Publications by authors named "Hidenori Suzuki"

474 Publications

Clarithromycin Ameliorates Early Brain Injury After Subarachnoid Hemorrhage via Suppressing Periostin-Related Pathways in Mice.

Neurotherapeutics 2021 Apr 7. Epub 2021 Apr 7.

Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.

Subarachnoid hemorrhage (SAH) remains a life-threatening disease, and early brain injury (EBI) is an important cause of poor outcomes. The authors have reported that periostin, a matricellular protein, is one of key factors of post-SAH EBI. Clarithromycin (CAM) is a worldwide antibiotic that can inhibit periostin expression. This study aimed to investigate whether CAM suppressed EBI after experimental SAH, focusing on blood-brain barrier (BBB) disruption, an important pathology of EBI. C57BL/6 male adult mice underwent endovascular perforation SAH modeling (n = 139) or sham operation (n = 30). Different dosages (25, 50, or 100 mg/kg) of CAM or the vehicle (n = 16, 52, 13, and 58, respectively) were randomly administered by an intramuscular injection 5 min after SAH induction. Post-SAH 50 mg/kg CAM treatment most effectively improved neurological scores and brain water content at 24 and 48 h and reduced immunoglobulin G extravasation at 24 h compared with vehicle-treated SAH mice (p < 0.01). Western blotting showed that post-SAH BBB disruption was associated with increased expressions of periostin, phosphorylated signal transducer and activator of transcription 1 and 3, matrix metalloproteinase-9, and the consequent degradation of zonula occludens-1, which were suppressed by 50 mg/kg CAM treatment (p < 0.05, respectively, versus vehicle-treated SAH mice). Periostin and its related molecules were upregulated in capillary endothelial cells and neurons after SAH. An intracerebroventricular injection of recombinant periostin blocked the neuroprotective effects of CAM in SAH mice (n = 6, respectively; p < 0.05). In conclusion, this study first demonstrated that CAM improved post-SAH EBI in terms of BBB disruption at least partly via the suppression of periostin-related pathways.
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http://dx.doi.org/10.1007/s13311-021-01050-5DOI Listing
April 2021

Clinical impact of weekly paclitaxel plus cetuximab is comparable to the EXTREME regimen for recurrent/metastatic head and neck squamous cell carcinoma.

Int J Clin Oncol 2021 Apr 5. Epub 2021 Apr 5.

Department of Head and Neck Surgery, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan.

Background: Until the emergence of immune checkpoint inhibitors, the EXTREME regimen comprising platinum-based chemotherapy plus cetuximab was the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Recent reports suggest the usefulness of regimens including taxanes in combination with cetuximab as treatment options for R/M HNSCC patients with contraindications for platinum. However, comparisons of weekly paclitaxel plus cetuximab (wPTX-Cmab) to the EXTREME regimen are limited.

Materials And Methods: We compared the clinical impact of wPTX-Cmab to EXTREME as first line treatment for R/M HNSCC in Aichi Cancer Center Hospital. The primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). Propensity score-adjusted Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: From 2012 to 2018, 77 patients, including 55 treated with EXTREME and 22 refractory or intolerant to platinum treated with wPTX-Cmab, were analyzed. wPTX-Cmab was comparable to EXTREME on OS [adjusted HR 0.82 (95% CI 0.39-1.48)], PFS [adjusted HR 0.90 (95% CI 0.49-1.65)], ORR [wPTX-Cmab 34.7% (12-43), EXTREME 30.9% (18-43), p = 0.877] and DCR [wPTX-Cmab 72.7% (52-92), EXTREME 65.4% (52-78), p = 0.337]. Survival trends remained similar after stratification by platinum-refractory or intolerance status. Disease control with wPTX-Cmab was significantly associated with better OS [adjusted HR 0.18 (0.05-0.57)].

Conclusion: wPTX-Cmab may be a suitable treatment option for R/M HNSCC patients with contraindications for platinum.
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http://dx.doi.org/10.1007/s10147-021-01907-xDOI Listing
April 2021

Urinary MicroRNA-Based Diagnostic Model for Central Nervous System Tumors Using Nanowire Scaffolds.

ACS Appl Mater Interfaces 2021 Apr 1. Epub 2021 Apr 1.

Department of Neurosurgery, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

There are no accurate mass screening methods for early detection of central nervous system (CNS) tumors. Recently, liquid biopsy has received a lot of attention for less-invasive cancer screening. Unlike other cancers, CNS tumors require efforts to find biomarkers due to the blood-brain barrier, which restricts molecular exchange between the parenchyma and blood. Additionally, because a satisfactory way to collect urinary biomarkers is lacking, urine-based liquid biopsy has not been fully investigated despite the fact that it has some advantages compared to blood or cerebrospinal fluid-based biopsy. Here, we have developed a mass-producible and sterilizable nanowire-based device that can extract urinary microRNAs efficiently. Urinary microRNAs from patients with CNS tumors ( = 119) and noncancer individuals ( = 100) were analyzed using a microarray to yield comprehensive microRNA expression profiles. To clarify the origin of urinary microRNAs of patients with CNS tumors, glioblastoma organoids were generated. Glioblastoma organoid-derived differentially expressed microRNAs (DEMs) included 73.4% of the DEMs in urine of patients with parental tumors but included only 3.9% of those in urine of noncancer individuals, which suggested that many CNS tumor-derived microRNAs could be identified in urine directly. We constructed the diagnostic model based on the expression of the selected microRNAs and found that it was able to differentiate patients and noncancer individuals at a sensitivity and specificity of 100 and 97%, respectively, in an independent dataset. Our findings demonstrate that urinary microRNAs extracted with the nanowire device offer a well-fitted strategy for mass screening of CNS tumors.
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http://dx.doi.org/10.1021/acsami.1c01754DOI Listing
April 2021

Effects of dosing frequency on the clinical efficacy of ampicillin/sulbactam in Japanese elderly patients with pneumonia: A single-center retrospective observational study.

Pharmacol Res Perspect 2021 Apr;9(2):e00746

Division of Pharmacokinetics and Pharmacodynamics, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University, Tokyo, Japan.

This study sought to investigate whether dosing frequency (the number of doses per day) affects the antimicrobial efficacy and safety of ampicillin/sulbactam (ABPC/SBT) in Japanese elderly pneumonia patients treated with ABPC/SBT at 6 g/day. This was a retrospective observational study that included hospitalized elderly patients (aged ≥75 years, 10 ml/min ≤CLcr <50 ml/min) who received 3 g every 12 h (BID; n = 61) or 1.5 g every 6 h (QID; n = 45) for the treatment of pneumonia. The primary endpoint was clinical response, assessed by measuring body temperature, white blood cell count, and C-reactive protein levels. Pharmacokinetic and pharmacodynamic simulations were conducted in silico to rationalize the clinical findings. The clinical response rates (extremely effective and effective) in the BID and QID groups were 36.1% and 55.6%, respectively (p = .0459). QID tended to be more effective in patients with gram-negative rods detected (p = .0563). According to the simulated minimum plasma ABPC concentrations at steady state for BID and QID were 2.5 and 7.3 μg/ml, respectively (p < .0001). Based on the simulated time above minimum inhibitory concentration (MIC), pharmacological (not clinical) efficacy was predicted to be higher with QID. Both groups had similar safety profiles. The main adverse event in both groups was liver damage. The present retrospective survey demonstrated that ABPC/SBT treatment for elderly patients with pneumonia and renal dysfunction was more effective with QID than with BID. Therefore, the QID regimen is worthy of consideration to improve the clinical outcomes of ABPC/SBT therapy in the present patient population.
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http://dx.doi.org/10.1002/prp2.746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992287PMC
April 2021

Randomized trial of granulocyte colony-stimulating factor for spinal cord injury.

Brain 2021 Mar 25. Epub 2021 Mar 25.

G-SPIRIT Study Group, Chiba, Japan.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.
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http://dx.doi.org/10.1093/brain/awaa466DOI Listing
March 2021

Randomized trial of granulocyte colony-stimulating factor for spinal cord injury.

Brain 2021 Mar 25. Epub 2021 Mar 25.

G-SPIRIT Study Group, Chiba, Japan.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.
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http://dx.doi.org/10.1093/brain/awaa466DOI Listing
March 2021

Treatment outcome and pattern of recurrence of sinonasal squamous cell carcinoma with EGFR-mutation and human papillomavirus.

J Craniomaxillofac Surg 2021 Feb 22. Epub 2021 Feb 22.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, Japan. Electronic address:

The objective of our study was to clarify the clinical features of EGFR-mutated sinonasal squamous cell carcinoma (SNSCC) and human papilloma virus (HPV)-related SNSCC. Patients with SNSCC treated from April 2008 to June 2019 at our institution were retrospectively reviewed. We examined EGFR mutation and HPV status for all patients. Main outcomes were overall survival, recurrence, and outcome of each treatment modality. A total of 85 patients with SNSCC were enrolled in this study. EGFR mutations and HPV DNA were detected in 24 (28%) and 7 (8%) patients, respectively. Patients with EGFR-mutated SNSCC showed a worse overall survival (OS) than those with EGFR wild-type in the multivariate analysis (p = 0.037). No death was observed in HPV-positive SNSCC. The cumulative incidence of local recurrence was significantly higher in EGFR mutant than EGFR wild-type tumors (p = 0.03). In patients with EGFR mutations, treatment with induction chemotherapy significantly improved OS (p = 0.01). EGFR-mutated SNSCC have a high-risk feature for recurrence and requires intensive attention for treatment and observation. A new treatment approach, such as EGFR tyrosine kinase inhibitors, may be needed.
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http://dx.doi.org/10.1016/j.jcms.2021.02.016DOI Listing
February 2021

Bupropion increases cerebral activation in auditory affective processing: A randomized controlled fMRI study.

Neurosci Lett 2021 04 13;749:135716. Epub 2021 Feb 13.

Department of Neuropsychiatry, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. Electronic address:

Introduction: Bupropion is an antidepressant with less possibility to give rise to emotional blunting as side effect, and it also acts on improving negative self-recognition in a depressive state. Previous neuroimaging studies indicated a change in brain function by facial expression as an effect of antidepressants. As well as facial expression, vocal affective processing is essential for accurately recognizing another's feelings, but to our knowledge, no study has investigated whether bupropion affects the cerebral function of recognition of auditory affective processing. In this study, we aimed to investigate the acute effect of bupropion on cerebral response to vocal affective processing.

Methods: Sixteen healthy volunteers (male = 8) participated in this study. With a randomized placebo-controlled within-subject trial, two series of fMRI scans, using either placebo or bupropion (150 mg), were examined. An auditory emotional valence judgement task was performed during fMRI scanning. The acute effects of bupropion on cerebral activation in the emotional circuit and behavioral performance during emotional processing were analyzed.

Results: Compared with placebo, bupropion caused a significantly greater activation of emotional voices in the left insula and right superior temporal gyrus, whereas the amygdala was not activated. By bupropion, a significantly greater activation of the positive emotional circuit was observed at the superior temporal gyrus and middle frontal gyrus. As for behavioral performance, no significant difference was observed between placebo and bupropion.

Conclusions: Our findings suggest that bupropion enhances the cerebral response to affective processing, especially positive emotional vocalizations, indicating a possible mechanism underlying the therapeutic effects for patients with depression.
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http://dx.doi.org/10.1016/j.neulet.2021.135716DOI Listing
April 2021

Effects of anodal transcranial direct current stimulation on implicit motor learning and language-related brain function: An fMRI study.

Psychiatry Clin Neurosci 2021 Feb 12. Epub 2021 Feb 12.

Department of Neuropsychiatry, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

Aim: Anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) is known as a useful application for improving depressive symptoms or cognitive performance. Antidepressive effects by anodal tDCS over the left DLPFC are expected, but the neural mechanisms of these effects are still unclear. Further, in depression, reduced performance and left prefrontal hypofunction during the verbal fluency task (VFT) are generally known. However, few studies have examined the effect of tDCS on the language-related cerebral network. We aimed to investigate whether anodal tDCS at the left DLPFC affects cognitive performance and the neural basis of verbal fluency.

Methods: Nineteen healthy volunteers participated in this study. The effects of tDCS on cognitive behavior and cerebral function were evaluated by (i) performance and accuracy of implicit/explicit motor learning task (serial reaction time task/sequential finger-tapping task), and (ii) cerebral activation while the subjects were performing the VFT by using a functional MRI protocol of a randomized sham-controlled, within-subjects crossover design.

Results: Reaction times of the implicit motor learning task were significantly faster with tDCS in comparison with the sham. Further, language-related left prefrontal-parahippocampal-parietal activation was significantly less with tDCS compared with the sham. Significant correlation was observed between shortened response time in serial reaction time task and decreased cerebral activation during VFT with tDCS.

Conclusion: Anodal tDCS over the left DLPFC could improve cognitive behavior of implicit motor learning by improving brain function of the frontoparietal-parahippocampal region related to motor learning, as well as language-related regions.
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http://dx.doi.org/10.1111/pcn.13208DOI Listing
February 2021

Serum CD109 levels reflect the node metastasis status in head and neck squamous cell carcinoma.

Cancer Med 2021 Feb 9;10(4):1335-1346. Epub 2021 Feb 9.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Various biomarkers are being developed for the early diagnosis of cancer and for predicting its prognosis. The aim of this study is to evaluate the diagnostic significance of serum CD109 in head and neck squamous cell carcinoma (HNSCC).

Methods: The serum CD109 levels in a total of 112 serum samples collected before and after surgery from 56 HNSCC patients were analyzed with an enzyme-linked immunosorbent assay (ELISA). The clinical factor that showed a statistically significant association with both the preoperative serum CD109 level, and the CD109 index: which was defined as the ratio of the preoperative serum CD109 level to the postoperative serum CD109 level, were assessed. The correlations between the serum CD109 levels and lymph node density (LND), pathological features such as lymphatic invasion, and serum SCC antigen levels were also assessed.

Results: The ELISA measurement revealed that preoperative serum CD109 levels were elevated in patients with node metastasis-positive and stage IV disease, in comparison to those with node metastasis-negative and Stage I+II+III disease, respectively. A multiple regression analysis indicated that serum CD109 level was significantly associated with the node metastasis status. A Spearman's rank correlation analysis also revealed a positive correlation between the preoperative serum CD109 level and LND. Furthermore, the probabilities of the overall and relapse-free survival were significantly lower in patients with a preoperative serum CD109 level of ≥38.0 ng/ml and a CD109 index of ≥1.6, respectively, than in others. There was no significant correlation between the serum CD109 and SCC antigen levels.

Conclusions: The serum CD109 levels were elevated in patients with advanced stage disease, reflecting the node metastasis status. CD109 in sera could be a novel prognostic marker for HNSCC involving lymph node metastasis.
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http://dx.doi.org/10.1002/cam4.3737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926025PMC
February 2021

The Role of Tenascin-C in Tissue Injury and Repair After Stroke.

Front Immunol 2020 21;11:607587. Epub 2021 Jan 21.

Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.

Stroke is still one of the most common causes for mortality and morbidity worldwide. Following acute stroke onset, biochemical and cellular changes induce further brain injury such as neuroinflammation, cell death, and blood-brain barrier disruption. Matricellular proteins are non-structural proteins induced by many stimuli and tissue damage including stroke induction, while its levels are generally low in a normal physiological condition in adult tissues. Currently, a matricellular protein tenascin-C (TNC) is considered to be an important inducer to promote neuroinflammatory cascades and the resultant pathology in stroke. TNC is upregulated in cerebral arteries and brain tissues including astrocytes, neurons, and brain capillary endothelial cells following subarachnoid hemorrhage (SAH). TNC may be involved in blood-brain barrier disruption, neuronal apoptosis, and cerebral vasospasm the activation of mitogen-activated protein kinases and nuclear factor-kappa B following SAH. In addition, post-SAH TNC levels in cerebrospinal fluid predicted the development of delayed cerebral ischemia and angiographic vasospasm in clinical settings. On the other hand, TNC is reported to promote fibrosis and exert repair effects for an experimental aneurysm macrophages-induced migration and proliferation of smooth muscle cells. The authors review TNC-induced inflammatory signal cascades and the relationships with other matricellular proteins in stroke-related pathology.
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http://dx.doi.org/10.3389/fimmu.2020.607587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859104PMC
January 2021

Higher Plasma Osteopontin Concentrations Associated with Subsequent Development of Chronic Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage.

Transl Stroke Res 2021 Jan 9. Epub 2021 Jan 9.

Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

A matricellular protein osteopontin (OPN) is considered to exert neuroprotective and healing effects on neurovascular injuries in an acute phase of aneurysmal subarachnoid hemorrhage (SAH). However, the relationships between OPN expression and chronic shunt-dependent hydrocephalus (SDHC) have never been investigated. In 166 SAH patients (derivation and validation cohorts, 110 and 56, respectively), plasma OPN levels were serially measured at days1-3, 4-6, 7-9, and 10-12 after aneurysmal obliteration. The OPN levels and clinical factors were compared between patients with and without subsequent development of chronic SDHC. Plasma OPN levels in the SDHC patients increased from days 1-3 to days 4-6 and remained high thereafter, while those in the non-SDHC patients peaked at days 4-6 and then decreased over time. Plasma OPN levels had no correlation with serum levels of C-reactive protein (CRP), a systemic inflammatory marker. Univariate analyses showed that age, modified Fisher grade, acute hydrocephalus, cerebrospinal fluid drainage, and OPN and CRP levels at days 10-12 were significantly different between patients with and without SDHC. Multivariate analyses revealed that higher plasma OPN levels at days 10-12 were an independent factor associated with the development of SDHC, in addition to a more frequent use of cerebrospinal fluid drainage and higher modified Fisher grade at admission. Plasma OPN levels at days 10-12 maintained similar discrimination power in the validation cohort and had good calibration on the Hosmer-Lemeshow goodness-of-fit test. Prolonged higher expression of OPN may contribute to the development of post-SAH SDHC, possibly by excessive repairing effects promoting fibrosis in the subarachnoid space.
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http://dx.doi.org/10.1007/s12975-020-00886-xDOI Listing
January 2021

Recurrent ameloblastoma with both hypercalcemia and BRAF mutation: A case report.

Clin Case Rep 2020 Dec 28;8(12):3463-3467. Epub 2020 Oct 28.

Department of Head and Neck Surgery Aichi Cancer Center Hospital Nagoya Japan.

This case report describes a mandibular ameloblastoma with both V600E mutation and rare hypercalcemia. The patient without distant metastasis underwent subtotal mandibulectomy using double flaps of fibula and anterolateral thigh. A whole body computed tomography scan taken 69 months after surgery revealed neither recurrence nor metastasis.
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http://dx.doi.org/10.1002/ccr3.3443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752588PMC
December 2020

Anticoagulant activity of apixaban can be estimated by multiple regression analysis.

J Arrhythm 2020 Dec 22;36(6):1032-1038. Epub 2020 Sep 22.

Department of Pharmacology Graduate School of Medicine Nippon Medical School Bunkyo-ku Japan.

Background: Information on apixaban anticoagulant activity is required to prevent major bleeding or thrombosis during its use.

Methods: We enrolled 194 patients with nonvalvular atrial fibrillation (NVAF) in whom warfarin was replaced with apixaban: 105 (54.1%) received the standard dose of apixaban (5 mg twice daily [BID]; 5 mg group) and 89 (45.9%) received a reduced dose (2.5 mg BID; 2.5 mg group). Multiple regression analysis was performed to predict the prothrombin time of apixaban (PTa) based on factors including age, body weight (BW), serum creatinine, and CHADS-VASc score.

Results: PTa and PT of warfarin (PTw) were significantly correlated in both groups (correlation coefficient R = 0.239 [ = .014] in the 5 mg group; R = 0.248 [ = .019] in the 2.5 mg group). PTa in the 5 mg group was predicted as follows: 16.952-0.036 × BW +0.299 × CHADS-VASc score ( < .0004; R = 0.378). However, in the 2.5 mg group, PTa could not be predicted. The mean of the predicted and measured PTa values in the 5 mg group was 15.6 s, which was similar to the mean measured PTa of 15.5 s in the 2.5 mg group.

Conclusions: PT can be predicted by a formula including simple clinical parameters in patients receiving the standard dose of apixaban. This simple predictive formula may help to stratify bleeding and thrombosis risks in patients treated with apixaban.
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http://dx.doi.org/10.1002/joa3.12435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733564PMC
December 2020

A Case of Miyazaki Syndrome Caused by Arachnoid Cyst-Peritoneal Shunt.

World Neurosurg 2021 Feb 23;146:85-89. Epub 2020 Oct 23.

Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.

Background: Miyazaki syndrome is overshunting-associated myelopathy, which is a rare complication of ventriculoperitoneal shunt. We present the first case of Miyazaki syndrome caused by cystoperitoneal (CP) shunt for an arachnoid cyst (AC) in this report.

Case Description: We report a case of a 42-year-old man with 12-year progressive spastic paraplegia, who underwent CP shunt for an AC at the age of 15 years. Although few findings suggested overshunting on symptoms and head computed tomography, contrast-enhanced magnetic resonance imaging revealed the engorgement of the cervical spinal epidural venous plexus compressing the spinal cord. Shunt valve replacement with a pressure-adjustable valve was performed. Postoperatively, the cervical cord compression by the enlarged spinal epidural venous plexus was completely improved, but, possibly due to delayed diagnosis and treatment, the patient's symptoms only partially improved.

Conclusions: When patients with a history of any kind of shunt surgery develop myelopathy, Miyazaki syndrome should be suspected and, for early diagnosis, cervical and/or contrast-enhanced magnetic resonance imaging should be performed.
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http://dx.doi.org/10.1016/j.wneu.2020.10.094DOI Listing
February 2021

Eosinophil prognostic scores for patients with head and neck squamous cell carcinoma treated with nivolumab.

Cancer Sci 2021 Jan 4;112(1):339-346. Epub 2020 Nov 4.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Although nivolumab, a programmed cell death 1 (PD-1) inhibitor, is a standard therapy for platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), no definitive biomarkers have been reported thus far. This study aimed to select promising prognostic markers in nivolumab therapy and to create a novel prognostic scoring system. In this retrospective cohort study, we reviewed patients with R/M HNSCC who were treated with nivolumab from April 2017 to April 2019. We developed a prognostic score for immune checkpoint inhibitor (ICI) therapy that was weighed using hazard ratio-based scoring algorithms. Significant variables were selected from the multivariate Cox proportional hazard analyses on overall survival (OS). A total of 85 patients with HNSCC were analyzed in the present study. The relative eosinophil count (REC), the ratio of eosinophil increase (REI), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) were selected as variables affecting the prognostic score. The patients were divided into four groups: very good (score = 0), good (score = 1), intermediate (score = 2), and poor (score = 3). The OS hazard ratios were 2.77, 10.18, and 33.21 for the good, intermediate, and poor risk groups compared with the very good risk group, respectively. The Eosinophil Prognostic Score is a novel prognostic score that is effective for predicting the prognosis of HNSCC patients treated with nivolumab. This score is more precise as it includes changes in biomarkers before and after the treatment.
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http://dx.doi.org/10.1111/cas.14706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780035PMC
January 2021

A Case of Suspected Metallic Embolism after Carotid Artery Stenting.

NMC Case Rep J 2020 Sep 17;7(4):229-231. Epub 2020 Sep 17.

Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

A case in which metallic embolism was suspected after carotid artery stenting (CAS) is described. A 79-year-old woman was referred to our hospital because of a severe stenosis of the left cervical internal carotid artery (ICA). Carotid ultrasound revealed that the plaque was fibrous and was accompanied with partial calcification. The carotid stenosis was treated by CAS. The magnetic resonance imaging (MRI) taken in the following day of the CAS demonstrated that a new abnormal spot at the left frontal lobe. The spot appeared as a signal void on T1, T2, diffusion, susceptibility-weighted image (SWI), and fluid attenuated inversion recovery (FLAIR) image, and was surrounded by a high-signal halo on T2 and diffusion-weighted images (DWIs). The spot also demonstrated "blooming" appearance on SWIs. Despite the lesion she was asymptomatic all through the postoperative course, and she left our hospital on postoperative day 6. Follow-up MRI obtained 27 months after the CAS demonstrated that the lesion remained at the left frontal lobe without any signal changes. The patient remained asymptomatic at the last follow-up. Considering the location of the new abnormal spot (in the vascular territory of the catheterized vessel), these imaging characteristics and asymptomatic clinical course, the spot likely suggested metallic embolism. This is the first case in which the metallic embolism was suspected after CAS.
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http://dx.doi.org/10.2176/nmccrj.cr.2020-0027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538461PMC
September 2020

The Impact of Anterior Spondylolisthesis and Kyphotic Alignment on Dynamic Changes in Spinal Cord Compression and Neurological Status in Cervical Spondylotic Myelopathy: A Radiological Analysis Involving Kinematic CT Myelography and Multimodal Spinal Cord Evoked Potentials.

Spine (Phila Pa 1976) 2021 Jan;46(2):72-79

Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

Study Design: A retrospective study of prospectively collected data.

Objective: This study aimed to examine how radiological parameters affect dynamic changes in the cross-sectional area of the spinal cord (CSA) in cervical spondylotic myelopathy (CSM) patients and how they correlate with the severity of myelopathy, by evaluating multi-modal spinal cord evoked potentials (SCEPs).

Summary Of Background Data: Appropriate assessments of dynamic factors should reveal hidden spinal cord compression and provide useful information for choosing surgical procedures.

Methods: Seventy-nine CSM patients were enrolled. They were examined with kinematic CT myelography (CTM), and the spinal levels responsible for their CSM were determined via SCEP examinations. The C2-7 angle, C2-7 range of motion, and percentage of slip were measured on the midsagittal view during flexion and extension, and the CSA was measured on the axial view in each neck position using kinematic CTM. The patients who exhibited the smallest CSA values during extension and flexion were classified into Groups E and F, respectively.

Results: Fifty-two (65.8%) and 27 (34.2%) cases were included in Groups E and F, respectively. The preoperative JOA score did not differ significantly between the groups; however, the preoperative lower-limb JOA score of Group F was significantly lower than that of Group E (2.24 ± 0.82 vs. 2.83 ± 1.09, P = 0.016). In the multiple logistic regression analysis, a small C2-7 angle during extension (β = 5°, odds ratio: 0.69, 95% confidence interval [CI]: 0.54-0.90) and the slip percentage during flexion (β = 5%, odds ratio: 1.42, 95% CI: 1.09-1.85) were identified as significant predictors of belonging to Group F.

Conclusion: Exhibiting more severe spinal cord compression during neck flexion was associated with a small C2-7 angle and anterior spondylolisthesis. The neurological status of the patients in Group F was characterized by severe lower limb dysfunction because of a disturbed blood supply to the anterior column.Level of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003735DOI Listing
January 2021

Cerebrovascular pathophysiology of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Histol Histopathol 2020 Sep 30:18253. Epub 2020 Sep 30.

Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.

Aneurysmal subarachnoid hemorrhage (SAH) remains a serious cerebrovascular disease. Even if SAH patients survive the initial insults, delayed cerebral ischemia (DCI) may occur at 4 days or later post-SAH. DCI is characteristics of SAH, and is considered to develop by blood breakdown products and inflammatory reactions, or secondary to early brain injury, acute pathophysiological events that occur in the brain within the first 72 hours of aneurysmal SAH. The pathology underlying DCI may involve large artery vasospasm and/or microcirculatory disturbances by microvasospasm, microthrombosis, dysfunction of venous outflow and compression of microvasculature by vasogenic or cytotoxic tissue edema. Recent clinical evidence has shown that large artery vasospasm is not the only cause of DCI, and that both large artery vasospasm-dependent and -independent cerebral infarction causes poor outcome. Animal studies suggest that mechanisms of vasospasm may differ between large artery and arterioles or capillaries, and that many kinds of cells in the vascular wall and brain parenchyma may be involved in the pathogenesis of microcirculatory disturbances. The impairment of the paravascular and glymphatic systems also may play important roles in the development of DCI. As pathological mediators for DCI, glutamate and several matricellular proteins have been investigated in addition to inflammatory molecules. Glutamate is involved in excitotoxicity contributing to cortical spreading ischemia and epileptic activity-related events. Microvascular dysfunction is an attractive mechanism to explain the cause of poor outcomes independently of large cerebral artery vasospasm, but needs more studies to clarify the pathophysiologies or mechanisms and to develop a novel therapeutic strategy.
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http://dx.doi.org/10.14670/HH-18-253DOI Listing
September 2020

Association between treatment package time and clinical predictors in oropharyngeal cancer.

Medicine (Baltimore) 2020 Sep;99(39):e22244

Department of Head and Neck Surgery, Aichi Cancer Center Hospital.

The aim of the present study is to investigate the association of treatment package time with the survival outcomes and clinical parameters in patients with oropharyngeal squamous cell carcinoma.A total of 49 patients who underwent definitive treatment were enrolled. The treatment package time was calculated in days from the start of any treatment to the completion of all treatments, including postoperative treatment and salvage surgery for residual tumor.On univariate analyzes, treatment package time ≥118 days, sake index ≥60, Brinkman index ≥450, maximum standardized uptake value ≥42.45, and the presence of synchronous cancer were significantly associated with shorter oropharyngeal squamous cell carcinoma-specific survival. Moreover, a treatment package time of ≥118 days was significantly correlated with shorter overall survival and distant metastasis-free survival. On multivariate analyzes, Brinkman index ≥450 was significantly associated with shorter oropharyngeal squamous cell carcinoma-specific and locoregional recurrence-free survival, and the presence of synchronous cancer was significantly associated with shorter overall and distant metastasis-free survival.In conclusion, a relatively long treatment package time was a predictor of low survival outcomes in oropharyngeal squamous cell carcinoma by univariate analysis.
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http://dx.doi.org/10.1097/MD.0000000000022244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523759PMC
September 2020

Dural Arteriovenous Fistula Formation as Eagle Jugular Syndrome: A Case Report and Literature Review.

World Neurosurg 2020 Dec 3;144:154-161. Epub 2020 Sep 3.

Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.

Background: An elongated styloid process can less frequently lead to symptomatic compression of the internal jugular vein (IJV). We present the first case of dural arteriovenous fistula (DAVF) in association with compressed IJV by an elongated styloid process.

Case Description: A 77-year-old woman presented with pulsating tinnitus. DAVF at the right hypoglossal canal was diagnosed, and she underwent transvenous embolization. The shunt flow was reduced, and the symptom disappeared after transvenous embolization. However, 2 years and 8 months later, retrograde sinus drainage from the residual shunt was asymptomatically found on magnetic resonance imaging, and angiography revealed progression of IJV stenosis caused by an elongated styloid process. Subsequently, she underwent a second transvenous embolization, and the arteriovenous shunt was almost completely obliterated.

Conclusions: The present case suggests that venous hypertension by compressed IJV can induce the development of DAVF. It is helpful for the diagnosis and treatment of DAVF to keep in mind the possibility of IJV stenosis owing to an elongated styloid process.
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http://dx.doi.org/10.1016/j.wneu.2020.08.214DOI Listing
December 2020

Upregulated 5-HT receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11-13 duplication mouse model of autism.

Mol Brain 2020 08 24;13(1):115. Epub 2020 Aug 24.

Department of Pharmacology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.

Serotonin (5-HT) is a well-known modulator of behavioral, physiological, and emotional functions of the forebrain region. We recently discovered alterations of serotonergic synaptic modulations in both, the prefrontal cortex (PFC) and the somatosensory cortex, in the 15q dup mouse model of autism spectrum disorder (ASD). To further understand the roles of the 5-HT system implicated in developmental disorders such as ASD, comparison with model animals exhibiting different phenotypes may be useful. In this study, we investigated the relationship between sociability and the magnitude of 5-HT receptor (5-HTR) activation-induced outward currents from layer 5 pyramidal neurons in the PFC, because a mouse model of Williams-Beuren syndrome (WBS; another developmental disorder exhibiting low innate anxiety and high sociability) reportedly showed larger 5-HT-induced currents. To investigate whether the 5-HTR activation-induced outward currents are involved in the endophenotype determination of social behavior, we examined 15q dup mice with a phenotype opposite to WBS. We found 5-HT elicited significantly larger outward currents in 15q dup mice than in WT controls, regardless of sociability. In contrast, baclofen-induced GABA receptor-mediated outward currents were not significantly different between genotypes, although GABA receptor was coupled to G as well as 5-HT. Further, we found the larger 5-HTR-mediated currents in 15q dup mice did not affect the magnitude of inhibitory action of NMDA receptor functions. Taken together, our results provide a potential physiological hallmark for developmental disorders that may involve the imbalance of the neuronal circuity in the PFC.
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http://dx.doi.org/10.1186/s13041-020-00655-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444243PMC
August 2020

Intracranial-Intracranial Bypass Using a Y-Shaped Artery Graft for Growing Unruptured Gemella morbillorum Infectious Aneurysm on Artery Supplying Sensory Cortex.

World Neurosurg 2020 10 17;142:328-333. Epub 2020 Jul 17.

Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

Background: Vascular reconstruction is required to treat infectious intracranial aneurysms (IIAs) on arteries supplying the eloquent area. However, extracranial-intracranial bypass is sometimes impossible because IIAs are frequently located distally on arteries and the length of a donor artery is limited. We report a rare case of an unruptured Gemella morbillorum IIA, which was successfully treated by intracranial-intracranial (IC-IC) bypass using a Y-shaped superficial temporal artery (STA) interposition graft.

Case Description: A 52-year-old man presented with heart failure and an unruptured IIA in the right anterior parietal artery because of acute G. morbillorum endocarditis. The patient was treated with urgent replacement of cardiac valves and antibiotic therapy. However, the IIA increased in size during the following 1 month, and therefore was treated surgically to prevent the rupture. End-to-side IC-IC bypass using a Y-shaped STA graft followed by aneurysmal trapping was performed to overcome the limited length of the STA as a donor artery to prevent cerebral ischemia in the artery territory and to avoid direct injury to the sensory cortex adhering tightly to the IIA. Postoperative courses were uneventful, and he recovered from the infectious diseases.

Conclusions: This case suggests that end-to-side IC-IC bypass using a Y-shaped STA graft can be a good option for surgical treatment of IIAs, which are located in eloquent areas.
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http://dx.doi.org/10.1016/j.wneu.2020.07.056DOI Listing
October 2020

Therapeutic potential of fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes as a haemostatic adjuvant for post-cardiopulmonary bypass coagulopathy.

Sci Rep 2020 07 9;10(1):11308. Epub 2020 Jul 9.

Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Japan.

Fibrinogen γ-chain peptide-coated, adenosine 5'-diphosphate (ADP)-encapsulated liposomes (H12-ADP-liposomes) are a potent haemostatic adjuvant to promote platelet thrombi. These liposomes are lipid particles coated with specific binding sites for platelet GPIIb/IIIa and encapsulating ADP. They work at bleeding sites, facilitating haemostasis by promoting aggregation of activated platelets and releasing ADP to strongly activate platelets. In this study, we investigated the therapeutic potential of H12-ADP-liposomes on post-cardiopulmonary bypass (CPB) coagulopathy in a preclinical setting. We created a post-CPB coagulopathy model using male New Zealand White rabbits (body weight, 3 kg). One hour after CPB, subject rabbits were intravenously administered H12-ADP-liposomes with platelet-rich plasma (PRP) collected from donor rabbits (H12-ADP-liposome/PRP group, n = 8) or PRP alone (PRP group, n = 8). Ear bleeding time was greatly reduced for the H12-ADP-liposome/PRP group (263 ± 111 s) compared with the PRP group (441 ± 108 s, p < 0.001). Electron microscopy showed platelet thrombus containing liposomes at the bleeding site in the H12-ADP-liposome/PRP group. However, such liposome-involved platelet thrombi were not observed in the end organs after H12-ADP-liposome administration. These findings suggest that H12-ADP-liposomes could help effectively and safely consolidate platelet haemostasis in post-CPB coagulopathy and may have potential for reducing bleeding complications after cardiovascular surgery with CPB.
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http://dx.doi.org/10.1038/s41598-020-68307-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347858PMC
July 2020

A screw position change at an early postoperative stage preceding the subsequent occurrence of screw loosening.

Eur Spine J 2021 Jan 23;30(1):136-141. Epub 2020 Jun 23.

Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Purpose: The authors recently proposed the novel radiologic assessment method to measure chronological screw position changes precisely. The aim of this study was to predict the late occurrence of screw loosening, which was diagnosed by the radiographic lucent zone, by evaluating screw position changes at an early postoperative stage using the novel method.

Methods: Forty-three patients who underwent thoracolumbar screw fixation and follow-up computed tomography (CT) scans on the day, between 1 and 5 weeks, and at more than 6 months after surgery were retrospectively evaluated. Screw images were generated from CT data. Screw position changes were evaluated by superposing screw images on the day and between 1 and 5 weeks after surgery. Screw loosening was diagnosed by the radiographic lucent zone on CT images at 6 months or later post-surgery, and patients were classified into screw loosening and non-loosening groups. The early screw position changes were compared between the two groups.

Results: Significant differences in early screw position changes were found between the screw loosening and non-loosening groups in Mann-Whitney U test (p = 0.001). On the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve was 0.791, and the best cutoff value of early screw position change for the prediction of screw loosening was 0.83 mm with a sensitivity of 64.0% and a specificity of 88.9%.

Conclusion: We calculated a cutoff value of the screw position changes at an early postoperative stage for the prediction of subsequent development of screw loosening with the radiographic lucent zone.
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http://dx.doi.org/10.1007/s00586-020-06510-8DOI Listing
January 2021

Isoflurane versus sevoflurane for early brain injury and expression of sphingosine kinase 1 after experimental subarachnoid hemorrhage.

Neurosci Lett 2020 08 6;733:135142. Epub 2020 Jun 6.

Departments of Physiology, Loma Linda University School of Medicine, Loma Linda, USA; Neurosurgery, Loma Linda University School of Medicine, Loma Linda, USA. Electronic address:

The first step to treat aneurysmal subarachnoid hemorrhage (SAH) is aneurysmal obliteration under general anesthesia but not treat the SAH itself and the secondary effects. However, the identification of anesthetics with properties that help to attenuate post-SAH brain injury can be useful for improving outcomes of SAH patients. We examined whether 2% isoflurane and 3% sevoflurane posttreatment are protective against early brain injury (EBI) after SAH. This study used 87 8-week-old male CD-1 mice. We induced SAH by endovascular perforation in mice. Animals were randomly divided into 4 groups: sham-operated (n = 16), SAH + vehicle-medical air (n = 26), SAH + 2% isoflurane (n = 22), and SAH + 3% sevoflurane (n = 23). Neurobehavioral function, brain water content and Western blotting were evaluated at 24 h. The expression of sphingosine kinase (SphK), cleaved caspase-3 and cyclooxygenase-2 (COX2) was determined by Western blotting. Cell death was examined by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling staining. Both 2% isoflurane and 3% sevoflurane significantly improved neurobehavioral function, and brain edema at 24 h after SAH and attenuated cell death, associated with an increase in SphK1, a decrease in cleaved caspase-3 and COX2. The neuroprotective effects were similar between 2% isoflurane and 3% sevoflurane. These findings suggest that both 2% isoflurane and 3% sevoflurane significantly inhibited EBI by suppressing post-SAH apoptosis and brain inflammation possibly via the SphK1-related pathway.
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http://dx.doi.org/10.1016/j.neulet.2020.135142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351136PMC
August 2020

Novel triple coaxial system to navigate 9 French balloon guiding catheter into common carotid artery.

Interv Neuroradiol 2020 Dec 5;26(6):719-724. Epub 2020 Jun 5.

Department of Neurosurgery, Faculty of Medicine, Mie University Graduate School of Medicine, Mie, Japan.

Background: It is often hard to navigate a 9 French (F) balloon guiding catheter in patients with type III or bovine aortic arch. Also, a common carotid artery stenosis is challenging, because a guidewire cannot be advanced distally. We developed the combination of a 4F Simmons-type catheter and a 6F distal access catheter as a coaxial inner catheter to navigate a 9F balloon guiding catheter to overcome these difficulties.

Materials And Methods: Medical record at our institution was retrospectively reviewed and carotid artery stenting cases in which the 4F Simmons-6F distal access catheter system was employed as a coaxial catheter to navigate a 9F balloon guiding catheter were identified. To construct this system, a 4F 145 cm SY3 (Hanako Medical, Saitama, Japan) and a 6F 118 cm Cerulean DD6 (Medikit Co. Ltd., Tokyo, Japan) were usually employed. A rotating hemostatic valve should be as short as possible and was attached to only a 9F balloon guiding catheter. The length of a 0.035-in. guidewire needed to be 180 cm or longer.

Results: During the study period, 106 carotid artery stenting cases were identified. Of these, this system was employed in 29 cases that included 5 cases with a steno-occlusive lesion at common carotid artery/external carotid artery, 10 with type III or bovine arch, and 11 harboring both. In all the cases, a 9F balloon guiding catheter was successfully navigated.

Conclusion: The 4F Simmons-6F distal access catheter system was useful in navigating a 9F balloon guiding catheter in patients with a common carotid artery stenosis, an external carotid artery occlusion, and an in-stent restenosis, especially when they also harbored type III or bovine aortic arch.
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http://dx.doi.org/10.1177/1591019920930169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724598PMC
December 2020

The Stroke-Induced Blood-Brain Barrier Disruption: Current Progress of Inspection Technique, Mechanism, and Therapeutic Target.

Curr Neuropharmacol 2020 ;18(12):1187-1212

Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA, Risley Hall, Room 219, 11041 Campus St, Loma Linda, CA 92354, USA

Stroke is one of the leading causes of mortality and morbidity worldwide. The bloodbrain barrier (BBB) is a characteristic structure of microvessel within the brain. Under normal physiological conditions, the BBB plays a role in the prevention of harmful substances entering into the brain parenchyma within the central nervous system. However, stroke stimuli induce the breakdown of BBB leading to the influx of cytotoxic substances, vasogenic brain edema, and hemorrhagic transformation. Therefore, BBB disruption is a major complication, which needs to be addressed in order to improve clinical outcomes in stroke. In this review, we first discuss the structure and function of the BBB. Next, we discuss the progress of the techniques utilized to study BBB breakdown in in-vitro and in-vivo studies, along with biomarkers and imaging techniques in clinical settings. Lastly, we highlight the mechanisms of stroke-induced neuroinflammation and apoptotic process of endothelial cells causing BBB breakdown, and the potential therapeutic targets to protect BBB integrity after stroke. Secondary products arising from stroke-induced tissue damage provide transformation of myeloid cells such as microglia and macrophages to pro-inflammatory phenotype followed by further BBB disruption via neuroinflammation and apoptosis of endothelial cells. In contrast, these myeloid cells are also polarized to anti-inflammatory phenotype, repairing compromised BBB. Therefore, therapeutic strategies to induce anti-inflammatory phenotypes of the myeloid cells may protect BBB in order to improve clinical outcomes of stroke patients.
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http://dx.doi.org/10.2174/1570159X18666200528143301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770643PMC
January 2020

p16-positive oropharyngeal cancer with rare thyroid metastasis : A case report.

J Med Invest 2020 ;67(1.2):189-191

Department of Head and Neck Surgery.

Thyroid metastasis is rarely diagnosed, and the treatment outcomes in p16-positive oropharyngeal squamous cell carcinoma patients with rare thyroid metastasis have not been fully investigated. Here we describe the case of a patient with p16-positive oropharyngeal squamous cell carcinoma who was diagnosed with cT4 N2M1 with rare thyroid metastasis. The patient was a current smoker and was positive for human papillomavirus DNA, with disease progression at 49 days and death at 113 days after completion of cisplatin-based concurrent chemoradiotherapy. J. Med. Invest. 67 : 189-191, February, 2020.
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http://dx.doi.org/10.2152/jmi.67.189DOI Listing
January 2020