Publications by authors named "Tsuyoshi Ohta"

96 Publications

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2018 and Annual Treatment Report for 2013.

J Obstet Gynaecol Res 2022 Jan 13. Epub 2022 Jan 13.

Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Japan.

To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2018 and the Annual Treatment Report for 2013, on the outcomes of patients who started treatment in 2013. The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2018 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2013 was analyzed by using the Kaplan-Meier, log-rank, and Wilcoxson tests. Treatment was initiated in 2018 for 7304 patients with cervical cancer; 11 230 with endometrial cancer; 7031 with ovarian, tubal, and peritoneal cancer; 2072 with ovarian borderline tumors; and with the others (222 vulvar cancer, 159 vaginal cancer, 413 uterine sarcoma, 54 uterine adenosarcoma, and 135 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5-year survival rates of the patients with cervical cancer were 93.1%, 75.9%, 59.1%, and 31.2% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 94.1%, 89.2%, 73.6%, and 25.8% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 89.7%, 76.8%, 49.1%, and 32.4% for Stages I, II, III, and IV, respectively. The annual report is important to provide knowledge on gynecological malignancy trends in Japan.
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http://dx.doi.org/10.1111/jog.15134DOI Listing
January 2022

Assisted Living and Medication Adherence in Super-Aged Patients With Heart Failure in the Japanese population.

J Cardiovasc Pharmacol 2021 Dec 27. Epub 2021 Dec 27.

Graduate school of Integrated Arts and Sciences, Kochi University, Kohasu, Oko-cho, Nankoku-shi, Kochi, Japan Department of Pharmacy, Kochi Medical School Hospital, 185-1 Kohasu, Oko town, Nankoku City, Kochi, Japan Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University, 185-1 Kohasu, Oko town, Nankoku City, Kochi, Japan Department of Cardiology, Chikamori Hospital, Kochi, Japan Department of Cardiology, Kochi Prefectural Hatakenmin Hospital, Sukumo, Japan Department of Cardiology, Kochi Prefectural Aki General Hospital, Aki, Japan Department of Cardiology, Susaki Kuroshio Hospital, Susaki, Japan Department of Neurosurgery, Kochi Medical School, Kochi University, Kohasu, Oko town, Nankoku City, Kochi, Japan Department of Neurosurgery, National Cerebral and Cardiovascular Center Hospital, 6-1 Kishibe-Shimmachi, Suita City, Osaka, Japan Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, Japan.

Abstract: Poor adherence to medication in patients with heart failure (HF) is associated with poor clinical outcomes. Although social support has been reported to improve medication adherence in patients with HF, the detailed underlying mechanism of this association is unclear. This study investigated appropriate social support types to ensure medication adherence, as well as patient characteristics that benefit from such social support in patients with HF. This was a retrospective observational study investigating the association of social support with medication adherence in 824 patients with HF who were registered in a prospective multicenter database. First, we analyzed the association between social support types and poor medication adherence leading to hospitalization. An interaction analysis was performed to detect patients' characteristics that benefited most from social support in terms of medical adherence. Fifty (6.1%) patients were hospitalized for poor adherence to medications. Multivariable analysis revealed that not receiving assisted living, which was defined as having supporting individuals at least once a week, was independently associated with poor medication adherence-related hospitalization. An interaction analysis revealed that patients with dementia benefited from assisted living significantly, while male patients or current smokers did not. Summarily, assisted living at least once a week was appropriate for improving medication adherence for patients with HF and was particularly effective for patients with dementia. Performed in a super-aging region in Japan, this study may also suggest the relevance of social support in preventing HF exacerbation in other developed countries that will experience an aging society in the near future.
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http://dx.doi.org/10.1097/FJC.0000000000001212DOI Listing
December 2021

Association of 5-aminolevulinic acid with intraoperative hypotension in malignant glioma surgery.

Photodiagnosis Photodyn Ther 2021 Nov 27;37:102657. Epub 2021 Nov 27.

Department of Pharmacy, Kochi Medical School Hospital, 185-1, Kohasu, Oko town, Nankoku, Kochi, Japan; Graduate School of Integrated Arts and Sciences Kochi University, 185-1, Kohasu, Oko town, Nankoku, Kochi, Japan.

Background: Use of 5-aminolevulinic acid for photodynamic malignant tumor diagnosis reportedly causes intraoperative hypotension (systolic blood pressure < 70 mmHg) during urologic surgery. However, its association with intraoperative hypotension in malignant glioma surgery and underlying mechanisms has not yet been elucidated.. This study aimed to investigate whether 5-aminolevulinic acid administration is associated with intraoperative hypotension in malignant glioma surgery and explore the mechanisms of 5-aminolevulinic acid-induced hypotension in vitro.

Methods: In this retrospective multicenter cohort study, we investigated intracellular nitric oxide as a candidate mediator of hypotension in response to 5-aminolevulinic acid in vitro in human umbilical vein endothelial cell cultures.

Results: Of 142 patients, 94 underwent 5-aminolevulinic acid-guided surgery. Systolic blood pressure was significantly lower throughout surgery with 5-aminolevulinic acid administration. 5-Aminolevulinic acid administration was an independent risk factor for intraoperative hypotension according to multivariable logistic regression analysis (89% vs. 56%; odds ratio = 6.72, 95% confidence interval [2.05-22.1], P = 002). In subgroup analysis of the 5-aminolevulinic acid group, increasing age and use of renin-angiotensin system inhibitors had a synergistic effect with 5-aminolevulinic acid on decreased blood pressure. In the vascular endothelial cell culture study, 5-aminolevulinic acid induced a significant increase in intracellular nitric oxide generation.

Conclusions: 5-Aminolevulinic acid administration was associated with intraoperative hypotension in malignant glioma surgery, with increasing age and use of renin-angiotensin system inhibitors boosting the blood pressure-lowering effect of 5-aminolevulinic acid. According to in vitro results, the low blood pressure induced by 5-aminolevulinic acid may be mediated by a nitric oxide increase in vascular endothelial cells.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102657DOI Listing
November 2021

Correction: Metabolomic analysis of uterine serous carcinoma with acquired resistance to paclitaxel.

Oncotarget 2021 Nov 9;12(23):2321-2322. Epub 2021 Nov 9.

Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Iidanishi, Yamagata 990-9585, Japan.

[This corrects the article DOI: 10.18632/oncotarget.25868.].
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http://dx.doi.org/10.18632/oncotarget.27474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590814PMC
November 2021

A multicenter prospective registry of Borden type I dural arteriovenous fistula: results of a 3-year follow-up study.

Neuroradiology 2021 Oct 10. Epub 2021 Oct 10.

Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: Although intracranial dural arteriovenous fistula (DAVF) without retrograde leptomeningeal venous drainage (Borden type I) is reported to have a benign nature, no study has prospectively determined its clinical course. Here, we report a 3-year prospective observational study of Borden type I DAVF.

Methods: From April 2013 to March 2016, consecutive patients with DAVF were screened at 13 study institutions. We collected data on baseline characteristics, clinical symptoms, angiography, and neuroimaging. Patients with Borden type I DAVF received conservative care while palliative intervention was considered when the neurological symptoms were intolerable, and were followed at 6, 12, 24, and 36 months after inclusion.

Results: During the study period, 110 patients with intracranial DAVF were screened and 28 patients with Borden type I DAVF were prospectively followed. None of the patients had conversion to higher type of Borden classification or intracranial hemorrhage during follow-up. Five patients showed spontaneous improvement or disappearance of neurological symptoms (5/28, 17.9%), and 5 patients showed a spontaneous decrease or disappearance of shunt flow on imaging during follow-up (5/28, 17.9%). Stenosis or occlusion of the draining sinuses on initial angiography was significantly associated with shunt flow reduction during follow-up (80.0% vs 21.7%, p = 0.02).

Conclusion: In this 3-year prospective study, patients with Borden type I DAVF showed benign clinical course; none of these patients experienced conversion to higher type of Borden classification or intracranial hemorrhage. The restrictive changes of the draining sinuses at initial diagnosis might be an imaging biomarker for future shunt flow reduction.
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http://dx.doi.org/10.1007/s00234-021-02752-5DOI Listing
October 2021

Impact of subcallosal artery origin and A1 asymmetry on surgical outcomes of anterior communicating artery aneurysms.

Acta Neurochir (Wien) 2021 11 27;163(11):2955-2965. Epub 2021 Aug 27.

Department of Neurosurgery, Kochi University Hospital, 185-1, Oko-cho, Kohasu, , Nankoku, Kochi, 783-8505, Japan.

Background: Surgical clipping of anterior communicating artery (ACoA) aneurysms remains challenging due to their complex anatomy. Anatomical risk factors for ACoA aneurysm surgery require further elucidation. The aim of this study is to investigate whether proximity of the midline perforating artery, subcallosal artery (SubCA), and associated anomaly of the ACoA complex affect functional outcomes of ACoA aneurysm surgery.

Methods: A total of 92 patients with both unruptured and ruptured ACoA aneurysms, who underwent surgical clipping, were retrospectively analyzed from a multicenter, observational cohort database. Association of ACoA anatomy with SubCA origin at the aneurysmal neck under microsurgical observation was analyzed in the interhemispheric approach subgroup (n = 56). Then, we evaluated whether anatomical factors associated with SubCA neck origin affected surgical outcomes in the entire cohort (both interhemispheric and pterional approaches, n = 92).

Results: In the interhemispheric approach cohort, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was stratified to have the highest probability of the SubCA neck origin by a decision tree analysis. Then, among the entire cohort using either interhemispheric or pterional approach, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was significantly associated with poor functional outcomes by multivariable logistic regression analysis (OR 6.76; 95% CI 1.19-38.5; p = 0.03) as compared with A1 symmetry group in the acute subarachnoid hemorrhage settings.

Conclusion: Combination of A1 asymmetry and larger aneurysmal size was significantly associated with SubCA aneurysmal neck origin and poor functional outcomes in ACoA aneurysm surgery. Interhemispheric approach may be proposed to provide a wider and unobstructed view of SubCA for ACoA aneurysms with this high-risk anatomical variant.
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http://dx.doi.org/10.1007/s00701-021-04979-wDOI Listing
November 2021

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan.

Int J Clin Oncol 2021 Dec 25;26(12):2318-2330. Epub 2021 Aug 25.

Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Japan.

Objective: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy.

Methods: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival.

Results: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS.

Conclusion: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.
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http://dx.doi.org/10.1007/s10147-021-02017-4DOI Listing
December 2021

PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study.

PLoS One 2021 5;16(8):e0254067. Epub 2021 Aug 5.

Department of Neurology, Graduate School of Medical Sciences, Neurological Institute, Kyushu University, Fukuoka, Japan.

Background And Purpose: The impact of the paraoxonase-1 (PON1) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of PON1 Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention.

Methods: Post-clopidogrel platelet reactivity was measured using a VerifyNow® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for PON1 Q192R and CYP2C19*2 and *3 (no function alleles), and *17. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 PON1 192R allele and HPR defined as original and corrected PRU ≥208.

Results: Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 PON1 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 PON1 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03-3.76) and corrected PRU (OR 2.34, 95% CI 1.21-4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 CYP2C19 no function allele.

Conclusions: Carrying ≥1 PON1 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254067PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341610PMC
November 2021

Added value of anxiolytic benzodiazepines in predictive models on severe delirium in patients with acute decompensated heart failure: A retrospective analysis.

PLoS One 2021 22;16(4):e0250372. Epub 2021 Apr 22.

Graduate School of Integrated Arts and Sciences Kochi University, Oko town, Nankoku City, Kochi, Japan.

Background: Delirium in patients with acute decompensated heart failure (ADHF) is associated with poor clinical outcomes. Although some medications have been reported as risk factors for delirium, their impact on patients with ADHF is still unclear. This study aimed to determine the association of specific medication use with delirium and their additive predictive value in models based on conventional risk factors.

Methods And Results: In this single-center, retrospective study, 650 patients treated for ADHF were included. Fifty-nine patients (9.1%) had delirium. In multivariate analysis, anxiolytic benzodiazepines [odds ratio (OR): 6.4, 95% confidence interval (CI): 2.8-15], mechanical ventilation or noninvasive positive pressure ventilation (OR: 6.0, 95% CI: 2.9-12), depression (OR: 3.2, 95% CI: 1.5-6.5), intensive care or high care unit admission (OR: 2.9, 95% CI: 1.5-5.6), male sex (OR: 2.0, 95% CI: 1-3.7), and age (OR: 1.1, 95% CI: 1-1.1) were independently associated with severe delirium. The predictive model that included anxiolytic benzodiazepines had a significantly better discriminatory ability for the incidence of severe delirium than the conventional model.

Conclusions: The use of anxiolytic benzodiazepines was independently correlated with severe delirium, and their use in models based on conventional risk factors had an additive value for predicting delirium in patients with ADHF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250372PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062069PMC
October 2021

Clopidogrel response predicts thromboembolic events associated with coil embolization of unruptured intracranial aneurysms: A prospective cohort study.

PLoS One 2021 8;16(4):e0249766. Epub 2021 Apr 8.

Department of Neurology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: Periprocedural thromboembolic events are a serious complication associated with coil embolization of unruptured intracranial aneurysms. However, no established clinical rule for predicting thromboembolic events exists. This study aimed to clarify the significance of adding preoperative clopidogrel response value to clinical factors when predicting the occurrence of thromboembolic events during/after coil embolization and to develop a nomogram for thromboembolic event prediction.

Methods: In this prospective, single-center, cohort study, we included 345 patients undergoing elective coil embolization for unruptured intracranial aneurysm. Thromboembolic event was defined as the occurrence of intra-procedural thrombus formation and postprocedural symptomatic cerebral infarction within 7 days. We evaluated preoperative clopidogrel response and patients' clinical information. We developed a patient-clinical-information model for thromboembolic event using multivariate analysis and compared its efficiency with that of patient-clinical-information plus preoperative clopidogrel response model. The predictive performances of the two models were assessed using area under the receiver-operating characteristic curve (AUC-ROC) with bootstrap method and compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results: Twenty-eight patients experienced thromboembolic events. The clinical model included age, aneurysm location, aneurysm dome and neck size, and treatment technique. AUC-ROC for the clinical model improved from 0.707 to 0.779 after adding the clopidogrel response value. Significant intergroup differences were noted in NRI (0.617, 95% CI: 0.247-0.987, p < .001) and IDI (0.068, 95% CI: 0.021-0.116, p = .005).

Conclusions: Evaluation of preoperative clopidogrel response in addition to clinical variables improves the prediction accuracy of thromboembolic event occurrence during/after coil embolization of unruptured intracranial aneurysm.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249766PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031457PMC
September 2021

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2017 and annual treatment report for 2012.

J Obstet Gynaecol Res 2021 May 25;47(5):1631-1642. Epub 2021 Feb 25.

Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Japan.

Aim: To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2017 and the Annual Treatment Report for 2012, on the outcomes of patients who started treatment in 2012.

Methods: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2017 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial and ovarian cancer in 2012 was analyzed by using the Kaplan-Meier, log-rank and Wilcoxon tests.

Results: Treatment was initiated in 2017 for 7710 patients with cervical cancer; 11 120 with endometrial cancer; 7029 with ovarian, tubal and peritoneal cancer; 2164 with ovarian borderline tumors; and with the others (213 vulvar cancer, 139 vaginal cancer, 366 uterine sarcoma, 41 uterine adenosarcoma and 131 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5-year survival rates of the patients with cervical cancer were 92.9, 75.5, 58.2 and 26.7% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 93.6, 85.6, 72.6 and 27.3% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 92.5, 83.5, 49.5 and 30.8% for stages I, II, III and IV, respectively.

Conclusion: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.
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http://dx.doi.org/10.1111/jog.14724DOI Listing
May 2021

An autopsy case of Trousseau's syndrome with tumor thrombosis in unknown primary squamous cell carcinoma of the head and neck.

Int Cancer Conf J 2021 Jan 19;10(1):15-19. Epub 2020 Aug 19.

Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558 Japan.

Trousseau's syndrome (TS) and tumor thrombosis (TT) are known as cancer-associated thrombosis with poor prognosis. TS is extremely rare in patients with squamous cell carcinoma. In this study, we report an unknown primary squamous cell carcinoma of the head and neck (SCCHN) patient with TS and TT in pulmonary artery definitely diagnosed by autopsy. A 73-year-old man had a past surgical history for unknown primary SCCHN and lung metastases. Three years after the initial surgery, the patient had multiple cerebral infarction, deep venous thrombosis in the legs and mediastinum metastases. Our diagnosis was TS and treatment with chemotherapy and unfractionated molecular heparin started. It could help control the hypercoagulative state and cancer progression, but finally, he died from progressive disease (mediastinum metastases and pulmonary embolism) five years after the initial surgery. An autopsy revealed multiple metastases and thrombosis in the pulmonary artery with squamous cell carcinoma microscopically. Although there is no established treatment for managing TS, intensive therapy such as a combination of chemotherapy and anticoagulant therapy can be effective in improving hypercoagulation therapy. In addition, an autopsy should be considered for patients with thrombosis to distinguish between TS and TT.
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http://dx.doi.org/10.1007/s13691-020-00440-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797400PMC
January 2021

A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery.

Med Mycol Case Rep 2020 Dec 25;30:22-25. Epub 2020 Sep 25.

Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

A 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis.
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http://dx.doi.org/10.1016/j.mmcr.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554319PMC
December 2020

Cortical Blood Flow Insufficiency Scores with Computed Tomography Perfusion can Predict Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients: A Cohort Study.

Neurocrit Care 2021 06 9;34(3):946-955. Epub 2020 Oct 9.

Department of Neurosurgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan.

Background: The World Federation of Neurosurgical Societies (WFNS) scale is widely accepted for predicting outcomes for subarachnoid hemorrhage (SAH) patients. However, it is difficult to definitely predict outcomes for the most poor grade, WFNS grade 5. The present study aimed to investigate the prognostic ability of a novel classification using computed tomography perfusion (CTP) findings, called the cortical blood flow insufficiency (CBFI) scores.

Methods: CTP was performed on admission for aneurysmal SAH followed by radical treatments within 72 hours of onset. Twenty-four cerebral cortex regions of interest (ROIs) were defined. CBFI was defined as Tmax > 4 s in each ROI, and CBFI scores were calculated based on the total number of ROIs with CBFI. Using the optimal cutoff value based on receiver operating characteristics (ROC) analysis to predict patient functional outcomes, CBFI scores were divided into "high" or "low" CBFI scores. Patient functional outcomes at 90 days were categorized based on modified Rankin Scale scores (0-3, favorable group; 4-6 unfavorable group) (0-4, non-catastrophic group; 5-6, catastrophic group).

Results: Fifty-seven patients were included in this study, of whom 21 (36.8%) and 13 (22.8%) were in the unfavorable and the catastrophic groups, respectively. A factor predicting unfavorable and catastrophic outcomes was CBFI score cutoff value of 7 points (area under the curve, 0.73 and 0.81, respectively). In multivariable logistic regression analysis for unfavorable outcome, high CBFI scores (odds ratio (OR), 8.6; 95% confidence interval (CI), 1.1-65.4; P = 0.04) and WFNS grade 5 (OR, 30.0; 95% CI, 4.5-201.0; P < 0.001) remained as independent predictors, while for catastrophic outcome, high CBFI scores (OR, 25.3; 95% CI, 3.3-194.0; P = 0.002) and age (OR, 1.1; 95% CI, 1.0-1.2; P = 0.02) remained as independent predictors. Conversely, WFNS grade 5 was not an independent predictor of catastrophic outcomes (OR, 3.8; 95% CI, 0.6-24.0; P = 0.15). In high CBFI scores, the OR of the delayed cerebral ischemia (DCI) occurrence was 9.6 (95% CI, 1.5-61.4; P = 0.02) after adjusting for age.

Conclusion: High CBFI scores could predict unfavorable and catastrophic outcomes for aneurysmal SAH patients and DCI occurrence.
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http://dx.doi.org/10.1007/s12028-020-01108-wDOI Listing
June 2021

Squamous cell carcinoma arising from a mature cystic teratoma of the ovary: Successful treatment with carboplatin, paclitaxel, and bevacizumab.

Gynecol Oncol Rep 2020 Nov 26;34:100632. Epub 2020 Aug 26.

Department of Obstetrics Gynecology, Faculty of Medicine, Yamagata University, Iida-nishi, 2-2-2, Yamagata 990-9585, Japan.

Ovarian mature cystic teratomas (MCT) are usually benign. However, squamous cell carcinoma (SCC) develops in 0.17-2% of MCT. Because of its low frequency, the optimal treatment for this disease is unclear. We present a case of SCC arising from MCT. Our patient was a 30-year-old nulliparous woman complaining of right lower abdominal pain, who was referred to our hospital for a pelvic solid mass with suspected malignant ovarian tumor. A diagnosis of SCC arising from MCT was suspected based on the elevation in SCC antigen and the imaging. After surgery to remove the tumor, the diagnosis was confirmed based on the pathology. Although the surgery by radical cytoreduction was optimal, the tumor showed early recurrence. Therefore, we administrated combination chemotherapy, consisting of carboplatin, paclitaxel, and bevacizumab, followed by maintenance therapy with bevacizumab. Response to the chemotherapy regimen was complete and the patient was alive with no evidence of recurrence for 45 months after starting the initial surgery. We discuss the clinical characteristics of the malignant transformation of MCT and the treatment of SCC arising from MCT.
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http://dx.doi.org/10.1016/j.gore.2020.100632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490979PMC
November 2020

Effect of lubiprostone on vinca alkaloid-induced constipation in patients with hematological malignancies: a propensity score-matched analysis.

Ann Hematol 2020 Oct 24;99(10):2429-2436. Epub 2020 Aug 24.

Department of Pharmacy, Kochi Medical Hospital School, 185-1 Kohasu, Oko town, Nankoku City, Kochi, Japan.

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.
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http://dx.doi.org/10.1007/s00277-020-04222-zDOI Listing
October 2020

xCT inhibitor sulfasalazine depletes paclitaxel-resistant tumor cells through ferroptosis in uterine serous carcinoma.

Oncol Lett 2020 Sep 6;20(3):2689-2700. Epub 2020 Jul 6.

Department of Obstetrics and Gynecology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.

Glutathione (GSH) is a primary antioxidant that protects cells against reactive oxygen species (ROS), and high levels of GSH promote cancer cell survival and resistance to chemotherapy. The glutamine transporter xCT is essential for the intracellular synthesis of GSH, whereby xCT determines the intracellular redox balance. However, whether xCT inhibition can overcome GSH-mediated resistance to chemotherapeutic agents in uterine serous carcinoma (USC) remains unclear. Thus, the present study investigated the effect of the xCT inhibitor, sulfasalazine (SAS) on cytotoxicity in paclitaxel-sensitive and -resistant USC cell lines. The molecular mechanism by which SAS induces ferroptotic cell death in paclitaxel-resistant cells was assessed. The results of the cytotoxicity assay demonstrated that SAS was more cytotoxic in paclitaxel-resistant cells compared with in -sensitive cells; however, paclitaxel cytotoxicity was not enhanced in either of the USC cell lines. Immunoblotting analysis and the cell death assays performed using ferroptosis inhibitors indicated that SAS-mediated cell death was induced through ferroptosis, and not apoptosis, in paclitaxel-resistant cells. Furthermore, ROS production was increased in paclitaxel-resistant but not in -sensitive cells, even at low SAS concentration, and JNK was activated, which is a downstream target in the Ras signaling pathway. Knockdown of JNK reversed the inhibitory effect of SAS on cell proliferation and cell death. The synthetic lethal interaction between ROS accumulation and Ras effector JNK activation may be critical for enhancing the sensitivity to ferroptotic cell death mediated by xCT inhibitor, SAS. Taken together, the results of the present study suggest that xCT inhibition may be an effective treatment for patients with recurrent paclitaxel-resistant USC.
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http://dx.doi.org/10.3892/ol.2020.11813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400102PMC
September 2020

Clinical and image features: large-vessel vasculitis after granulocyte colony stimulating factor administration.

Acta Radiol 2020 Jun 14:284185120931685. Epub 2020 Jun 14.

Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata, Japan.

Background: Granulocyte colony stimulating factor (G-CSF) is known to cause vasculitis, mainly in the small vessels. Several cases of large-vessel vasculitis (LVV) caused by G-CSF have recently been reported in the literature; we retrospectively suspect that some cases of LVV in our institution were associated with administration of G-CSF.

Purpose: To evaluate the clinical and radiological findings in our cases and to compare them with those in previous reports.

Material And Methods: We retrospectively evaluated clinical and radiological findings in four cases of LVV that occurred after administration of G-CSF in our institution. We also reviewed papers on G-CSF-related LVV and compared their findings to ours.

Results: G-CSF-related LVV occurred in patients aged > 50 years and more frequently in women. Most patients developed vasculitis within 15 days after the last administration. While 14/16 patients were symptomatic, the remaining two patients were asymptomatic and diagnosed incidentally. In all cases, laboratory inflammatory markers increased, but there were no autoantibodies that clearly indicated other autoimmune vasculitis. Computed tomography revealed elevated soft tissue density around the affected vessels.

Conclusion: LVV is among the potential adverse events of G-CSF administration. We should keep this outcome in mind when we interpret medical images of patients with previous G-CSF treatment history even if they are asymptomatic.
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http://dx.doi.org/10.1177/0284185120931685DOI Listing
June 2020

Clinical and reproductive outcomes of fertility-sparing surgery in stage I epithelial ovarian cancer.

Mol Clin Oncol 2020 Jan 22;12(1):44-50. Epub 2019 Nov 22.

Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.

The aim of the present study was to evaluate the oncologic safety and reproductive outcome in patients with stage I epithelial ovarian cancer (EOC) treated with fertility-sparing surgery (FSS). Women aged ≤40 years with stage I EOC who had undergone FSS between 2000 and 2010 were retrospectively reviewed. Survival was examined using the Kaplan-Meier method and statistical significance was analyzed using the log-rank test. A total of 29 EOC patients (stage IA, n=14; stage IC1 n=6; stage IC3, n=9) from seven participating institutions belonging to the Tohoku Gynecologic Cancer Unit were enrolled. After a median follow-up duration of 60.6 months (range, 6-135 months), five patients (17.2%) experienced tumor recurrence. The respective five-year relapse-free survival (RFS) and overall survival (OS) rates were 90.9 and 100% for stage IA/IC1, and 43.8 and 87.5% for stage IC3. Significant differences in RFS were observed between stage IA/IC1 and IC3 patients (P=0.026). However, there was no significant difference in OS between patients with 1A/1C1 and those with 1C3 (P=0.712). After FSS, seven pregnancies occurred in five patients, which resulted in the birth of six healthy children. The results of the present study confirmed that FSS may be an acceptable treatment method for stage IA and IC1 EOC, exhibiting a favorable reproductive outcome. However, the safety of FSS for treating stage IC3 EOC is uncertain and warrants further investigation.
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http://dx.doi.org/10.3892/mco.2019.1954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904870PMC
January 2020

A Visual Task Management Application for Acute Ischemic Stroke Care.

Front Neurol 2019 30;10:1118. Epub 2019 Oct 30.

Department of Neurology, Graduate School of Medical Sciences, Neurological Institute, Kyushu University, Fukuoka, Japan.

To maximize the effect of intravenous (IV) thrombolysis and/or endovascular therapy (EVT) for acute ischemic stroke (AIS), stroke centers need to establish a parallel workflow on the basis of a code stroke (CS) protocol. At Kokura Memorial Hospital (KMH), we implemented a CS system in January 2014; however, the process of information sharing within the team has occasionally been burdensome. To solve this problem using information communication technology (ICT), we developed a novel application for smart devices, named "Task Calc. Stroke" (TCS), and aimed to investigate the impact of TCS on AIS care. TCS can visualize the real-time progress of crucial tasks for AIS on a dashboard by changing color indicators. From August 2015 to March 2017, we installed TCS at KMH and recommended its use during normal business hours (NBH). We compared the door-to-computed tomography time, the door-to-complete blood count (door-to-CBC) time, the door-to-needle for IV thrombolysis time, and the door-to-puncture for EVT time among three treatment groups, one using TCS ("TCS-based CS"), one not using TCS ("phone-based CS"), and one not based on CS ("non-CS"). A questionnaire survey regarding communication problems was conducted among the CS teams at 3 months after the implementation of TCS. During the study period, 74 patients with AIS were transported to KMH within 4.5 h from onset during NBH, and 53 were treated using a CS approach (phone-based CS: 26, TSC-based CS: 27). The door-to-CBC time was significantly reduced in the TCS-based CS group compared to the phone-based CS group, from 31 to 19 min ( = 0.043). Other processing times were also reduced, albeit not significantly. The rate of IV thrombosis was higher in the TCS-based CS group (78% vs. 46%, = 0.037). The questionnaire was correctly filled in by 34/38 (89%) respondents, and 82% of the respondents felt a reduction in communication burden by using the TCS application. TCS is a novel approach that uses ICT to support information sharing in a parallel CS workflow in AIS care. It shortens the processing times of critical tasks and lessens the communication burden among team members.
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http://dx.doi.org/10.3389/fneur.2019.01118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831722PMC
October 2019

Successful management of cutaneous lymphangitis carcinomatosa arising from cervical cancer with paclitaxel-cisplatin and bevacizumab combination therapy: a case report and review of the literature.

J Med Case Rep 2019 Nov 7;13(1):328. Epub 2019 Nov 7.

Department of Obstetrics and Gynecology, Yamagata University, School of Medicine, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-9585, Japan.

Background: Globally, cervical cancer is the fourth most common cancer in women. Here, we report a case of cutaneous lymphangitis carcinomatosa arising from cervical cancer, an extremely rare and treatment-resistant condition.

Case Presentation: A 64-year-old Japanese woman presented with genital bleeding. She was diagnosed as having stage IB1 squamous cell cervical cancer and subsequently treated with radiotherapy. Approximately 2 years after the curative radiotherapy, she developed itching, skin rash, and small nodules on her left femoral and pubic area. Slight F-fluorodeoxyglucose uptake was detected at her left femoral skin on positron emission tomography with computed tomography. A histopathological examination was performed on a biopsy sample from an erythematous macule on her left femoral skin and vulva. Consequently, she was diagnosed as having cutaneous lymphangitis carcinomatosa arising from cervical cancer. Paclitaxel (135 mg/m), cisplatin (50 mg/m), and bevacizumab (15 mg/kg) combination therapy was administered every 21 days. Both itching and rash improved after three treatment cycles. After the completion of six cycles, skin erythema in the femoral and vulval area disappeared completely. Our patient experienced a 25-month symptom-free interval after the last chemotherapy session.

Conclusion: Our findings suggest that combination chemotherapy plus bevacizumab is an effective therapeutic option in patients with cutaneous lymphangitis carcinomatosa arising from cervical cancer.
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http://dx.doi.org/10.1186/s13256-019-2262-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836488PMC
November 2019

Optimizing in-hospital triage for large vessel occlusion using a novel clinical scale (GAIAA).

Neurology 2019 11 24;93(22):e1997-e2006. Epub 2019 Oct 24.

From the Department of Neurosurgery (T.O., K.O., M.F., N.M., T.T., T.M., M.T.), Kochi Health Sciences Center; Department of Comprehensive Strokology (I.N., S.M., S.W.), Fujita Health University, Aichi; Department of Neurology (D.K.), Kokura Memorial Hospital, Fukuoka; and Department of Neurosurgery (H.F., N.F., T.U), Kochi Medical School, Japan.

Objective: To identify a proximal anterior circulation occlusion for effectively administering immediate mechanical thrombectomy by developing a novel, simple diagnostic scale to predict the occlusion, to compare its validity with available scales, and to assess its utility.

Methods: To develop a novel clinical scale, we retrospectively analyzed a cohort of 429 patients with acute ischemic stroke from a single center. The novel scale GAIAA was applied to a prospective cohort of 259 patients from 3 stroke centers for external validation. The utility of the scale as an in-hospital triage was compared for the temporal factors of 158 patients with the occlusion.

Results: In a scale-developmental phase, those with a proximal anterior circulation occlusion had significantly more frequent signs of hemispheric symptoms, including gaze palsy, aphasia, inattention, arm paresis, and atrial fibrillation. The GAIAA scale was developed using consolidated hemispheric symptoms and was scored as follows: score = 2, arm paresis score = 1, and atrial fibrillation score = 1. A cutoff value ≥3 was optimal for the correlation between sensitivity (88%) and specificity (81%), with a C statistic of 0.90 (95% confidence interval 0.87-0.93). External validation indicated that discrimination was significantly better than or not different from that of available complex scales. Door-to-puncture time was significantly reduced (91 [82-111] vs 52 [32-75] minutes, < 0.001).

Conclusion: The GAIAA scale showed high sensitivity and specificity when an optimal cutoff score was used and was useful as an in-hospital triage tool.
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http://dx.doi.org/10.1212/WNL.0000000000008550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913326PMC
November 2019

Impact of temperature decline from the previous day as a trigger of spontaneous subarachnoid hemorrhage: case-crossover study of prefectural stroke database.

J Neurosurg 2019 Jul 5:1-9. Epub 2019 Jul 5.

1Department of Neurosurgery and.

Objective: Several environmental factors have been reported to correlate with incidence of spontaneous subarachnoid hemorrhage (SAH). However, because of different patient selection and study designs among these studies, meteorological factors that trigger the incidence of SAH in a short hazard period remain unknown. Among meteorological factors, daily temperature changes may disrupt and violate homeostasis and predispose to cerebrovascular circulatory disturbances and strokes. The authors aimed to investigate whether a decline in the temperature from the highest of the previous day to the lowest of the event day (temperature decline from the previous day [TDP]) triggers SAH in the prefecture-wide stroke database.

Methods: All 28 participating institutions with primary or comprehensive stroke centers located throughout Kochi Prefecture, Japan, were included in the study. Data collected between January 2012 and December 2016 were analyzed, and 715 consecutive SAH patients with a defined date of onset were enrolled. Meteorological data in this period were obtained from the Kochi Local Meteorological Observatory. A case-crossover study was performed to investigate association of TDP and other environmental factors with onset of SAH.

Results: The increasing TDP in 1°C on the day of the SAH event was associated with an increased incidence of SAH (OR 1.041, 95% CI 1.007-1.077) after adjustment for other environmental factors. According to the stratified analysis, a significant association between TDP and SAH was observed in women, patients < 65 years old, and patients with weekday onset. Among these factors, increasing TDP had a great impact on SAH onset in patients < 65 years old (p = 0.028, Mann-Whitney U-test).

Conclusions: TDP, temperature decline from the highest of the previous day to the lowest of the day, was correlated with the incidence of spontaneous SAH, particularly in younger patients < 65 years old.
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http://dx.doi.org/10.3171/2019.4.JNS19175DOI Listing
July 2019

Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: Annual patients report for 2015 and annual treatment report for 2010.

J Obstet Gynaecol Res 2019 Feb 13;45(2):289-298. Epub 2018 Nov 13.

Department of Obstetrics and Gynecology, Niigata University Medical School, Niigata, Japan.

Aim: To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2015 and the Annual Treatment Report for 2010 on the outcomes of patients who started treatment in 2010.

Methods: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment was initiated in 2015 were analyzed retrospectively. Survival of the patients who started treatment in 2010 was analyzed by using the Kaplan-Meier, log-rank and Wilcoxson tests.

Results: Treatment was initiated in 2015 for 7527 patients with cervical cancer, 10 119 with endometrial cancer, 6424 with ovarian cancer and 2181 with ovarian borderline tumors. This clinicopathological information was summarized as the Patient Annual Report. Prognoses were analyzed across 4309 patients with cervical cancer, 5054 with endometrial cancer and 3423 with ovarian cancer, whose treatment was initiated in 2010. The 5-year survival rates of the patients with cervical cancer were 92.1%, 74.2%, 52.0%, and 29.8% for stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 94.3%, 88.8%, 74.0% and 26.6% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 88.5%, 80.1%, 46.3% and 36.2% for stages I, II, III and IV, respectively.

Conclusion: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.
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http://dx.doi.org/10.1111/jog.13863DOI Listing
February 2019

Vagal Nerve Palsy After Transarterial Embolization of Transverse-Sigmoid Dural Arteriovenous Fistula Using Onyx.

J Stroke Cerebrovasc Dis 2019 Feb 10;28(2):464-469. Epub 2018 Nov 10.

Department of Neurosuragery, Stroke Center, Kokura Memorial Hospital, Japan. Electronic address:

Objective: We report a case of a 70-year-old man who developed a transverse-sigmoid dural arteriovenous fistula (TS-DAVF) that was successfully treated by transarterial embolization (TAE) with Onyx.

Case Presentation: The patient presented with sudden and progressive disturbance of consciousness and left hemiparesis. Magnetic resonance imaging (MRI) revealed venous infarction and hemorrhagic changes with brain swelling in the right parietal lobe. Angiography revealed a right TS-DAVF and multiple occlusions with retrograde leptomeningeal venous drainage into the cortical veins. The TS-DAVF was graded as Borden type III and Cognard type IIa+b. Because of its progressive clinical nature and wide distribution of DAVF in the occluded sinus wall, he underwent emergent TAE with liquid embolic materials including n-butyl cyanoacrylate and Onyx under informed consent by his family. Complete obliteration of the TS-DAVF was achieved, leading to a marked amelioration of symptoms, and MRI after treatment confirmed a decrease in the brain swelling. However, he suffered transient dysphagia due to right vagal nerve palsy caused by occlusion of vasa nervorum of ascending pharyngeal artery. He returned home 5 months later with a modified Rankin Scale of 1.

Conclusions: TAE with Onyx appears to be effective for aggressive TS-DAVF with a widely distributed shunt. However, the blood supply to the cranial nerves and potentially dangerous anastomoses between the external-internal carotid artery and vertebral artery should be taken into account to avoid serious complications.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.10.023DOI Listing
February 2019

Anaerobic respiration coupled with mitochondrial fatty acid synthesis in wax ester fermentation by Euglena gracilis.

FEBS Lett 2018 12 30;592(24):4020-4027. Epub 2018 Oct 30.

Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Japan.

In Euglena gracilis, wax ester fermentation produces ATP during anaerobiosis. Here, we report that anaerobic wax ester production is suppressed when the mitochondrial electron transport chain complex I is inhibited by rotenone, whereas it is increased by the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP). The ADP/ATP ratio in anaerobic cells is elevated by treatment with either rotenone or CCCP. Gene silencing experiments indicate that acyl-CoA dehydrogenase, electron transfer flavoprotein (ETF), and rhodoquinone (RQ) participate in wax ester production. These results suggest that fatty acids are synthesized in mitochondria by the reversal of β-oxidation, where trans-2-enoyl-CoA is reduced mainly by acyl-CoA dehydrogenase using the electrons provided by NADH via the electron transport chain complex I, RQ, and ETF, and that ATP production is highly supported by anaerobic respiration utilizing trans-2-enoyl-CoA as a terminal electron acceptor.
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http://dx.doi.org/10.1002/1873-3468.13276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587861PMC
December 2018

Addition of Suvorexant to Ramelteon Therapy for Improved Sleep Quality with Reduced Delirium Risk in Acute Stroke Patients.

J Stroke Cerebrovasc Dis 2019 Jan 12;28(1):142-148. Epub 2018 Oct 12.

Pharmaceutical Department, Kochi Health Sciences Center, Kochi, Japan.

Background And Purpose: Delirium in acute stroke is associated with poor clinical outcome. The purpose of this study was to examine the effect of sleep medications on sleep quality and delirium in acute stroke.

Methods: In this retrospective cohort study, sleep disturbances, and delirium were investigated in acute stroke patients treated in April 2013-March 2017 who were prescribed ramelteon plus either an alpha-aminobutyric acid receptor (GABAR) agonist or a selective dual orexin receptor antagonist (suvorexant).

Results: Of the patients included, 104 received a GABAR agonist and 128 received suvorexant in addition to ramelteon. Patient characteristics did not differ significantly between the groups, except for a higher proportion of cerebral infarction in suvorexant group (P = .033). Subjective sleep quality was significantly improved in suvorexant group compared to GABAR agonist group (difficulty staying asleep: 6.3% versus 34%, P < .001; daytime sleepiness: 33% versus 63%, P < .001). Delirium was significantly less frequent in suvorexant group than GABAR agonist group (7.0% versus 31%, P < .001). The length of hospital stay was significantly shorter in suvorexant group than in GABAR agonist group (in days, 21 [15-29] versus 25 [18-33]; P = .019). Multivariable logistic regression analysis revealed that the addition of suvorexant was significantly associated with a reduced occurrence of delirium (odds ratios .19, 95% confidence interval .085-.43, P < .001).

Conclusions: Addition of suvorexant to ramelteon therapy, rather than a GABA receptor agonist, can improve subjective sleep quality without inducing delirium in acute stroke patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.09.024DOI Listing
January 2019
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