HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease.

Anti-IgLON5 disease is a rare and likely underdiagnosed subtype of autoimmune encephalitis. The disease displays a heterogeneous phenotype that includes sleep, movement and bulbar-associated dysfunction. The presence of IgLON5-antibodies in CSF/serum, together with a strong association with HLA-DRB1*10:01∼DQB1*05:01, supports an autoimmune basis. In this study, a multicentric human leukocyte antigen (HLA) study of 87 anti-IgLON5 patients revealed a stronger association with HLA-DQ than HLA-DR. Specifically, we identified a predisposing rank-wise association with HLA-DQA1*01:05∼DQB1*05:01, HLA-DQA1*01:01∼DQB1*05:01 and HLA-DQA1*01:04∼DQB1*05:03 in 85% of patients. HLA sequences and binding cores for these three DQ heterodimers were similar, unlike those of linked DRB1 alleles, supporting a causal link to HLA-DQ. This association was further reflected in an increasingly later age of onset across each genotype group, with a delay of up to 11 years, while HLA-DQ-dosage dependent effects were also suggested by reduced risk in the presence of non-predisposing DQ1 alleles. The functional relevance of the observed HLA-DQ molecules was studied with competition binding assays. These proof-of-concept experiments revealed preferential binding of IgLON5 in a post-translationally modified, but not native, state to all three risk-associated HLA-DQ receptors. Further, a deamidated peptide from the Ig2-domain of IgLON5 activated T cells in two patients, compared with one control carrying HLA-DQA1*01:05∼DQB1*05:01. Taken together, these data support a HLA-DQ-mediated T-cell response to IgLON5 as a potentially key step in the initiation of autoimmunity in this disease.

Measuring auditory event-related potentials at the external ear canal: A demonstrative study using a new electrode and error-feedback paradigm.

Although ear canal electroencephalogram (EEG) recording has received interest from basic and applied research communities, evidence on how it can be implemented in practice is limited. The present study involving eight male participants including the authors presents the utility of our ear canal electrode and method by demonstrating both comparability of ear canal EEG to those at nearby sites and distinctiveness that ear canal event-related potentials (ERPs) could have. For this purpose, we used the balanced noncephalic electrode reference and an experimental paradigm with an error-feedback sound. Clear auditory ERPs were detected at the ear canal sites with a sufficiently low noise level comparable with those at conventional sites. The N1c, a temporal maximum subcomponent, spread over the bilateral temporal sites, including the ear canals and earlobes. While consecutive signals are generally highly similar between the ear canal and the earlobe, the N1c was larger at the ear canal than the earlobe, as demonstrated by the conventional frequentist and the hierarchical Bayesian modelling approaches. Although an evident caveat is that our sample was limited in terms of size and sex, the general capability indicates that the structure of our ear canal electrode provides EEG measurement that can be used in basic and applied settings. Our experimental method can also be an ERP-based test that conveniently assesses the capability of existing and future ear canal electrodes. The distinctive nature of the ERPs to the error-feedback sound may be utilized to examine the basic aspects of auditory ERPs and to test the processes involved in feedback-guided behaviour of participants.

Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for adult convulsive status epilepticus: a multicentre non-inferiority randomised control trial.

OBJECTIVE: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is crucial. Although fosphenytoin (FPHT) is recommended as a second-line treatment, levetiracetam (LEV) reportedly has similar efficacy, but higher safety. Therefore, we herein compared LEV with FPHT in adult SE. METHODS: We initiated a multicentre randomised control trial in emergency departments with adult patients with convulsive SE. Diazepam was initially administered, followed intravenously by FPHT at 22.5 mg/kg or LEV at 1000-3000 mg. The primary outcome was assigned as the seizure cessation rate within 30 min of the administration of the study drug. RESULTS: A total of 176 adult patients with SE were enrolled (82 FPHT and 94 LEV), and 3 were excluded from the full analysis set. Seizure cessation rates within 30 min were 83.8% (67/80) in the FPHT group and 89.2% (83/93) in the LEV group. The difference in these rates was 5.5% (95% CI -4.7 to 15.7, p=0.29). The non-inferiority of LEV to FPHT was confirmed with p<0.001 by the Farrington-Manning test. No significant differences were observed in the seizure recurrence rate or intubation rate within 24 hours. Serious adverse events developed in three patients in the FPHT group and none in the LEV group (p=0.061). CONCLUSION: The efficacy of LEV was similar to that of FPHT for adult SE following the administration of diazepam. LEV may be recommended as a second-line treatment for SE along with phenytoin/FPHT. TRIAL REGISTRATION NUMBER: jRCTs031190160.

Clinical Features and Neuroimaging Findings of Neuropil Antibody-Positive Idiopathic Sporadic Ataxia of Unknown Etiology.

Idiopathic sporadic ataxia (ISA) is the clinical term for nonfamilial ataxia with adult-onset and a slowly progressive course. However, immune-mediated cerebellar ataxia cannot be completely excluded from ISA. The current study investigated the neuropil antibodies against cell-surface antigens and clarified the clinical features and neuroimaging findings of patients with these antibodies. Using tissue-based immunofluorescence assays (TBAs), we examined antibodies against the cerebellum in serum samples from 67 patients who met the ISA diagnostic criteria, including 30 patients with multiple system atrophy with predominant cerebellar features (MSA-C) and 20 patients with hereditary ataxia (HA), and 18 healthy control subjects. According to the TBA results, we divided subjects into three groups: subjects positive for neuropil antibodies, subjects positive for intracellular antibodies only, and subjects negative for antibodies. We compared clinical features and neuroimaging findings in ISA patients among these three groups. The prevalence of neuropil antibodies in ISA (17.9%) was significantly higher than that in MSA-C (3.3%), HA (0%), or healthy subjects (0%). The neuropil antibody-positive ISA patients showed pure cerebellar ataxia more frequently than the other ISA patients. Two neuropil antibody-positive patients showed significant improvement of cerebellar ataxia after immunotherapy. We detected neuropil antibodies in 17.9% of ISA patients. Characteristic clinical features of neuropil antibody-positive ISA patients were pure cerebellar ataxia. Some cases of neuropil antibody-positive ISA responded to immunotherapy.

Autoimmune glial fibrillary acidic protein astrocytopathy associated with breast cancer: a case report.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is an autoimmune inflammatory central nervous system disorder characterized by the detection of autoantibodies that recognize GFAP in CSF. The pathogenesis of GFAP-A is poorly understood. Some patients had a neoplasm detected and GFAP expressed by neoplasms is plausible as immunogen triggering paraneoplastic neurological autoimmunity. CASE PRESENTATION: We report a case of 76-year-old female patient with GFAP-A complicated with breast cancer. She presented with altered consciousness, nuchal rigidity, speech disturbances, and weakness. Her clinical symptoms were improved by immunotherapy and cancer treatments. Immunohistochemical analysis showed that the restricted tumor expressed GFAP. The infiltration of CD3 + T cells were observed in the peritumoral and intratumoral areas. The most common infiltrating lymphocytes were CD8 + T cells. CD4 + T cells and CD20 + B cells were also observed in the predominant peritumoral area. CONCLUSIONS: These results suggest that GFAP-A may occur in a paraneoplastic neurological syndrome associated with breast cancer.

We Should Pay More Attention to Sex Differences to Predict the Risk of Severe COVID-19: Men Have the Same Risk of Worse Prognosis as Women More Than 10 Years Older.

BACKGROUND: Prioritization for novel coronavirus disease 2019 (COVID-19)-related health policies usually considers age and certain other characteristics, but sex is rarely included, despite the higher risk of severe disease in men. The aim of this study was to compare the impact of sex and age on the severity of COVID-19 by estimating the age difference in years for which the risk for men versus women is the same. METHODS: We analyzed 23,414 Japanese COVID-19 inpatients aged 20-89 years (13,360 men and 10,054 women). We graded the severity of COVID-19 (0 to 5) according to the most intensive treatment required during hospitalization. The risk of grade 2/3/4/5 (non-invasive positive pressure ventilation/invasive mechanical ventilation/extracorporeal membrane oxygenation/death), grade 3/4/5, and separately grade 5 was analyzed using a multiple logistic regression model. RESULTS: The odds ratio (OR) of grades 2/3/4/5, 3/4/5 (primary outcome), and 5 for men relative to women was 2.76 (95% CI, 2.44-3.12), 2.78 (95% CI, 2.42-3.19), and 2.60 (95% CI, 2.23-3.03), respectively, after adjustment for age and date of admission. These risks for men were equivalent to those for women 14.1 (95% CI, 12.3-15.8), 11.2 (95% CI, 9.7-12.8), and 7.5 (95% CI, 6.3-8.7) years older, respectively. CONCLUSION: The risks of worse COVID-19 prognosis (grades 3/4/5) in men were equivalent to those of women 11.2 years older. Reanalyzing data extracted from four previous studies also revealed a large impact of sex difference on the severity of COVID-19. We should pay more attention to sex differences to predict the risk of COVID-19 severity and to formulate public health policy accordingly.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Presenting with Area Postrema Syndrome-Like Symptoms without Medulla Oblongata Lesions.

INTRODUCTION: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently described steroid-responsive meningoencephalomyelitis positive for cerebrospinal fluid (CSF) anti-GFAP antibody. Area postrema syndrome (APS) involves intractable hiccups, nausea, and vomiting, which is caused by medulla oblongata (MO) impairment. APS is a characteristic symptom of aquaporin-4 (AQP4) autoimmunity, and it helps to differentiate between AQP4 and GFAP autoimmunity. Conversely, although 6 cases of autoimmune GFAP astrocytopathy with APS and MO lesions have been reported, the association between GFAP autoimmunity and APS is unclear. We report the case of a patient with autoimmune GFAP astrocytopathy presenting with APS-like symptoms without MO lesions and discuss the mechanisms underlying the symptoms. METHODS: CSF anti-GFAP antibody was detected using cell-based assays and immunohistochemical assays. RESULTS: A 54-year-old Japanese man developed persistent hiccups, intermittent vomiting, fever, anorexia, and inattention. Brain magnetic resonance imaging (MRI) showed periventricular lesions with radial linear periventricular enhancement, suggesting autoimmune GFAP astrocytopathy. However, no obvious MO lesions were identified on thin-slice images. Spinal cord MRI revealed hazy lesions with patchy enhancement along the cervical and thoracic cord. CSF analysis demonstrated inflammation, with positive results for anti-GFAP antibodies. Anti-AQP4 antibodies in the serum and CSF were negative. Esophagogastroduodenoscopy revealed gastroparesis and gastroesophageal reflux disease, and vonoprazan, mosapride, and rikkunshito were effective only against persistent hiccups. Steroid therapy was initiated, allowing clinical and radiological improvements. Repeated MRIs demonstrated no obvious MO lesions. CONCLUSION: This report suggests that autoimmune GFAP astrocytopathy presents with APS-like symptoms without obvious MO lesions. The possible causes of hiccups were gastroparesis and cervical cord lesions. Gastroesophageal reflux disease was not considered a major cause of the hiccups. Intermittent vomiting appeared to be associated with gastroparesis, cervical cord lesions, and viral-like symptoms. Testing for anti-GFAP antibodies should be considered in patients with APS-like symptoms in the context of typical clinical-MRI features of autoimmune GFAP astrocytopathy.

Progressive supranuclear palsy with predominant frontal presentation exhibiting progressive nonfluent aphasia due to crossed aphasia.

Progressive supranuclear palsy (PSP) with predominant frontal presentation (PSP-F) is a clinical phenotype of PSP that is characterized by frontal cognitive impairment and behavioral changes. Here, we report on a patient with pathologically diagnosed PSP-F in whom we were able to observe temporal changes of the clinical manifestations. A 77-year-old right-handed man developed progressive nonfluent aphasia (PNFA) at the age of 69 years, festinating gait, and clumsiness of his left arm at age 75, disinhibition at age 76, and unprovoked falls at age 77. Neurological examination at age 77 revealed limb-kinetic apraxia of the left upper and lower limbs, rigidity, cortical sensory loss, and vertical supranuclear gaze palsy. According to the Movement Disorder Society clinical diagnostic criteria for PSP, his clinical manifestations shifted from suggestive PSP with predominant speech/language disorder to probable PSP-F over nine years. Cerebral atrophy on brain magnetic resonance imaging and decreased accumulation of 99m Tc-ECD on cerebral blood flow single-photon emission computed tomography were noted with right side predominance. Pathologically, 4-repeat tau-immunoreactive globose-type neurofibrillary tangles, coiled bodies, tufted astrocytes, and neuropil threads were observed predominantly in the frontal cortex. Tau pathology of the substantia nigra, locus coeruleus and subthalamic nucleus was mild. These findings suggested that localized tau pathology involving the pars opercularis extended to the precentral gyrus, prefrontal cortex, and brainstem. This case report demonstrates that PSP-F can present as a PNFA due to crossed aphasia.

Persistent intrathecal interleukin-8 production in a patient with SARS-CoV-2-related encephalopathy presenting aphasia: a case report.

BACKGROUND: Neurological manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized and include encephalopathy, although direct infection of the brain by SARS-CoV-2 remains controversial. We herein report the clinical course and cytokine profiles of a patient with severe SARS-CoV-2-related encephalopathy presenting aphasia. CASE PRESENTATION: An 81-year-old man developed acute consciousness disturbance and status epileptics several days after SARS-CoV-2 infection. Following treatment with remdesivir and dexamethasone, his consciousness and epileptic seizures improved; however, amnestic aphasia and agraphia remained. Two months after methylprednisolone pulse and intravenous immunoglobulin, his neurological deficits improved. We found increased levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1), but not IL-2 and IL-10 in the serum and cerebrospinal fluid (CSF), and the levels of serum IL-6 and MCP-1 were much higher than those in the CSF. The level of IL-8 in the CSF after immunotherapy was four times higher than that before immunotherapy. CONCLUSION: The cytokine profile of our patient was similar to that seen in severe SARS-CoV-2-related encephalopathy. We demonstrated (i) that the characteristic aphasia can occur as a focal neurological deficit associated with SARS-CoV-2-related encephalopathy, and (ii) that IL8-mediated central nervous system inflammation follows systemic inflammation in SARS-CoV-2-related encephalopathy and can persist and worsen even after immunotherapy. Monitoring IL-8 in CSF, and long-term corticosteroids may be required for treating SARS-CoV-2-related encephalopathy.

Effect of antiplatelet agent number, types, and pre-endoscopic management on post-polypectomy bleeding: validation of endoscopy guidelines.

BACKGROUND: It remains unclear whether type of antiplatelet (AP) therapy, AP combination therapy, and AP continuing or switching strategy affect the risk of post-polypectomy bleeding (PPB). In this study, we sought to elucidate this risk. METHODS: We analyzed 1050 patients who underwent colonoscopic polypectomy: 525 AP users and 525 controls matched for age, sex, comorbidities, concomitant non-steroidal anti-inflammatory drugs use, and polyp characteristics who did not receive antithrombotics. PPB risk was evaluated by AP number, type, and continuing or switching strategies during the peri-endoscopic period. RESULTS: In multivariate analysis, bleeding risk increased significantly as the number of AP agents used increased (monotherapy, adjusted odds ratio [aOR], 3.7; dual antiplatelet therapy (DAPT), 4.6; triple antiplatelet therapy (TAPT), 11.1) compared with controls. With monotherapy, significantly increased PPB risk was found for aspirin (aOR 4.3), thienopyridine (aOR 6.3), and cilostazol (aOR 5.9), but not for eicosapentaenoic acid or other APs (beraprost, limaprost, sarpogrelate, dilazep, or dipyridamole). With DAPT, significantly increased PPB risk was found for combination aspirin plus cilostazol, but not aspirin plus other APs. Bleeding rates for continuing monotherapy were 4.3% for aspirin and 0% for thienopyridine, cilostazol, and other APs, respectively. CONCLUSIONS: Analysis of this large polypectomy dataset showed that the use of low-dose aspirin, thienopyridine, or cilostazol and a combination of these is associated with increased PPB risk. Although PPB risk was high with DAPT or TAPT, PPB rate in any antiplatelet monotherapy even with a continuing strategy was low at < 5%.

Clinicopathological findings of a mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes/Leigh syndrome overlap patient with a novel m.3482A>G mutation in MT-ND1.

We report clinicopathological findings of a patient with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes/Leigh syndrome (MELAS/LS) associated with a novel m.3482A>G mutation in MT-ND1. A 41-year-old woman had experienced multiple stroke-like episodes since age 16. She developed akinetic mutism two months before admission to our hospital. Neurological examination revealed akinetic mutism, bilateral deafness, and muscular atrophy. Cerebrospinal fluid tests revealed elevated pyruvate and lactate levels. Fluid-attenuated inversion recovery images on magnetic resonance imaging showed hyperintense areas in the right frontal and both sides of temporal and occipital lobes, both sides of the striatum, and the midbrain. Muscle biopsy revealed strongly succinate dehydrogenase-reactive blood vessels. L-arginine therapy improved her consciousness and prevented further stroke-like episodes. However, she died from aspiration pneumonia. Postmortem autopsy revealed scattered infarct-like lesions with cavitation in the cerebral cortex and necrotic lesions in the striatum and midbrain. The patient was pathologically confirmed as having MELAS/LS based on two characteristic clinicopathological findings: presenting MELAS/LS overlap phenotype and effectiveness of L-arginine treatment.

Direct hemoperfusion using a polymyxin B-immobilized polystyrene column for COVID-19.

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.

Association between prehospital time and outcome of trauma patients in 4 Asian countries: A cross-national, multicenter cohort study.

BACKGROUND: Whether rapid transportation can benefit patients with trauma remains controversial. We determined the association between prehospital time and outcome to explore the concept of the "golden hour" for injured patients. METHODS AND FINDINGS: We conducted a retrospective cohort study of trauma patients transported from the scene to hospitals by emergency medical service (EMS) from January 1, 2016, to November 30, 2018, using data from the Pan-Asia Trauma Outcomes Study (PATOS) database. Prehospital time intervals were categorized into response time (RT), scene to hospital time (SH), and total prehospital time (TPT). The outcomes were 30-day mortality and functional status at hospital discharge. Multivariable logistic regression was used to investigate the association of prehospital time and outcomes to adjust for factors including age, sex, mechanism and type of injury, Injury Severity Score (ISS), Revised Trauma Score (RTS), and prehospital interventions. Overall, 24,365 patients from 4 countries (645 patients from Japan, 16,476 patients from Korea, 5,358 patients from Malaysia, and 1,886 patients from Taiwan) were included in the analysis. Among included patients, the median age was 45 years (lower quartile [Q1]-upper quartile [Q3]: 25-62), and 15,498 (63.6%) patients were male. Median (Q1-Q3) RT, SH, and TPT were 20 (Q1-Q3: 12-39), 21 (Q1-Q3: 16-29), and 47 (Q1-Q3: 32-60) minutes, respectively. In all, 280 patients (1.1%) died within 30 days after injury. Prehospital time intervals were not associated with 30-day mortality. The adjusted odds ratios (aORs) per 10 minutes of RT, SH, and TPT were 0.99 (95% CI 0.92-1.06, p = 0.740), 1.08 (95% CI 1.00-1.17, p = 0.065), and 1.03 (95% CI 0.98-1.09, p = 0.236), respectively. However, long prehospital time was detrimental to functional survival. The aORs of RT, SH, and TPT per 10-minute delay were 1.06 (95% CI 1.04-1.08, p < 0.001), 1.05 (95% CI 1.01-1.08, p = 0.007), and 1.06 (95% CI 1.04-1.08, p < 0.001), respectively. The key limitation of our study is the missing data inherent to the retrospective design. Another major limitation is the aggregate nature of the data from different countries and unaccounted confounders such as in-hospital management. CONCLUSIONS: Longer prehospital time was not associated with an increased risk of 30-day mortality, but it may be associated with increased risk of poor functional outcomes in injured patients. This finding supports the concept of the "golden hour" for trauma patients during prehospital care in the countries studied.

Visualizing Half-Metallic Bulk Band Structure with Multiple Weyl Cones of the Heusler Ferromagnet.

Using a well-focused soft x-ray synchrotron radiation beam, angle-resolved photoelectron spectroscopy was applied to a full-Heusler-type Co_{2}MnGe alloy to elucidate its bulk band structure. A large parabolic band at the Brillouin zone center and several bands that cross the Fermi level near the Brillouin zone boundary were identified in line with the results from first-principles calculations. These Fermi-level crossings are ascribed to majority spin bands that are responsible for electron transport with extremely high spin polarization especially along the direction perpendicular to the interface of magnetoresistive devices. The spectroscopy confirms there is no contribution of the minority spin bands to the Fermi surface, signifying half-metallicity for the alloy. Furthermore, two topological Weyl cones with band crossing points were identified around the X point, yielding the conclusion that Co_{2}MnGe could exhibit topologically meaningful behavior such as large anomalous Hall and Nernst effects driven by the Berry flux in its half-metallic band structure.

Higher levels of progranulin in cerebrospinal fluid of patients with lymphoma and carcinoma with CNS metastasis.

Assessing central nervous system (CNS) involvement in patients with lymphoma or carcinoma is important in determining therapy and prognosis. Progranulin (PGRN) is a secreted glycosylated protein with roles in cancer growth and survival; it is highly expressed in aggressive cancer cell lines and specimens from many cancer types. We examined PRGN levels by Enzyme Immuno-Assay (EIA) in cerebrospinal fluid (CSF) samples from 230 patients, including 18 with lymphoma [12 with CNS metastasis (CNS+); 6 without CNS metastasis (CNS-)], 21 with carcinomas (10 CNS+; 11 CNS-), and 191 control patients with non-cancer neurological diseases, and compared PRGN levels among these disease groups. Median CSF PGRN levels in the CNS+ lymphoma group were significantly higher than in the CNS- lymphoma and control non-cancer groups; and were also significantly higher in the CNS+ carcinoma group than in the CNS- carcinoma and control groups, except for patients with infectious neurological disorders. Receiver operating characteristic curve analyses revealed that CSF PGRN levels distinguished CNS+ lymphoma from CNS- lymphoma and non-cancer neurological diseases [area under curve (AUC): 0.969]; and distinguished CNS+ carcinomas from CNS- carcinomas and non-cancer neurological diseases (AUC: 0.918). We report here, for the first time, that CSF PGRN levels are higher in patients with CNS+ lymphoma and carcinomas compared to corresponding CNS- diseases. This would imply that measuring CSF PGRN levels could be used to monitor CNS+ lymphoma and metastasis.

Reverse shock index multiplied by Glasgow Coma Scale score (rSIG) is a simple measure with high discriminant ability for mortality risk in trauma patients: an analysis of the Japan Trauma Data Bank.

BACKGROUND: The shock index (SI), defined as heart rate (HR) divided by systolic blood pressure (SBP), is reported to be a more sensitive marker of shock than traditional vital signs alone. In previous literature, use of the reverse shock index (rSI), taken as SBP divided by HR, is recommended instead of SI for hospital triage. Among traumatized patients aged > 55 years, SI multiplied by age (SIA) might provide better prediction of early post-injury mortality. Separately, the Glasgow Coma Scale (GCS) score has been shown to be a very strong predictor. When considering these points together, rSI multiplied by GCS score (rSIG) or rSIG divided by age (rSIG/A) could provide even better prediction of in-hospital mortality. METHODS: This retrospective, multicenter study used data from 168,517 patients registered in the Japan Trauma Data Bank for the period 2006-2015. We calculated areas under receiver operating characteristic curves (AUROCs) to measure the discriminant ability by comparing those of SI (or rSI), SIA, rSIG, and rSIG/A for in-hospital mortality and for 24-h blood transfusion. RESULTS: The highest ROC AUC (AUROC), 0.901(0.894-0.908) for in-hospital mortality in younger patients (aged < 55 years), was seen for rSIG. In older patients (aged ≥ 55 years), the AUROC of rSIG/A, 0.845(0.840-0.850), was highest for in-hospital mortality. However, the difference between rSIG and rSIG/A was slight and did not seem to be clinically important. rSIG also had the highest AUROC of 0.745 (0.741-749) for 24-h blood transfusion. CONCLUSIONS: rSIG ((SBP/HR) × GCS score) is easy to calculate without the need for additional information, charts or equipment, and can be a more reliable triage tool for identifying risk levels in trauma patients.

Pan-Asian Trauma Outcomes Study (PATOS): Rationale and Methodology of an International and Multicenter Trauma Registry.

BACKGROUND: Trauma is a major health burden and a time-dependent critical emergency condition among developing and developed countries. In Asia, trauma has become a rapidly expanding epidemic and has spread out to many underdeveloped and developing countries through rapid urbanization and industrialization. Most casualties of severe trauma, which results in significant mortality and disability are assessed and transported by prehospital providers including physicians, professional providers, and volunteer providers. Trauma registries have been developed in mostly developed countries and measure care quality, process, and outcomes. In general, existing registries tend to focus on inhospital care rather than prehospital care. METHODS: The Pan-Asia Trauma Outcomes Study (PATOS) was proposed in 2013 and initiated in November, 2015 in order to establish a collaborative standardized study to measure the capabilities, processes and outcomes of trauma care throughout Asia. The PATOS is an international, multicenter, and observational research network to collect trauma cases transported by emergency medical services (EMS) providers. Data are collected from the participating hospital emergency departments in various countries in Asia which receive trauma patients from EMS. Data variables collected include 1) injury epidemiologic factors, 2) EMS factors, 3) emergency department care factors, 4) hospital care factors, and 5) trauma system factors. The authors expect to achieve a sample size of 67,230 cases over the next 2 years of data collection to analyze the association between potential risks and outcomes of trauma. CONCLUSION: The PATOS network is expected to provide comparison of the trauma EMS systems and to benchmark best practice with participating communities.

Development of a new clinical decision rule for cervical CT to detect cervical spine injury in patients with head or neck trauma.

OBJECTIVE: Previous cervical spine imaging decision rules have been based on positive findings on plain X-ray and are limited by lack of specificity, age restrictions and complicated algorithms. We previously derived and validated a clinical decision rule (Rule 1) for detecting cervical spine injury (CSI) on CT in a single-centre study. This recommended CT for patients with (1) GCS score <14, (2) GCS 14-15 and posterior cervical tenderness or neurological deficit, (3) age ≥60 years and fall down stairs, or (4) age <60 and injured in a motorcycle collision or fallen from height. This study assessed the accuracy and reliability of this rule and refined the rule. METHODS: We conducted a prospective, dual-centre study at two Japanese EDs between August 2012 and March 2014. Patients with head or neck injury ≥16 years of age were included. Clinical data were collected from medical records. Imaging was at the discretion of the treating physician. CSI was diagnosed as a fracture or dislocation seen on CT; patients who were not imaged were followed for 14 days. We analysed the sensitivity and specificity of Rule 1 and refined it post hoc using recursive partitioning. RESULTS: 1192 patients were enrolled. 927 completed follow-up. Of these, 584 (63.0%) underwent CT imaging and 38 had CSI. Sensitivity and specificity of Rule 1 were 92.1% (95% CI 79.2% to 97.3%) and 58.6% (95% CI 55.4% to 61.9%). A second rule (Rule 2) was derived recommending CT for those with any of the following: GCS <14, cervical tenderness, neurological deficit or mechanism of injury (fall down stairs, motorcycle collision or fall from height) without age limits. Sensitivity and specificity were 100% (95% CI 90.8% to 100%) and 51.9% (95% CI 48.6% to 55.2%), respectively. CONCLUSIONS: Our initial CT decision rule had lower sensitivity than in our initial validation study. A refined decision rule based on GCS, neck tenderness, neurological deficit and mechanism of injury showed excellent sensitivity with a small loss of specificity. Rule 2 will now need validation in an independent cohort.