Brain retraction injury: systematic literature review.

Cerebral retraction is frequently required in cranial surgery to access deep areas. Brain retractors have been systematically used in the past, but they have been associated with brain injury. Nonetheless, they are still used and, even recently, new systems have been advocated. The aim of this study is to provide a systematic and critical review of brain retraction injury. A systematic literature review was performed in February 2023 according to PRISMA statement. Search terms included brain retraction and injury, with their variations and pertinent associations. Studies reporting qualitative and quantitative data on brain retraction injury were included. Out of 1689 initially retrieved articles, 90 and 26 were included in the systematic review for qualitative and quantitative data, respectively. The definition of brain retraction injury varies and its reported incidence in clinical studies is 5-10%, up to 47% if cerebral edema is considered. Some studies have hypothesized threshold values of pressures to be respected in order to prevent complications, with most data deriving from animal studies. At present, there are no instruments for brain retraction that can guarantee full safety. Some form of cerebral retraction might always be necessary for specific scenarios. Further studies are needed to collect quantitative and, ideally, clinical and comparative data on pressure thresholds to develop retraction systems that can reduce injury to a minimum.

Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy.

BACKGROUND: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. METHODS: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017-2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. RESULTS: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The "diagnostic delay" was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while "therapeutic delay" did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. CONCLUSIONS: We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.

Stimulation-related intraoperative seizures during awake surgery: a review of available evidences.

Awake surgery is a well-defined procedure with a very low morbidity. In particular, stimulation-related intraoperative seizure (IOS) is a commonly discussed and serious complication associated with awake surgery. Here, we reviewed the literature on awake surgery and IOS and sought to obtain evidences on the predictive factors of IOS and on the effect of IOS on postoperative outcomes. We conducted a comprehensive search of the Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases to identify potentially relevant articles from 2000 to 2019. We used combinations of the following search terms: "intraoperative seizure awake craniotomy," "awake surgery seizures," and pertinent associations; the search was restricted to publications in English and only to papers published in the last 20 years. The search returned 141 articles, including 39 papers that reported the IOS rate during awake craniotomy. The reported IOS rates ranged between 0 and 24% (mean, 7.7%). Only few studies have assessed the relationships between awake surgery and IOS, and hence, drawing clear conclusions is difficult. Nevertheless, IOS does not cause permanent and severe postoperative deficits, but can affect the patient's status perioperatively and the hospitalization duration. Anterior tumor location is an important perioperative factor associated with high IOS risk, whereas having seizures at tumor diagnosis does not seem to influence. However, the role of antiepileptic drug administration and prophylaxis remains unclear. In conclusion, given the difficulty in identifying predictors of IOS, we believe that prompt action at onset and awareness of appropriate management methods are vital.

Anxiety in neurosurgical patients undergoing nonurgent surgery during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has forced many countries into lockdown and has led to the postponement of nonurgent neurosurgical procedures. Although stress has been investigated during this pandemic, there are no reports on anxiety in neurosurgical patients undergoing nonurgent surgical procedures. METHODS: Neurosurgical patients admitted to hospitals in eastern Lombardy for nonurgent surgery after the lockdown prospectively completed a pre- and postoperative structured questionnaire. Recorded data included demographics, pathology, time on surgical waiting list, anxiety related to COVID-19, primary pathology and surgery, safety perception during hospital admission before and after surgery, and surgical outcomes. Anxiety was measured with the State-Trait Anxiety Inventory. Descriptive statistics were computed on the different variables and data were stratified according to pathology (oncological vs nononcological). Three different models were used to investigate which variables had the greatest impact on anxiety, oncological patients, and safety perception, respectively. Because the variables (Xs) were of a different nature (qualitative and quantitative), mostly asymmetrical, and related to outcome (Y) by nonlinear relationships, a machine learning approach composed of three steps (1, random forest growing; 2, relative variable importance measure; and 3, partial dependence plots) was chosen. RESULTS: One hundred twenty-three patients from 10 different hospitals were included in the study. None of the patients developed COVID-19 after surgery. State and trait anxiety were reported by 30.3% and 18.9% of patients, respectively. Higher values of state anxiety were documented in oncological compared to nononcological patients (46.7% vs 25%; p = 0.055). Anxiety was strongly associated with worry about primary pathology, surgery, disease worsening, and with stress during waiting time, as expected. Worry about positivity to SARS-CoV-2, however, was the strongest factor associated with anxiety, even though none of the patients were infected. Neuro-oncological disease was associated with state anxiety and with worry about surgery and COVID-19. Increased bed distance and availability of hand sanitizer were associated with a feeling of safety. CONCLUSIONS: These data underline the importance of psychological support, especially for neuro-oncological patients, during a pandemic.

Bend-Direction and Rotation Plastic Optical Fiber Sensor.

A plastic filament of poly (methyl methacrylate) (PMMA) was fabricated by extrusion. The mode confinement was simulated using numerical software. The idea is to study how the light intensity changes inside the plastic optical fiber (POF) when a bending in multiple directions is applied. The results obtained from the simulation were compared to the experimental observations. The non-circular shape of the POF allows sensing a rotation applied as well. The angle of rotation was obtained processing two images of the end facet of the fiber (one with the fiber in a reference position and one with the rotated fiber), using an intensity-based automatic image registration. The accuracy in the rotation calculation was of 0.01°.

Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.

INTRODUCTION: During surgery for lesions in eloquent areas the goal is to achieve the widest resection possible, without loss of neurological function. Intraoperative seizures may lead to abandonment of the procedure or damages to the patient. Awareness regarding the predictors of IOS would help the surgeon. The aim of this retrospective study was to identify the factors associated with the occurrence of IOS in patients who underwent awake surgery for removal of gliomas in eloquent areas. METHODS: This was a retrospective analysis of prospectively collected data of 109 patients who underwent awake craniotomy between January 2010 and December 2017 for removal of gliomas. IOS were defined as tonic-clonic seizures or loss of consciousness resulting in communication difficulties with the patient occurring during cortical and subcortical mapping. RESULTS: A total of 109 patients were included in this study and IOS occurred in 9 (8.2%) patients. Demographic and clinical factors were comparable between patients with and without IOS. In the IOS group, 7 (77.8%) patients had seizures preoperatively and 4 (57.1%) were on more than one perioperative antiepileptic drugs (AED). CONCLUSIONS: The current series add some hints to the poorly studied IOS risk during awake surgery. The risk of IOS appears to be relatively higher in patients with anteriorly located tumors and in patients operated without intraoperative brain activity monitoring and different patterns of stimulation for language and sensory-motor mapping. Further studies are needed to clarify the role of intraoperative techniques.

Endonasal and Transoral Approaches to the Craniovertebral Junction: A Quantitative Anatomical Study.

BACKGROUND: The endoscopic endonasal approach has recently been added to the surgical armamentarium to access the anterior craniovertebral junction (CVJ). Comparative analyses with the transoral approach are scarce. The aim of this study was to provide a quantitative anatomical analysis of both approaches. METHODS: In four specimens the endoscopic endonasal approach (before and after sphenoidectomy) and the transoral approach (without and with a soft palate split) were performed. ApproachViewer-part of GTx-UHN (Guided Therapeutics software, developed at University Health Network, Toronto, ON, Canada)-was used to quantify and visualize the working volume, as well as the exposed area, of each surgical approach. Different modalities (crossing and non-crossing) were used to quantify the exposure of the deep surface, providing an indirect quantitative value of the 'surgical freedom'. The lowest point exposed by the endonasal approaches was compared with that predicted by preoperative radiological lines. Non-parametric Welch analysis of variance (ANOVA) was used for statistical analyses. RESULTS: The working volume was significantly larger and the distance to the target was shorter with the transoral approaches than with the endonasal approaches. Clival exposure was better with the endonasal approaches than with the non-crossing transoral approach without a soft palate split; areas below C1 were better exposed with the transoral routes. The nasoaxial line best predicted surgical exposure with the endonasal approaches. CONCLUSION: Endoscopic endonasal and transoral approaches to the anterior CVJ provide optimal exposure of different areas that overlap at the level of C1 when no anatomical anomalies are present. A split of the soft palate is not necessary during the transoral approach if it is combined with an endoscopic endonasal approach.

Acute functional reactivation of the language network during awake intraoperative brain mapping.

Acute brain plasticity during resection of central lesions has been recently described. In the cases reported, perilesional latent networks, useful to preserve the neurological functions, were detected in asymptomatic patients. In this paper, we presented a case of acute functional reactivation (AFR) of the language network in a symptomatic patient. Tumor resection allowed to acutely restore the neurological deficit. Intraoperative direct cortical stimulation (DCS) and functional neuroimaging showed new epicentres of activation of the language network after tumor excision. DCS in awake surgery is mandatory to reveal AFR needful to improve the extent of resection preserving the quality of life.

An expandable chamber for safe brain retraction: new technologies in the field of transcranial endoscopic surgery. / ä¸€ç§ç”¨äºŽå¤§è„‘ç‰µæ‹‰çš„å¯æ‰©å±•è ”ï¼šé¢ å† çª¥é•œæ‰‹æœ¯é¢†åŸŸçš„æ–°æŠ€æœ¯.

Neurosurgery is a highly specialized field: it often involves surgical manipulation of noble structures and cerebral retraction is frequently necessary to reach deep-seated brain lesions. There are still no reliable methods preventing possible retraction complications. The objective of this study was to design work chambers well suited for transcranial endoscopic surgery while providing safe retraction of the surrounding brain tissue. The chamber is designed to be inserted close to the intracranial point of interest; once it is best placed it can be opened. This should guarantee an appreciable workspace similar to that of current neurosurgical procedures. The experimental aspect of this study involved the use of a force sensor to evaluate the pressures exerted on the brain tissue during the retraction phase. Following pterional craniotomy, pressure measurements were made during retraction with the use of a conventional metal spatula with different inclinations. Note that, although the force values necessary for retraction and exerted on the spatula by the neurosurgeon are the same, the local pressure exerted on the parenchyma at the edge of the spatula at different inclinations varied greatly. A new method of cerebral retraction using a chamber retractor (CR) has been designed to avoid any type of complication due to spatula edge overpressures and to maintain acceptable pressure values exerted on the parenchyma.

Using the 6-min walk test to assess the clinical response to mepolizumab and conventional therapy in severe eosinophilic asthma.

Background: Severe asthma limits exercise to avoid respiratory symptoms. The objective of the present study was to investigate the role of the 6-min walk test (6MWT) in severe asthma. Methods: Consecutive patients with severe eosinophilic asthma were enrolled. A 6MWT was performed before and after 12 months. Inhaled therapy dose, oral corticosteroids dose, pulmonary function tests, eosinophil blood count, fractional exhaled nitric oxide (FeNO), Asthma Control Test (ACT) score and responses to the Asthma Quality of Life Questionnaire (AQLQ) were also recorded. Results: Of the 22 patients enrolled, 13 were treated with mepolizumab 100 mg every 4 weeks in addition to conventional therapy and nine with conventional therapy only. The majority of the patients were treated with high-dose inhaled corticosteroids/long-acting ß-agonists/long-acting muscarinic receptor antagonists, while approximately half were on continuous oral corticosteroids. After 12 months, the mepolizumab group only showed a significant improvement in pulmonary function tests (percentage forced expiratory volume in 1 s and percentage forced expiratory flow at 25-75% forced vital capacity (FEF25-75%), both p<0.001; percentage forced vital capacity, p<0.01) and clinical laboratory parameters (eosinophil count, FeNO measured at a flow rate of 50 mL·s-1, ACT and AQLQ, p<0.001). No significant changes in the proportion of patients using continuous oral corticosteroids and high-dose inhaled corticosteroids/long-acting ß-agonists/long-acting muscarinic receptor antagonists were observed in either group (p>0.05). By paired comparisons, statistically significant improvements of the mean 6-min walk distance (6MWD) were observed in the mepolizumab (p<0.001) and conventional therapy (p<0.01) groups, while no improvement was seen in dyspnoea Borg scale, heart rate, percentage oxygen saturation or systolic and diastolic blood pressure. 6MWD showed significant direct correlations with ACT (r=0.5998, p<0.001), AQLQ (r=0.3978, p=0.009) and FEF25-75% (r=0.3589, p=0.017). Conclusions: The 6MWT could complement severe asthma assessment and be relevant in evaluating the objective response to treatment, including biological therapies like mepolizumab.

Pseudomonas baetica sp. nov., a fish pathogen isolated from wedge sole, Dicologlossa cuneata (Moreau).

Five Gram-negative bacterial isolates, recovered from an outbreak that occurred in March 2006 in Huelva, Spain, affecting adult diseased cultured wedge sole [Dicologlossa cuneata (Moreau)], were characterized phenotypically and genotypically in order to clarify their taxonomic position. On the basis of 16S rRNA gene sequence analysis, the isolates were included in the genus Pseudomonas, within the Pseudomonas fluorescens-related species group, their closest relatives being the Pseudomonas jessenii and Pseudomonas koreensis subgroups. The highest sequence similarities were recorded with the type strains of Pseudomonas reinekei, P. moorei, P. umsongensis, P. jessenii and P. mohnii (99.4-99.3 % similarity). Sequence analysis of the housekeeping genes gyrB and rpoD clearly differentiated the isolates from currently described Pseudomonas species, the highest sequence similarities recorded to type strains being below 95 % for both genes. Phylogenetic analysis using concatenated sequences of the three genes showed Pseudomonas moraviensis DSM 16007T and P. koreensis DSM 16610T as the closest reference strains. DNA-DNA hybridization assays with related strains confirmed that these isolates belong to a novel species of the genus Pseudomonas, for which the name Pseudomonas baetica sp. nov. is proposed. The type strain is strain a390T (=CECT 7720T=LMG 25716T). The novel species could be easily distinguished from phylogenetically related species by several phenotypic characteristics, including gelatin hydrolysis, acid production from glucose and growth at 6 % NaCl. Virulence assays revealed that the novel species is pathogenic for wedge sole.

Supramarginal Resection for Glioblastoma: It Is Time to Set Boundaries! A Critical Review on a Hot Topic.

Glioblastoma are the most common primary malignant brain tumors with a highly infiltrative behavior. The extent of resection of the enhancing component has been shown to be correlated to survival. Recently, it has been proposed to move the resection beyond the contrast-enhanced portion into the MR hyper intense tissue which typically surrounds the tumor, the so-called supra marginal resection (SMR). Though it should be associated with better overall survival (OS), a potential harmful resection must be avoided in order not to create new neurological deficits. Through this work, we aimed to perform a critical review of SMR in patients with Glioblastoma. A Medline database search and a pooled meta-analysis of HRs were conducted; 19 articles were included. Meta-analysis revealed a pooled OS HR of 0.64 (p = 0.052). SMR is generally considered as the resection of any T1w gadolinium-enhanced tumor exceeding FLAIR volume, but no consensus exists about the amount of volume that must be resected to have an OS gain. Equally, the role and the weight of several pre-operative features (tumor volume, location, eloquence, etc.), the intraoperative methods to extend resection, and the post-operative deficits, need to be considered more deeply in future studies.

Effect of static offsets on the nonlinear dynamic mechanical properties of human brain tissue.

This study focuses on the variations in the brain tissue dynamic behaviour pointing out new insight into the material nonlinear viscoelasticity. Shear dynamic response curves are obtained in different working conditions in terms of strain sweep and superimposed static compression offsets (SCO) applied in orthogonal direction to the shear. The strain sweep mode is used to study the storage and loss moduli dependence on the amplitude of the applied strain. It is found that the material exhibits linear viscoelastic behaviour up to about 0.1% strain amplitude. Above this critical threshold, the storage modulus G' decreases rapidly with increasing dynamic strain amplitude and this effect is gradually intensified as the SCO are increased. In addition, it is observed that the loss factor (G''/G') increases by increasing the SCO applied to the specimens. The dynamic strain amplitude results of the storage modulus reveal that the elastic component of the brain tissue's stiffness (G') evaluated at low strain strongly increases with increasing static superimposed compression strain while the loss factor in the same strain range appears to be SCO independent. Finally, dynamic stiffness recovery after a large strain deformation is considered. The reduction in low amplitude dynamic modulus and subsequent recovery kinetics due to a perturbation is found to be independent of the level of the SCO. The same assessments were carried out on 5 consecutive strain sweep cycle loading. It has been noticed that at the last cycle, the dissipation peak is reduced, and the non-linearity of the curve begins earlier. This could be explained by the effects of cerebral edema on cells and their surrounding environment.

Are convexity meningiomas all the same? A clinico-radiological analysis of surgically treated eloquent areas convexity meningiomas.

BACKGROUND: Convexity meningiomas are considered low-risk tumors, with high possibility of cure and low risk of relapse after resection. Very few studies have investigated meningiomas located in or around highly eloquent regions (namely perirolandic and perisylvian fissures). This study aimed to determine the differences in preoperative characteristics and postoperative outcomes between convexity meningiomas at eloquent area and non-eloquent areas. METHODS: Retrospective study on patients who underwent surgical resection for convexity meningioma. Patients were divided into eloquent and non-eloquent area. Statistical analysis was made comparing preoperative and postoperative data of both groups. RESULTS: The study included a total of 117 patients: 80 with eloquent area tumor and 37 with non-eloquent area tumor. Statistically significant differences were detected between the groups in preoperative KPS (93±10 in eloquent vs. 97±6 in non-eloquent; P=0.008) and in large-caliber vein involvement (76.3% in cases vs. 16.2% in controls; P<0.001). Postoperatively, patients with eloquent area tumors showed initial deterioration in neurological status followed by recovery; final outcomes were comparable to that of patients with non-eloquent area tumors. However, patients with eloquent area meningiomas had higher propensity to suffer from seizures postoperatively. Postoperative complications and long-term outcomes were not significantly different between the two groups. CONCLUSIONS: Patients with eloquent areas convexity meningiomas do not appear to have higher surgical risk. Neurological status is more likely to worsen immediately after surgery, but long-term recovery is satisfactory. Seizure control after surgery appears to be poorer in patients with perirolandic meningioma.

Thoracic Spinal Angiolipomas: A Systematic Review.

BACKGROUND: Spinal angiolipomas (SAs) are rare, benign tumors, representing 0.0004 to 1.2% of angiolipomas, usually located at the extradural and posterior thoracic level, with multimetameric extension. METHODS: A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The authors searched on PubMed and Scopus databases for published articles with the Mesh term "spinal angiolipoma" and pertinent associations. Language restriction to English papers was applied. The authors also reported three emblematic cases of patients who underwent surgical resection of spindle-shaped (type IA) and dumbbell-shaped (type II) SAs between 2014 and 2020. RESULTS: Of the 256 retrieved articles, 33 were included in the meta-analysis. These 33 studies, together with our 3 reported cases, included a total of 60 patients, 36 females (60%) and 24 males (40%), with a mean age of 53.12 ± 12.82 years (range: 12-77 years).T5 was the most represented level (22 patients). Usually, the localization of SA was extradural, with 53 patients suffering from spindle-shaped type IA SA (88.3%) and 7 patients from dumbbell-shaped type II SA (11.6%). Almost all patients underwent laminectomy (78.3%) and presented a full recovery of motor deficits (85%). Gross total removal (GTR) was performed in 93.3% of patients. The mean follow-up was of 22.71 ± 21.45 months (range: 2-80 months). There was no documented recurrence at follow-up magnetic resonance imaging in any of the patients. CONCLUSIONS: SAs are rare, benign tumors with a great vascular component that presents a favorable outcome. GTR is the gold standard treatment and usually an adjuvant therapy is not required. Even infiltrative lesions, which are more complex, can be treated successfully with a good prognosis. Dumbbell-shaped SAs must be differentiated from schwannomas and meningiomas, and require different surgical techniques, given the profuse bleeding associated with the attempt of debulking. En block resection is the key to treat these common benign tumors with acceptable blood loss.

Preliminary Validation of FoRCaSco: A New Grading System for Cerebral and Cerebellar Cavernomas.

OBJECTIVE: Surgical indications for cerebral cavernous malformations (CCMs) remain significantly center- and surgeon-dependent; available grading systems are potentially limited, as they do not include epileptologic and radiologic data. Several experienced authors proposed a new grading system for CCM and the first group of patients capable of providing its statistical validation was analyzed. METHODS: A retrospective series of 289 CCMs diagnosed between 2008 and 2021 was collected in a shared anonymous database among 9 centers. The new grading system ranges from -1 to 10. For each patient with cortical and cerebellar cavernous malformations the grading system was applied, and a retrospective outcome analysis was performed. We proposed a score of 4 as a cutoff for surgical indication. RESULTS: Operated patients with a score ≥4 were grouped with non-operated patients with a score <4, as they constituted the group that received correct treatment according to the new grading system. Patients with a score ≥4, who underwent surgery and had an improved outcome, were compared to patients with a score ≥4 who were not operated (P = 0.04), and to patients with a score <4 who underwent surgery (P < 0.001). CONCLUSIONS: This preliminary statistical analysis demonstrated that this new grading would be applicable in surgical reality. The cutoff score of 4 correctly separated the patients who could benefit from surgical intervention from those who would not. The outcome analysis showed that the treated patients in whom the grading system has been correctly applied have a better outcome than those in whom the grading system has not been applied.

Immune and cellular damage biomarkers to predict COVID-19 mortality in hospitalized patients.

Early prediction of COVID-19 in-hospital mortality relies usually on patients' preexisting comorbidities and is rarely reproducible in independent cohorts. We wanted to compare the role of routinely measured biomarkers of immunity, inflammation, and cellular damage with preexisting comorbidities in eight different machine-learning models to predict mortality, and evaluate their performance in an independent population. We recruited and followed-up consecutive adult patients with SARS-Cov-2 infection in two different Italian hospitals. We predicted 60-day mortality in one cohort (development dataset, n = 299 patients, of which 80% was allocated to the development dataset and 20% to the training set) and retested the models in the second cohort (external validation dataset, n = 402). Demographic, clinical, and laboratory features at admission, treatments and disease outcomes were significantly different between the two cohorts. Notably, significant differences were observed for %lymphocytes (p < 0.05), international-normalized-ratio (p < 0.01), platelets, alanine-aminotransferase, creatinine (all p < 0.001). The primary outcome (60-day mortality) was 29.10% (n = 87) in the development dataset, and 39.55% (n = 159) in the external validation dataset. The performance of the 8 tested models on the external validation dataset were similar to that of the holdout test dataset, indicating that the models capture the key predictors of mortality. The shap analysis in both datasets showed that age, immune features (%lymphocytes, platelets) and LDH substantially impacted on all models' predictions, while creatinine and CRP varied among the different models. The model with the better performance was model 8 (60-day mortality AUROC 0.83 ± 0.06 in holdout test set, 0.79 ± 0.02 in external validation dataset). The features that had the greatest impact on this model's prediction were age, LDH, platelets, and %lymphocytes, more than comorbidities or inflammation markers, and these findings were highly consistent in both datasets, likely reflecting the virus effect at the very beginning of the disease.