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To determine how percutaneous tracheostomy (PT) impacts on respiratory system compliance (Crs) and end-expiratory lung volume (EELV) during volume control ventilation and to test whether a recruitment maneuver (RM) at the end of PT may reverse lung derecruitment. This is a single center, prospective, applied physiology study. 25 patients with acute brain injury who underwent PT were studied. Patients were ventilated in volume control ventilation. Electrical impedance tomography (EIT) monitoring and respiratory mechanics measurements were performed in three steps: (a) baseline, (b) after PT, and (c) after a standardized RM (10 sighs of 30 cmH2O lasting 3 s each within 1 min). End-expiratory lung impedance (EELI) was used as a surrogate of EELV. PT determined a significant EELI loss (mean reduction of 432 arbitrary units p = 0.049) leading to a reduction in Crs (55 ± 13 vs. 62 ± 13 mL/cmH2O; p < 0.001) as compared to baseline. RM was able to revert EELI loss and restore Crs (68 ± 15 vs. 55 ± 13 mL/cmH2O; p < 0.001). In a subgroup of patients (N = 8, 31%), we observed a gradual but progressive increase in EELI. In this subgroup, patients did not experience a decrease of Crs after PT as compared to patients without dynamic inflation. Dynamic inflation did not cause hemodynamic impairment nor raising of intracranial pressure. We propose a novel and explorative hyperinflation risk index (HRI) formula. Volume control ventilation did not prevent the PT-induced lung derecruitment. RM could restore the baseline lung volume and mechanics. Dynamic inflation is common during PT, it can be monitored real-time by EIT and anticipated by HRI. The presence of dynamic inflation during PT may prevent lung derecruitment.
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Assessing quality of care is essential for improving the management of patients experiencing traumatic brain injury (TBI). This study aimed at devising a rigorous framework to evaluate the quality of TBI care provided by intensive care units (ICUs) and applying it to the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) consortium, which involved 83 ICUs from seven countries. The performance of the centers was assessed in terms of patients' outcomes, as measured by the 6-month Glasgow Outcome Scale-Extended (GOS-E). To account for the between-center differences in the characteristics of the admitted patients, we developed a multinomial logistic regression model estimating the probability of a four-level categorization of the GOS-E: good recovery (GR), moderate disability (MD), severe disability (SD), and death or vegetative state (D/VS). A total of 5928 patients admitted to the participating ICUs between March 2014 and March 2019 were analyzed. The model included 11 predictors and demonstrated good discrimination (area under the receiver operating characteristic [ROC] curve in the validation set for GR: 0.836, MD: 0.802, SD: 0.706, D/VS: 0.890) and calibration, both overall (Hosmer-Lemeshow test p value: 0.87) and in several subgroups, defined by prognostically relevant variables. The model was used as a benchmark for assessing quality of care by comparing the observed number of patients experiencing GR, MD, SD, and D/VS to the corresponding numbers expected in each category by the model, computing observed/expected (O/E) ratios. The four center-specific ratios were assembled with polar representations and used to provide a multidimensional assessment of the ICUs, overcoming the loss of information consequent to the traditional dichotomizations of the outcome in TBI research. The proposed framework can help in identifying strengths and weaknesses of current TBI care, triggering the changes that are necessary to improve patient outcomes.
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Lesiones Traumáticas del Encéfalo , Unidades de Cuidados Intensivos , Humanos , Lesiones Traumáticas del Encéfalo/terapia , Lesiones Traumáticas del Encéfalo/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Unidades de Cuidados Intensivos/normas , Adulto , Anciano , Calidad de la Atención de Salud/normas , Escala de Consecuencias de Glasgow , Evaluación de la Discapacidad , Europa (Continente) , Cuidados Críticos/normasRESUMEN
BACKGROUND: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. METHODS: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls. RESULTS: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. CONCLUSIONS: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.
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Enfermedad de Alzheimer , Lesiones Traumáticas del Encéfalo , Encefalopatía Traumática Crónica , Humanos , Biomarcadores , Proteínas tau , Imagen por Resonancia Magnética , Ubiquitina Tiolesterasa , Atrofia , Péptidos beta-AmiloidesRESUMEN
Prehospital field triage often fails to accurately identify the need for emergent surgical or non-surgical procedures, resulting in inefficient resource utilization and increased costs. This study aimed to analyze prehospital factors associated with the need for emergent procedures (such as surgery or interventional angiography) within 6 h of hospital admission. Additionally, our goal was to develop a prehospital triage tool capable of estimating the likelihood of requiring an emergent procedure following hospital admission. We conducted a retrospective observational study, analyzing both prehospital and in-hospital data obtained from the Lombardy Trauma Registry. We conducted a multivariable logistic regression analysis to identify independent predictors of emergency procedures within the first 6 h from admission. Subsequently, we developed and internally validated a triage score composed of factors associated with the probability of requiring an emergency procedure. The study included a total of 3985 patients, among whom 295 (7.4%) required an emergent procedure within 6 h. Age, penetrating injury, downfall, cardiac arrest, poor neurological status, endotracheal intubation, systolic pressure, diastolic pressure, shock index, respiratory rate and tachycardia were identified as predictors of requiring an emergency procedure. A triage score generated from these predictors showed a good predictive power (AUC of the ROC curve: 0.81) to identify patients requiring an emergent surgical or non-surgical procedure within 6 h from hospital admission. The proposed triage score might contribute to predicting the need for immediate resource availability in trauma patients.
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Acute ischemic stroke (AIS) in childhood is a relatively rare but significant condition that can result in long-term disabilities. There is a lack of standardized strategies for diagnosing and treating pediatric AIS due to limited evidence-based data on thrombolytic and endovascular treatments in children. This comprehensive literature review focuses on the experience of a single center in Italy and aims to highlight the main peculiarities of endovascular treatment (EVT) for AIS in childhood. The review covers the diagnostic workup, the endovascular procedures, and the need for a specific thrombectomy program for pediatric AIS. The review discusses the indications and considerations for thrombectomy in children, including the risk of complications and the challenges of extrapolating results from adult studies. The diagnostic protocols for pediatric AIS are also discussed, emphasizing the use of MRI to avoid X-ray and contrast medium exposure in children. The combination of intravenous thrombolysis and mechanical thrombectomy has been examined, considering the differences between pediatric and adult thrombi. Technical considerations related to the size of pediatric patients are addressed, including the use of large bore catheters and potential concerns with access points. The organization of a thrombectomy program for pediatric AIS is discussed, emphasizing the need for specialized facilities and expertise. Although evidence for EVT in the pediatric population is based on case series, the importance of specialized centers and the lack of validated guidelines are evident.
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Importance: While the relationship between persistent elevations in intracranial pressure (ICP) and poorer outcomes is well established for patients with traumatic brain injury (TBI), there is no consensus on how ICP measurements should drive treatment choices, and the effectiveness of ICP monitoring remains unknown. Objective: To evaluate the effectiveness of ICP monitoring on short- and mid-term outcomes of patients with TBI. Design, Setting, and Participants: CREACTIVE was a prospective cohort study that started in March 2014 and lasted 5 years. More than 8000 patients with TBI were enrolled at 83 intensive care units (ICUs) from 7 countries who joined the CREACTIVE Consortium. Patients with TBI who met the Brain Trauma Foundation guidelines for ICP monitoring were selected for the current analyses, which were performed from January to November 2022. Exposure: Patients who underwent ICP monitoring within 2 days of injury (exposure group) were propensity score-matched to patients who were not monitored or who underwent monitoring 2 days after the injury (control group). Main Outcome and Measure: Functional disability at 6 months as indicated by Glasgow Outcome Scale-Extended (GOS-E) score. Results: A total of 1448 patients from 43 ICUs in Italy and Hungary were eligible for analysis. Of the patients satisfying the ICP-monitoring guidelines, 503 (34.7%) underwent ICP monitoring (median [IQR] age: 45 years [29-61 years]; 392 males [77.9%], 111 females [22.1%]) and 945 were not monitored (median [IQR] age: 66 years [48-78 years]; 656 males [69.4%], 289 females [30.6%]). After matching to balance the variables, worse 6-month recovery was observed for monitored patients compared with nonmonitored patients (death/vegetative state: 39.2% vs 40.6%; severe disability: 33.2% vs 25.4%; moderate disability: 15.7% vs 14.9%; good recovery: 11.9% vs 19.1%, respectively; P = .005). Monitored patients received medical therapies significantly more frequently. Conclusions and Relevance: In this cohort study, ICP monitoring was associated with poorer recovery and more frequent medical interventions with their relevant adverse effects. Optimizing the value of ICP monitoring for TBI requires further investigation on monitoring indications, clinical interventions, and management protocols.
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Lesiones Traumáticas del Encéfalo , Presión Intracraneal , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Estudios Prospectivos , Enfermedad Crítica/terapia , Lesiones Traumáticas del Encéfalo/complicacionesRESUMEN
OBJECTIVES: To compare respiratory system compliance (C rs ) calculation during controlled mechanical ventilation (MV) and, subsequently, during assisted MV. DESIGN: This is a single-center, retrospective, observational study. SETTING: This study was conducted on patients admitted to Neuro-ICU of Niguarda Hospital (tertiary referral hospital). PATIENTS: We analyzed every patient greater than or equal to 18 years old having a C rs measurement in controlled and in assisted MV within 60 minutes. Plateau pressure (P plat ) was considered reliable if it was deemed visually stable for at least 2 seconds. INTERVENTIONS: Inspiratory pause was incorporated to detect P plat in controlled and assisted MV. Calculation of C rs and driving pressure were achieved. MEASUREMENTS AND MAIN RESULTS: A total of 101 patients were studied. An acceptable agreement was found (Bland-Altman plot bias -3.9, level of agreement upper 21.6, lower -29.6). C rs in assisted MV was 64.1 (52.6-79.3) and in controlled MV it was 61.2 (50-71.2) mL/cm H 2o ( p = 0.006). No statistical difference was found in C rs (assisted vs controlled MV) when peak pressure was lower than P plat nor when peak pressure was higher than P plat . CONCLUSIONS: A P plat visually stable for at least 2 seconds leads to reliable C rs calculation during assisted MV.
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Respiración Artificial , Sistema Respiratorio , Humanos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Volumen de Ventilación PulmonarRESUMEN
BACKGROUND: Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension. METHODS: This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd. RESULTS: Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6-40.5%), and Bland-Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7-92.6%) and a specificity of 72% (95% CI 51.9-94.0%) with an AUC of 76% (95% CI 65.6-85.5%). CONCLUSIONS AND RELEVANCE: ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. TRIAL REGISTRATION: NCT02322970 .
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Hipertensión Intracraneal , Encéfalo , Humanos , Hipertensión Intracraneal/diagnóstico , Hipertensión Intracraneal/etiología , Presión Intracraneal , Estudios Prospectivos , Ultrasonografía Doppler Transcraneal/métodosRESUMEN
BACKGROUND: Organ donation (OD) remains the only therapeutic option for end-stage disease in some cases. Unfortunately, the gap between donors and recipients is still substantial. Trauma patients represent a potential yet underestimated pool of organ donors. In this article, we present our data on OD after damage control strategy (DCS). MATERIALS AND METHODS: A retrospective, observational cohort study was conducted through a complete revision of data of consecutive adult trauma patients (>18 years old) who underwent OD after DCS between January 2018 and May 2021. Four subgroups were created [Liver (Li), Lungs (Lu), Heart (H), Kidneys (K)] to compare variables between those who donated the organ of interest and those who did not. RESULTS: Thirty-six patients underwent OD after DCS. Six patients (16.7%) were excluded: 2(5.6%) for missing data about admission; 4(11.1%) didn't receive DCS. Mean ISS was 47.2 (SD ± 17.4). Number of donated organs was 113 with an organs/patient ratio of 3.8. The functional response rate was 91.2%. Ten organs (8.8%) had primary nonfunction after transplantation: 2/15 hearts (13.3%), 1/28 livers (3.6%), 4/53 kidneys (7.5%) and 3/5 pancreases (60%). No lung primary nonfunction were registered. Complete results of subgroup analysis are reported in supplementary materials. CONCLUSION: Organ donation should be considered a possible outcome in any trauma patient. Aggressive damage control strategy doesn't affect the functional response rate of transplanted organs.
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BACKGROUND: Issues remain on the optimal management of subarachnoid hemorrhage (SAH) patients once they are admitted to the referring center, before and after the aneurysm treatment. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI). In this manuscript, we aim to provide a list of experts' recommendations regarding the early management of SAH patients from hospital admission, in a center with neurosurgical/neuro-endovascular facilities, until securing of the bleeding aneurysm. METHODS: A multidisciplinary consensus panel composed of 24 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different background (anesthesia/intensive care, neurosurgery, and interventional neuroradiology) was created. A modified Delphi approach was adopted. RESULTS: Among 19 statements discussed. The consensus was reached on 18 strong recommendations. In one case, consensus could not be agreed upon and no recommendation was provided. CONCLUSIONS: This consensus provides practical recommendations for the management of SAH patients in hospitals with neurosurgical/neuroendovascular facilities until aneurysm securing. It is intended to support clinician's decision-making and not to mandate a standard of practice.
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BACKGROUND: Questions remain on the optimal management of subarachnoid hemorrhage (SAH) patients once they are admitted to the referring center, before and after the aneurysm treatment. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI) to provide clinical guidance regarding this topic. Specifically, in this manuscript (part 2), we aim to provide a list of experts' recommendations regarding the management of SAH patients in a center with neurosurgical/neuroendovascular facilities after aneurysm treatment. METHODS: A multidisciplinary consensus panel composed by 24 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different specializations (anesthesia/intensive care, neurosurgery, and interventional neuroradiology) was created. A modified Delphi approach was adopted. RESULTS: A total of 33 statements were discussed, voted, and approved. Consensus was reached on 30 recommendations (28 strong and 2 weak). In 3 cases, where consensus could not be agreed upon, no recommendation was provided. CONCLUSIONS: This consensus provides practical recommendations (and not mandatory standard of practice) to support clinician's decision-making in the management of SAH patients in centers with neurosurgical/neuroendovascular facilities after aneurysm securing.
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BACKGROUND: We leveraged the data of the international CREACTIVE consortium to investigate whether the outcome of traumatic brain injury (TBI) patients admitted to intensive care units (ICU) in hospitals without on-site neurosurgical capabilities (no-NSH) would differ had the same patients been admitted to ICUs in hospitals with neurosurgical capabilities (NSH). METHODS: The CREACTIVE observational study enrolled more than 8000 patients from 83 ICUs. Adult TBI patients admitted to no-NSH ICUs within 48 h of trauma were propensity-score matched 1:3 with patients admitted to NSH ICUs. The primary outcome was the 6-month extended Glasgow Outcome Scale (GOS-E), while secondary outcomes were ICU and hospital mortality. RESULTS: A total of 232 patients, less than 5% of the eligible cohort, were admitted to no-NSH ICUs. Each of them was matched to 3 NSH patients, leading to a study sample of 928 TBI patients where the no-NSH and NSH groups were well-balanced with respect to all of the variables included into the propensity score. Patients admitted to no-NSH ICUs experienced significantly higher ICU and in-hospital mortality. Compared to the matched NSH ICU admissions, their 6-month GOS-E scores showed a significantly higher prevalence of upper good recovery for cases with mild TBI and low expected mortality risk at admission, along with a progressively higher incidence of poor outcomes with increased TBI severity and mortality risk. CONCLUSIONS: In our study, centralization of TBI patients significantly impacted short- and long-term outcomes. For TBI patients admitted to no-NSH centers, our results suggest that the least critically ill can effectively be managed in centers without neurosurgical capabilities. Conversely, the most complex patients would benefit from being treated in high-volume, neuro-oriented ICUs.
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Lesiones Traumáticas del Encéfalo , Neurocirugia , Adulto , Escala de Coma de Glasgow , Escala de Consecuencias de Glasgow , Hospitales , Humanos , Unidades de Cuidados IntensivosRESUMEN
Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.
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Lesiones Traumáticas del Encéfalo , Filamentos Intermedios , Axones , Biomarcadores , Encéfalo , Lesiones Traumáticas del Encéfalo/complicaciones , HumanosRESUMEN
BACKGROUNDS: The COVID-19 pandemic drastically strained the health systems worldwide, obligating the reassessment of how healthcare is delivered. In Lombardia, Italy, a Regional Emergency Committee (REC) was established and the regional health system reorganized, with only three hospitals designated as hubs for trauma care. The aim of this study was to evaluate the effects of this reorganization of regional care, comparing the distribution of patients before and during the COVID-19 outbreak and to describe changes in the epidemiology of severe trauma among the two periods. METHODS: A cohort study was conducted using retrospectively collected data from the Regional Trauma Registry of Lombardia (LTR). We compared the data of trauma patients admitted to three hub hospitals before the COVID-19 outbreak (September 1 to November 19, 2019) with those recorded during the pandemic (February 21 to May 10, 2020) in the same hospitals. Demographic data, level of pre-hospital care (Advanced Life Support-ALS, Basic Life Support-BLS), type of transportation, mechanism of injury (MOI), abbreviated injury score (AIS, 1998 version), injury severity score (ISS), revised trauma score (RTS), and ICU admission and survival outcome of all the patients admitted to the three trauma centers designed as hubs, were reviewed. Screening for COVID-19 was performed with nasopharyngeal swabs, chest ultrasound, and/or computed tomography. RESULTS: During the COVID-19 pandemic, trauma patients admitted to the hubs increased (46.4% vs 28.3%, p < 0.001) with an increase in pre-hospital time (71.8 vs 61.3 min, p < 0.01), while observed in hospital mortality was unaffected. TRISS, ISS, AIS, and ICU admission were similar in both periods. During the COVID-19 outbreak, we observed substantial changes in MOI of severe trauma patients admitted to three hubs, with increases of unintentional (31.9% vs 18.5%, p < 0.05) and intentional falls (8.4% vs 1.2%, p < 0.05), whereas the pandemic restrictions reduced road- related injuries (35.6% vs 60%, p < 0.05). Deaths on scene were significantly increased (17.7% vs 6.8%, p < 0.001). CONCLUSIONS: The COVID-19 outbreak affected the epidemiology of severe trauma patients. An increase in trauma patient admissions to a few designated facilities with high level of care obtained satisfactory results, while COVID-19 patients overwhelmed resources of most other hospitals.
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COVID-19/epidemiología , Atención a la Salud/tendencias , Unidades de Cuidados Intensivos/estadística & datos numéricos , Pandemias , Sistema de Registros , Centros Traumatológicos/estadística & datos numéricos , Heridas y Lesiones/epidemiología , Adulto , Comorbilidad , Femenino , Mortalidad Hospitalaria/tendencias , Hospitalización/tendencias , Humanos , Puntaje de Gravedad del Traumatismo , Italia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/terapiaRESUMEN
Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.
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Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/mortalidad , Citocinas/sangre , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Proteína Ácida Fibrilar de la Glía/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Adulto , Biomarcadores/sangre , Lesiones Traumáticas del Encéfalo/diagnóstico , Estudios de Cohortes , Cuidados Críticos , Enfermedad Crítica , Europa (Continente) , Femenino , Escala de Consecuencias de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , PronósticoRESUMEN
BACKGROUND: Lombardy was the epicenter in Italy of the first wave of COVID-19 pandemic. To face the contagion growth, from March 8 to May 8, 2020, a regional law redesigned the hub-and-spoke system for time-dependent diseases to better allocate resources for COVID-19 patients. METHODS: We report the reorganization of the major hospital in Lombardy during COVID-19 pandemic, including the rearrangement of its ICU beds to face COVID-19 pandemic and fulfill its role as extended hub for time-dependent diseases while preserving transplant activity. To highlight the impact of the emergently planned hub-and-spoke system, all patients admitted to a COVID-19-free ICU hub for trauma, neurosurgical emergencies and stroke during the two-month period were retrospectively collected and compared to 2019 cohort. Regional data on organ procurement was retrieved. Observed-to-expected (OE) in-ICU mortality ratios were computed to test the impact of the pandemic on patients affected by time-dependent diseases. RESULTS: Dynamic changes in ICU resource allocation occurred according to local COVID-19 epidemiology/trends of patients referred for time-dependent diseases. The absolute increase of admissions for trauma, neurosurgical emergencies and stroke was roughly two-fold. Patients referred to the hub were older and characterized by more severe conditions. An increase in crude mortality was observed, though OE ratios for in-ICU mortality were not statistically different when comparing 2020 vs. 2019. An increase in local organ procurement was observed, limiting the debacle of regional transplant activity. CONCLUSIONS: We described the effects of a regional emergently planned hub-and-spoke system for time-dependent diseases settled in the epicenter of COVID-19 pandemic in Italy.