External validation of 5A score model for predicting in-hospital mortality among the accidental hypothermia patients: JAAM-Hypothermia study 2018–2019 secondary analysis

[Background] The 5A score including five components “Age, Activities of daily living, Arrest, Acidemia and Albumin” was developed as an easy-to-use screening tool for predicting in-hospital mortality among patients with accidental hypothermia. However, the external validity of the 5A score has not yet been evaluated. We aimed to perform an external validation of the 5A score model. [Method] This secondary analysis of the multicenter, prospective cohort Japanese Association for Acute Medicine-Hypothermia Study (2018–2019), which was conducted at 87 and 89 institutions throughout Japan, collected data from December 2018 to February 2019 and from December 2019 to February 2020. Adult accidental hypothermia patients whose body temperature was 35 °C or less were included in this analysis. The probability of in-hospital mortality was calculated using a logistic regression model of the 5A score. The albumin was not recorded in this database; thus, it was imputed by estimation. Predictions were compared with actual observations to evaluate the calibration of the model. Furthermore, decision-curve analysis was used to evaluate the clinical usefulness. [Results] Of the 1363 patients registered in the database, data of 1139 accidental hypothermia patients were included for analysis. The median [interquartile range] age was 79 [68–87] years, and there were 625 men (54.9%) in the study cohort. The predicted probability and actual observation by risk groups produced the following results: low 7% (5.4–8.6), mild 19.1% (17.4–20.8), moderate 33.2% (29.9–36.5), and high 61.9% (55.9–67.9) predicted risks, and the low 12.4% (60/483), mild 17.7% (59/334), moderate 32.6% (63/193), and high 69% (89/129) observed mortality. These results indicated that the model was well calibrated. Decision-curve analysis visually indicated the clinical utility of the 5A score model. [Conclusion] This study indicated that the 5A score model using estimated albumin value has external validity in a completely different dataset from that used for the 5A model development. The 5A score is potentially helpful to predict the mortality risk and may be one of the valuable information for discussing the treatment strategy with patients and their family members

Difference between 5A score and the HOPE score

Recently, a letter to the editor was published to comment on the 5A score which is the prediction model for accidental hypothermia patients comparing the HOPE score. In this letter, we responded to the comments to clarify the difference between the 5A score and the HOPE score

Feasibility of Human Neural Stem Cell Transplantation for the Treatment of Acute Subdural Hematoma in a Rat Model: A Pilot Study

Human neural stem cells (hNSCs) transplantation in several brain injury models has established their therapeutic potential. However, the feasibility of hNSCs transplantation is still not clear for acute subdural hematoma (ASDH) brain injury that needs external decompression. Thus, the aim of this pilot study was to test feasibility using a rat ASDH decompression model with two clinically relevant transplantation methods. Two different methods, in situ stereotactic injection and hNSC-embedded matrix seating on the brain surface, were attempted. Athymic rats were randomized to uninjured or ASDH groups (F344/NJcl-rnu/rnu, n = 7–10/group). Animals in injury group were subjected to ASDH, and received decompressive craniectomy and 1-week after decompression surgery were transplanted with green fluorescent protein (GFP)-transduced hNSCs using one of two approaches. Histopathological examinations at 4 and 8 weeks showed that the GFP-positive hNSCs survived in injured brain tissue, extended neurite-like projections resembling neural dendrites. The in situ transplantation group had greater engraftment of hNSCs than matrix embedding approach. Immunohistochemistry with doublecortin, NeuN, and GFAP at 8 weeks after transplantation showed that transplanted hNSCs remained as immature neurons and did not differentiate toward to glial cell lines. Motor function was assessed with rotarod, compared to control group (n = 10). The latency to fall from the rotarod in hNSC in situ transplanted rats was significantly higher than in control rats (median, 113 s in hNSC vs. 69 s in control, P = 0.02). This study first demonstrates the robust engraftment of in situ transplanted hNSCs in a clinically-relevant ASDH decompression rat model. Further preclinical studies with longer study duration are warranted to verify the effectiveness of hNSC transplantation in amelioration of TBI induced deficits

Enduring Neuroprotective Effect of Subacute Neural Stem Cell Transplantation After Penetrating TBI

Traumatic brain injury (TBI) is the largest cause of death and disability of persons under 45 years old, worldwide. Independent of the distribution, outcomes such as disability are associated with huge societal costs. The heterogeneity of TBI and its complicated biological response have helped clarify the limitations of current pharmacological approaches to TBI management. Five decades of effort have made some strides in reducing TBI mortality but little progress has been made to mitigate TBI-induced disability. Lessons learned from the failure of numerous randomized clinical trials and the inability to scale up results from single center clinical trials with neuroprotective agents led to the formation of organizations such as the Neurological Emergencies Treatment Trials (NETT) Network, and international collaborative comparative effectiveness research (CER) to re-orient TBI clinical research. With initiatives such as TRACK-TBI, generating rich and comprehensive human datasets with demographic, clinical, genomic, proteomic, imaging, and detailed outcome data across multiple time points has become the focus of the field in the United States (US). In addition, government institutions such as the US Department of Defense are investing in groups such as Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug-screening consortium to address the barriers in translation. The consensus from such efforts including “The Lancet Neurology Commission” and current literature is that unmitigated cell death processes, incomplete debris clearance, aberrant neurotoxic immune, and glia cell response induce progressive tissue loss and spatiotemporal magnification of primary TBI. Our analysis suggests that the focus of neuroprotection research needs to shift from protecting dying and injured neurons at acute time points to modulating the aberrant glial response in sub-acute and chronic time points. One unexpected agent with neuroprotective properties that shows promise is transplantation of neural stem cells. In this review we present (i) a short survey of TBI epidemiology and summary of current care, (ii) findings of past neuroprotective clinical trials and possible reasons for failure based upon insights from human and preclinical TBI pathophysiology studies, including our group's inflammation-centered approach, (iii) the unmet need of TBI and unproven treatments and lastly, (iv) present evidence to support the rationale for sub-acute neural stem cell therapy to mediate enduring neuroprotection

Blush in Lung Contusions Is Not Rare and Has a High Risk of Mortality in Patients With Blunt Chest Trauma

BackgroundPatients with blunt chest trauma have a high mortality rate. The assessment of blush in hepatic and splenic trauma is important for determining the need for emergency hemostatic interventions. However, the frequency and importance of blush in lung contusions are unknown. Therefore, this study aimed to evaluate the frequency of blush in patients with lung contusions and elucidate the relationship between blush and the clinical outcomes of patients with blunt chest trauma. Materials and MethodsIn this retrospective observational study, we enrolled patients with an injury severity score of 16 or higher and a chest abbreviated injury scale (AIS) score of 3 or higher who were admitted to the emergency department of Hokkaido University Hospital from January 1, 2003, to December 31, 2016. Blush was defined as active extravasation of an intravascular contrast agent recognized on contrast-enhanced computed tomography. The date of trauma, trauma severity, treatments, and outcomes were obtained from the patients' electronic medical records. ResultsDuring the study period, 83 patients had severe lung contusions and 13 had blush. In-hospital mortality of patients with blush was significantly higher than that of patients without blush (53 vs. 10%, P < 0.001). Patients with blush required thoracic drainage more frequently (100 vs. 71%, P < 0.001) and support through mechanical ventilation more often (100 vs. 64%, P < 0.001) and for a longer duration (median duration, 0 vs. 25 days, P = 0.001) than patients without blush. ConclusionsOur study revealed that blush in lung contusions was not rare and was associated with a high risk of mortality in patients with severe blunt chest trauma. Clinicians should not hesitate to intervene if blush is detected in a lung contusion of a patient with blunt chest trauma

Molecular Mechanism of Reperfusion Injury

In the 1950s, hypothermia was induced prior to surgery to assist procedures that caused prolonged ischemia, including heart surgery [1–3] and organ transplants [4]. Within its first decade, hypothermia was applied to emergent medical situations that were characterized by cerebral ischemia and stroke [5, 6] myocardial infarction (MI) [7, 8], and cardiac arrest patients [9, 10]_ENREF_10

Microdialysis in the Neurocritical Care Unit

Effective monitoring is critical for neurologically compromised patients, and several techniques are available. One of these tools, cerebral microdialysis (MD), was designed to detect derangements in cerebral metabolism. Although this monitoring device began as a research instrument, favorable results and utility have broadened its clinical applications. Combined with other brain monitoring techniques, MD can be used to estimate cerebral vulnerability, to assess tissue outcome, and possibly to prevent secondary ischemic injury by guiding therapy. This article reviews the literature regarding the past, present, and future uses of MD along with its advantages and disadvantages in the intensive care unit setting

Use of a Compact, Lightweight X-ray Unit to Reduce the Risk of Five Invasive Procedures in the Emergency Room

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