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Mutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T2-weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay.
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Objective: Develop a novel machine learning (ML) model to rapidly identify trauma patients with severe hemorrhage at risk of early mortality. Background: The critical administration threshold (CAT, 3 or more units of red blood cells in a 60-minute period) indicates severe hemorrhage and predicts mortality, whereas early identification of such patients improves survival. Methods: Patients from the PRospective, Observational, Multicenter, Major Trauma Transfusion and Pragmatic, Randomized Optimal Platelet, and Plasma Ratio studies were identified as either CAT+ or CAT-. Candidate variables were separated into 4 tiers based on the anticipated time of availability during the patient's assessment. ML models were created with the stepwise addition of variables and compared with the baseline performance of the assessment of blood consumption (ABC) score for CAT+ prediction using a cross-validated training set and a hold-out validation test set. Results: Of 1245 PRospective, Observational, Multicenter, Major Trauma Transfusion and 680 Pragmatic, Randomized Optimal Platelet and Plasma Ratio study patients, 1312 were included in this analysis, including 862 CAT+ and 450 CAT-. A CatBoost gradient-boosted decision tree model performed best. Using only variables available prehospital or on initial assessment (Tier 1), the ML model performed superior to the ABC score in predicting CAT+ patients [area under the receiver-operator curve (AUC = 0.71 vs 0.62)]. Model discrimination increased with the addition of Tier 2 (AUC = 0.75), Tier 3 (AUC = 0.77), and Tier 4 (AUC = 0.81) variables. Conclusions: A dynamic ML model reliably identified CAT+ trauma patients with data available within minutes of trauma center arrival, and the quality of the prediction improved as more patient-level data became available. Such an approach can optimize the accuracy and timeliness of massive transfusion protocol activation.
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The objectives of this review are to assess the current state of hypertonic saline as a prehospital resuscitation fluid in hypotensive trauma patients, particularly after the 3 major Resuscitation Outcomes Consortium trauma trials in the US and Canada were halted due to futility. Hemorrhage and traumatic brain injury are the leading causes of death in both military and civilian populations. Prehospital fluid resuscitation remains controversial in civilian trauma, but small-volume resuscitation with hypertonic fluids is of utility in military scenarios with prolonged or delayed evacuation times. A large body of pre-clinical and clinical literature has accumulated over the past 30 years on the hemodynamic and, most recently, the anti-inflammatory properties of hypertonic saline, alone or with dextran-70. This review assesses the current state of hypertonic fluid resuscitation in the aftermath of the failed Resuscitation Outcomes Consortium trials.
Assuntos
Ensaios Clínicos como Assunto , Serviços Médicos de Emergência/métodos , Ressuscitação/métodos , Solução Salina Hipertônica/uso terapêutico , Lesões Encefálicas/terapia , Canadá , Humanos , Choque Hemorrágico/terapia , Estados UnidosRESUMO
The objectives of this review are to assess the current state of hypertonic saline as a prehospital resuscitation fluid in hypotensive trauma patients, particularly after the 3 major Resuscitation Outcomes Consortium trauma trials in the US and Canada were halted due to futility. Hemorrhage and traumatic brain injury are the leading causes of death in both military and civilian populations. Prehospital fluid resuscitation remains controversial in civilian trauma, but small-volume resuscitation with hypertonic fluids is of utility in military scenarios with prolonged or delayed evacuation times. A large body of pre-clinical and clinical literature has accumulated over the past 30 years on the hemodynamic and, most recently, the anti-inflammatory properties of hypertonic saline, alone or with dextran-70. This review assesses the current state of hypertonic fluid resuscitation in the aftermath of the failed Resuscitation Outcomes Consortium trials.