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Objective: Tixagevimab/cilgavimab is a cocktail of two long-acting monoclonal antibodies approved for pre-exposure prophylaxis (PrEP) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (cause of coronavirus disease 2019 [COVID-19]) in immunocompromised (IC) or high-risk patients. We investigated the patient characteristics and clinical outcomes of IC patients administered tixagevimab/cilgavimab for PrEP in real-world use in Japan., Methods: This observational study used anonymous secondary data from Real-World Data Co., Ltd. for IC patients aged ≥12 years administered tixagevimab/cilgavimab between September 2022 and September 2023. We analyzed the baseline characteristics and event-rates of COVID-19-related clinical outcomes within 6 months of administration., Results: Data were analyzed for 397 IC patients. About half (53.4 %) were male and the median age was 71.0 (interquartile range 61.0, 77.0) years. Malignancy (97.2 %), cardiovascular disease (71.3 %), and diabetes (66.5 %) were frequent comorbidities. Systemic corticosteroids and immunosuppressants were prescribed to 87.4 % and 24.9 %, respectively. The two most common target clinical conditions were active therapy for hematologic malignancies (88.2 %) and treatment with B cell-depleting therapies (57.4 %). The event-rates per 100 person-months (95 % confidence interval; number) for medically attended COVID-19, COVID-19 hospitalization, in-hospital mortality due to COVID-19, and all-cause death were 4.14 (3.06-5.48; n = 49), 1.74 (1.09-2.64; n = 22), 0.07 (0.00-0.42; n = 1), and 0.60 (0.26-1.17; n = 8), respectively., Conclusion: This is the first report using a multicenter database to describe the clinical characteristics and COVID-19-related outcomes of IC patients administered with tixagevimab/cilgavimab in real-world settings in Japan. This cohort of IC patients who received tixagevimab/cilgavimab included many elderly patients with comorbidities., Competing Interests: Declaration of competing interest Toshibumi Taniguchi has received lecture fees from AstraZeneca K.K. Tomoyuki Homma, Yoichi Tamai, Yoshifumi Arita, Masakazu Fujiwara, Naho Kuroishi, Keiji Sugiyama, Shinichi Kanazu and Atsushi Maruyama are employees of AstraZeneca K.K., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Oral drug absorption involves drug permeation across the apical and basolateral membranes of enterocytes. Although transporters mediating the influx of anionic drugs in the apical membranes have been identified, transporters responsible for efflux in the basolateral membranes remain unclear. Monocarboxylate transporter 6 (MCT6/SLC16A5) has been reported to localize to the apical and basolateral membranes of human enterocytes and to transport organic anions such as bumetanide and nateglinide in the Xenopus oocyte expression system; however, its transport functions have not been elucidated in detail. In this study, we characterized the function of MCT6 expressed in HEK293T cells and explored fluorescent probes to more easily evaluate MCT6 function. The results illustrated that MCT6 interacts with CD147 to localize at the plasma membrane. When the uptake of various fluorescein derivatives was examined in NaCl-free uptake buffer (pH 5.5), the uptake of 5-carboxyfluorescein (5-CF) was significantly greater in MCT6 and CD147-expressing cells. MCT6-mediated 5-CF uptake was saturable with a K m of 1.07 mM and inhibited by several substrates/inhibitors of organic anion transporters and extracellular Cl ion with an IC 50 of 53.7 mM. These results suggest that MCT6 is a chloride-sensitive organic anion transporter that can be characterized using 5-CF as a fluorescent probe., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Depression can be associated with chronic systemic inflammation, and production of peripheral proinflammatory cytokines and upregulation of the kynurenine pathway have been implicated in pathogenesis of depression. However, the mechanistic bases for these comorbidities are not yet well understood. As tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), which convert tryptophan to kynurenine, are rate-limiting enzymes of the kynurenine pathway, we screened TDO or IDO inhibitors for effects on the production of proinflammatory cytokines in a mouse macrophage cell line. The TDO inhibitor 680C91 attenuated LPS-induced pro-inflammatory cytokines including IL-1β and IL-6. Surprisingly, this effect was TDO-independent, as it occurred even in peritoneal macrophages from TDO knockout mice. Instead, the anti-inflammatory effects of 680C91 were mediated through the suppression of signal transducer and activator of transcription(STAT) signaling. Furthermore, 680C91 suppressed production of proinflammatory cytokines and STAT signaling in an animal model of inflammatory bowel disease. Specifically, 680C91 effectively attenuated acute phase colon cytokine responses in male mice subjected to dextran sulfate sodium (DSS)-induced colitis. Interestingly, this treatment also prevented the development of anxiodepressive-like neurobehaviors in DSS-treated mice during the recovery phase. The ability of 680C91 to prevent anxiodepressive-like behavior in response to chemically-induced colitis appeared to be due to rescue of attenuated dopamine responses in the nucleus accumbens. Thus, inhibition of STAT-mediated, but TDO-independent proinflammatory cytokines in macrophages can prevent inflammation-associated anxiety and depression. Identification of molecular mechanisms involved may facilitate the development of new treatments for gastrointestinal-neuropsychiatric comorbidity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Little is known about blunt traumatic diaphragmatic injury (BTDI). This study aimed to investigate the epidemiological state of BTDI, using a nationwide trauma registry in Japan., Methods: Data of patients aged ≥18 years who experienced blunt injury between January 2004 and May 2019 were extracted from the Japan Trauma Data Bank. Demographics, cause of trauma, mechanism of injury, physiological parameters, organ injuries, and bone fractures were compared between patients with and those without BTDI. Multivariable logistic regression analysis was performed to identify factors associated with BTDI., Results: A total of 305,141 patients from 244 hospitals were analyzed. The median patient age (interquartile range) was 65 (44-79) years, and 185,750 (60.9%) were men. BTDI was diagnosed in 868 patients (0.3%). The prevalence of BTDI was stable, between 0.2 and 0.6%, over the study period. Among the 868 patients with BTDI, 408 (47.0%) fatalities were recorded. Mortality rates in each year were 42.5-68.2%, with no significant trend toward an improved outcome (P = 0.925). Our multivariable logistic regression analysis found that mechanism of injury, Glasgow Coma Scale score (9-12 or 3-8) on hospital arrival, hypotension (systolic blood pressure <90 mmHg) on hospital arrival, organ injuries (lung, heart, spleen, bladder, kidney, pancreas, stomach, and liver), and bone fractures (rib, pelvis, lumbar spine, and upper extremities) were independently associated with BTDI., Conclusion: Using a nationwide trauma registry, this study revealed the epidemiological state of BTDI in Japan. BTDI was found to be a very rare but devastating injury, with high in-hospital mortality. Some clinical factors, such as mechanism of injury, Glasgow Coma Scale score, organ injuries, and bone fractures, were independently associated with BTDI., Competing Interests: Declaration of Competing Interest The author has no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lipids, proteins, and nucleic acids have closely associated water molecules (Bound water), which exhibit considerably different physical properties compared to bulk water. Here we investigate the possibility of resolving Raman spectra of the specific hydration shell of these biomolecules in intracellular regions using Raman imaging. Lipids and proteins + nucleic acids Raman spectral components resolved in the analysis showed associated water spectral features, which are uniquely different from that of bulk water. These spectral profiles agree with water spectral profile observed in the case of corresponding hydrated pure biomolecules. The results show the prospects of Raman imaging in examining intracellular hydration in biomolecules and its functional relation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Haruko Takeyama reports financial support was provided by Japan Society for the Promotion of Science., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To investigate the characteristics and outcomes of patients who experienced cardiac arrest in nursing homes compared with those in private residences and determine prognostic factors for survival., Design: This was a retrospective study that analyzed data from an Utstein-style registry of the Tokyo Fire Department., Setting and Participants: We identified patients aged ≥65 years who experienced cardiac arrest in a nursing home or private residence from the population-based registry of out-of-hospital cardiac arrests in Tokyo, Japan, from 2014 to 2018., Methods: Patients were grouped into the nursing home or the private residence groups according to their cardiac arrest location. We compared the characteristics and outcomes between the 2 groups and determined prognostic factors for survival in the nursing home group. The primary outcome was 1-month survival after cardiac arrest., Results: In total, 37,550 patient records (nursing home group = 6271; private residence group = 31,279) were analyzed. Patients in the nursing home group were significantly older and more often had witnessed arrest, bystander cardiopulmonary resuscitation (CPR), and shock delivery using an automated external defibrillator. The 1-month survival rate was significantly higher in the nursing home group (2.6% vs 1.8%, P < .001). In the best scenario (daytime emergency call, witnessed cardiac arrest, bystander CPR provided), the 1-month survival rate after cardiac arrest in the nursing home group was 8.0% (95% confidence interval 6.4-9.9%), while none survived if they had neither witness nor bystander CPR., Conclusions and Implications: Survival outcome was significantly better in the nursing home group than in the private residence group and was well stratified by 3 prognostic factors: emergency call timing, witnessed status, and bystander CPR provision. Our results suggest that a decision to withhold vigorous treatment solely based on nursing home residential status is not justified, while termination of resuscitation may be determined by considering significant prognostic factors., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation., Design: Retrospective case study., Participants: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort., Methods: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account., Main Outcome Measures: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation., Results: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001)., Conclusions: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: The hospital volume-outcome relationship in patients with severe traumatic brain injury (TBI) remains unclear. This study investigated the association between the volume of patients with severe TBI and in-hospital mortality., Methods: This observational study identified patients with severe TBI (Glasgow Coma Scale score <9 and Abbreviated Injury Scale head score ≥3) from the Japan Trauma Databank (2010-2018). Hospitals were grouped on the basis of annual patient volume as follows: low-volume (4-19 patients/year); middle-volume (20-35 patients/year); and high-volume (36-51 patients/year) groups. The association between hospital volume categories and in-hospital mortality was examined using a multivariate mixed-effect logistic regression analysis. A subgroup analysis was performed based on the presence of severe extracranial injuries., Results: A total of 11,344 patients from 64 hospitals were included. The median age of the patients was 57 years (interquartile range, 40-77), and 7933 (70.0%) patients were men. A total of 4879 (43.1%) patients died in the hospital. The medium-volume (adjusted odds ratio [OR], 0.76; 95% confidence interval [CI], 0.62-0.93) and high-volume (adjusted OR, 0.69; 95% CI, 0.52-0.94) groups were significantly associated with lower in-hospital mortality. The subgroup analysis revealed that the medium-volume (adjusted OR, 0.70; 95% CI, 0.54-0.92) and high-volume (adjusted OR, 0.64; 95% CI, 0.42-0.96) groups were significantly associated with lower in-hospital mortality for isolated TBI patients., Conclusions: Higher hospital volumes were significantly associated with lower in-hospital mortality after severe TBI. Regionalization and referral to higher-volume hospitals are beneficial for severe TBI patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Endoscopic third ventriculostomy (ETV) for obstructive hydrocephalus and endoscopic biopsy (EB) for intraventricular and paraventricular tumors are standard therapies because they are minimally invasive procedures. Although EB-associated hemorrhagic risk has been well documented, there have been only a few reports on hemorrhagic risk associated with ETV. We conducted a single-institution retrospective study on the incidence of hemorrhage secondary to EB and/or ETV., Methods: We retrospectively reviewed patient characteristics, procedure, pathological findings, and complications including hemorrhage of 100 patients with intraventricular and paraventricular tumors who underwent EB and/or ETV at our institution from 2000 to 2020., Results: EB/ETV combined surgery (combined group), EB-alone surgery (EB-alone group), and ETV-alone surgery (ETV-alone group) were performed in 44 (44%), 24 (24%), and 32 (32%) patients, respectively, and all procedures were successful. The rates of definitive and suggestive diagnoses in EB were 76.5% and 23.5%, respectively. Adverse events were observed in 6 patients. In the combined group, acute obstruction of the ETV stoma was observed in 1 patient and transient double vision was observed in 1 patient. Transient aqueductal stenosis/obstruction was observed in 2 patients in the EB-alone group. In the ETV-alone group, hemorrhage was observed in 2 patients; these patients developed intratumoral hemorrhage despite ETV-alone surgery. Subsequently, these 2 patients underwent tumor removal, and the histopathological diagnosis was atypical teratoid/rhabdoid tumor in both., Conclusions: For obstructive hydrocephalus with atypical teratoid/rhabdoid tumor, physicians must be aware of the risk of postoperative intratumoral hemorrhage after performing ETV., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We created a handmade 3D-printed air sampler to effectively collect live airborne bacteria, and determined which environmental factors influenced the bacteria. Bacterial colony forming units (CFUs) in the air samples (n = 37) were monitored by recording the environmental changes occurring over time, then determining the presence/absence of correlations among such changes. The bacterial CFUs changed sharply and were significantly correlated with the DNA concentrations, indicating that the captured bacteria made up most of the airborne bacteria. Spearman's rank correlation analysis revealed significant correlations between the bacterial CFU values and some environmental factors (humidity, wind speed, insolation, and 24-h rainfall). Similarly the significant associations of CFU with humidity and wind speed were also found by multiple regression analysis with box-cox transformation. Among our panel of airborne bacteria (952 strains), 70 strains were identified as soil-derived Bacillus via the production of Escherichia coli- and Staphylococcus aureus-growth inhibiting antibiotics and by 16S rDNA typing. Soil-derived protozoa were also isolated from the air samples. We conclude that the airborne bacteria mainly derived from soil can alter in number according to environmental changes. Our sampler, which was created by easy-to-customize 3D printing, is a useful device for understanding the dynamics of live airborne bacteria., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2021 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder in children. Although animal models and human brain imaging studies indicate a significant role for glutamatergic dysfunction in ADHD, there is no direct evidence that glutamatergic dysfunction is sufficient to induce ADHD-like symptoms. The glial glutamate transporter GLT1 plays a critical role in glutamatergic neurotransmission. We report here the generation of mice expressing only 20% of normal levels of the GLT1. Unlike conventional GLT1 knockout mice, these mice survive to adulthood and exhibit ADHD-like phenotypes, including hyperactivity, impulsivity and impaired memory. These findings indicate that glutamatergic dysfunction due to GLT1 deficiency, a mechanism distinct from the dopaminergic deficit hypothesis of ADHD, underlies ADHD-like symptoms., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Previous studies have reported inconsistent results on the mortality from trauma among psychiatric patients comparing to non-psychiatric population, which may be partly explained by the inclusion of both suicidal and accidental trauma. This study aimed to investigate the association of psychiatric diagnoses on admission with the outcomes of hospitalized patients for accidental trauma, namely road traffic injury., Methods: Detailed information of patients aged 15 years or older who were hospitalized for road traffic injury between 2004 and 2017 was extracted from the Japan Trauma Data Bank. The primary outcome was to compare in-hospital mortality between patients with and without a psychiatric disorder. We also conducted a subgroup analysis among patients with and without a serious head injury., Results: Altogether, 85,069 patients were included. Of these, 3,895 patients (4.6%) had a psychiatric diagnosis. The in-hospital mortality rate was significantly lower among patients with a psychiatric diagnosis than those without (5.4% vs. 8.3%; adjusted odds ratio [OR] 0.57, 95% confidence interval [CI] 0.47-0.70, p<0.001). In a subgroup analysis of patients with a serious head injury, in-hospital mortality was significantly lower in patients with a psychiatric diagnosis than in those without (10.5% vs. 17.3%; adjusted OR 0.48, 95% CI 0.37-0.62, p<0.001); in-hospital mortality of patients without a serious head injury showed no differences between patients with or without a psychiatric diagnosis (2.8% vs. 3.5%; adjusted OR 0.84, 95% CI 0.61-1.16, p=0.295)., Conclusions: In-hospital mortality from road traffic injury was significantly lower among patients with a psychiatric diagnosis than those without, which was primarily evident in a subgroup of patients with a serious head injury. While further replication is necessary, results might be indicative of the neuroprotective effect of psychotropic medications., Competing Interests: Declaration of Competing Interest Dr. Ishida has received manuscript fees from Dainippon Sumitomo Pharma within the past three years, outside the submitted work. Dr. Mimura has received grants, or consultant fees from Daiichi Sankyo, Eisai, Pfizer, Takeda Yakuhin, Tsumura, Tanabe Mitsubishi, Shionogi, and received speaker or manuscript fee from Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, FujiFilm RI Pharma, Janssen Pharmaceutical, Mochida Pharmaceutical, MSD, Nippon Chemipher, Novartis Pharma, Ono Yakuhin, Otsuka Pharmaceutical, Pfizer, Takeda Yakuhin, Tsumura, and Yoshitomi Yakuhin within the past three years, outside the submitted work. Dr. Suzuki has received grants from Eisai, Mochida Pharmaceutical, and Meiji Seika pharma, and received speaker or manuscript fee from Astellas Pharma, Dainippon Sumitomo Pharma, Eli Lilly, Elsevier Japan, Janssen Pharmaceuticals, Kyowa Yakuhin, Meiji Seika Pharama, Mitsubishi Tanabe Pharma, MSD, Novartis, Otsuka Pharmaceutical, Shionogi, Tsumura, Wiley Japan, and Yoshitomi Yakuhin within the past three years, outside the submitted work. Dr. Uchida has received grants from Pfizer, Eisai, Otsuka Pharmaceutical, Dainippon-Sumitomo Pharma, Meiji-Seika Pharma, and received speaker's honoraria from Eli Lilly, Yoshitomi Yakuhin, MSD within the past three years, outside the submitted work. |Other authors have nothing to disclose., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Despite the increasing numbers of older adults with traumatic brain injury (TBI), minimal data are available to support the development of treatment strategies. We aimed to comprehensively describe the incidence, characteristics, outcomes, and predictive accuracy of the severity indicators among older adults with TBI., Methods: Using the Japan Trauma Data Bank, we identified patients aged ≥18 years with TBI from 2004 to 2019. The patients were grouped according to age, and their baseline characteristics, radiological findings, severity, complications, and in-hospital mortality were assessed. Receiver operating characteristic curves were used to assess the accuracy of severity indicators for predicting in-hospital mortality., Results: Of the 94,180 patients who met the inclusion criteria, 50,990 (54.1%) were older adults (aged ≥65 years). Their proportion had increased at 2.1% annually, which exceeded the 0.5% annual increase in the general population. The proportion of women and the prevalence of comorbidities increased significantly with age. Traffic accidents were the leading cause of TBI among young adults, and falling at ground level was the leading cause for those aged ≥75 years. The radiological findings were significantly different among the age groups. The proportion of acute epidural hemorrhage, skull fracture, and diffuse axonal injury decreased and that of acute subdural hemorrhage increased with age. The predictive accuracy of the Glasgow coma scale, revised trauma score, and injury severity score decreased with increasing age., Conclusions: The proportion of older patients with TBI increased more quickly than did the proportion of older people in the general population. The characteristics and predictive accuracy of the severity indicators differed significantly among the different age groups. TBI studies that focus on older patients are necessary., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to investigate the prognostic effects of clinical and histologic findings in patients with mucoepidermoid carcinoma (MEC) of minor salivary glands., Study Design: This retrospective clinical review included 63 patients (30 males, mean age 52.8 years) with minor salivary gland MEC treated at our hospital from 1994 to 2019. Overall survival (OS) or disease-free survival was determined using the Kaplan-Meier limit method. Correlations between different factors and survival rates were assessed using chi-square tests., Results: The 10-year OS rate was 91.2%. Low- or intermediate-grade MEC had a good prognosis regardless of the surgical margin, whereas high-grade MEC had a poor 10-year OS rate (64.2%). Ten patients developed recurrence or metastasis after primary surgical resection, of whom 6 were diagnosed with a high-grade tumor. The most frequently affected site was the palate, whereas the mandibular gingiva was the most commonly affected site during recurrence. Of 4 patients who received chemotherapy and/or radiotherapy postsurgery, 2 had local recurrence and/or neck lymph node metastasis and 1 died from MEC., Conclusion: Patients with low- or intermediate-grade MEC exhibited satisfactory survival after surgery. In patients with high-grade tumors, it has been suggested that survival rates are poor and do not improve following adjuvant therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Posterior fossa ependymoma (PF-EPN) was categorized into PF-EPN-A and PF-EPN-B subgroups based on the DNA methylation profiling. PF-EPN-A was reported to have poorer prognosis compared with PF-EPN-B. In this study, we particularly evaluated preoperative imaging to distinguish PF-EPN-A from PF-EPN-B., Methods: Sixteen cases of PF-EPN were treated in our institution from 1999 to 2018. The patients were divided into PF-EPN-A and PF-EPN-B groups based on H3K27me3 immunostaining positivity. We evaluated progression-free survival, overall survival, as well as preoperative magnetic resonance imaging and computed tomography scan images in both groups. Based on T1WI and Gd-T1WI magnetic resonance images, the tumor contrast rate was determined from dividing the volume of gadolinium enhanced tumor by the overall tumor volume., Results: Nine cases (4 male, 5 female) were grouped as PF-EPN-A, and 7 (4 male, 3 female) as PF-EPN-B. The median age of PF-EPN-A and PF-EPN-B were 4 and 43 years old, respectively. In the PF-EPN-A group, the progression-free survival median value was 32.6 months, and the overall survival median was 96.9 months. In contrast, PFS in PF-EPN-B did not reach a median value (P < 0.05) and all the patients were alive (P < 0.05) at the end of the study. With imaging, tumor contrast rate in PF-EPN-B was more than 50% and significantly different from PF-EPN-A (P = 0.0294). Calcification was mainly observed in PF-EPN-A, whereas cystic formation was only seen in PF-EPN-B., Conclusions: Contrast rate less than 50%, based on the magnetic resonance images, was characteristic in the PF-EPN-A group. Comparatively, cystic component and absence of calcification were more characteristic in the PF-EPN-B group., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Topoisomerase I (TOP1) resolves DNA topology during replication and transcription. The enzyme forms an intermediate TOP1 cleavage complex (TOP1cc) through transient TOP1-DNA-protein crosslinks. Camptothecin is a frontline anticancer agent that freezes this reaction intermediate, leading to the generation of irreversible TOP1ccs that act as 3'-blocking lesions. It is widely accepted that TOP1cc is repaired via a two-step pathway involving proteasomal degradation of TOP1cc to the crosslinked peptide, followed by removal of the TOP1cc-derived peptide from DNA by tyrosyl-DNA phosphodiesterase 1 (TDP1). In the present study, we developed an assay system to estimate repair kinetics of TOP1cc separately in the first and second steps, using monoclonal antibodies against the TOP1 protein and the TOP1 catalytic site peptide-DNA complex, respectively. Although TDP1-deficient (TDP1 -/- ) TK6 cells had normal kinetics of the first step, a delay in the kinetics of the second step was observed relative to that in wild-type cells. Tyrosyl-DNA phosphodiesterase 2 (TDP2) reportedly promotes the repair of TOP1-induced DNA damage in the absence of TDP1. The present assays additionally demonstrated that TDP2 promotes the second, but not the first, step of TOP1cc repair in the absence of TDP1. We also analyzed sensitivities of TK6 cells with deficiencies in TDP1 and/or TDP2 to agents that produce 3' -blocking lesions. These experiments showed that TDP1 -/- TDP2 -/- cells were more sensitive to the agents Azidothymidine (zidovudine), Cytarabine, Abacavir, Gemcitabine, and Trifluridine than TDP1 -/- or TDP2 -/- cells. Taken together, our findings confirm the roles of TDP2 in the repair of 3'-blocking lesions., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: An ongoing outbreak of a novel coronavirus disease (coronavirus disease 2019, COVID-19) has become a global threat. While clinical reports from China to date demonstrate that the majority of cases remain relatively mild and recover with supportive care, it is also crucial to be well prepared for severe cases warranting intensive care. Initiating appropriate infection control measures may not always be achievable in primary care or in acute-care settings., Case: A 45-year-old man was admitted to the intensive care unit due to severe pneumonia, later confirmed as COVID-19. His initial evaluation in the resuscitation room and treatments in the intensive care unit was performed under droplet and contact precaution with additional airborne protection using the N95 respirator mask. He was successfully treated in the intensive care unit with mechanical ventilation and extracorporeal membrane oxygenation for respiratory support; and antiretroviral treatment with lopinavir/ritonavir. His total intensive care unit stay was 15 days and was discharged on hospital day 24., Conclusions: Strict infection control precautions are not always an easy task, especially under urgent care in an intensive care unit. However, severe cases of COVID-19 pneumonia, or another novel infectious disease, could present at any moment and would be a continuing challenge to pursue appropriate measures. We need to be well prepared to secure healthcare workers from exposure to infectious diseases and nosocomial spread, as well as to provide necessary intensive care., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: We aimed to investigate the association between prehospital times and outcomes of patients who had hypotension at the scene after trauma incidents., Methods: We retrospectively analysed records from a nationwide database (2004-2017) of adults (aged ≥15 years) who were hypotensive (systolic blood pressure <90 mmHg) at the scene after trauma. The endpoint was in-hospital mortality. We used multivariable logistic regression analysis to adjust for confounding factors and to estimate the odds ratio (OR) of prehospital times for in-hospital mortality. Stratified analyses were performed based on patient age and type and severity of the trauma., Results: Among 5,499 patients included, 906 (16.5%) died in the hospital. The median Injury Severity Score (ISS) was 17 (interquartile range, 9-29). There was a significant trend towards patients having higher in-hospital mortality and ISS when their prehospital times were shorter (P < 0.001). However, the association between prehospital times and in-hospital mortality was not significant after adjusting for confounding factors, with an adjusted odds ratio of 1.00 (95% confidence interval: 0.98-1.01) per 10 min increments in prehospital time. The association remained insignificant when patients were stratified according to age and type and severity of the trauma., Conclusions: Our analysis revealed that prehospital time was not significantly associated with in-hospital mortality among patients who had hypotension at the scene after trauma in the current emergency medical service system in Japan. Further studies are needed to validate our findings., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The term "growing teratoma syndrome (GTS)" has been used as follows: patients with germ cell tumor (GCT) who present with enlarging original/metastatic masses during or after appropriate systemic chemotherapy despite normalized serum markers. In other words, the definition of the term GTS is not fully established. We analyzed and reviewed our case series regarding GTS that developed after the treatment of central nervous system (CNS) nongerminoatous germ cell tumors (NGGCTs)., Methods: Our institutional review board approved this retrospective study. Between 2003 and 2018, we treated 16 patients (16 males; age ranging from 5.4 to 51.9 years, median 13.8) with CNS-NGGCT at our institution. We reviewed those patients and also reviewed the literature about GTS of CNS. We defined primary GTS (p-GTS) as the enlargement of cyst size and/or solid tumor occurred during treatment in the absence of marker elevation, and recurrent GTS (r-GTS) as the enlargement of teratoma after complete response of initial tumors., Results: Among 16 patients with CNS-NGGCT, we surgically confirmed mature/immature teratoma components in 15 patients. Two patients underwent surgical removal of tumor before neoadjuvant therapy, and among the rest 14 patients, 6 developed p-GTS, and 2 patients underwent salvage surgery during chemo-/chemoradiotherapy. Those with histologic diagnosis of immature teratoma during salvage surgery had a shorter interval from the initiation of chemoradiotherapy compared with mature teratoma (P < 0.05). One patient developed r-GTS. In the literature review, most of the p-GTS consisted of enlargement with the multicystic component. Histologic diagnosis of immature teratoma during salvage surgery was observed in earlier stages of chemoradiotherapy (P < 0.05, log-rank test). Previous history of p-GTS might be a risk factor of r-GTS., Conclusions: The incidence of p-GTS, enlargement of the cystic component during treatment, is not rare. Physicians need to be aware of this important phenomenon., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Sudden unexpected deaths occur more frequently among patients with severe mental illness (SMI), but direct evidence on the causes is still scarce., Objective: The objective of this study is to investigate initial rhythms and characteristics of out-of-hospital cardiac arrest among patients with SMI., Methods: We conducted a systematic chart review of adult patients who suffered from out-of-hospital cardiac arrest and transferred to Tokyo Metropolitan Bokutoh Hospital in Japan between January 2011 and December 2017. The initial rhythms, clinical characteristics, and outcomes were compared between patients with schizophrenia or mood disorders (i.e., SMI) and nonpsychiatric control patients. Values of interest were compared using Fisher's exact test or Mann-Whitney U-test, as appropriate. Multiple regression analysis was also conducted to investigate the effect of SMI on the initial rhythms., Results: A total of 2631 patients were included in this study. Of these, 157 patients had SMI. Fatal arrhythmias (i.e., ventricular fibrillation and ventricular tachycardia) were less frequently noted as the initial rhythms among patients with SMI than among controls (5.7% vs. 18.8%, adjusted odds ratio = 0.27, 95% confidence interval = 0.13-0.55, P < 0.001). Patients with SMI were significantly younger (median [range], 58 years [22-85] vs. 72 years [18-108], P < 0.001) and less frequently had comorbid physical illnesses than controls (the proportion of patients without comorbidities; 58.6% vs. 37.1%, P < 0.001). Survival and neurological function at discharge were not different between the 2 groups., Conclusion: Fatal arrhythmia may account for a relatively small portion in excess of sudden death among patients with SMI. Furthermore, appropriate medical checkups for the patients with SMI at earlier ages would be important to prevent sudden cardiac death., (Copyright © 2019 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Data for establishing the optimal management modalities for pancreatic injury are lacking. Herein, we aimed to describe the epidemiology, identify mortality predictors, and determine the optimal management strategy for pancreatic injury., Methods: We identified patients with pancreatic injury between 2004 and 2017 recorded in the Japan Trauma Data Bank. The primary outcome was mortality. Multivariable logistic regression analyses were used to identify factors significantly associated with mortality and to develop a predictive model. Patients were also classified according to the Organ Injury Scaling of the American Association for the Surgery of Trauma (AAST grade I/II or III/IV). Outcomes were compared based on significant confounder-adjusted treatment strategy., Results: Overall, 743 (0.25%) patients had pancreatic injury. Traffic accident was the most common aetiology. The overall mortality rate was 17.5%, while it was 4.7% for isolated pancreatic injury. AAST grade, Revised Trauma Scale score on arrival, age, and coexistence of severe abdominal injury aside from pancreatic injury were independently associated with mortality. A predictive model for mortality comprising these four variables showed excellent performance, with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval [CI], 0.85-0.93). The in-hospital mortality was higher in patients who underwent celiotomy than in those who did not among those with AAST grade I/II (15.1% vs. 5.3%) and III/IV (13.8% vs. 12.3%). After adjusting for confounders, these differences were not significant with the adjusted odds ratios of 1.41 (95% CI, 0.55-3.60) and 0.54 (95% CI, 0.17-1.67) for AAST grade I/II and III/IV, respectively., Conclusions: AAST grade, Revised Trauma Scale score on arrival, age, and coexistence of severe abdominal injury aside from pancreatic injury were prognostic factors of mortality after pancreatic injury. Confounder-adjusted analysis did not show that operative management was superior to non-operative management for survival. Non-operative management may be a reasonable strategy for select pancreatic injury patients, especially in institutions where expertise in interventional endoscopy is available., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Several intracranial pathologies present as a ring-enhancing lesion on conventional magnetic resonance imaging (MRI), creating diagnostic difficulty. We studied the characteristics of the anatomical border of gadolinium enhancement on T1-weighted imaging (WI) and hypointensity on T2WI to employ a simple technique of histogram-profile analysis of MRI for differentiation of various ring-enhancing intracranial lesions., Methods: After approval from the institutional review board, preoperative MRI (T2WI, postcontrast T1WI) scans were analyzed retrospectively in 18 patients with histologically confirmed brain abscess, 66 glioblastomas, 46 brain-metastases, and 16 tumefactive multiple sclerosis (MS). T2WI and postcontrast T1WI were overlapped, and histogram-profile analysis was performed with in-house image-fusion software. The pattern of differential-peaks in histogram-profile was assessed visually. Kaplan-Meier survival analysis incorporating histogram-profile patterns was performed in patients with glioblastoma., Results: The histogram-profile study revealed 4 distinct patterns. Pattern 1 showed no differential T2-hypointensity trough, pattern 2 had T2-hypointensity trough inside, whereas pattern 3 had T2-hypointensity trough overlapping the enhanced margin. Pattern 4 had T2-hypointensity trough immediately external to the enhanced margin. Pattern 1 was specific for tumefactive MS (93.3%), whereas pattern 4 was specific for glioblastoma (40.7%). Pattern 4 glioblastoma was subdivided into rim (T2-hypointensity ≥50% of circumference of contrast-enhanced tumor) and arc (T2-hypointensity <50% of circumference of contrast-enhanced tumor). Pattern 4 glioblastoma was further subdivided into group A (edema: T2-hyperintensity ≥50% of circumference of contrast-enhanced tumor) and group B (less edema: T2-hyperintensity <50% of circumference of contrast-enhanced tumor). Patients with pattern 3 glioblastoma (37.6%) had better survival compared with others (P = 0.0341) and pattern 4B had decreased survival compared with pattern 4A (P = 0.0001) and others (P = 0.0003)., Conclusions: Tumefactive MS and a subset of glioblastomas show specific patterns in histogram-profile analysis. The difference in anatomical border also determines difference in survival in glioblastoma. Histogram-profile analysis is a simple and efficient technique to differentiate these pathologies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tetrandrine (TET) and cepharanthine (CEP) are two bisbenzylisoquinoline alkaloids isolated from the traditional herbs. Recent molecular investigations firmly supported that TET or CEP would be a potential candidate for cancer chemotherapy. Prognosis of patients with glucocorticoid resistant T cell acute lymphoblastic leukemia (T-ALL) remains poor; here we examined the anti-T-ALL effects of TET and CEP and the underlying mechanism by using the glucocorticoid resistant human leukemia Jurkat T cell line in vitro. TET and CEP significantly inhibited cell viabilities and induced apoptosis in dose- and time-dependent manner. Further investigations showed that TET or CEP not only upregulated the expression of initiator caspases such as caspase-8 and 9, but also increased the expression of effector caspases such as caspase-3 and 6. As the important markers of apoptosis, p53 and Bax were both upregulated by the treatment of TET and CEP. However, TET and CEP paradoxically increased the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1, and activated the survival protein NF-κB, leading to high expression of p-NF-κB. Cell cycle arrest at S phase accompanied by increase in the amounts of cyclin A2 and cyclin B1, and decrease in cylcin D1 amount in cells treated with TET or CEP will be another possible mechanism. During the process of apoptosis in Jurkat T cells, treatment with TET or CEP also increased the phosphorylation of JNK and p38. The PI3K/Akt/mTOR signaling pathway modification appears to play significant role in the Jurkat T cell apoptosis induced by TET or CEP. Moreover, TET and CEP seemed to downregulate the expressions of p-PI3K and mTOR in an independent way from Akt, since these two drugs strongly stimulated the p-Akt expression. These results provide fundamental insights into the clinical application of TET or CEP for the treatment of patients with relapsed T-ALL., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To characterize the natural history and define the risk factors associated with the progression of normal-tension glaucoma (NTG) in Japanese patients who were followed up closely without treatment., Design: Prospective 5-year study., Participants: Patients with NTG with intraocular pressure (IOP) consistently ≤15 mmHg without treatment at baseline., Methods: Visual field (VF) examinations were performed every 3 months, and disc/peripapillary retina photographs were taken every 6 months. Patients were followed up without treatment., Main Outcome Measures: Deterioration in VF was defined by reference to Guided Progression Analysis Software of the Humphrey VF Swedish Interactive Thresholding Algorithm 24-2 (Carl Zeiss Meditec, Jena, Germany) and disc/peripapillary retina deterioration as adjudged by 3 independent observers. Life table analysis was used for evaluating the time to disease progression, as defined by VF or deterioration of the optic nerve head structure. The Cox proportional hazards model was used to identify risk factors for glaucoma progression., Results: We enrolled 90 patients (mean age, 53.9 years; baseline IOP, 12.3 mmHg; mean deviation [MD], -2.8 decibels [dB]). The MD slope averaged -0.33 dB/year (median, -0.23; 95% confidence interval [CI], -0.44 to -0.22). Glaucoma progression probability at 5 years was 66% (95% CI, 55-78), as defined by VF deterioration or disc/peripapillary retina deterioration (criterion 1): 52% (95% CI, 37-60), as defined by VF deterioration (criterion 2), and 50% (95% CI, 38-71), as defined by disc/peripapillary retina deterioration (criterion 3). Presence or history of disc hemorrhage (DH) (P < 0.001), long-term IOP fluctuation (P = 0.020), and a greater vertical cup-to-disc ratio (v-C/D) (P = 0.018) were significant predictors for progression defined by criterion 1. Long-term IOP fluctuation (P = 0.011) and a greater v-C/D (P = 0.036) were significant predictors for progression by criterion 2. Presence or history of DH (P = 0.0018) and long-term IOP fluctuation (P = 0.022) were significant predictors for progression by criterion 3., Conclusions: In Japanese patients with NTG with mean baseline IOP of 12.3 mmHg without treatment, estimated mean MD slope for 5 years was -0.33 dB/year; probability of glaucoma progression based on VF or disc/peripapillary end points at 5 years was 66%. Presence or history of DH, long-term IOP fluctuation, and greater v-C/D significantly contributed to progression., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate quantitatively whether the presence of cough associated with dysphagia (laryngeal cough reflex) increased mortality through respiratory disease among community-dwelling older Japanese., Design: A 6-year follow-up prospective cohort study (from 2010 to 2017)., Setting: Thirteen municipalities in Japan., Participants: Community-dwelling individuals aged 65 years or older (N = 32,682)., Measures: The baseline survey was conducted through self-reported questionnaire. Exposure was experience of laryngeal cough reflex while drinking. The outcome was all-cause mortality. All covariates were selected from demographic, socioeconomic variables, baseline health and functional status, smoking, alcohol drinking, number of remaining teeth, and stroke. The mediator variable was respiratory disease. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for mortality. Parametric mediation analysis was conducted to estimate the effect of laryngeal cough reflex on the mean residual time to death mediated through respiratory disease., Results: Among the 32,682 participants (mean age = 74.1 years, standard deviation = 5.9 years), 5550 (17.0%) experienced laryngeal cough reflex at baseline. A total of 4037 deaths occurred. Crude mortality rates of the participants with or without laryngeal cough reflex were 16.3% and 11.6%, respectively. After adjusting for covariates, laryngeal cough reflex [HR = 1.10; 95% confidence interval (CI) = 1.02 to 1.19] and respiratory disease (HR = 1.80; 95% CI = 1.62 to 2.00) were associated with mortality. The mediation analysis showed that respiratory disease significantly (P < .001) and partially mediated the association between laryngeal cough reflex, an indicator of 1 or more conditions such as chronic aspiration and mortality., Conclusions/implications: Laryngeal cough reflex was a prevalent condition, and it was associated with all-cause mortality in community-dwelling older Japanese individuals. Clinicians could contribute to reduce mortality risk by addressing swallowing function problems using their interprofessional collaboration team (speech-language pathologist, dentist, rehabilitation doctor, otolaryngologist, respiratory physician, and gerontologist)., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Occludin (OCLN), an integral tetra-spanning plasma membrane protein, is a host entry factor essential for hepatitis C virus (HCV) infection, making it a promising host-targeting molecule for HCV therapeutic intervention. We previously generated rat anti-OCLN monoclonal antibodies (mAbs) that strongly prevented HCV infection in vitro and in vivo. In the present study, we attempted to improve the druggability of the extracellular loop domain-recognizing anti-OCLN mAbs, namely clones 1-3 and 37-5, using genetic engineering. To avoid adverse reactions induced by antibody-dependent cellular cytotoxicity and enhance the antibody stability, we developed human-rat chimeric immunoglobulin G4 S228P mutant (IgG4m) forms of clones 1-3 and 37-5 (named Xi 1-3 and Xi 37-5, respectively) by grafting the variable regions of the light and heavy chains of each rat anti-OCLN mAb into those of human IgG4m. The constructed Xi 1-3 and Xi 37-5 chimeras demonstrated levels of affinity and specificity similar to each parental rat anti-OCLN mAb, and the Fcγ receptor Ⅲa was not activated by the antigen-bound chimeric mAbs, as expected. Both chimeric mAbs inhibited in vitro infection with various HCV genotypes. These results indicate that the IgG4m forms of human-rat chimeric anti-OCLN mAbs may be potential candidate molecules of host-targeting antivirals with pan-genotypic anti-HCV activity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Hypotension, a risk factor for increased mortality following traumatic brain injury (TBI), is traditionally defined as systolic blood pressure (SBP) <90 mm Hg. We aimed to redefine hypotension and determine its optimal threshold in patients with TBI., Methods: We identified patients with severe TBI (Glasgow Coma Scale score ≤8 on admission) between 2004 and 2015 using data from the Japan Trauma Data Bank. Our endpoint was in-hospital mortality. Mixed effects logistic regression models were used to investigate the association between SBP on admission and in-hospital mortality, with hospitals considered as a random effects variable. We also conducted analyses stratified by age (≤60 years and >60 years) to determine age-specific optimal levels of SBP., Results: A total of 12,537 patients (5665 patients ≤60 years old and 6872 patients >60 years old) were eligible for the analyses. Overall, SBP of 110 mm Hg was the optimal threshold for hypotension, and adjusted odds ratio and C-statistic for mortality at SBP <110 mm Hg on admission were 1.58 (95% confidence interval, 1.42-1.76, P < 0.001) and 0.78 (95% confidence interval, 0.77-0.79), respectively. Stratified analyses showed that optimal thresholds for hypotension in patients ≤60 years old and >60 years old were 100 mm Hg and 120 mm Hg., Conclusions: The threshold for hypotension in patients with severe TBI should be redefined and modified by age, and patients ≤60 years old should be considered hypotensive at SBP <100 mm Hg, whereas in older patients, SBP <120 mm Hg should be diagnosed as hypotension., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Traumatic posterior fossa subdural hemorrhage (SDH) is a rare subtype of subdural hemorrhage in head injuries. Existing data on its pathophysiology and outcome are currently limited; therefore, the condition is not yet fully understood. The present study aimed to determine the incidence, outcome, and prognostic factors for traumatic posterior fossa SDH., Methods: We performed a retrospective cohort study using the nationwide trauma registry Japan Trauma Data Bank. We identified adult patients (i.e., aged ≥18 years) who had posterior fossa SDH after blunt head trauma from 2004 to 2015. The primary endpoint was in-hospital mortality. We compared patients with and without posterior fossa SDH and adjusted for confounders using a multivariate logistic regression model., Results: A total of 75,838 patients had blunt head injuries. Of these, 266 (0.35%) had posterior fossa SDH, and 177 (median age, 69 years; interquartile range, 55-76) were eligible for analysis. The distribution of the Glasgow Coma Scale (GCS) score was bimodal, and the median score was 14 (interquartile range, 9-15). The mortality rate was 16.9% (95% confidence interval [CI], 11.7%-23.3%). A large posterior fossa SDH (>30 cm 3 ; >1 cm thick), low GCS score on arrival, and the presence of a skull fracture were significantly associated with mortality, with an adjusted odds ratio of 4.51 (95% CI, 1.46-13.9), 0.82 (95% CI, 0.73-0.92), and 4.59 (95% CI, 1.52-13.9), respectively., Conclusions: Traumatic posterior fossa SDH was extremely rare in our data set. Mortality correlated with the size of the SDH, GCS score on admission, and the presence of a skull fracture., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Perfusion computed tomography (PCT) reflects blood flow and capillary condition, which is valuable in assessing brain tumors. We evaluated PCT parameters at the tumor (t) and peritumoral (p) region to differentiate malignant brain tumors., Methods: We performed PCT in 39 patients with supratentorial malignant brain tumors (22 glioblastomas, 6 lymphomas, 11 metastases). Regions of interests were placed manually at tumor, peritumoral region, and contralateral normal-appearing white matter. Cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability surface (PS) were measured. These parameters were divided by those of contralateral normal-appearing white matter to normalize at tumor (relative [r]CBVt, rCBFt, rMTTt, rPSt) and peritumoral regions (rCBVp, rCBFp, rMTTp, rPSp). The parameters were evaluated with Mann-Whitney U test and receiver operating characteristics analyses. Stepwise analyses also were performed to select useful PCT parameters for differentiating these tumors., Results: The rCBFt and rCBVt of glioblastoma (GBM) were greater than those of primary central nervous system lymphoma (PCNSL) (P = 0.0005, 0.0002) and brain metastasis (METS) (P = 0.0044, 0.0028). The rMTTp of METS was greater than that of GBM and PCNSL (P = 0.0001, 0.0007). The combination of rCBVt and rPSt could differentiate GBM from other tumors with sensitivity and specificity of 81.8% and 94.1%. The combination of rCBFp and rMTTp could differentiate METS from other tumors with sensitivity and specificity of 90.9% and 82.1%., Conclusions: Our study introduces and supports the usefulness of PCT parameters for differentiation among GBM, PCNSL, and METS. rCBVt and rPSt may be the best predictors of GBM. rCBFp and rMTTp may be the best predictors of METS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on dexterity remains controversial despite its recognition as an effective strategy for Parkinson disease. The present study investigated the efficacy of STN-DBS for ameliorating bradykinesia and dexterity compared with dopaminergic medications., Methods: Part III of the Unified Parkinson's Disease Rating Scale was used for the evaluation of bradykinesia, whereas the Purdue Pegboard Test and the Box and Block test were selected for dexterity., Results: Our findings indicate that bradykinesia is significantly improved with both DBS and dopaminergic medication, whereas dexterity is improved only with DBS. Dopaminergic medication did not show a satisfactory efficacy on dexterity, and there was little synergistic effect of dopaminergic medication and STN-DBS for improving dexterity associated with Parkinson disease., Conclusions: Our results suggest that DBS is potentially more effective than dopaminergic medications for improving dexterity. The disparities in efficacy for bradykinesia and dexterity between DBS and dopaminergic medication hint at the potential mechanisms of STN-DBS. We speculate that DBS follows at least 2 different mechanisms for improving parkinsonian symptoms: 1) the dopaminergic system, primarily for the improvement of bradykinesia and 2) the nondopaminergic system, for the improvement of dexterity. This hypothesis requires further verification and investigation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Data on traumatic intraventricular hemorrhage (IVH) are currently limited, and therefore, the condition is not fully understood. The aim of this study was to determine the epidemiology of traumatic IVH and its effects on outcome in patients with blunt head trauma., Methods and Materials: Using a nationwide trauma registry-the Japan Trauma Data Bank, we identified patients who underwent head computed tomography (CT) after blunt head trauma and had intracranial injuries between 2004 and 2015. The endpoint was in-hospital mortality. We compared patients with IVH and without IVH and adjusted for potential confounders using a multivariate logistic regression model., Results: A total of 236,698 patients were registered in the database. Of the 139,058 patients who underwent head CT after blunt trauma, 906 (0.7%) had traumatic IVH. Among the 53,618 patients who were eligible for analysis, 871 had IVH. Traumatic IVH was associated with the occurrence of traffic accidents that caused trauma and severe injuries. Mortality was significantly higher in patients with IVH than in those without IVH (33.5% vs. 18.5%; P < 0.001); however, the difference was not significant after adjusting for confounding factors, with an adjusted odds ratio of 1.13 (95% confidence interval: 0.91-1.40)., Conclusions: Traumatic IVH is associated with a high mortality. However, the outcome in patients with traumatic IVH was worse than that in patients without IVH, which could be a result of factors associated with IVH rather than of IVH alone., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: The purpose was to characterize public perceptions in Japan of mental illness and how they related to stigma-related attitudes for the same., Methods: Data were obtained using a vignette survey conducted as a part of the Stigma in Global Context - Mental Health Study and contained a nationally representative sample (n = 994). The survey was conducted using a multi-mode approach (face-to-face interviews, the drop-off-and-pick-up, postal collection) from September to December 2006, with a multi-stage probability sample of Japanese residents aged 18-64 years. Respondents were randomly assigned one of four vignette conditions that described psychiatric disorders meeting the diagnostic criteria for schizophrenia and major depressive disorder (one vignette for each gender exhibiting each diagnosis). We compared respondents' stigma-related attitudes and perceptions toward mental illness between vignettes., Results: Over 80% of Japanese participants believed that depressive disorder or schizophrenia could be cured via treatment. However, Japanese people still had relatively strong vigilance and denial of competency toward schizophrenia., Conclusions: Participants expressed the belief that mental illnesses are curable, but stigma toward people with schizophrenia was still relatively strong., (Copyright © 2018 Elsevier B.V. All rights reserved.)