 2019. Modified Rankin Scale (mRS) at discharge was the main outcome measure.
Results
Among the 208 included patients (mean age 73.4 ± 13.6 years), 105 (50.5%) were women. Women were significantly older (75.3 ± 13.8 vs. 71.4 ± 13.2 years, respectively, p = 0.041), and less often had a history of smoking habit (27% vs. 50%, p < 0.001). No gender differences emerged for vascular risk factors and comorbidities, pre‐stroke functional status, length of hospital stay, stroke type, and number of clinical deficits. At admission to the rehabilitation hospital, mRS score distributions were not different (p = 0.795). At discharge, mRS score distributions and destinations did not differ between men and women (p = 0.391, p = 0.785, respectively). A significant interaction between gender and the change in mRS score from admission to discharge was found (F = 6.6, p = 0.011) taking into account age, stroke type, and number of initial clinical deficits. Dividing the cohort according to age, elderly women showed a better functional recovery compared to men.
Conclusions
At admission to an intensive rehabilitation hospital, men and women presented a similar functional and clinical status and a substantial overlap of functional recovery after stroke. At higher ages, the potential for recovery appeared better in women compared to men.
Gender differences in recovery after stroke rehabilitation are poorly investigated. In our study on admission to rehabilitation hospital, men and women were clinically similar. Functional recovery was similar despite women being older than men. At higher ages, the potential for recovery appears better in women.
In this multi-center study, we provide a systematic evaluation of the clinical variability associated with paroxysmal sympathetic hyperactivity (PSH) in patients with acquired brain injury (ABI) to ...determine how these signs can impact outcomes. A total of 156 ABI patients with a disorder of consciousness (DoC) were admitted to neurorehabilitation subacute units (intensive rehabilitation unit; IRU) and evaluated at baseline (T0), after 4 months from event (T1), and at discharge (T2). The outcome measure was the Glasgow Outcome Scale-Extended, whereas age, sex, etiology, Coma Recovery Scale-Revised (CRS-r), Rancho Los Amigos Scale (RLAS), Early Rehabilitation Barthel Index (ERBI), PSH-Assessment Measure (PSH-AM) scores and other clinical features were considered as predictive factors. A machine learning (ML) approach was used to identify the best predictive model of clinical outcomes. The etiology was predominantly vascular (50.8%), followed by traumatic (36.2%). At admission, prevalence of PSH was 31.3%, which decreased to 16.6% and 4.4% at T1 and T2, respectively. At T2, 2.8% were dead and 61.1% had a full recovery of consciousness, whereas 36.1% remained in VS or MCS. A support vector machine (SVM)-based ML approach provides the best model with 82% accuracy in predicting outcomes. Analysis of variable importance shows that the most important clinical factors influencing the outcome are the PSH-AM scores measured at T0 and T1, together with neurological diagnosis, CRS-r, and RLAS scores measured at T0. This joint multi-center effort provides a comprehensive picture of the clinical impact of PSH signs in ABI patients, demonstrating its predictive value in comparison with other well-known clinical measurements.
Restoration of functions in Huntington's disease (HD) by neurotransplantation stems from the formation of a striatum-like structure capable of establishing host connections as a result of grafted ...striatal neuroblast maturation. For the first time, we demonstrated some developmental steps accomplished by progenitor cells in the brain of an HD patient and analysed the molecular asset of the human primordium.
Surgery involved bilateral (two sessions) stereotactic, caudate-putaminal transplantation of whole ganglionic eminence fragments from single legally aborted fetuses. MRI showed that the tissue deposits of the left hemisphere grew and joined to constitute a single tissue mass that remodelled basal ganglia anatomy and remained stable in size over time. No evidence of graft growth was observed contralaterally. PET demonstrated increased striatal and stable cortical metabolism. Unified Huntington's Disease Rating Scale assessments demonstrated improvement of motor performances, which faded over the 36-month follow-up. Cognitive performance tended to decrease at a lower rate than before transplantation.
The striatal primordium grew into the host brain and this process was associated with metabolic change and some clinical benefit. The study suggests the plasticity and reparative potential of un-manipulated primordium in an era where promising cell-based therapies are still in their infancy.
Podocyte loss is a general mechanism of glomerular dysfunction that initiates and drives the progression of chronic kidney disease, which affects 10% of the world population. Here, we evaluate ...whether the regenerative response to podocyte injury influences chronic kidney disease outcome. In models of focal segmental glomerulosclerosis performed in inducible transgenic mice where podocytes are tagged, remission or progression of disease was determined by the amount of regenerated podocytes. When the same model was established in inducible transgenic mice where renal progenitors are tagged, the disease remitted if renal progenitors successfully differentiated into podocytes, while it persisted if differentiation was ineffective, resulting in glomerulosclerosis. Treatment with BIO, a GSK3s inhibitor, significantly increased disease remission by enhancing renal progenitor sensitivity to the differentiation effect of endogenous retinoic acid. These results establish renal progenitors as critical determinants of glomerular disease outcome and a pharmacological enhancement of their differentiation as a possible therapeutic strategy.
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•Renal progenitors can generate differentiated podocytes after glomerular injury•Renal progenitor response critically determines glomerular disease remission•Inefficient renal progenitor to podocyte differentiation dictates disease chronicization•Renal progenitor differentiation into podocytes can be enhanced with drugs
In this article, Romagnani, Lasagni, and colleagues show that podocyte regeneration is a critical determinant of the outcome of glomerular disorders and that enhancement of renal progenitor differentiation into podocyte through pharmacological treatment shifts the disease from progression to remission.
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