Disorders of sodium balance in patients with hypothalamic-pituitary lesions in traumatic brain injury

Background. Traumatic brain injury (TBI) still remains the leading cause of death in people of working age. In Ukraine, the frequency of TBI varies from 2.3 to 6 cases (average of 4–4.2) per 1,000 population annually depending on the regions. Patients with primary damage to the brain and hypothalamic-pituitary system are at risk of developing cerebral edema due to the water-electrolyte imbalance and, accordingly, osmolar imbalance between cellular and extracellular spaces. Water-electrolyte imbalance as a result of damage to the hypothalamic-pituitary system in traumatic brain injury is not described enough in the literature. The functioning of the central and peripheral links of the endocrine system depending on the location, nature and severity of injury is examined not enough. The question of diagnostic and prognostic values of various indicators of volume status in patients with trauma is also underinvestigated. The purpose of this study was to examine the types of disorders of sodium balance in patients with isolated TBI and hypothalamic-pituitary lesions; to clarify the influence of sodium imbalance type on mortality in patients with TBI and hypothalamic-pituitary lesions. Material and methods. We examined 74 patients (men/women = 60/14) with focal cerebral contusion and lesions of the hypothalamic region. Forty-seven of them were diagnosed with hypovolemia combined with hyponatremia. Hypernatremia with hypervolemia was found in 15 patients. Intracranial pressure monitoring was performed using a multifunction monitor (BSM-3562, Japan, 2018, Nihon Kohden Corporation) with a line for invasive pressure measurement. Continuous non-invasive measurement of organ tissue oxygenation (rSO2) was carried out using Somanetics Invos Oximeter Cerebral/Somatic monitor (Covidien, Mansfield, MA, USA, 2020). Plasma electrolytes were evaluated in all patients. Conclusions. Patients with TBI and hypothalamic-pituitary lesion have different types of water-sodium imbalance, which demand the differentiated approach to their treatment. Given the small number of observations, we do not dare to link the type of sodium imbalance with lethality in patients with brain trauma and hypothalamic-pituitary lesions. We consider this requires further researches.

Establishment and validation of prognosis model for patients with cerebral contusion

Background And Objective Cerebral Contusion (CC) is one of the most serious injury types in patients with traumatic brain injury (TBI). In this study, the baseline data, imaging features and laboratory examinations of patients with CC were summarized and analyzed to develop and validate a prediction model of nomogram to evaluate the clinical outcomes of patients. Methods A total of 426 patients with cerebral contusion (CC) admitted to the People’s Hospital of Qinghai Province and Affiliated Hospital of Qingdao University from January 2018 to January 2021 were included in this study, We randomly divided the cohort into a training cohort (n = 284) and a validation cohort (n = 142) with a ratio of 2:1.At Least absolute shrinkage and selection operator (Lasso) regression were used for screening high-risk factors affecting patient prognosis and development of the predictive model. The identification ability and clinical application value of the prediction model were analyzed through the analysis of receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Results Twelve independent prognostic factors, including age, Glasgow Coma Score (GCS), Basal cistern status, Midline shift (MLS), Third ventricle status, intracranial pressure (ICP) and CT grade of cerebral edema,etc., were selected by Lasso regression analysis and included in the nomogram. The model showed good predictive performance, with a C index of (0.87, 95% CI, 0.026–0.952) in the training cohort and (0.93, 95% CI, 0.032–0.965) in the validation cohort. Clinical decision curve analysis (DCA) also showed that the model brought high clinical benefits to patients. Conclusion This study established a high accuracy of nomogram model to predict the prognosis of patients with CC, its low cost, easy to promote, is especially applicable in the acute environment, at the same time, CSF-glucose/lactate ratio(C-G/L), volume of contusion, and mean CT values of edema zone, which were included for the first time in this study, were independent predictors of poor prognosis in patients with CC. However, this model still has some limitations and deficiencies, which require large sample and multi-center prospective studies to verify and improve our results.

Genetic inhibition of RIPK3 ameliorates functional outcome in controlled cortical impact independent of necroptosis

Traumatic brain injury (TBI) is a leading cause of death and disability with no specific effective therapy, in part because disease driving mechanisms remain to be elucidated. Receptor interacting protein kinases (RIPKs) are serine/threonine kinases that assemble multi-molecular complexes that induce apoptosis, necroptosis, inflammasome and nuclear factor kappa B activation. Prior studies using pharmacological inhibitors implicated necroptosis in the pathogenesis of TBI and stroke, but these studies cannot be used to conclusively demonstrate a role for necroptosis because of the possibility of off target effects. Using a model of cerebral contusion and RIPK3 and mixed lineage kinase like knockout (MLKL−/−) mice, we found evidence for activation of RIPK3 and MLKL and assembly of a RIPK1-RIPK3-MLKL necrosome complex in pericontusional brain tissue. Phosphorylated forms of RIPK3 and MLKL were detected in endothelium, CD11b + immune cells, and neurons, and RIPK3 was upregulated and activated in three-dimensional human endothelial cell cultures subjected to CCI. RIPK3−/− and MLKL−/− mice had reduced blood-brain barrier damage at 24 h (p < 0.05), but no differences in neuronal death (6 h, p = ns in CA1, CA3 and DG), brain edema (24 h, p = ns), or lesion size (4 weeks, p = ns) after CCI. RIPK3−/−, but not MLKL−/− mice, were protected against postinjury motor and cognitive deficits at 1–4 weeks (RIPK3−/− vs WT: p < 0.05 for group in wire grip, Morris water maze hidden platform trials, p < 0.05 for novel object recognition test, p < 0.01 for rotarod test). RIPK3−/− mice had reduced infiltrating leukocytes (p < 0.05 vs WT in CD11b + cells, microglia and macrophages), HMGB1 release and interleukin-1 beta activation at 24–48 h (p < 0.01) after CCI. Our data indicate that RIPK3 contributes to functional outcome after cerebral contusion by mechanisms involving inflammation but independent of necroptosis.

A Machine Learning Approach to Investigate the Uncertainty of Tissue-Level Injury Metrics for Cerebral Contusion

Controlled cortical impact (CCI) on porcine brain is often utilized to investigate the pathophysiology and functional outcome of focal traumatic brain injury (TBI), such as cerebral contusion (CC). Using a finite element (FE) model of the porcine brain, the localized brain strain and strain rate resulting from CCI can be computed and compared to the experimentally assessed cortical lesion. This way, tissue-level injury metrics and corresponding thresholds specific for CC can be established. However, the variability and uncertainty associated with the CCI experimental parameters contribute to the uncertainty of the provoked cortical lesion and, in turn, of the predicted injury metrics. Uncertainty quantification via probabilistic methods (Monte Carlo simulation, MCS) requires a large number of FE simulations, which results in a time-consuming process. Following the recent success of machine learning (ML) in TBI biomechanical modeling, we developed an artificial neural network as surrogate of the FE porcine brain model to predict the brain strain and the strain rate in a computationally efficient way. We assessed the effect of several experimental and modeling parameters on four FE-derived CC injury metrics (maximum principal strain, maximum principal strain rate, product of maximum principal strain and strain rate, and maximum shear strain). Next, we compared the in silico brain mechanical response with cortical damage data from in vivo CCI experiments on pig brains to evaluate the predictive performance of the CC injury metrics. Our ML surrogate was capable of rapidly predicting the outcome of the FE porcine brain undergoing CCI. The now computationally efficient MCS showed that depth and velocity of indentation were the most influential parameters for the strain and the strain rate-based injury metrics, respectively. The sensitivity analysis and comparison with the cortical damage experimental data indicate a better performance of maximum principal strain and maximum shear strain as tissue-level injury metrics for CC. These results provide guidelines to optimize the design of CCI tests and bring new insights to the understanding of the mechanical response of brain tissue to focal traumatic brain injury. Our findings also highlight the potential of using ML for computationally efficient TBI biomechanics investigations.

A Retrospective Study of 51 Pediatric Cases of Traumatic Asphyxia

Backgroundtraumatic asphyxia (TA) is a rarely reported disease characterized as thoraco-cervico-facial petechiae, facial edema and cyanosis, subconjunctival hemorrhage and neurological symptoms. This study aimed to report 51 children of TA at the pediatric medical center of west China.Methodsscanned medical reports were reviewed and specific variables as age, sex, cause of injury, clinical manifestations and associated injuries were analyzed using SPSS 25.0.Resultsaged as 5.3±2.9 (1.3-13.2), 30 (58.8%) were boys and 21 (41.2%) were girls. Most TAs occurred during vehicle accident, object compression and stampede. All patients showed facial petechiae (100.0%, CI 93.0%-100.0%), 25 (49.0%, CI 34.8%-63.2%) out of 51 presented with facial edema, 29 (56.9%, CI 42.8%-70.9%) presented with subconjunctival hemorrhage, including bilateral 27 and unilateral 2. 6 patients had facial cyanosis (11.8%, CI 2.6%-20.9%). Other symptoms were also presented as epileptic seizure, vomiting, incontinence, paraplegia, etc. The most frequent companion injury was pulmonary contusion (76.5%, CI 64.4%-88.5%). Other companion injuries included mediastinal emphysema, fracture, cerebral contusion and hemorrhage, hypoxic-ischemic brain injury, abdominal organ contusion, mastoid hemorrhage, hematocele of paranasal sinuses, spinal injury, hepatic insufficiency, myocardial injury and retinal hemorrhage and edema. Treatment was mainly supportive. No death occurred in our study. The prognosis is rather good if without damage of central nervous system.ConclusionTA could bring out multiple symptoms, among which retinal hemorrhage and edema, spinal injury and viscera impairment have been less observed. Comprehensive physical and auxiliary examination should be performed considering TA. Its prognosis is rather good with focus on life-threatening complications.

Associated injury complicated by pediatric lower limb shaft fractures and clinical efficacy of flexible stainless-steel intramedullary nailing in children less than 15 years old

Although pediatric lower limb shaft fractures are common, little is known about associated injuries. The purpose of this study was to examine associated injuries complicated by pediatric lower limb shaft fractures and the efficacy of surgical treatment using a flexible stainless-steel intramedullary Ender nail in children less than 15 years old. This is a retrospective review of 29 children younger than 15 years old who were diagnosed with femoral or tibial shaft fractures and treated using Ender nails from 2005 to 2016. Baseline data, etiology, associated injuries, fracture site and patterns, operative and post-operative assessment were evaluated. The average age of the patients was 9.0 years, and mean follow-up was 18.2 months. Eleven patients (79%) had associated injury. At the final follow up, six patients (43%) sustained complications associated with the insertion area of the nail. There was no evidence of deep infection or nonunion at either fracture site. The clinical results were excellent in 10 (67%) fractures, and good in 5 (33%) fractures, based on the modified Flynn criteria. Almost all patients with a femoral fracture had an associated injury including abdominal visceral injury, cerebral contusion or other fractures. This study indicated good clinical and functional outcomes. On the other hand, the minor complications rate was high. Nevertheless, elastic stable intramedullary nailing recently has become available in Japan, and a prospective and comparative study is needed.

Retrospective clinical evaluation of patients undergoing surgery for acute epidural hematoma

We aimed to evaluate mortality-associated factors among patients with acute epidural hematoma due to head trauma. Demographic characteristics, preoperative Glasgow Coma Scale score, epidural hematoma aetiology and radiological findings, accompanying systemic trauma results, hospitalisation duration, sequelae, and mortality features of patients experiencing epidural hematoma between 2014 and 2018 were evaluated. Overall, 79 patients were examined. The most frequent epidural hematoma aetiology was traffic accidents (51.9%), with temporal region being the most common epidural hematoma location (38 [48.2%] patients). Among all, 12 (15.2%) patients died and 67 (84.8%) were discharged. Of them, 57 (85.1%) patients were discharged without and 10 (14.9%) with neurological sequelae. Age>65 years (p=0.001) and low Glasgow Coma Scale score (p<0.05) were significantly associated with higher mortality. Overall mortality rate was 91.7% (p<0.001) in patients with systemic trauma accompanying epidural hematoma, with thoracic (12%) and orthopaedic (9%) trauma being the most common. Cranial injuries included linear fracture, 78.5%; pneumocephalus, 48.1%; cerebral contusion, 44.3%; traumatic subarachnoid haemorrhage, 32.9%; acute subdural hematoma; 26.6%, and collapse fracture, 15%. All cranial injuries except linear fractures were associated with high mortality (p<0.05). Epidural hematoma is associated with high mortality. Aetiology, Glasgow Coma Scale score, cranial pathology, age, and additional trauma are the major predictive mortality-associated factors.