Impact of the COVID-19 pandemic on prehospital and in-hospital treatment and outcomes of patients after out-of-hospital cardiac arrest: a Japanese multicenter cohort study.

BACKGROUND: In the chain of survival for Out-of-hospital cardiac arrest (OHCA), each component of care contributes to improve the prognosis of the patient with OHCA. The SARS-CoV-2 (COVID-19) pandemic potentially affected each part of care in the chain of survival. The aim of this study was to compare prehospital care, in-hospital treatment, and outcomes among OHCA patients before and after the COVID-19 pandemic. METHODS: We analyzed data from a multicenter prospective study in Kanto area, Japan, named SOS-KANTO 2017. We enrolled patients who registered during the pre-pandemic period (September 2019 to December 2019) and the post-pandemic period (June 2020 to March 2021). The main outcome measures were 30-day mortality and the proportion of favorable outcomes at 1 month, and secondary outcome measures were changes in prehospital and in-hospital treatments between the pre- and post-pandemic periods. RESULTS: There were 2015 patients in the pre-pandemic group, and 5023 in the post-pandemic group. The proportion of advanced airway management by emergency medical service (EMS) increased (p < 0.01), and EMS call-to-hospital time was prolonged (p < 0.01) in the post- versus pre-pandemic group. There were no differences between the groups in defibrillation, extracorporeal membrane oxygenation, or temperature control therapy (p = 0.43, p = 0.14, and p = 0.16, respectively). Survival rate at 1 month and favorable outcome rate at 1 month were lower (p = 0.01 and p < 0.01, respectively) in the post- versus pre-pandemic group. CONCLUSION: Survival rate and favorable outcome rate 1 month after return of spontaneous circulation of OHCA worsened, EMS response time was prolonged, and advanced airway management by EMS increased in the post- versus pre-pandemic group; however, most prehospital and in-hospital management did not change between pre- and post-COVID-19 pandemic.

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.

Ultra-Early Induction of General Anesthesia for Reducing Rebleeding Rates in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Rebleeding of aneurysmal subarachnoid hemorrhage (aSAH) is one of the significant risk factors for poor clinical outcome. The rebleeding risk is the highest during the acute phase with an approximate rebleeding rate of 9-17% within the first 24 h. Theoretically, general anesthesia can stabilize a patient's vital signs; however, its effectiveness as initial management for preventing post-aSAH rebleeding remains unclear. The purpose of this study was to determine the feasibility and safety of ultra-early general anesthesia induction for reducing the rebleeding rates among patients with aSAH. MATERIALS AND METHODS: We retrospectively evaluated patients with aSAH who were admitted to our department between January 2013 and December 2019. All the patients underwent ultra-early general anesthesia induction as initial management regardless of their severity. We evaluated the rebleeding rate before definitive treatment, factors influencing rebleeding, and general anesthesia complications. RESULTS: We included 191 patients with two-third of them having a poor clinical grade (World Federation of Neurological Society [WFNS] grade IV or V). The median duration from admission to general anesthesia induction was 22 min. Rebleeding before definitive treatment occurred in nine patients (4.7%). There were significant differences in the Glasgow Coma Scale score (p = 0.047), WFNS grade (p = 0.02), and dissecting aneurysm (p <0.001) between the rebleeding and non-rebleeding patients. There were no cases of unsuccessful tracheal intubation or rebleeding during general anesthesia induction. CONCLUSION: Ultra-early general anesthesia induction could be performed safely in patients with aSAH, regardless of the WFNS grade; moreover, it resulted in lower rebleeding rate than that reported in previous epidemiological reports.

Negative impact of Interhospital Transfer on Clinical Outcomes of Mechanical Thrombectomy for Fast Progressive Stroke.

OBJECTIVES: The time-dependence of the clinical outcome of mechanical thrombectomy is higher in the "fast progressor" in whom cerebral ischemia progresses rapidly. The impact of time-consuming interhospital transfer (IT) on the clinical outcome of such patients is unknown. The effect on clinical outcomes of IT of fast progressors was investigated. METHODS: Among the patients enrolled in the Tokyo/Tama REgistry of Acute endovascular Thrombectomy, fast progressor cerebral ischemia cases were retrospectively investigated. In this study, a fast progressor was defined as a case with an Alberta Stroke Program Early CT Score less than 6 and last known well (LKW) to arterial puncture within 6 h. Patients' background characteristics, treatment progress, and the modified Rankin Scale (mRS) score at 3 months were examined. RESULTS: Of a total of 1182 patients, 92 (7.8%) were included, with 76 patients in the direct transfer (DT) group, and 16 patients in the IT group. Median LKW to reperfusion was 190 min and 272 min, respectively (P<.001). The number of patients with mRS scores 0-2 at three months was 22 (28.9%) in the DT group and 1 (6.2%) in the IT group. Interhospital transfer was an independent factor associated with worse outcomes (odds ratio 0.08, 95% confidence interval 0.01-0.87, P=.038). CONCLUSION: This study showed that, among fast progressor patients, the IT group had a worse prognosis than the DT group. To provide good clinical outcomes for fast progressor patients, those who are likely to undergo mechanical thrombectomy should be sent directly to a thrombectomy-capable center.

Impact of Coronavirus Disease 2019 on Time Delay and Functional Outcome of Mechanical Thrombectomy in Tokyo, Japan.

OBJECTIVES: An association has been reported between delays in the onset-to-door (O2D) time for mechanical thrombectomy (MT) and outbreaks of coronavirus disease 2019 (COVID-19). However, the association between other MT time courses or functional outcomes and COVID-19 outbreaks remains unclear. We compared the time courses of stroke pathways or functional outcomes in 2020 (the COVID-19 era) with those in 2019 (the pre-COVID-19 era) in Tokyo, Japan. MATERIALS AND METHODS: This retrospective observational study used data from the Tokyo-tama-REgistry of Acute endovascular Thrombectomy (TREAT), a multicenter registry of MT for acute large vessel occlusion in the Tokyo Metropolitan Area. Patients who had undergone acute MT from January 2019 to December 2020 were included. Patients were classified by the year they had undergone MT (2019 or 2020). RESULTS: In total, 477 patients were analyzed. O2D time was significantly longer in 2020 (146.0 min) than in 2019 (105.0 min; p = 0.034). No significant difference in door-to-puncture time (D2P) time or modified Rankin Scale (mRS) score 0-2 at 90 days was seen between 2019 and 2020. In the subgroup analysis, O2D time was significantly longer in the first half of 2020 compared with 2019. Multivariable logistic regression analysis revealed that the year 2020 was a independent predictor of longer O2D time, but not for mRS score 0-2 at 90 days. CONCLUSIONS: Although O2D time was significantly longer in the COVID-19 compared with the pre-COVID-19 era, D2P may not be significantly delayed and functional outcomes may not be different, despite the COVID-19 pandemic.

Intracranial pressure management and neurological outcome for patients with mild traumatic brain injury who required neurosurgical intervention: a Japanese database study.

Purpose: Among mild traumatic brain injuries (mTBI; a Glasgow Coma Scale score ≥13 on arrival), few result in severe neurological deficit, especially when they needed neurosurgical intervention. We investigated the association of intracranial pressure (ICP) control management with neurological outcome in patients with mTBI who needed neurosurgical intervention. Methods: From 1,092 records of the Japan Neurotrauma Data Bank during 2009-2011, we retrospectively identified 195 patients with neurosurgical intervention for mTBI. Using the Glasgow Outcome Scale, we grouped records into two: favorable and poor outcome. We analyzed neurological outcomes using a logistic regression analysis adjusted for ICP control managements. Results: Seventy patients had a poor outcome. Logistic regression analysis revealed that sedatives, hyperosmotic agents, and hyperventilation therapy were significantly associated with poor outcome (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.31-4.26; OR: 2.81, 95% CI: 1.17-6.75; OR: 9.36, 95% CI: 1.81-48.35). However, temperature management was significantly related with favorable outcome (OR: 0.26, 95% CI: 0.10-0.66). Conclusions: Our study, using a Japanese multicenter brain trauma registry, suggested that requirement of sedatives, hyperosmotic agents, and hyperventilation is associated with poor neurological outcome for patients with mTBI who underwent neurosurgical intervention, although temperature management was associated with favorable neurological outcome.

Ky-2, a hybrid compound histone deacetylase inhibitor, regulated inflammatory response in LPS-driven human macrophages.

Histone deacetylase has attracted much attention as an epigenetic factor, and the modulation of histone and transcription factor acetylation status is important for regulating gene expression. Moreover, histone deacetylase inhibitors are involved in cellular growth and differentiation. In the present study, we examined the effects of Ky-2, a hybrid-compound HDAC inhibitor, on inflammatory reactions and the polarization of macrophages in vitro. Human monocyte-like THP-1 cells were polarized to macrophage-like cells using phorbol 12-myristate 13-acetate, and then polarized to M1 macrophages with LPS. Ky-2 inhibited HDAC2 expression and enhanced the acetylation of histone H3 in THP-1 cells. It also downregulated the expression of the IL-1ß-encoding gene and the LPS-induced phosphorylation of p38 mitogen-activated protein kinases in THP-1 cells. Moreover, the expression of nod-like receptor protein 3 and cleaved caspase-1 p20 was downregulated in Ky-2-treated THP-1 cells. In contrast, this agent upregulated the expression of IL-1ra in LPS-treated THP-1 cells. These results indicate that Ky-2-treatment downregulates the expression of the inflammatory cytokine, IL-1ß, in LPS-treated THP-1 cells, suggesting that Ky-2 might regulate M1 macrophage polarization through the suppression of inflammatory responses such as NLRP3 inflammasome activation.

Amiodarone Compared with Lidocaine for Out-Of-Hospital Cardiac Arrest with Refractory Ventricular Fibrillation on Hospital Arrival: a Nationwide Database Study.

PURPOSE: The latest resuscitation guidelines recommend the use of amiodarone in adult patients with out-of-hospital cardiac arrest (OHCA) and refractory ventricular fibrillation (VF) to improve the rates of return of spontaneous circulation. However, there is limited evidence to suggest that amiodarone is superior to lidocaine with respect to survival at discharge. The purpose of the present study was to evaluate the hypothesis that amiodarone is superior to lidocaine with regard to the rate of survival to hospital discharge for OHCA patients with VF/pulseless VT (pVT) on hospital arrival. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we identified 3951 patients from 795 hospitals who experienced cardiogenic OHCA and had refractory ventricular fibrillation on hospital arrival between July 2007 and March 2013. The patients were categorized into amiodarone (n = 1743) and lidocaine (n = 2208) groups, from which 801 propensity score-matched pairs were generated. RESULTS: There was no significant difference in the rate of survival to hospital discharge between the amiodarone and lidocaine groups (15.2 % vs. 17.1 %; difference, -1.9 %; 95 % CI, -5.5 to 1.7) in propensity score-matched analyses. Cox regression analyses did not indicate significant in-hospital mortality differences between the amiodarone and lidocaine groups for the propensity score-matched groups (hazard ratio, 1.05; 95 % CI, 0.94 to 1.17). CONCLUSIONS: The present nationwide study suggested that there was no significant difference in the rate of survival to hospital discharge between cardiogenic OHCA patients with persistent ventricular fibrillation on hospital arrival treated with amiodarone or lidocaine.

Early antibiotics administration during targeted temperature management after out-of-hospital cardiac arrest: a nationwide database study.

BACKGROUND: Patients resuscitated after cardiac arrest are reportedly at high risk for infection and sepsis, especially those treated with targeted temperature management (TTM). There is, however, limited evidence suggesting that early antibiotic use improves patient outcomes. We examined the hypothesis that early treatment with antibiotics reduces mortality in patients with cardiac arrest receiving TTM. METHODS: We identified 2803 patients with cardiogenic out-of-hospital cardiac arrest (OHCA) that were treated with TTM and were admitted to 371 hospitals that contribute to the Japanese Diagnosis Procedure Combination inpatient database between July 2007 and March 2013. Of these, 1272 received antibiotics within the first 2 days (antibiotics) and 1531 did not (control). We generated 802 propensity score-matched pairs. RESULTS: There was no significant difference in 30-day mortality between the groups (control vs. antibiotics; 33.0 % vs. 29.9 %; difference, 3.1 %; 95 % confidence interval [CI], -1.4 to 7.7 %, p = 0.18). Analysis using the hospital antibiotics prescribing rate as an instrumental variable showed that antibiotic use was not significantly associated with a reduction in 30-day mortality (6.6 %, CI 95 %, -0.5 to 13.7 %, p = 0.28). A subgroup analysis of patients who required extracorporeal membrane oxygenation (ECMO) indicated a significant difference in 30-day mortality between the 2 groups (62.9 % vs. 43.5 %; difference 19.3 %, CI 95 %, 5.9 to 32.7 %, p = 0.005). In the instrumental variable model, the estimated reduction in 30-day mortality associated with antibiotics was 18.2 % (CI 95 %, 21.3 to 34.4 %, p = 0.03) in ECMO patients. CONCLUSIONS: Although there was no significant association between the use of antibiotics and mortality after overall cardiogenic OHCA treated with TTM, antibiotics may be beneficial in patients who require ECMO.

Risk factors for the need for advanced care among prescription and over-the-counter drug overdose patients.

Aim: Prescription drug and over-the-counter (OTC) drug overdose is a major problem in emergency departments in Japan, and some need advanced care which is more than observation. We aimed to identify the prehospital risk factors for the need of advanced care among overdose patients. Methods: This was a single-center retrospective cohort study. We included overdoses patients of prescription drugs or OTC drugs, who admitted to our hospital between 2016 and 2021. We grouped them into advanced care and non-advanced care. The main outcome was the need for advanced care. We performed a multiple logistic regression analysis, calculated the PAV score (Paracetamol use, Alcohol use, abnormal Vital signs on scene) and performed a receiver operating characteristic (ROC) analysis. Results: There were 229 subjects. The logistic regression analysis revealed that alcohol, paracetamol, and the abnormal vital signs on scene were associated with advanced care (alcohol-odds ratio [OR]: 2.95; 95% confidence interval [CI]: 1.29-6.75; paracetamol-OR: 5.47; 95% CI: 2.18-13.71; abnormal vital signs-OR: 4.61, 95% CI: 2.07-10.27). The rate of advanced care in the high PAV score (2 and 3) group was statistically higher than that in the low PAV score (0-1) group (p = 0.04). Area under the ROC curve of the PAV score was 0.72 (95% CI, 0.65-0.80). Conclusion: Alcohol, paracetamol use and abnormal vital signs on scene might be risk factors for advanced care among prescription drugs or OTC drugs overdose patients, and the PAV score may predict the need for advanced care.

Mechanical Thrombectomy for Acute Common Carotid Artery Occlusion.

Mechanical thrombectomy (MT) is the standard treatment for acute large occlusion of the cerebral artery. Evidence for the success of this procedure was based on the treatment of patients with internal carotid artery and middle cerebral artery thrombi. There are a few reports on thrombi extending to the common carotid artery (CCA). We document our endovascular procedure and the clinical outcome in seven consecutive patients who underwent MT for CCA thrombi between September 2016 and April 2021. Their mean National Institutes of Health Stroke Scale score was 20.0 (range, 9-30), and the mean diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score on magnetic resonance images was 8.7 (range, 7-10). In six patients, MT of the CCA occlusion was successful, and the mean puncture-to-reperfusion time was 84 minutes (range, 39-211 minutes). In five patients, successful reperfusion was obtained. The mean total pass number was 4.1 (range, 2-7). Due to large thrombi, we performed balloon guide catheter (BGC) occlusion in three patients. Sheath occlusion occurred in two, and thrombus migration into the femoral artery around the sheath was observed in two patients. The mean modified Rankin Scale score 3 months post-stroke was 3.6 (range, 2-5). When the removal of a large CCA thrombus is attempted in a single step, catheter and sheath occlusion may occur, and this increases the risk for critical systemic artery occlusion. Therefore, we suggest that MT be combined with the BGC technique and propose the use of a large aspiration catheter to decrease the volume of the thrombus.

Utility of a Compatibility Chart for Continuous Infusions in the Intensive Care Unit.

BACKGROUND: In the intensive care unit (ICU), multiple intravenous drugs are often administered through the same catheter line, greatly increasing the risk of drug incompatibility. We previously developed a compatibility chart including 27 drugs and have used it to avoid drug incompatibilities in the ICU. This retrospective study evaluated the utility of this chart by analyzing prescriptions and incidents of incompatibilities in an ICU. METHODS: We analyzed 257 ICU prescriptions of two or more continuous infusions on the same day during the period between March 2016 and February 2017 and investigated the rate of compliance with the compatibility chart. Drug combinations were classified as "compatible," "tolerable compatible," "incompatible," and "no data." For all combinations, the compliance rate was defined as the ratio of compatible and tolerable compatible combinations. Additionally, using our hospital incident report database, we analyzed 27,117 injections administered in the ICU between March 2016 and February 2017 and investigated incidents related to incompatibility. RESULTS: Three hundred infusion combinations were identified in the prescriptions. The compliance rate was 97% (n = 293). Of the 113 combinations judged to be tolerable compatible, 98% (n = 111) consisted of three or more continuous medications injected through the same intravenous line. Of the two incidents related to incompatibility in the incident report database, the combination "nicardipine and furosemide" was defined as incompatible in the compatibility chart. CONCLUSIONS: The high rate of compliance with the compatibility chart suggested it was useful in preventing drug incompatibility.

An Initial High National Institutes of Health Stroke Scale Score and Any Intracranial Hemorrhage Are Independent Factors for a Poor Outcome in Nonagenarians Treated with Thrombectomy for Acute Large Vessel Occlusion: The Tokyo/Tama-REgistry of Acute Endovascular Thrombectomy (TREAT) Study.

BACKGROUND: Mechanical thrombectomy (MT) is effective in acute ischemic stroke patients ≥80 years old with large vessel occlusion (LVO). However, data for patients ≥90 years old remain very limited, and factors influencing functional outcomes are unclear. This study aimed to investigate factors influencing functional outcomes in patients ≥90 years old treated with MT for acute LVO. METHODS: This retrospective observational study used prospectively collected data from the Tokyo/tama-REgistry of Acute endovascular Thrombectomy (TREAT) study. Inclusion criteria were as follows: 1) patients ≥90 years old treated with MT for LVO and 2) prestroke modified Rankin Scale (mRS) score, 0-3. The functional outcome was defined based on the mRS score at 90 days after the procedure: good functional outcome, mRS score 0-3 and poor functional outcome, mRS score 4-6. RESULTS: Data were analyzed for 104 patients ≥90 years old. The good functional outcome was observed in 25 patients (24.0%), and the poor functional outcome was observed in the remaining 79 patients. Significant differences were identified in initial National Institutes of Health Stroke Scale (NIHSS) score, modified Thrombolysis in Cerebral Infarction grade 2b-3, modified Thrombolysis in Cerebral Infarction grade 3, and any intracranial hemorrhage and hemorrhagic infarction in univariate analyses. Multivariable analysis confirmed the initial NIHSS score (odds ratio, 1.08; 95% confidence interval, 1.01-1.17; P = 0.045) and any intracranial hemorrhage (odds ratio, 11.6; 95% confidence interval, 1.43-95.0; P = 0.022) as independent factors for the functional outcome. CONCLUSIONS: An initial high NIHSS score and any intracranial hemorrhage are independent factors for the poor functional outcome in acute ischemic stroke patients ≥90 years old treated with MT.

Effect of angioembolization for isolated complex pelvic injury: A post-hoc analysis of a nationwide multicenter trauma database in Japan.

BACKGROUND AND IMPORTANCE: Complex pelvic injuries are among the types of trauma with the highest mortality. Treatment strategies should be based on the hemodynamic status, the anatomical type of fracture, and the associated injuries. Combination therapies, including preperitoneal pelvic packing, temporary mechanical stabilization, resuscitative endovascular balloon occlusion of the aorta, and angioembolization, are recommended for pelvic injuries. OBJECTIVE: To investigate the effect of urgent angioembolization alone on severe pelvic injury-associated mortality. DESIGN, SETTINGS, AND PARTICIPANTS: We used the Japan Trauma Data Bank database, a multicenter observational study, to retrospectively identify adult patients with isolated blunt pelvic injuries (Abbreviated Injury Scale [AIS] score: 3-5) from 2004 to 2018. OUTCOME MEASURES AND ANALYSIS: The primary outcome measure was in-hospital mortality. We subdivided patients into two groups, those who underwent urgent angioembolization and non-urgent angioembolization, and compared their mortality rates. We performed multiple imputation and multivariable analyzes to compare the mortality rates between groups after adjusting for known potential confounding factors (age, sex, Glasgow Coma Scale score, systolic blood pressure on hospital arrival, Injury Severity Score, pelvic AIS score, laparotomy, resuscitative endovascular balloon occlusion of the aorta, and external fixation) and for within-hospital clustering using the generalized estimating equation. MAIN RESULTS: We analyzed 4207 of 345,932 trauma patients, of whom 799 underwent urgent angioembolization. The in-hospital mortality rate was significantly higher in the urgent embolization group than in the non-urgent embolization group (7.4 vs. 4.0%; p < 0.01). However, logistic regression analysis revealed that the mortality rates of patients with urgent angioembolization significantly decreased after adjusting for factors independently associated with mortality (odds ratio: 0.60; 95% confidence interval: 0.37-0.96; p = 0.03). CONCLUSION: Urgent angioembolization may be an effective treatment for severe pelvic injury regardless of the pelvic AIS score and the systolic blood pressure on hospital arrival.

Neurointensive Care of Traumatic Brain Injury Patients Based on Coagulation and Fibrinolytic Parameter Monitoring.

Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will "talk and deteriorate." Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients.

Comparisons of Characteristics and Outcomes after Mechanical Thrombectomy for Vertebrobasilar Occlusion with Cardioembolism or Atherosclerotic Brain Infarction: Data from the Tokyo-Tama-Registry of Acute Endovascular Thrombectomy (TREAT).

BACKGROUND: Some reports suggest the efficacy of mechanical thrombectomy (MT) for acute vertebrobasilar artery (VBA) occlusion. The major causes of VBA occlusion include cardioembolism (CE) and large-artery atherosclerosis (LAA). However, the clinical characteristics of each cause remain unclear, and they might be important for decision making related to the indications and strategy of MT. OBJECTIVE: This study aimed to compare functional outcomes and factors affecting outcomes between patients with CE and LAA with acute VBA occlusion. METHODS: This was a retrospective and prospective observational study using data from TREAT (Tokyo-Tama-Registry of Acute Endovascular Thrombectomy), a multicenter registry of MT for acute large-vessel occlusion in the Tokyo metropolitan area. Patients with VBA occlusion classified into CE and LAA groups were analyzed. The primary outcome was a modified Rankin Scale score of 0-2 at 90 days. RESULTS: Seventy-nine patients (57 with CE and 22 with LAA) were eligible from January 2015 to March 2020. Despite significantly shorter puncture-to-recanalization and onset-or-last-well-known-to-recanalization times in the CE group, the primary outcome was not significantly different between the 2 groups (CE, 31.6% vs. LAA, 45.5%; P = 0.248). In the subgroup analysis, patients with CE had worse clinical outcomes in the onset-or-last-well-known-to-door time ≥180 minutes, onset-or-last-well-known-to-door time ≥300 minutes, and low posterior circulation Alberta Stroke Program Early CT Score (≤7) subgroups. CONCLUSIONS: Functional outcomes of VBA occlusion were not significantly different between CE and LAA. Based on the subgroup analysis, patients with CE might have poorer collateral status than do patients with LAA, and earlier recanalization might therefore be desired.

Blood concentration of levetiracetam after bolus administration in patients with status epilepticus.

PURPOSE: We aimed to evaluate the blood concentration of levetiracetam (LEV), as a second-line drug, in patients with status epilepticus (SE) in an emergency clinical setting. METHODS: We prospectively evaluated 20 consecutive patients with SE admitted to our department between July 2017 and July 2019. LEV (2500 mg) was administered via bolus infusion after diazepam infusion, followed by 500 mg every 12 h for 48 h and then 500 mg orally. The primary outcomes were LEV blood concentration 15 min, 12 h, 48 h, and 96 h after administration and the proportion of patients showing trough LEV concentration within the therapeutic range. The secondary outcomes were the discontinuation of apparent convulsive seizure, epileptic wave on electroencephalogram, tracheal intubation, adverse events related to blood parameters, and abnormal findings in vital signs examination. RESULTS: Median blood LEV (2500 mg) concentration at 15 min after administration was 81.6 µg/mL. The median trough concentration after 12, 48, and 96 h was 28.8, 10.5, and 9.1 µg/mL, respectively. Moreover, 95% of patients had trough concentration above the lower limit of the therapeutic blood concentration (>12 µg/mL) after 12 h. Regarding secondary outcomes, endotracheal intubation, seizure suppression, and abnormal electroencephalogram findings were observed in approximately 40%, 90%-95%, and 41% of patients, respectively. No abnormal findings were noted in blood tests and vital sign examination, although the AST/ALT levels increased in 10% of the patients. CONCLUSION: After bolus administration of 2500 mg, the blood LEV concentration reached the therapeutic window in patients with early-stage SE.

Endovascular treatment of acute basilar artery occlusion: Outcomes, influencing factors and imaging characteristics from the Tama-REgistry of acute thrombectomy (TREAT) study.

OBJECTIVE: The effectiveness of mechanical thrombectomy (MT) for acute basilar artery occlusion (ABAO) remains unknown. We evaluated the feasibility, safety, and efficacy of endovascular treatment for ABAO. METHODS: We retrospectively investigated patients with ABAO who underwent MT using modern stent retrievers and an aspiration device between January 2015 and March 2019 at 12 comprehensive stroke centers. Functional outcomes and 90-day mortality rates were analyzed as primary outcomes. Factors influencing outcomes were analyzed as secondary outcomes. Relationships between outcome and affected area of infarction on arrival were also analyzed. RESULTS: Seventy-three patients were included. Good outcome (modified Rankin Scale (mRS) score 0-2) was achieved in 25/73 patients (34.2%) and the all-cause 90-day mortality rate was 23.3% (17/73). Successful recanalization (modified Thrombolysis In Cerebral Infarction grade 2b and 3) was achieved in 70/73 patients (95.9%). In univariate analyses, age, National Institutes of Health Stroke Scale score, and posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) differed significantly between good and poor functional outcome groups. Age and pc-ASPECTS were significantly associated with functional outcomes in the logistic regression model. Positive findings for the midbrain on diffusion-weighted imaging on pc-ASPECTS and brainstem score were significantly associated with poor outcomes. CONCLUSION: MT with modern devices for ABAO resulted in highly successful recanalization and good outcomes. A positive finding for the midbrain on initial imaging might predict poor outcomes. Further studies are required to confirm our results.

Validation of sepsis-induced coagulopathy score in critically ill patients with septic shock: post hoc analysis of a nationwide multicenter observational study in Japan.

Coagulation disorder is a major cause of death in sepsis patients. Recently, sepsis-induced coagulopathy (SIC) scoring was developed as a new criterion for coagulopathy-associated sepsis. We aimed to evaluate the accuracy of the SIC score for predicting the prognosis of septic shock. We analyzed data from a multicenter observational study conducted from 2011 to 2013. We grouped the participants into those who did and did not use vasopressors, and compared the in-hospital mortality rates of SIC and non-SIC patients. Patients who needed vasopressors were considered to have septic shock. We performed survival analysis adjusted by factors independently associated with mortality. SIC developed in 66.4% of patients who used vasopressors and 42.2% of patients who did not. The in-hospital mortality difference between the SIC and non-SIC groups was statistically significant in those who needed vasopressors (35.8% vs 27.9%, p < 0.01). Cox regression analysis indicated that SIC was significantly correlated with mortality risk in patients who used vasopressors (hazard ratio [HR] 1.39; 95% confidence interval [CI] 1.13-1.70; p < 0.01), but not in those who did not (HR 1.38; 95% CI 0.81-2.34; p = 0.23). In conclusion, the SIC score might be a good diagnostic indicator of fatal coagulopathy among sepsis patients who need vasopressors.

Association between mortality and age among mechanically ventilated COVID-19 patients: a Japanese nationwide COVID-19 database study.

BACKGROUND: Only a few studies have reported the association between age and mortality in COVID-19 patients who require invasive mechanical ventilation (IMV). We aimed to evaluate the effect of age on COVID-19-related mortality among patients undergoing IMV therapy. METHODS: This cohort study was conducted using the COVID-19 Registry Japan database, a nationwide multi-centre study of hospitalized patients with laboratory-confirmed COVID-19. Of all 33,808 cases registered between 1 January 2020 to 28 February 2021, we analysed 1555 patients who had undergone IMV. We evaluated mortality rates between age groups using multivariable regression analysis after adjusting for known potential components, such as within-hospital clustering, comorbidities, steroid use, medication for COVID-19, and vital signs on admission, using generalized estimation equation. RESULTS: By age group, the mortality rates in the IMV group were 8.6%, 20.7%, 34.9%, 49.7% and 83.3% for patients in their 50s, 60s, 70s, 80s, and 90s, respectively. Multivariable analysis showed that compared with those for patients aged < 60 years, the odds ratios (95% confidence interval) of death were 2.6 (1.6-4.1), 6.9 (4.2-11.3), 13.2 (7.2-24.1), 92.6 (16.7-515.0) for patients in their 60s, 70s, 80s, and 90s, respectively. CONCLUSIONS: In this cohort study, age had a great effect on mortality in COVID-19 patients undergoing IMV, after adjusting for variables independently associated with mortality. This study suggested that age was associated with higher mortality and that preventing progression to severe COVID-19 in elderly patients may be a great public health issue.