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The relationship between mechanical ventilation-induced brain volume changes and ICU-acquired weakness (ICU-AW) is not clear. We assessed brain volume change in ventilated patients and identified associations with changes in extremity muscle strength. Patients admitted to the ICU due to the need for ventilation, and who underwent at least two head CT scans during hospitalization, were included. We employed an automated segmentation method to measure brain volume, recording changes in volume from baseline. Cases with brain volume reduction > 0% were assigned to the "brain atrophy group" and those with ≤ 0% reduction to the "preserved brain volume group." Medical Research Council (MRC) scores as an indicator of ICU-AW at discharge were compared between groups. There were 84 eligible patients, 71 in the brain atrophy group and 13 in the preserved brain volume group. Analysis of the brain atrophy group showed a significant brain volume reduction of - 3.3% over a median of 30 days. The median MRC scores were significantly lower in the brain atrophy group than in the preserved brain volume group (36 vs. 48, difference [95% CI]: - 12 [- 19.5- - 7.1]). Many ICU patients on mechanical ventilation showed rapidly progressive brain atrophy, and most of these patients developed ICU-AW., Competing Interests: Declarations. Competing interests: One author (Geoffrey Warnock) is an employee of PMOD Technologies GmbH. Only non-PMOD employees had control of inclusion of data and information., (© 2024. The Author(s).)

Purpose: To determine the effectiveness of vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM) in patients undergoing open abdomen management (OAM)., Methods: Data from cases with OAM for at least five days who were admitted to our institution between January 2011 and December 2020 were included. We compared the patient's age, sex, medical history, indication for initial surgery, APACHE II scores, indication for OAM, operative time, intraoperative blood loss, intraoperative transfusion, success of primary fascial closure (rectus fascial closure and bilateral anterior rectus abdominis sheath turnover flap method), success of planned ventral hernia, duration of OAM, and in-hospital mortality between patients undergoing VAWCM (VAWCM cases, n = 27) and vacuum-assisted wound closure (VAWC) alone (VAWC cases, n = 25)., Results: VAWCM cases had a significantly higher success rate of primary fascial closure (70% vs. 36%, p = 0.030) and lower in-hospital mortality (26% vs. 72%, p = 0.002) than VAWC cases. A multivariate logistic regression analysis showed that VAWCM was an independent factor influencing in-hospital mortality (odds ratio, 0.14; 95% confidence interval: 0.04-0.53; p = 0.004)., Conclusion: VAWCM is associated with an increased rate of successful primary fascial closure and may reduce in-hospital mortality., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

A reactive force field (ReaxFF) molecular dynamics simulation is performed for the sliding of diamond-like carbon (DLC) and yttria-stabilized zirconia (YSZ) under an ethanol gas environment, motivated by the previous experiment of ultralow friction phenomenon (friction fade-out). We observe (i) dissociation of ethanol into ethoxy and hydrogen, both of which simultaneously adsorb on the YSZ surface, and (ii) dissociation of ethanol into ethyl and hydroxy, the former of which forms a bond with another ethanol molecule and the latter of which adsorbs on the DLC surface. Reaction (i) is enhanced by the sliding motion, but occurs even without it, while reaction (ii) only occurs during sliding with a sufficiently high load pressure. The potentials of mean force for the two reactions are also calculated combining the steered MD and Jarzynski equality. It is shown that the activation energies of reactions (i) and (ii) are significantly lowered by the YSZ and DLC surfaces, respectively, as compared to those in a vacuum. The resultant activation energy is higher for reaction (ii) than for reaction (i).

Background: We measured postoperative changes in cerebrospinal fluid (CSF) interleukin (IL)-6 levels in subarachnoid hemorrhage (SAH) due to aneurysm rupture and examined factors associated with outcomes and cerebral vasospasm. We used physiologic saline or artificial CSF as the intraoperative irrigation fluid and examined the differences., Methods: The participants were 16 men and 41 women who were transported to our facility for SAH and underwent surgical treatment during the period from February 2012 through March 2015. In terms of severity, 31 cases were World Federation of Neurological Surgeons (WFNS) grade I-III and 26 cases were grade IV-V. All cases underwent clipping. Physiologic saline and artificial CSF were used as intraoperative irrigation fluid. We placed a ventricular drainage tube intraoperatively and collected CSF daily from postoperative day (POD) 1 through 10 or until drain removal., Results: IL-6 level varied from 74 pg/mL to 407,936 pg/mL and peaked on PODs 1 and 5. Patients with favorable outcomes had significantly lower postoperative IL-6 levels. POD 1 IL-6 level significantly differed in relation to the presence of cerebral vasospasm but was not associated with its timing or severity. Use of artificial CSF was associated with a significantly lower incidence of cerebral vasospasm. Age and WFNS grade were significantly associated with outcome, and use of artificial CSF had a tendency toward favorable outcomes., Conclusions: Artificial CSF is a potentially useful intervention when managing subarachnoid hemorrhage.

Moyamoya disease (MMD) is a cerebrovascular disorder that is predominantly observed in women of East Asian descent, and is characterized by progressive stenosis of the internal carotid artery, beginning in early childhood, and a distinctive network of collateral vessels known as "moyamoya vessels" in the basal ganglia. Additionally, a prevalent genetic variant found in most MMD cases is the p.R4810K polymorphism of RNF213 on chromosome 17q25.3. Recent studies have revealed that RNF213 mutations are associated not only with MMD, but also with other systemic vascular disorders, including intracranial atherosclerosis and systemic vascular abnormalities such as pulmonary artery stenosis and coronary artery diseases. Therefore, the concept of "RNF213-related vasculopathy" has been proposed. This review focuses on polymorphisms in the RNF213 gene and describes a wide range of clinical and genetic phenotypes associated with RNF213-related vasculopathy. The RNF213 gene has been suggested to play an important role in the pathogenesis of vascular diseases and developing new therapies. Therefore, further research and knowledge sharing through collaboration between clinicians and researchers are required.

Sphingolipidoses are inherited metabolic disorders associated with glycosphingolipids accumulation, neurodegeneration, and neuroinflammation leading to severe neurological symptoms. Lysoglycosphingolipids (lysoGSLs), also known to accumulate in the tissues of sphingolipidosis patients, exhibit cytotoxicity. LysoGSLs are the possible pathogenic cause, but the mechanisms are still unknown in detail. Here, we first show that lysoGSLs are potential inhibitors of phosphoinositide 3-kinase (PI3K) to reduce cell survival signaling. We found that phosphorylated Akt was commonly reduced in fibroblasts from patients with sphingolipidoses, including GM1/GM2 gangliosidoses and Gaucher's disease, suggesting the contribution of lysoGSLs to the pathogenesis. LysoGSLs caused cell death and decreased the level of phosphorylated Akt as in the patient fibroblasts. Extracellularly administered lysoGM1 permeated the cell membrane to diffusely distribute in the cytoplasm. LysoGM1 and lysoGM2 also inhibited the production of phosphatidylinositol-(3,4,5)-triphosphate and the translocation of Akt from the cytoplasm to the plasma membrane. We also predicted that lysoGSLs could directly bind to the catalytic domain of PI3K by in silico docking study, suggesting that lysoGSLs could inhibit PI3K by directly interacting with PI3K in the cytoplasm. Furthermore, we revealed that the increment of lysoGSLs amounts in the brain of sphingolipidosis model mice correlated with the neurodegenerative progression. Our findings suggest that the down-regulation of PI3K/Akt signaling by direct interaction of lysoGSLs with PI3K in the brains is a neurodegenerative mechanism in sphingolipidoses. Moreover, we could propose the intracellular PI3K activation or inhibition of lysoGSLs biosynthesis as novel therapeutic approaches for sphingolipidoses because lysoGSLs should be cell death mediators by directly inhibiting PI3K, especially in neurons., (© 2023 International Society for Neurochemistry.)

The re-rupture of a subarachnoid hemorrhage(SAH)due to a ruptured cerebral aneurysm is a poor prognostic factor, and initial treatment to prevent re-rupture is important in the acute phase of SAH. Prevention of re-rupture is performed by reducing blood pressure, by sedation, and by analgesia until the patient undergoes radical surgery. It is recommended that the systolic blood pressure be lowered to below 120-140 mmHg. When SAH is suspected, a head CT scan should be obtained after the initial treatment. If the SAH is not clearly visible on CT but is strongly suspected, MRI should be performed. Once a SAH is diagnosed, three-dimensional CT angiography should be performed to search for cerebral aneurysms. SAHs may also cause breathing and circulation problems due to neurogenic pulmonary edema and Takotsubo cardiomyopathy. Clipping is more curative than coil embolization, but coil embolization has been shown to have better long-term survival and independence rates than clipping for aneurysms that can be treated with either technique. Ideally, ruptured cerebral aneurysms should be treated at institutions that offer both clipping and coil embolization, and the choice of treatment should be based on a comprehensive assessment of the patient's age; the severity, location, size and shape of the aneurysm; the clipping and coil embolization techniques of the treating physician; and the wishes of the patient and family.

Middle cerebral artery (MCA) dissection is rare, and various clinical presentations, including hemorrhage, ischemia, or comorbidities, and the changes in imaging findings over time hinder treatment decisions. The European Stroke Organization guidelines exclude MCA dissection. Few cases have been reported with no review of the relevant literature. Therefore, we reviewed the relevant literature and our own experience with non-traumatic MCA dissection cases to determine appropriate treatment strategies. At our institution and affiliated institutions, we encountered six cases of MCA dissection-five with infarction and one with hemorrhage. Two patients underwent revascularization, and one underwent an aneurysmectomy. We reviewed English and Japanese articles in PubMed and Medical Journal Web and summarized the results based on the relationships among age, sex, location, the presence of an aneurysm, the presence of angiography, history, treatment, and mode of onset. The clinical course, changes in imaging, treatment strategies, and prognosis were discussed. Eighty cases were included in the review. Cerebral aneurysms were more common distal to the M2 area (p = 0.00) and were correlated with hemorrhage (p < 0.001). Most hemorrhagic cases with aneurysms were treated surgically, while ischemic cases were treated with antithrombotic agents, and both had a similar neurological prognosis. There were some cases of rebleeding after antithrombotic therapy, especially in older adults.Surgical treatment is recommended in cases of hemorrhage and confirmed aneurysms, particularly for lesions distal to the M2 area. Patients with aneurysm-associated ischemia should be followed up, and antithrombotic treatment should be considered with particular care in older adults., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is reportedly associated with air leak syndrome (ALS), including mediastinal emphysema and pneumothorax, and has a high mortality rate. In this study, we compared values obtained every minute from ventilators to clarify the relationship between ventilator management and risk of developing ALS., Methods: This single-center, retrospective, observational study was conducted at a tertiary care hospital in Tokyo, Japan, over a 21-month period. Information on patient background, ventilator data, and outcomes was collected from adult patients with SARS-CoV-2 pneumonia on ventilator management. Patients who developed ALS within 30 days of ventilator management initiation (ALS group) were compared with those who did not (non-ALS group)., Results: Of the 105 patients, 14 (13%) developed ALS. The median positive-end expiratory pressure (PEEP) difference was 0.20 cmH 2 O (95% confidence interval [CI], 0.20-0.20) and it was higher in the ALS group than in the non-ALS group (9.6 [7.8-20.2] vs. 9.3 [7.3-10.2], respectively). For peak pressure, the median difference was -0.30 cmH 2 O (95% CI, -0.30 - -0.20) (20.4 [17.0-24.4] in the ALS group vs. 20.9 [16.7-24.6] in the non-ALS group). The mean pressure difference of 0.0 cmH 2 O (95% CI, 0.0-0.0) (12.7 [10.9-14.6] vs. 13.0 [10.3-15.0], respectively) was also higher in the non-ALS group than in the ALS group. The difference in single ventilation volume per ideal body weight was 0.71 mL/kg (95% CI, 0.70-0.72) (8.17 [6.79-9.54] vs. 7.43 [6.03-8.81], respectively), and the difference in dynamic lung compliance was 8.27 mL/cmH 2 O (95% CI, 12.76-21.95) (43.8 [28.2-68.8] vs. 35.7 [26.5-41.5], respectively); both were higher in the ALS group than in the non-ALS group., Conclusions: There was no association between higher ventilator pressures and the development of ALS. The ALS group had higher dynamic lung compliance and tidal volumes than the non-ALS group, which may indicate a pulmonary contribution to ALS. Ventilator management that limits tidal volume may prevent ALS development., (© 2023. The Author(s).)

Background: The effect of posterior cranial fossa stroke on changes in cerebral volume is not known. We assessed cerebral volume changes in patients with acute posterior fossa stroke using CT scans, and looked for risk factors for cerebral atrophy., Methods: Patients with cerebellar or brainstem hemorrhage/infarction admitted to the ICU, and who underwent at least two subsequent inpatient head CT scans during hospitalization were included (n = 60). The cerebral volume was estimated using an automatic segmentation method. Patients with cerebral volume reduction > 0% from the first to the last scan were defined as the "cerebral atrophy group (n = 47)," and those with ≤ 0% were defined as the "no cerebral atrophy group (n = 13).", Results: The cerebral atrophy group showed a significant decrease in cerebral volume (first CT scan: 0.974 ± 0.109 L vs. last CT scan: 0.927 ± 0.104 L, P < 0.001). The mean percentage change in cerebral volume between CT scans in the cerebral atrophy group was -4.7%, equivalent to a cerebral volume of 46.8 cm 3 , over a median of 17 days. The proportions of cases with a history of hypertension, diabetes mellitus, and median time on mechanical ventilation were significantly higher in the cerebral atrophy group than in the no cerebral atrophy group., Conclusions: Many ICU patients with posterior cranial fossa stroke showed signs of cerebral atrophy. Those with rapidly progressive cerebral atrophy were more likely to have a history of hypertension or diabetes mellitus and required prolonged ventilation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Both coronavirus disease 2019 (COVID-19) and heat stroke have symptoms of fever or hyperthermia and the difficulty in distinguishing them could lead to a strain on emergency medical care. To mitigate the potential confusion that could arise from actions for preventing both COVID-19 spread and heat stroke, particularly in the context of record-breaking summer season temperatures, this work offers new knowledge and evidence that address concerns regarding indoor ventilation and indoor temperatures, mask wearing and heat stroke risk, and the isolation of older adults. Specifically, the current work is the second edition to the previously published guidance for handling heat stroke during the COVID-19 pandemic, prepared by the "Working group on heat stroke medical care during the COVID-19 epidemic," composed of members from four organizations in different medical and related fields. The group was established by the Japanese Association for Acute Medicine Heatstroke and Hypothermia Surveillance Committee. This second edition includes new knowledge, and conventional evidence gleaned from a primary selection of 60 articles from MEDLINE, one article from Cochrane, 13 articles from Ichushi, and a secondary/final selection of 56 articles. This work summarizes the contents that have been clarified in the prevention and treatment of infectious diseases and heat stroke to provide guidance for the prevention, diagnosis, and treatment of heat stroke during the COVID-19 pandemic., (© 2023 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Coagulation function differs by gender, with women being characterized as more hypercoagulable. Even in the early stages of trauma, women have been shown to be hypercoagulable. Several studies have also examined the relationship between gender and the prognosis of trauma patients, but no certain conclusions have been reached. Patients with isolated traumatic brain injury (iTBI) are known to have coagulopathy, but no previous studies have examined the gender differences in detail. This is a retrospective analysis of a prospective registry conducted at 2 centers. The study included adult patients with iTBI enrolled from April 2018 to March 2021. Coagulofibrinolytic markers were measured in each patient at 1 hour, 24 hours, 3 days, and 7 days after injury, and neurological outcomes were assessed with the Glasgow Outcome Scale Extended at 6 months. Subgroup analysis was also performed by categorizing patients into groups according to neurological prognosis or age at 50 years. Males (n = 31) and females (n = 21) were included in the analysis. In males, there was a significant difference in the levels of activated partial thromboplastin time (P = .007), fibrin/fibrinogen degradation products (P = .025), D-dimer (P = .034), α2-plasmin inhibitor (P = .030), plasmin-α2-plasmin inhibitor complex (P = .004) at 1 hour after injury between favorable and unfavorable long-term neurological outcome groups, while in females there was no significant difference in these markers between 2 groups. In the age group under 50 years, there were significant gender differences in fibrinogen (day 3: P = .018), fibrin/fibrinogen degradation products (1 hour: P = .037, day 3: P = .009, day 7: P = .037), D-dimer (day 3: P = .005, day 7: P = .010), plasminogen (day 3: P = .032, day 7: P = .032), and plasmin-α2-plasmin inhibitor complex (day 3: P = .001, day 7: P = .001), and these differences were not evident in the age group over 50 years. There were differences in coagulofibrinolytic markers depending on gender in patients with iTBI. In male patients, aggravation of coagulofibrinolytic markers immediately after traumatic brain injury may be associated with poor neurologic outcome 6 months after injury., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rupture of a racemose hemangioma causing dilatation and tortuosity of the bronchial artery can result in massive bleeding and respiratory failure. Bronchial artery embolization (BAE) can treat this life-threatening condition, as we show in two cases. The first case was of an 89-year-old female complaining of sudden-onset chest and back pain. Bronchial artery angiography demonstrated a racemose hemangioma with a 2 cm aneurysm. The second case was of a 50-year-old male with hemoptysis and dyspnea, eventually requiring intubation. Bronchial arteriography showed a racemose hemangioma and a bronchial artery-pulmonary arterial fistula. BAE was successfully performed in both cases, with no recurrent hemorrhage. Therapeutic interventions in bronchial artery racemose hemangiomas include lobectomy or segmentectomy, bronchial arterial ligation, and BAE. BAE should be considered as first-line therapy for bleeding racemose hemangiomas of the bronchial artery because of its low risk of adverse effects on respiratory status, minimal invasiveness, and faster patient recovery.

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.

Traumatic brain injury (TBI) is associated with coagulation/fibrinolysis disorders. We retrospectively evaluated 61 TBI cases transported to hospital within 1 h post-injury. Levels of thrombin-antithrombin III complex (TAT), D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were measured on arrival and 3 h, 6 h, 12 h, 1 day, 3 days and 7 days after injury. Multivariate logistic regression analysis was performed to identify prognostic factors for coagulation and fibrinolysis. Plasma TAT levels peaked at admission and decreased until 1 day after injury. Plasma D-dimer levels increased, peaking up to 3 h after injury, and decreasing up to 3 days after injury. Plasma PAI-1 levels increased up to 3 h after injury, the upward trend continuing until 6 h after injury, followed by a decrease until 3 days after injury. TAT, D-dimer, and PAI-1 were elevated in the acute phase of TBI in cases with poor outcome. Multivariate logistic regression analysis showed that D-dimer elevation from admission to 3 h after injury and PAI-1 elevation from 6 h to 1 day after injury were significant negative prognostic indicators. Post-TBI hypercoagulation, fibrinolysis, and fibrinolysis shutdown were activated consecutively. Hyperfibrinolysis immediately after injury and subsequent fibrinolysis shutdown were associated with poor outcome., (© 2022. The Author(s).)

Lysosomal storage disorders (LSDs) are inherited metabolic diseases caused by genetic defects in lysosomal enzymes or related factors. LSDs are associated with excessive accumulation of natural substrates in lysosomes leading to central nervous system and peripheral tissue damage. Abnormal autophagy is also involved in pathogenesis, although the underlying mechanisms remain unclear. We demonstrated that impairment of lysosome-autophagosome fusion is due to suppressed endocytosis in LSDs. The fusion was reduced in several LSD cells and the brains of LSD model mice, suggesting that the completion of autophagy is suppressed by the accumulation of substrates. In this brain, the expression of the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins, VAMP8 and Syntaxin7, was decreased on the lysosomal surface but not intracellular. This aberrant autophagy preceded the development of pathological phenotypes in LSD-model mice. Furthermore, the enzyme deficiency leading to the substrate accumulation could suppress endocytosis, and the inhibited endocytosis decreased SNARE proteins localized on lysosomes. These findings suggest that the shortage of SNARE proteins on lysosomes is one of the reasons for the impairment of lysosome-autophagosome fusion in LSD cells. Defects in lysosomal enzyme activity suppress endocytosis and decrease the supply of intracellular SNARE proteins recruited to lysosomes. This shortage of lysosomal SNARE proteins impairs lysosome-autophagosome fusion in lysosomal storage disorders., (© 2022 SSIEM.)

Aim: During the coronavirus disease 2019 pandemic, the number of traffic accidents and injured patients was reported to be lower than that before the pandemic. However, little is known regarding the relationship between periods of the state of emergency and the number of patients who met with traffic accidents., Methods: The numbers of trauma patients and deaths due to traffic accidents in Tokyo and Osaka were collected monthly from the statistics published by the police department. A state of emergency was declared four times in both cities. The number of trauma patients and deaths was compared between the emergency and other periods., Results: The number of monthly patients per 100,000 due to traffic accidents during the state of emergency was significantly lower than that during other periods in Tokyo (16.56 versus 18.20; P  = 0.008) and Osaka (24.12 versus 28.79; P  = 0.002). However, the monthly number of deaths during the state of emergency was not significantly different compared with those during the other periods in Tokyo (0.08 versus 0.08; P  = 0.65) and Osaka (0.10 versus 0.14; P  = 0.082). A decrease in the number of trauma patients was observed before the emergency period; however, the reduction rate dropped as the period passed., Conclusion: There were significantly fewer trauma patients due to traffic accidents during the state of emergency than during the other periods, with no significant difference in the number of deaths., (© 2022 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Coagulopathy management is an important strategy for preventing secondary brain damage in patients with traumatic brain injury (TBI). Antithrombin (AT) is a natural anticoagulant that controls coagulation and inflammation pathways. However, the significance of AT activity levels for outcomes in patients with trauma remains unclear. This study aimed to investigate the relationship between AT activity levels and long-term outcomes in patients with TBI; this was a sub-analysis of a prior study that collected blood samples of trauma patients prospectively in a tertiary care center in Kawaguchi City, Japan. We included patients with isolated TBI (iTBI) aged ≥16 years admitted directly to our hospital within 1 h after injury between April 2018 and March 2021. General coagulofibrinolytic and specific molecular biomarkers, including AT, were measured at 1, 3, 6, 12, and 24 h after injury. We analyzed changes in the AT activity levels during the study period and the impact of the AT activity levels on long-term outcomes, the Glasgow Outcome Scale-Extended (GOSE), 6 months after injury. 49 patients were included in this study; 24 had good neurological outcomes (GOSE 6-8), and 25 had poor neurological outcomes (GOSE 1-5). Low AT activity levels were shown within 1 h after injury in patients in the poor GOSE group; this was associated with poor outcomes. Furthermore, AT activity levels 1 h after injury had a strong predictive value for long-term outcomes (area under the receiver operating characteristic curve of 0.871; 95% CI: 0.747-0.994). Multivariate logistic regression analysis with various biomarkers showed that AT was an independent factor of long-term outcome (adjusted odds ratio: 0.873; 95% CI: 0.765-0.996; p=0.043). Another multivariate analysis with severity scores showed that low AT activity levels were associated with poor outcomes (adjusted odds ratio: 0.909; 95% CI: 0.822-1.010; p=0.063). We demonstrated that the AT activity level soon after injury could be a predictor of long-term neurological prognosis in patients with iTBI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Takahashi, Wada, Nakae, Fujiki, Kanaya, Takayama, Suzuki, Naoe and Yokobori.)

Coagulopathy is a common sequela of traumatic brain injury. Consumptive coagulopathy and secondary hyperfibrinolysis are associated with hypercoagulability. In addition, fibrinolytic pathways are hyperactivated as a result of vascular endothelial cell damage in the injured brain. Coagulation and fibrinolytic parameters change dynamically to reflect these pathologies. Fibrinogen is consumed and degraded after injury, with fibrinogen concentrations at their lowest 3-6 h after injury. Hypercoagulability causes increased fibrinolytic activity, and plasma levels of D-dimer increase immediately after traumatic brain injury, reaching a maximum at 3 h. Owing to disseminated intravascular coagulation in the presence of fibrinolysis, the bleeding tendency is highest within the first 3 h after injury, and often a condition called "talk and deteriorate" occurs. In neurointensive care, it is necessary to measure coagulation and fibrinolytic parameters such as fibrinogen and D-dimer routinely to predict and prevent the development of coagulopathy and its negative outcomes. Currently, the only evidence-based treatment for traumatic brain injury with coagulopathy is tranexamic acid in the subset of patients with mild-to-moderate traumatic brain injury. Coagulation and fibrinolytic parameters should be closely monitored, and treatment should be considered on a patient-by-patient basis.

Objective: We conducted a systematic review to determine the prevalence and characteristics of earthquake-associated head injuries for better disaster preparedness and management., Methods: We searched for all publications related to head injuries and earthquakes from 1985 to 2018 in MEDLINE and other major databases. A search was conducted using "earthquakes," "wounds and injuries," and "cranio-cerebral trauma" as a medical subject headings., Results: Included in the analysis were 34 articles. With regard to the commonly occurring injuries, earthquake-related head injury ranks third among patients with earthquake-related injuries. The most common trauma is lower extremity (36.2%) followed by upper extremity (19.9%), head (16.6%), spine (13.1%), chest (11.3%), and abdomen (3.8%). The most common earthquake-related head injury was laceration or contusion (59.1%), while epidural hematoma was the most common among inpatients with intracranial hemorrhage (9.5%) followed by intracerebral hematoma (7.0%), and subdural hematoma (6.8%). Mortality rate was 5.6%., Conclusion: Head injuries were found to be a commonly occurring trauma along with extremity injuries. This knowledge is important for determining the demands for neurosurgery and for adequately managing patients, especially in resource-limited conditions.

Background: Maintaining the patency of extracranial-to-intracranial (EC-IC) bypass is critical for long-term stroke prevention. However, reports on the factors influencing long-term bypass patency and quantitative assessments of bypass patency are limited., Objective: To quantitatively evaluate blood flow in EC-IC bypass using four-dimensional (4D) flow magnetic resonance imaging (MRI) and investigate factors influencing the long-term patency of EC-IC bypass., Methods: Thirty-six adult Japanese patients who underwent EC-IC bypass for symptomatic internal carotid or middle cerebral artery occlusive disease were included. We examined the relationships between decreased superficial temporal artery (STA) blood flow volume and perioperative complications, long-term ischemic complications, patient background, and postoperative antithrombotic medications in patients for whom STA flow could be quantitatively assessed for at least 5 months using 4D flow MRI., Results: The mean follow-up time was 54.7 ± 6.1 months. One patient presented with a stroke during the acute postoperative period that affected postoperative outcomes. No recurrent strokes were recorded during long-term follow-up. Two patients died of malignant disease. Seven cases of reduced flow occurred in the STA, which were correlated with single bypass (P = .0294) and nonuse of cilostazol (P = .0294). STA occlusion was observed in 1 patient during the follow-up period. Hypertension, age, smoking, dyslipidemia, and diabetes mellitus were not correlated with reduced blood flow in the STA., Conclusion: Double anastomoses and cilostazol resulted in long-term STA blood flow preservation. No recurrence of cerebral infarction was noted in either STA hypoperfusion or occlusion cases., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

The present study created an artificial intelligence (AI)-automated diagnostics system for uterine cervical lesions and assessed the performance of these images for AI diagnostic imaging of pathological cervical lesions. A total of 463 colposcopic images were analyzed. The traditional colposcopy diagnoses were compared to those obtained by AI image diagnosis. Next, 100 images were presented to a panel of 32 gynecologists who independently examined each image in a blinded fashion and diagnosed them for four categories of tumors. Then, the 32 gynecologists revisited their diagnosis for each image after being informed of the AI diagnosis. The present study assessed any changes in physician diagnosis and the accuracy of AI-image-assisted diagnosis (AISD). The accuracy of AI was 57.8% for normal, 35.4% for cervical intraepithelial neoplasia (CIN)1, 40.5% for CIN2-3 and 44.2% for invasive cancer. The accuracy of gynecologist diagnoses from cervical pathological images, before knowing the AI image diagnosis, was 54.4% for CIN2-3 and 38.9% for invasive cancer. After learning of the AISD, their accuracy improved to 58.0% for CIN2-3 and 48.5% for invasive cancer. AI-assisted image diagnosis was able to improve gynecologist diagnosis accuracy significantly (P<0.01) for invasive cancer and tended to improve their accuracy for CIN2-3 (P=0.14)., Competing Interests: The present study was a cooperative research project with Kyocera Corporation., (Copyright © 2020, Spandidos Publications.)

Background: Sepsis is often associated with multiple organ failure; however, changes in brain volume with sepsis are not well understood. We assessed brain atrophy in the acute phase of sepsis using brain computed tomography (CT) scans, and their findings' relationship to risk factors and outcomes., Methods: Patients with sepsis admitted to an intensive care unit (ICU) and who underwent at least two head CT scans during hospitalization were included (n = 48). The first brain CT scan was routinely performed on admission, and the second and further brain CT scans were obtained whenever prolonged disturbance of consciousness or abnormal neurological findings were observed. Brain volume was estimated using an automatic segmentation method and any changes in brain volume between the two scans were recorded. Patients with a brain volume change < 0% from the first CT scan to the second CT scan were defined as the "brain atrophy group (n = 42)", and those with ≥ 0% were defined as the "no brain atrophy group (n = 6)." Use and duration of mechanical ventilation, length of ICU stay, length of hospital stay, and mortality were compared between the groups., Results: Analysis of all 42 cases in the brain atrophy group showed a significant decrease in brain volume (first CT scan: 1.041 ± 0.123 L vs. second CT scan: 1.002 ± 0.121 L, t (41) = 9.436, p < 0.001). The mean percentage change in brain volume between CT scans in the brain atrophy group was -3.7% over a median of 31 days, which is equivalent to a brain volume of 38.5 cm 3 . The proportion of cases on mechanical ventilation (95.2% vs. 66.7%; p = 0.02) and median time on mechanical ventilation (28 [IQR 15-57] days vs. 15 [IQR 0-25] days, p = 0.04) were significantly higher in the brain atrophy group than in the no brain atrophy group., Conclusions: Many ICU patients with severe sepsis who developed prolonged mental status changes and neurological sequelae showed signs of brain atrophy. Patients with rapidly progressive brain atrophy were more likely to have required mechanical ventilation., (© 2021. The Author(s).)

The ring finger protein 213 (RNF213) susceptibility gene has been detected in more than 80% of Japanese and Korean patients with moyamoya disease (MMD), a bilateral internal carotid artery (ICA) occlusion. Furthermore, RNF213 has been detected in more than 20% of East Asians with atherosclerotic ICA stenosis. In this study, we evaluated the frequency of RNF213 mutations in congenital occlusive lesions of the ICA system. This case series was conducted jointly at four university hospitals. Patients with a family history of MMD, quasi-MMD, or related diseases were excluded. Ten patients were diagnosed with abnormal ICA or middle cerebral artery (MCA) angiogenesis. Patients with neurofibromatosis were excluded. Finally, nine patients with congenital vascular abnormalities were selected; of these, five had ICA deficiency and four had twig-like MCA. The RNF213 c.14576G > A mutation was absent in all patients. Therefore, the RNF213 c.14576G > A mutation may not be associated with ICA and MCA congenital dysplasia-rare vascular anomalies making it difficult to study a large number of cases. However, an accumulation of cases is required for accurate determination. The results of this study may help differentiate congenital vascular diseases from MMD., (© 2021. The Author(s).)

A mutation in RNF213 (c.14576G>A), a gene associated with moyamoya disease (>80%), plays a role in terminal internal carotid artery (ICA) stenosis (>15%) (ICS). Studies on RNF213 and cerebral aneurysms (AN), which did not focus on the site of origin or morphology, could not elucidate the relationship between the two. However, a report suggested a relationship between RNF213 and AN in French-Canadians. Here, we investigated the relationship between ICA saccular aneurysm (ICA-AN) and RNF213 . We analyzed RNF213 expression in subjects with ICA-AN and atherosclerotic ICS. Cases with a family history of moyamoya disease were excluded. AN smaller than 4 mm were confirmed as AN only by surgical or angiographic findings. RNF213 was detected in 12.2% of patients with ICA-AN and 13.6% of patients with ICS; patients with ICA-AN and ICS had a similar risk of RNF213 mutation expression (odds ratio, 0.884; 95% confidence interval, 0.199-3.91; p = 0.871). The relationship between ICA-AN and RNF213 (c.14576G>A) was not correlated with the location of the ICA and bifurcation, presence of rupture, or multiplicity. When the etiology and location of AN were more restricted, the incidence of RNF213 mutations in ICA-AN was higher than that reported in previous studies. Our results suggest that strict maternal vessel selection and pathological selection of AN morphology may reveal an association between genetic mutations and ICA-AN development. The results of this study may form a basis for further research on systemic vascular diseases, in which the RNF213 (c.14576G>A) mutation has been implicated.

This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody-drug conjugate (CD70-ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock- or nuclear factor (NF)-κB-p65-small interfering RNA. We developed an ADC with an anti-CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P < .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780-NF-κB-p65-silenced cells. CD70-ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC 50 values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70-ADC treated mice was significantly inhibited compared to that in the control-ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm 3 , P < .01; SKOV3cisR: 232.2 vs 584.9 mm 3 , P < .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: To examine the relationship between trap location and cerebral infarction in the anterior choroidal artery (AChA) region and associated risks in ruptured internal carotid artery blood blister-like aneurysm (BLA) treatment with high-flow bypass and lesion trapping., Methods: We included 26 patients diagnosed with BLAs and treated with high-flow bypass and trapping. We examined clinical characteristics including age, aneurysm trap location, final prognosis, cerebral infarction on postoperative magnetic resonance imaging, and modified Rankin Scale score at discharge. We also searched the literature for similar studies., Results: The modified Rankin Scale score at discharge was 0-2 in 20 patients, 3-5 in 2 patients, and 6 in 2 patients. In 19/26 patients (73.1%), the trapped segment was between the posterior communicating (PcomA) and the ophthalmic arteries. In 2 patients (7.7%), the trapped segment included the PcomA and the AChA; in 4 patients (15.4%), the trapped segment was within the PcomA. In these patients, the PcomA was occluded, and blood from the high-flow bypass flowed out to the AChA alone. No patient showed cerebral infarction. Our systematic review identified 70 patients. Of all 96 patients, 12 had AChA cerebral infarction; however, the infarction affected the prognosis of only 2 patients., Conclusions: When treating BLAs with high-flow bypass and lesion trapping, the frequency of AChA cerebral infarction is low even when the PcomA is occluded, leaving the AChA as the only outflow vessel during high-flow bypass. However, PcomA occlusion may be associated with risks when treating patients with advanced arteriosclerosis near C1-2., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Traumatic brain injury(TBI)is associated with coagulation and fibrinolytic disorder. It is characterized by consumptive coagulopathy and secondary hyperfibrinolysis associated with hypercoagulability and by hyperfibrinolysis due to the release of tissue plasminogen activator from the injured brain. Thrombin antithrombin III complex, a coagulation parameter, is abnormally high immediately after TBI and declines 6 hours after TBI. Fibrinogen, a coagulation factor, is rapidly consumed and degraded within 3 hours of TBI. D-dimer, a fibrinolytic parameter, is abnormally high on arrival at the hospital and reaches its maximum value 3 hours after TBI; during this time, bleeding tendency increases. Plasminogen activator inhibitor-1, a parameter of fibrinolysis shutdown, peaks at 6 hours after TBI. D-dimer is also known to be a prognostic factor. Patients with a high D-dimer level despite a good level of consciousness on admission are more likely to be "talk and deteriorate." Administration of tranexamic acid, an anti-fibrinolytic agent, early in the acute phase of TBI may reduce mortality. Fresh frozen plasma transfusion should be performed within 3 hours of TBI with monitoring of fibrinogen levels, and the administration dose should be set with a target fibrinogen level of ≧ 150 mg/dL. However, excessive administration should also be avoided. Thus, in the acute phase of TBI, coagulation and fibrinolytic activity changes dynamically and may adversely affect the complicated injury; therefore, monitoring coagulation and fibrinolytic parameters while conducting treatment is recommended.

Objective: Coagulopathy is a well-recognized risk factor for poor outcomes in patients with traumatic brain injury (TBI). Differences in the time courses of coagulation and fibrinolytic parameters between pediatric and adult patients with TBI have not been defined., Methods: Patients with TBI and an Abbreviated Injury Scale of the head score ≥ 3, in whom the prothrombin time (PT)-international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen concentration, and plasma D-dimer levels were measured on arrival and at 3, 6, and 12 hours after injury, were retrospectively analyzed. Propensity score-matched analyses were performed to adjust baseline characteristics between pediatric patients (aged < 16 years) and adult patients (aged ≥ 16 years)., Results: A total of 468 patients (46 children and 422 adults) were included. Propensity score matching resulted in a matched cohort of 46 pairs. Higher PT-INR and APTT values at 1 to 12 hours after injury and lower fibrinogen concentrations at 1 to 6 hours after injury were observed in the pediatric group compared with the adult group. Plasma levels of D-dimer were elevated in both groups at 1 to 12 hours after injury, but no significant differences were seen between the groups. Multivariate logistic regression analysis of the initial coagulation and fibrinolytic parameters in the pediatric group revealed no prognostic significance of the coagulation parameter values, but elevation of the fibrinolytic parameter D-dimer was an independent negative prognostic factor., Conclusions: In the acute phase of TBI, pediatric patients were characterized by prolongation of PT-INR and APTT and lower fibrinogen concentrations compared with adult patients, but these did not correlate with outcome. D-dimer was an independent prognostic outcome factor in terms of the Glasgow Outcome Scale in pediatric patients with TBI.

Background: Because of the aging of the Japanese population, traumatic brain injuries (TBI) have increased in elderly adults. However, the effectiveness and prognosis of intensive treatment for geriatric TBI have not yet been determined. Thus, we used nationwide data from the Japan Neurotrauma Data Bank (JNTDB) projects to analyze prognostic factors for intensive and aggressive treatments., Methods: We analyzed 1,879 geriatric TBI cases (age ≥65 years) registered in four JNTDB projects: Project 1998 (P1998) to Project 2015 (P2015). Clinical features, use of aggressive treatment, and 6-month outcomes on the Glasgow Outcome Scale (GOS) were compared among study projects. Logistic regression was used to identify prognostic factors in aggressively treated patients., Results: The percentage of geriatric TBI cases significantly increased with time-P1998: 30.1%; Project 2004 (P2004): 34.6%; Project 2009 (P2009): 43.9%; P2015: 53.6%, p<0.0001). Use of aggressive treatment also significantly increased, from 67.0% in P1998 to 69.3% in P2015 (p<0.0001). Less invasive methods, such as trepanation and normothermic targeted temperature management, were more often chosen for geriatric patients. These efforts resulted in a significant decrease in the 6-month mortality rate, from 76.2% in P1998 to 63.1% in P2015 (p=0.0003), although the percentage of severely disabled patients increased, from 8.9% in P1998 to 11.1% in P2015 (p=0.0003). Intraventricular hemorrhage was the factor most strongly associated with unfavorable 6-month outcomes (OR 3.79, 95% CI 1.78-8.06, p<0.0001)., Conclusions: Less invasive treatments reduced mortality in geriatric TBI but did not improve functional outcomes. Patient age was not the strongest prognostic factor; thus, physicians should consider characteristics other than age.

Background: Coronavirus disease 2019 (COVID-19) and heat-related illness are systemic febrile diseases. These illnesses must be differentiated during a COVID-19 pandemic in summer. However, no studies have compared and distinguished heat-related illness and COVID-19. We compared data from patients with early heat-related illness and those with COVID-19., Methods: This retrospective observational study included 90 patients with early heat-related illness selected from the Heatstroke STUDY 2017-2019 (nationwide registries of heat-related illness in Japan) and 86 patients with laboratory-confirmed COVID-19 who had fever or fatigue and were admitted to one of two hospitals in Tokyo, Japan., Results: Among vital signs, systolic blood pressure (119 vs. 125 mm Hg, p = 0.02), oxygen saturation (98% vs. 97%, p < 0.001), and body temperature (36.6°C vs. 37.6°C, p<0.001) showed significant between-group differences in the heatstroke and COVID-19 groups, respectively. The numerous intergroup differences in laboratory findings included disparities in white blood cell count (10.8 × 10 3 /μL vs. 5.2 × 10 3 /μL, p<0.001), creatinine (2.2 vs. 0.85 mg/dL, p<0.001), and C-reactive protein (0.2 vs. 2.8 mg/dL, p<0.001), although a logistic regression model achieved an area under the curve (AUC) of 0.966 using these three factors. A Random Forest machine learning model achieved an accuracy, precision, recall, and AUC of 0.908, 0.976, 0.842, and 0.978, respectively. Creatinine was the most important feature of this model., Conclusions: Acute kidney injury was associated with heat-related illness, which could be essential in distinguishing or evaluating patients with fever in the summer during a COVID-19 pandemic.

Background: Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy originating in the myometrium of the uterine corpus that tends to recur even after complete surgical excision. Current therapeutic agents have only modest effects on uterine leiomyosarcoma. Although antibodies and antibody-drug conjugates have been recognized as useful targeted therapies for other cancers, no study has yet evaluated the effects of this approach on uterine leiomyosarcoma., Objective: This study aimed to examine the activity of tumoral CD70 in uterine leiomyosarcoma and assess the antitumor activity of CD70-antibody-drug conjugate treatment in uterine leiomyosarcoma., Study Design: Target membrane proteins were screened by profiling and comparing membrane protein expression in 3 uterine leiomyosarcoma cell lines (SK-UT-1, SK-LMS-1, and SKN) and normal uterine myometrium cells using the isobaric tags for relative and absolute quantitation labeling method. Western blotting, fluorescence-activated cell sorting analyses, and immunohistochemistry were used to examine CD70 expression in the membrane proteins in uterine leiomyosarcoma cell lines and clinical samples. We developed an antibody-drug conjugate with a monoclonal antibody of the target membrane protein linked to monomethyl auristatin F and investigated its antitumor effects against uterine leiomyosarcoma (in vitro, in vivo, and in patient-derived xenograft models)., Results: CD70 was identified as a specific antigen highly expressed in uterine leiomyosarcoma cell lines. Of the 3 uterine leiomyosarcoma cell lines, CD70 expression was confirmed in SK-LMS-1 cells by western blotting and fluorescence-activated cell sorting analysis. CD70 overexpression was observed in 19 of 21 (90.5%) tumor specimens from women with uterine leiomyosarcoma. To generate CD70-antibody-drug conjugate, anti-CD70 monoclonal antibody was conjugated with a novel derivative of monomethyl auristatin F. CD70-antibody-drug conjugate showed significant antitumor effects on SK-LMS-1 cells (half maximal inhibitory concentration, 0.120 nM) and no antitumor effects on CD70-negative uterine leiomyosarcoma cells. CD70-antibody-drug conjugate significantly inhibited tumor growth in the SK-LMS-1 xenograft mouse model (tumor volume, 129.8 vs 285.5 mm 3 ; relative reduction, 54.5%; P<.001) and patient-derived xenograft mouse model (tumor volume, 128.1 vs 837.7 mm 3 ; relative reduction, 84.7%; P<.001)., Conclusion: Uterine leiomyosarcoma tumors highly express CD70 and targeted therapy with CD70-antibody-drug conjugate may have a potential therapeutic implication in the treatment of uterine leiomyosarcoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

High mobility group AT-hook 2 (HMGA2) is a non-histone transcriptional regulator protein. Aberrant expression of the HMGA2 gene (HMGA2) and structural rearrangement at the chromosomal region 12q14 with HMGA2 involvement have been reported in several mesenchymal tumors. We analyzed truncated and full-length HMGA2 expression in 55 cases of meningioma, the most common brain tumor of mesenchymal origin. Fluorescence in situ hybridization and 3'-rapid amplification of cDNA ends were used to investigate the possibility of gene rearrangements. Moreover, the relationship between HMGA2 expression and clinicopathological features was assessed. Compared with normal brain tissues, 95% of the meningioma tissues exhibited increased HMGA2 expression. In 14 cases, the expression of truncated HMGA2 was more than two-fold higher than that of paired full-length HMGA2. Chromosomal translocation involving the chromosomal region 12q14 was undetectable. No significant correlation was found between the Ki-67 labeling index and HMGA2 expression and between the HMGA2 expression and the clinicopathological features. The majority of the meningioma cases displayed increased HMGA2 expression, which was not attributed to the chromosomal rearrangement at the corresponding region. Similar to that in the other mesenchymal tumors, increased HMGA2 expression was not associated with tumor cell proliferation in meningiomas., (© 2020 Japanese Society of Neuropathology.)

Aim: Assessment of brainstem function plays a key role in predicting the neurological outcome after cardiac arrest. However, the relationship of the two quantitative brainstem assessment methods-automated infrared pupillometry (AIP) and auditory brainstem response (ABR)-with neurological prognoses remains unclear. This study compares the prognostic value of AIP and ABR after cardiopulmonary arrest., Methods: This retrospective observational study included 124 comatose patients after cardiopulmonary arrest. ABR and AIP measurements were performed simultaneously within 72 h after return of spontaneous circulation. Neurological outcome was assessed at discharge by estimating the cerebral performance category (CPC) score; favourable neurological outcome (CPC score, 1-2) or poor neurological outcome (CPC score, 3-5). The correlation of each AIP parameter and ABR I-V wave latency was tested using Pearson's product moment correlation coefficient, and the prognostic value was compared using the area under the receiver operating characteristics curve (AUC)., Results: Pupillary light reflex (PLR) was not detected in 69 patients, and ABR wave V was not detected in 47 patients. All these patients had poor neurological outcome. Among those whose PLR and ABR could be measured, each AIP parameter had a tendency to be correlated with ABR I-V wave latency. Pupil constriction velocity provided the greatest AUC (0.819), with 81% sensitivity and 77% specificity. ABR I-V wave latency provided extremely low AUC (0.560)., Conclusions: Although AIP and ABR were correlated, the AIP measures were superior in predicting the neurological outcome after cardiac arrest as compared with the ABR measures., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Coagulopathy and older age are common and well-recognized risk factors for poorer outcomes in traumatic brain injury (TBI) patients; however, the relationships between coagulopathy and age remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more pronounced in older patients and may be a factor in poorer outcomes. We retrospectively evaluated severe TBI cases in which fibrinogen and D-dimer were measured on arrival and 3-6 h after injury. Propensity score-matched analyses were performed to adjust baseline characteristics between older patients (the "elderly group," aged ≥75 y) and younger patients (the "non-elderly group," aged 16-74 y). A total of 1294 cases (elderly group: 395, non-elderly group: 899) were assessed, and propensity score matching created a matched cohort of 324 pairs. Fibrinogen on admission, the degree of reduction in fibrinogen between admission and 3-6 h post-injury, and D-dimer levels between admission and 3-6 h post-injury were significantly more abnormal in the elderly group than in the non-elderly group. On multivariate logistic regression analysis, independent risk factors for poor prognosis included low fibrinogen and high D-dimer levels on admission. Posttraumatic coagulation and fibrinolytic abnormalities are more severe in older patients, and fibrinogen and D-dimer abnormalities are negative predictive factors.

Introduction: The HPV vaccination rate in Japan has been dismally low. Our previous survey work found that mothers in Japan, who have a strong influence over their daughters, often are receptive to the fathers' participation in the family's decision-making process about getting their daughter HPV vaccinated., Methods: We conducted a survey to investigate the nature of the influence of fathers' participation on the mother's decision-making process. From an internet survey panel, we selected a pool of 1,499 eligible mothers who had 12-18 years old daughters. The mothers were randomized into three Groups. To the mothers in Group A, we gave an educational leaflet regarding HPV vaccination and a second leaflet which recommended that they talk with their husbands about the vaccination. To Group B, we gave only the educational leaflet. No leaflets were sent to Group C. A structured survey questionnaire was then distributed through the internet to the mothers., Results: In Groups A, B, and C, their intention to have their daughter receive the HPV vaccine was 21.6%, 20.7% and 8.2%, respectively. The percent of Group A mothers who thought their husband's opinion was important for when they made the decision was significantly higher (70%) than in Group B (56.6%) or Group C (47.1%)., Conclusions: The fathers' participation in the mothers' decision-making does not increase the likelihood of HPV vaccination for their daughters. On the other hand, the educational leaflet proved to be effective for this cause.

Introduction: Pleomorphic xanthoastrocytomas (PXA) are rare, typically benign, slow-growing tumors that commonly occur in the cerebral hemispheres. We describe two cases of clinically aggressive PXA with uncommon locations; one was in the tectal plate, and the other had simultaneous multicentric lesions., Patient Concerns: The both cases presented with severe headache with no significant past medical history., Diagnosis: PXA World Health Organization grade II were histopathologically diagnosed from surgically resected specimens, and immunohistochemical and sequence analysis revealed a high Ki-67 proliferative index and BRAF V600E mutation in both the cases., Interventions: The first case presented with multicentric lesions and underwent partial resection, whereas the second case presented with a tectal plate tumor that was managed by gross total surgical resection. Strong 5-aminolevulinic acid (5-ALA)-induced fluorescence was observed in both the lesions. Postoperative radiotherapy plus concomitant and adjuvant temozolomide was administered to both the patients., Outcomes: Despite completing adjuvant chemo-radiotherapy, both the patients had local tumor recurrence at 2 and 5 months after the operation, respectively., Conclusion: The progressive clinical courses in our cases suggest that additional postoperative therapy should be considered during the treatment of PXA with a high Ki67 index, and that temozolomide with radiotherapy, followed by temozolomide maintenance therapy, may not prevent recurrence in such tumors. Importantly, our experience implies that unlike other subtypes of low grade gliomas, 5-ALA fluorescence is useful for intraoperative visualization of PXA.

Background: The association between traumatic brain injury (TBI) and coagulopathy is well established. While coagulopathy prophylaxis in TBI involves replenishing coagulation factors with fresh frozen plasma (FFP), its effectiveness is controversial. We investigated the relationship between plasma fibrinogen concentration 3 h after initiating FFP transfusion and outcomes and evaluated the correlation with D-dimer levels at admission., Methods: We retrospectively examined data from 380 patients with severe isolated TBI with blood samples collected a maximum of 1 h following injury. Plasma fibrinogen and D-dimer concentrations were obtained at admission, and plasma fibrinogen concentration was again assessed 3-4 h following injury. The patients were divided into two groups based on whether or not they received FFP transfusion. Patients were also divided into subgroups according their fibrinogen level: ≥ 150 mg/dL (high-fibrinogen subgroup) or < 150 mg/dL (low-fibrinogen subgroup) 3 h after injury. Demographic, clinical, radiological and laboratory data were compared between these subgroups., Results: Glasgow Outcome Scale (GOS) scores at discharge and 3 months after injury were significantly lower in the FFP transfusion group than in the FFP non-transfusion group. Among patients who received FFP, GOS scores at discharge and 3 months after injury were significantly higher in the high-fibrinogen subgroup than in the low-fibrinogen subgroup. Elevated admission D-dimer predicted subsequent fibrinogen decrease., Conclusions: In FFP transfusion, fibrinogen level ≥ 150 mg/dL 3 h after injury was associated with better outcomes in TBI patients. Assessing the admission D-dimer and tracking the fibrinogen are crucial for optimal coagulopathy prophylaxis in TBI patients.

Background: Neuroendovascular therapy is typically performed via the femoral artery, but there are rare cases in which a tortuous upstream angioarchitecture makes it difficult to access the intracranial circulation via this route., Methods: In this case series, we describe six cases treated by surgical cut-down in the neck, with puncture of the carotid artery. Antiplatelet and anticoagulation agents were used in all cases. The indications for the technique were postsurgical thoracic aortic aneurysm (two cases), postsurgical abdominal aortic aneurysm (one case), major vessel tortuosity of the common carotid artery (two cases) and aortic arch anomaly (one case)., Results: The surgical cut-down technique permitted successful neuroendovascular therapy. Although one patient had a small cervical haematoma, he was treated without surgical evacuation., Conclusion: Overall, our findings indicate that the surgical cut-down technique is safe and useful for patients in whom the femoral approach is unsuitable.

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.

Rationale: Endodermal cysts are rare benign lesions in the central nervous system. Their common symptoms include headache and neck pain caused by mass effect or inflammatory reaction. We report the case of an elderly woman with intracranial endodermal cyst who presented with nonobstructive hydrocephalus., Patient Concerns: A 78-year-old woman presented with acute deterioration of consciousness caused by acute hydrocephalus. She subsequently underwent ventriculoperitoneal shunt placement. Eighteen months after this operation, she developed numbness of extremities and gait and progressive cognitive disturbances., Diagnosis: Initially, the endodermal cyst could not be recognized, but it became clinically evident in the craniocervical junction after ventriculoperitoneal shunt placement. MRI revealed multiple cystic lesions in the pontomedullary cistern. Postoperative pathology confirmed the diagnosis of endodermal cyst., Interventions: Subtotal resection of the cystic lesion was performed. Intra-operatively, multiple cysts containing a milky white fluid were noted and the medullary surface including the median and lateral apertures of the fourth ventricle were covered by thick, cloudy arachnoid membrane., Outcomes: Although the numbness of extremities improved after the surgery, she remained bedridden due to deterioration in cognitive function and generalized muscle weakness. The patient developed recurrence 2 months after the surgery; however, no additional surgery was performed owing to her poor general condition., Lessons: Endodermal cysts rarely present with nonobstructive hydrocephalus caused by recurrent meningitis. In such cases, the lesions are often invisible on initial diagnostic imaging, and complete resection of the lesions is typically difficult because of strong adhesion between the cyst walls and contiguous vital structures.

This study aimed to identify neurological and pathophysiological factors that predicted return of spontaneous circulation (ROSC) among patients with out-of-hospital cardiac arrest (OHCA). This prospective 1-year observational study evaluated patients with cardiogenic OHCA who were admitted to a tertiary medical center, Nippon Medical School Hospital. Physiological and neurological examinations were performed at admission for quantitative infrared pupillometry (measured with NPi-200, NeurOptics, CA, USA), arterial blood gas, and blood chemistry. Simultaneous blood samples were also collected to determine levels of neuron-specific enolase (NSE), S-100b, phosphorylated neurofilament heavy subunit, and interleukin-6. In-hospital standard advanced cardiac life support was performed for 30 minutes.The ROSC (n = 26) and non-ROSC (n = 26) groups were compared, which a revealed significantly higher pupillary light reflex ratio, which was defined as the percent change between maximum pupil diameter before light stimuli and minimum pupil diameter after light stimuli, in the ROSC group (median: 1.3% [interquartile range (IQR): 0.0-2.0%] vs. non-ROSC: (median: 0%), (Cut-off: 0.63%). Furthermore, NSE provided the great sensitivity and specificity for predicting ROSC, with an area under the receiver operating characteristic curve of 0.86, which was created by plotting sensitivity and 1-specificity. Multivariable logistic regression analyses revealed that the independent predictors of ROSC were maximum pupillary diameter (odds ratio: 0.25, 95% confidence interval: 0.07-0.94, P = 0.04) and NSE at admission (odds ratio: 0.96, 95% confidence interval: 0.93-0.99, P = 0.04). Pupillary diameter was also significantly correlated with NSE concentrations (r = 0.31, P = 0.027). Conclusively, the strongest predictors of ROSC among patients with OHCA were accurate pupillary diameter and a neuronal biomarker, NSE. Quantitative pupillometry may help guide the decision to terminate resuscitation in emergency departments using a neuropathological rationale. Further large-scale studies are needed.

Background: Inflow into an aneurysm sac immediately following flow diverter (FD) treatment is an assumed cause of delayed aneurysmal rupture. The significance of delayed posttreatment residual flow occurring months after FD treatment is unknown., Case Description: A 76-year-old woman with a large intracranial aneurysm measuring 23.0 × 18.1 mm in the cavernous segment of the right internal carotid artery was treated with placement of a single FD (Pipeline Embolization Device, Covidien, Irvine, California, USA). Postprocedure digital subtraction angiography (DSA) demonstrated flow stagnation inside the aneurysm dome. The patient was discharged 9 days post procedure without new neurologic deficits. A 6-month follow-up DSA demonstrated delayed posttreatment residual flow into the aneurysm sac. Although she was scheduled for additional FD placement because of concern for aneurysmal rupture, the operation was not conducted due to an interim motor vehicle accident. Oral treatment with aspirin (100 mg/day) and clopidogrel (75 mg/day) was continued during her recovery. DSA performed 12 months post procedure showed that the aneurysm had completely thrombosed., Conclusions: Our findings suggest that delayed post-treatment residual flow into an aneurysm may form part of the normal clinical course post FD placement and may not preclude eventual thrombosis of the aneurysm. Larger studies are needed to determine whether more frequent follow-up DSAs after FD placement are necessary and whether all patients exhibiting delayed post-treatment residual flow into an aneurysm require additional FD placement or if watchful waiting is a more suitable course., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The authors sought to demonstrate that hemorrhagic transformation of ischemic lesions is the main cause of delayed intracerebral hemorrhage (ICH) after Pipeline embolization device (PED) treatment and to estimate the rate of hemorrhagic transformation of new postprocedure ischemic lesions., Methods: Patients who underwent PED placement (PED group) from November 2015 to March 2017 or stent-mediated embolization (EN group) from December 2010 to October 2015 were retrospectively analyzed. Pre- and postprocedural MR images and 6-month follow-up MR images for each patient were scored for the presence of postprocedural bland ischemic and hemorrhagic lesions using diffusion-weighted MRI (DWI) and T2*-weighted MRI (T2*WI), respectively., Results: The PED group comprised 28 patients with 30 intracranial aneurysms, and the EN group comprised 24 patients with 27 intracranial aneurysms. The mean number of ischemic lesions on DWI 1 day postprocedure was higher in the PED group than in the EN group (5.2 vs 2.7, p = 0.0010). The mean number of microbleeds detected on T2*WI 6 months postprocedure was higher in the PED group than in the EN group (0.6 vs 0.15, p = 0.028). A total of 36.7% of PED-treated patients exhibited new microbleeds on T2*WI at 6 months postprocedure, with at least 77.8% of these lesions representing hemorrhagic transformations of the new ischemic lesions observed on day 1 postprocedure. The rate of adjunctive coil embolization (27.3% vs 0.0%, p = 0.016) and the mean number of ischemic lesions observed 1 day postprocedure (6.6 vs 4.3, p = 0.020) were predictors of subsequent microbleeds in the PED group., Conclusions: New microbleeds detected using T2*WI at 6 months postprocedure were more common after PED treatment than after stent-mediated embolization. Approximately three-quarters of these lesions were hemorrhagic transformations of new ischemic lesions observed on day 1 postprocedure. Prevention of intraprocedural or postprocedural infarcts is necessary to reduce the risk of hemorrhagic complications following PED placement.

The Pipeline embolization device (PED), a type of flow diverter, has become an appealing alternative treatment option for large or giant and wide-necked intracranial aneurysms. Carotid cavernous fistula (CCF) resulting from delayed aneurysmal rupture is a rare complication of PED placement with unknown pathophysiology. Here, we describe a case of CCF resulting from aneurysmal rupture following PED placement, and present the details of treatment by transvenous coil embolization. An 81-year-old woman was referred to our hospital for treatment of an 18.0 × 10.3 mm intracranial aneurysm located in the cavernous segment of the left internal carotid artery, noted during an examination of her diplopia. Endovascular treatment was conducted by positioning a single PED (4.75 × 25 mm) across the neck of the aneurysm. The postoperative course was uneventful, and the patient was discharged 8 days post procedure. On post-procedure day 10, her left oculomotor nerve palsy had worsened and she had developed left abducens nerve palsy, left exophthalmos, and left chemosis. Angiography demonstrated left direct CCF because of rupture of the aneurysm that had been treated with PED. Transvenous coil embolization was performed on post-procedure day 11 to treat the CCF, and complete resolution of the CCF and significant thrombus formation within the aneurysm sac were confirmed 11 days after the second procedure. Our angiographic results suggest that the aneurysmal rupture was caused by aneurysmal volume expansion associated with PED-induced thrombosis. Transvenous coil embolization for the treatment of CCF following PED placement constitutes a new challenge., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The prognosis for patients with traumatic brain injury (TBI) with subdural hematoma (SDH) remains poor. In accordance with an increasing elderly population, the incidence of geriatric TBI with SDH is rising. An important contributor to the neurological injury associated with SDH is the ischemic damage which is caused by raised intracranial pressure (ICP) producing impaired cerebral perfusion. To control intracranial hypertension, the current management consists of hematoma evacuation with or without decompressive craniotomy. This removal of the SDH results in the immediate reversal of global ischemia accompanied by an abrupt reduction of mass lesion and an ensuing reperfusion injury. Experimental models can play a critical role in improving our understanding of the underlying pathophysiology and in exploring potential treatments for patients with SDH. In this review, we describe the epidemiology, pathophysiology and clinical background of SDH., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: In Japan, the cervical cancer preventative HPV vaccination rate has dramatically declined, directly as a result of repeated broadcasts of so-called adverse events and the resulting suspension of the government's recommendation. Our previous survey of obstetricians and gynecologists in Japan regarding their opinions toward HPV vaccination revealed that these key specialists were as negatively influenced by the reports of purported negative events as were the general population. Here, we report a 3-year follow-up survey of these clinicians., Methods: We reused the same questionnaire format as used in our 2014 survey, but added new questions concerning opinions regarding a WHO statement and reports of a Japanese nation-wide epidemiological study related to the adverse events, released in 2015 and 2016, respectively., Results: The response rate was 46% (259/567): 5 (16.1%) of 31 doctors had inoculated their own teenaged daughters during the time period since the previous survey, despite the continued suspension of the governmental recommendation, whereas in the previous survey none of the doctors had done so. Among the respondents, the majority claimed awareness of the recent pro-vaccine WHO statement (66.5%), and of the report of a Japanese epidemiological study (71.5%), and a majority affirmed they currently held positive opinions of the safety (72.7%) and effectiveness (84.3%) of the HPV vaccine., Conclusions: Our re-survey of Japan's obstetricians and gynecologists regarding their opinions about the HPV vaccine found that their opinions have changed, potentially leading to a more positive future re-engagement for HPV vaccination in Japan.