Timing of Initiation of Acute Stroke Rehabilitation and Management Corresponding to Complications at Primary Stroke Centers in Japan: A Nationwide Cross-Sectional Web-Based Questionnaire Survey.

INTRODUCTION: Many guidelines now recommend early rehabilitation for acute stroke patients. However, evidence remains lacking regarding the specific timings for initiation of various rehabilitation steps and management when complications are encountered in acute stroke rehabilitation. This survey aimed to investigate actual clinical situations in acute stroke rehabilitation in Japan and to improve the medical systems for rehabilitation and plan further studies. METHODS: This nationwide, cross-sectional, web-based questionnaire survey was administered between February 7, 2022, and April 21, 2022, targeting all primary stroke centers (PSCs) in Japan. Among several components of the survey, this paper focused on the timing of the initiation of three rehabilitation steps (passive bed exercise; head elevation; and out-of-bed mobilization), along with the management of rehabilitation (continued or suspended) in the event of complications during acute stroke rehabilitation. We also investigated the influence of facility features on these contents. RESULTS: Responses were obtained from 639 of the 959 PSCs surveyed (response rate: 66.6%). In cases of ischemic stroke and intracerebral hemorrhage, most PSCs initiated passive bed exercise on day 1, head elevation on day 1, and out-of-bed mobilization on day 2 (with day of admission defined as day 1). In cases with subarachnoid hemorrhage, rehabilitation steps were delayed compared to other stroke subtypes or showed wide variation depending on the facility. Passive bed exercise was accelerated by the presence of protocols for rehabilitation and weekend rehabilitation. Out-of-bed mobilization was accelerated by the presence of a stroke care unit. Facilities with board-certified rehabilitation doctors were cautious regarding the initiation of head elevation. Most PSCs suspended rehabilitation training in the event of symptomatic systemic/neurological complications. CONCLUSION: Our survey revealed the actual situation of acute stroke rehabilitation in Japan and indicated that some facility features appear to influence early increases in physical activity levels and early mobilization. Our survey provides fundamental data to improve the medical systems for acute stroke rehabilitation in the future.

Impact of the COVID-19 Pandemic on Acute Stroke Rehabilitation in Japanese Primary Stroke Centers: A Nationwide Cross-Sectional Study Using a Web-based Questionnaire Survey.

INTRODUCTION: Acute stroke rehabilitation is crucial for achieving good functional recovery, even during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to clarify the impact of the COVID-19 pandemic on acute stroke rehabilitation and identify which components in the acute stroke rehabilitation provision system were susceptible to the pandemic. METHODS: A web-based questionnaire survey was conducted in all primary stroke centers (PSCs) in Japan between February 7 and April 21, 2022. The survey included questions about the current status of acute stroke rehabilitation and the influence of the pandemic. We classified the influences and investigated the relationship between the influence of the pandemic and the provision of rehabilitation. Additionally, we investigated a group of prefectures divided according to the grade of the pandemic. RESULTS: The survey response rate was 67% (639 of 959 PSCs). Among them, 387 PSCs (61%) reported that the COVID-19 pandemic affected acute stroke rehabilitation. In PSCs affected by the pandemic, more rehabilitation-related staff were working, and the proportion of weekend/holiday rehabilitation implementation was higher compared to those unaffected. In PSCs from highly infected prefectures, no significant relationship was observed between the influence of the pandemic and the rehabilitation provision system. CONCLUSIONS: PSCs that provide denser acute stroke rehabilitation may be affected to a greater extent by the pandemic. We conclude that stroke hospitals should formulate infection control procedures for acute stroke rehabilitation in advance, depending on the conditions of the region and facility.

Comorbidity burden and outcomes after mechanical thrombectomy for large vessel occlusion: A retrospective analysis.

OBJECTIVES: Patients with acute ischemic stroke (AIS) often have an accumulation of pre-existing comorbidities, but its clinical impact on outcomes after mechanical thrombectomy (MT) remains unknown. Therefore, we examined whether comorbidity burden before AIS onset could predict clinical outcomes after MT. METHODS: In this retrospective cohort, we enrolled consecutive patients with community-onset AIS who underwent MT between April 2016 and December 2021. To evaluate each patient's comorbidity burden, we calculated Charlson comorbidity index (CCI), then classified the patients into the High CCI (≥ 3) and the Low CCI (< 3) groups. The primary outcome was a good neurological outcome at 90 days, defined as a modified Rankin scale 0-2 or no worse than the previous daily conditions. All-cause mortality at 90 days and hemorrhagic complications after MT were also compared between the two groups. We estimated the odds ratios and their confidence intervals using a multivariable logistic regression model. RESULTS: A total of 388 patients were enrolled, of whom 86 (22.2%) were classified into the High CCI group. Patients in the High CCI group were less likely to achieve a good neurological outcome (adjusted odds ratio of 0.26 [95% confidence interval, 0.12-0.58]). Moreover, symptomatic intracranial hemorrhage was more common in the High CCI (14.0% vs. 4.6%; adjusted odds ratio, 4.10 [95% confidence interval, 1.62-10.3]). CONCLUSIONS: Comorbidity burden assessed by CCI was associated with clinical outcomes after MT. CCI has the potential to become a simple and valuable tool for predicting neurological prognosis among patients with AIS and MT.

A nationwide survey for the provision of acute stroke rehabilitation in Japan: initial dose and weekend/holiday rehabilitation.

OBJECTIVES: The early initiation of acute stroke rehabilitation with a sufficient dose, including at weekends/holidays, is important to improve functional outcome. We investigated the status of acute stroke rehabilitation in Japan by using a nationwide survey. MATERIALS AND METHODS: Facility features, rehabilitation dose provided in the first week in each stroke subtype, and weekend/holiday rehabilitation were investigated by using the results of a web-based survey among primary stroke centers. The relationships between facility features and weekend/holiday rehabilitation were also analyzed. RESULTS: A total of 639 stroke centers (66.6%) completed the questionnaire. The overall median dose was 2.0 (interquartile range, 1.7-3.0) U/day (1U = 20 min). After 7 days, the overall median dose increased to 4.0 (2.0-5.4) U/day. Almost 50% of facilities replied that they could not provide a sufficient dose of rehabilitation; the main reason was a lack of therapists (31%). For rehabilitation on long weekends, no rehabilitation was provided on 3-day weekends in 19% of facilities, and in 5% of facilities on ≥4-day weekends. The mean number of therapists was almost 50% less in the facilities that provided no rehabilitation on 3-day weekends compared to those that provided daily rehabilitation (19.4 vs. 36.2 therapists, respectively, p < 0.001). CONCLUSIONS: In this survey, the provision of acute stroke rehabilitation, including non-working days, was clarified. According to the results, prospective interventional or observational studies are needed to design more effective rehabilitation programs to improve outcome. In particular, it is important to determine the optimal dose and intensity of acute stroke rehabilitation.

Mechanism of Cell Death by Combined Treatment with an xCT Inhibitor and Paclitaxel: An Alternative Therapeutic Strategy for Patients with Ovarian Clear Cell Carcinoma.

Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian carcinoma that responds poorly to chemotherapy. Glutathione (GSH) is a primary antioxidant, which protects cells against reactive oxygen species (ROS). High levels of GSH are related to chemotherapeutic resistance. The glutamine/cystine transporter xCT is essential for intracellular GSH synthesis. However, whether xCT inhibition can overcome the resistance to chemotherapeutic agents in OCCC remains unclear. This study demonstrated that combined treatment with paclitaxel (PTX) and the xCT inhibitor sulfasalazine (SAS) significantly enhanced cytotoxicity more than the individual drugs did in OCCC cells. Treatment with PTX and SAS induced apoptosis more effectively than did individual drug treatments in the cells with significant generation of ROS. Moreover, combined treatment with PTX and SAS induced ferroptosis in the cells with low expression of glutathione peroxidase (GPx4), high levels of intracellular iron and significant lipid ROS accumulation. Therefore, our findings provide valuable information that the xCT inhibitor might be a promising therapeutic target for drug-resistant OCCC. The strategy of combined administration of PTX and SAS can potentially be used to treat OCCC and help to develop novel therapeutic methods.

Internal Carotid Artery Tortuosity: Impact on Mechanical Thrombectomy.

BACKGROUND: Although tortuosity of the internal carotid artery (ICA) can pose a significant challenge when performing mechanical thrombectomy, few studies have examined the impact of ICA tortuosity on mechanical thrombectomy outcomes. METHODS: In a registry-based hospital cohort, consecutive patients with anterior circulation stroke in whom mechanical thrombectomy was attempted were divided into 2 groups: those with tortuosity in the extracranial or cavernous ICA (tortuous group) and those without (nontortuous group). The extracranial ICA tortuosity was defined as the presence of coiling or kinking. The cavernous ICA tortuosity was defined by the posterior deflection of the posterior genu or the shape resembling Simmons-type catheter. Outcomes included first pass effect (FPE; extended Thrombolysis in Cerebral Infarction score 2c/3 after first pass), favorable outcome (3-month modified Rankin Scale score of 0-2), and intracranial hemorrhage. RESULTS: Of 370 patients, 124 were in the tortuous group (extracranial ICA tortuosity, 35; cavernous ICA tortuosity, 70; tortuosity at both sites, 19). The tortuous group showed a higher proportion of women and atrial fibrillation than the nontortuous group. FPE was less frequently achieved in the tortuous group than the nontortuous group (21% versus 39%; adjusted odds ratio, 0.45 [95% CI, 0.26-0.77]). ICA tortuosity was independently associated with the longer time from puncture to extended Thrombolysis in Cerebral Infarction ≥2b reperfusion (ß=23.19 [95% CI, 13.44-32.94]). Favorable outcome was similar between groups (46% versus 48%; P=0.87). Frequencies of any intracranial hemorrhage (54% versus 42%; adjusted odds ratio, 1.61 [95% CI, 1.02-2.53]) and parenchymal hematoma (11% versus 6%; adjusted odds ratio, 2.41 [95% CI, 1.04-5.58]) were higher in the tortuous group. In the tortuous group, the FPE rate was similar in patients who underwent combined stent retriever and contact aspiration thrombectomy and in those who underwent either procedure alone (22% versus 19%; P=0.80). However, in the nontortuous group, the FPE rate was significantly higher in patients who underwent combined stent retriever and contact aspiration (52% versus 35%; P=0.02). CONCLUSIONS: ICA tortuosity was independently associated with reduced likelihood of FPE and increased risk of postmechanical thrombectomy intracranial hemorrhage. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02251665.

Nuclear receptor coactivator-6 is essential for the morphological change of human uterine stromal cell decidualization via regulating actin fiber reorganization.

Nuclear receptor coactivator 6 (Ncoa6), a modulator of several nuclear receptors and transcription factors, is essential for the decidualization of endometrial stromal cells in mice. However, the function of Ncoa6 in the human endometrium remains unclear. We investigated its function in the decidualization of human endometrial stromal cells (HESCs) isolated from resected uteri. Knockdown of Ncoa6 was performed using two independent small interfering RNAs. Decidualization was induced in vitro via medroxyprogesterone and cyclic adenosine monophosphate. We compared decidualized cellular morphology between the Ncoa6 knockdown cells and control cells. Messenger RNA (mRNA) sequencing was performed to determine the Ncoa6 target genes in undecidualized HESCs. We found that the knockdown of Ncoa6 caused the failure of morphological changes in decidualized HESCs compared to that in the control cells. mRNA sequencing revealed that Ncoa6 regulates the expression of genes associated with the regulation of actin fibers. Ncoa6 knockdown cells failed to reorganize actin fibers during the decidualization of HESCs. Ncoa6 was shown to play an essential role in decidualization via the appropriate regulation of actin fiber regulation in HESCs. Herein, our in vitro studies revealed a part of the mechanisms involved in endometrial decidualization. Future research is needed to investigate these mechanisms in women with implantation defects.

Assisted Living and Medication Adherence in Super-aged Patients With Heart Failure in the Japanese Population.

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 patients (6.1%) 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, whereas male patients or current smokers did not. Summarily, assisted living at least once a week was appropriate for improving medication adherence in patients with HF and was particularly effective in 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.

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

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.

Association of Aggression and Antiepileptic Drugs: Analysis Using the Japanese Adverse Drug Event Report (JADER) Database.

Aggression is the most common adverse effect of antiepileptic drugs (AEDs). This study aimed to investigate the association of aggression with AED use. The reporting odds ratio (ROR) from adverse event reports, submitted to the Japanese Adverse Drug Event Report database between 2004 and 2020, was used to calculate and investigate the association between AEDs and aggression. We also analyzed the association of aggression with the combined use of AEDs and the relationship between AED-associated aggression and patient characteristics. A total of 433 patients developed aggression. Significant aggression signals were detected for perampanel (crude ROR: 325.04, 95% confidence interval (CI): 118.48-752.58, p < 0.01), levetiracetam (crude ROR: 17.14, 95% CI: 10.33-26.90, p < 0.01), lacosamide (crude ROR: 16.90, 95% CI: 2.02-62.51, p < 0.01), lamotrigine (crude ROR: 15.98, 95% CI: 9.99-24.39, p < 0.01), valproate (crude ROR: 6.68, 95% CI: 4.27-10.02, p < 0.01), and carbamazepine (crude ROR: 2.47, 95% CI: 1.17-4.59, p < 0.01). The combined therapy with perampanel and levetiracetam had a significant aggression signal (adjusted ROR: 25.90, 95% CI: 1.14-59.10, p < 0.01). In addition, we found that aggression frequently occurred in patients <60 year (adjusted ROR: 2.88, 95% CI: 1.49-5.56, p < 0.01) treated with levetiracetam. These results may be useful for minimizing the risk of aggression during the treatment of AEDs.

Comparison of treatment outcomes between first-line chemotherapy with or without bevacizumab for advanced ovarian, fallopian tube, and primary peritoneal cancer (Tohoku gynecologic cancer unit: TGCU-RS001 study).

BACKGROUND: Outcomes with and without bevacizumab as first-line chemotherapy in Japanese-only ovarian cancer patients have not been reported. In this study, we report a retrospective study conducted at the Tohoku Gynecologic Cancer Unit. PATIENTS AND METHODS: The study included 453 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer who received first-line platinum-based chemotherapy. The patients were divided into two groups: bevacizumab (168 patients) and without bevacizumab (285 patients). The primary endpoint was the rate of platinum-resistant recurrence and the secondary endpoints were the antitumor response, progression-free survival, overall survival, and adverse events. RESULTS: The objective response rates for patients with measurable diseases treated with and without bevacizumab were 84.5% and 73.0%, respectively (P = 0.0066). Platinum-resistant recurrence in the groups treated with and without bevacizumab was noted in 31 (18.4%) and 111 (38.6%) patients, respectively (P < 0.0001). The median progression-free survival for the bevacizumab and without bevacizumab groups was 23 and 15 months, respectively (P = 0.0002), and the median overall survival was not reached and 49 months, respectively (P = 0.0005). Hypertension of grade 3 or higher was observed in 21 patients (12.5%) in the bevacizumab group (P < 0.001), and proteinuria was observed in 18 patients (10.7%) and 1 patient (0.3%) in the bevacizumab and without bevacizumab groups, respectively (P < 0.001). Intestinal perforation was observed in only one patient (0.6%) in the bevacizumab group. CONCLUSION: Combination and maintenance with bevacizumab in primary chemotherapy for advanced ovarian, fallopian tube, and primary peritoneal cancer was effective in reducing platinum-resistant recurrence rates and prolonging progression-free and overall survival.

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.

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.

Safety of early rehabilitation in patients with aneurysmal subarachnoid hemorrhage: A retrospective cohort study.

OBJECTIVE: To investigate the safety and efficacy of early rehabilitation in patients with aneurysmal subarachnoid hemorrhage (aSAH) patients. METHODS: One hundred eleven patients with aSAH admitted between April 2015 and March 2019, were retrospectively evaluated. The early rehabilitation program was introduced in April 2017 to actively promote mobilization and walking training for aSAH patients. Therefore, patients were divided into two groups (The conventional group (n = 55) and the early rehabilitation group (n == 56). Clinical characteristics, mobilization progression, and treatment variables were analyzed. Complications (rebleeding, symptomatic cerebral vasospasm, hydrocephalus, disuse complications,) and a modified Rankin Scale (mRS) at 90 days were compared in two groups. Factors associated with favorable outcomes (mRS≤2) at 90 days were also assessed. RESULTS: The early rehabilitation group had a significantly shorter span to first walking (9 vs. 5 days; P = 0.007). The prevalence of complications was not significantly increased in the early rehabilitation group. Approximately 40% of patients in both groups had pneumonia and urinary tract infections but significantly reduced antibiotic-administration days (13 vs. 6 days; P < 0.001). mRS at 90 days also showed significant improvement in the early rehabilitation group (3 vs. 2; P=0.01). Multivariate logistic regression analysis of favorable outcomes associated that the administration of the early rehabilitation program has a significant independent factor (odds ratio, 3.03; 95% confidence interval, 1.1-8.37). CONCLUSIONS: Early rehabilitation for patients with aSAH can be feasible without increasing complication occurrences. The early rehabilitation program with active mobilization and walking training reduced antibiotic use and was associated with improved independence.

The impact of the approval of prothrombin complex concentrates for vitamin K antagonist-related intracerebral hemorrhage: A retrospective study.

OBJECTIVES: This study aimed to determine the impact of the approval of prothrombin complex concentrates on the treatment of vitamin K antagonist-related intracerebral hemorrhage. MATERIALS AND METHODS: We retrospectively studied all patients with vitamin K antagonist-related intracerebral hemorrhage treated with prothrombin complex concentrate at our institutes between January 2010 and June 2021. Before approval, prothrombin complex concentrate was administered as either 500 or 1000 IU at the physician's discretion (previous dose group). After approval, we adopted the manufacturer's recommended regimen (recommended dose group). The primary outcome was post-administration international normalized ratio. Secondary outcomes were the amount of prothrombin complex concentrate administered and proportion of post-administration international normalized ratio <1.5, hematoma expansion, thrombotic events within 30 days, modified Rankin scale 0-3 at discharge, and in-hospital mortality. RESULTS: Thirty-two and 19 patients in the previous and recommended dose groups, respectively, were included. The post-administration international normalized ratio significantly differed between groups. The prothrombin complex concentrate dose and proportion of patients achieving post-administration international normalized ratio <1.5 were significantly higher in the recommended dose group than in the previous dose group (1500 IU vs. 500 IU, p<0.001 and 100% vs. 68%, p = 0.008). The proportions of hematoma expansion, thromboembolic events, modified Rankin scale 0-3, and mortality did not differ between groups. CONCLUSION: After prothrombin complex concentrate approval, prothrombin time-international normalized ratio correction was more effective with a significant increase in the prothrombin complex concentrates dose for vitamin K antagonist-associated intracerebral hemorrhage; however, there was no apparent difference in clinical outcomes.

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

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

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.

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

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.

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.

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.

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

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.

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

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.