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The role of the adenosine neurochemical system in human cognition is under-studied, despite such receptors being distributed throughout the brain. The aim of this study was to shed light on the role of the adenosine A2A receptors in human cognition using single-dose istradefylline. Twenty healthy male participants, aged 19-49, received 20 mg istradefylline and placebo, in a randomized, double-blind, placebo-controlled cross-over design. Cognition was assessed us-ing computerized cognitive tests, covering both cold (non-emotional) and hot (emotion-laden) domains. Cardiovascular data were recorded serially. Cognitive effects of istradefylline were explored using repeated measures analysis of variance and paired t-tests as appropriate. On the EMOTICOM battery, there was a significant effect of istradefylline versus placebo on the Social Information Preference task ( t = 2.50, p = 0.02, d =-0.59), indicating that subjects on istradefylline interpreted social situations more positively. No other significant effects were observed on other cognitive tasks, nor in terms of cardiovascular measures (pulse and blood pressure). De-briefing indicated that blinding was successful, both for participants and the research team. Further exploration of the role of adenosine A2A receptors in emotional pro-cessing may be valuable, given that abnormalities in related cognitive functions are implicated in neuropsychiatric disorders. The role of adenosine systems in human cognition requires fur-ther clarification, including with different doses of istradefylline and over different schedules of administration.(c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Aneurysms of the recurrent artery of Heubner (RAH) are known to be one of the uncommon cerebral aneurysms, predominantly presenting with bleeding symptoms. Previously, nine cases of the RAH aneurysms have been reported, all of which were treated surgically or endovascularly and most cases developed postoperative cerebral infarct in the ipsilateral caudate nucleus. Herein, we report a man presenting with transient ischemic attack due to diffuse cerebral vasospasm from a minor non-disabling subarachnoid hemorrhage (SAH) from an RAH aneurysm. He visited our hospital 7 days after the first experience of a thunderclap headache complaining with transient unilateral motor weakness and thin SAH in the right sylvian fissure. Diagnostic catheter angiography revealed a dissecting fusiform aneurysm (8 mm in size) originating from the left RAH contralateral to the thin SAH. Contrast-enhanced magnetic resonance vessel wall imaging (MR-VWI) helped to identify the ruptured nature of the RAH aneurysm. Owing to his delayed ischemic condition after minor SAH, he was conservatively treated with serial MR-VWI monitoring. The aneurysm was spontaneously obliterated with an asymptomatic lacunar infarct in the ipsilateral caudate nucleus in a month. Together, this case was considered as the dissecting aneurysm of RAH with a favorable outcome after the conservative management. Although long-term follow-up is mandatory because the disappearance of the vessel wall enhancement does not necessarily secure the permanent cure of the lesion, serial MR-VWI is helpful to diagnose the ruptured nature and monitor its chronological change in combination with conventional radiological imaging techniques.

Although brain morphological abnormalities have been reported in anorexia nervosa (AN), the reliability and reproducibility of previous studies were limited due to insufficient sample sizes, which prevented exploratory analysis of the whole brain as opposed to regions of interest (ROIs). Objective was to identify brain morphological abnormalities in AN and the association with severity of AN by brain structural magnetic resonance imaging (MRI) in a multicenter study, and to conduct exploratory analysis of the whole brain. Here, ｗe conducted a cross-sectional multicenter study using T1-weighted imaging (T1WI) data collected between May 2014 and February 2019 in Japan. We analyzed MRI data from 103 female AN patients (58 anorexia nervosa restricting type [ANR] and 45 anorexia nervosa binge-purging type [ANBP]) and 102 age-matched female healthy controls (HCs). MRI data from five centers were preprocessed using the latest harmonization method to correct for intercenter differences. Gray matter volume (GMV) was calculated from T1WI data of all participants. Of the 205 participants, we obtained severity of eating disorder symptom scores from 179 participants, including 87 in the AN group (51 ANR, 36 AMBP) and 92 HCs using the Eating Disorder Examination Questionnaire (EDE-Q) 6.0. GMV reduction were observed in the AN brain, including the bilateral cerebellum, middle and posterior cingulate gyrus, supplementary motor cortex, precentral gyrus medial segment, and thalamus. In addition, the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), rostral anterior cingulate cortex (ACC), and posterior insula volumes showed positive correlations with severity of symptoms. This multicenter study was conducted with a large sample size to identify brain morphological abnormalities in AN. The findings provide a better understanding of the pathogenesis of AN and have potential for the development of brain imaging biomarkers of AN. Trial Registration: University Hospital Medical Information Network Individual Case Data Repository: UMIN000017456. https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000019303

Supplemental Digital Content is available in the text., Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258–0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206–2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

Background and hypothesisWhile the conservatism bias refers to the human need for more evidence for decision-making than rational thinking expects, people with schizophrenia and delusion require less evidence, known as the jumping to conclusions (JTC) bias. The midbrain-striatal aberrant salience of schizophrenia is postulated to form delusion; however, the association between conservatism/JTC and aberrant salience and their neural correlates are unclear.Study designThirty-seven patients with schizophrenia and 33 healthy controls performed the beads task, with large/small numbers of bead draws to decision (DTD) used as an index of conservative/hasty (JTC) decisions, respectively. We performed meta-independent component analysis and thresholded dual regression of resting functional magnetic resonance imaging (MRI) data, and structural covariance network analysis (SCNA) of structural and diffusion MRI data. We investigated interactions between diagnosis and DTD, and main effects of DTD for each imaging modality.Study resultsWe found no significant interactions. We identified main effects of DTD (positive correlation) for: 1) functional connectivity between the striatum and default mode network (DMN), 2) DMN-like structural SCNA network, and 3) the diffusion SCNA network connecting networks of 1) and 2) (all p < 0.05, family-wise error [FWE] correction). The functional connectivity between the striatum and DMN was also negatively correlated with delusion severity in patients (p < 0.05, FWE), indicating that the greater the anti-correlation, the stronger the JTC and delusion.ConclusionsOur results support a novel concept that conservatism/JTC biases are associated with aberrant salience of schizophrenia and the default brain mode.

The symptoms of obsessive–compulsive disorder (OCD) are suggestive of cognitive rigidity, and previous work identified impaired flexible responding on set-shifting tasks in such patients. The basal ganglia are central to habit learning and are thought to be abnormal in OCD, contributing to inflexible, rigid habitual patterns of behaviour. Here, we demonstrate that increased cognitive inflexibility, indexed by poor performance on the set-shifting task, correlated with putamen morphology, and that patients and their asymptomatic relatives had common curvature abnormalities within this same structure. The association between the structure of the putamen and the extradimensional errors was found to be significantly familial in OCD proband–relative pairs. The data implicate changes in basal ganglia structure linked to cognitive inflexibility as a familial marker of OCD. This may reflect a predisposing heightened propensity toward habitual response patterns and deficits in goal-directed planning.

Entrapment of the middle cluneal nerve (MCN), a peripheral nerve in the buttock, can elicit low back pain (LBP). We examined the epidemiology, clinical course, and treatment of MCN entrapment (MCN-EN). Among 383 LBP patients who visited our institute, 105 were admitted for intractable LBP. They were 42 men and 63 women; their average age was 64 years. Based on clinical symptoms, palpation, and the effects of MCN block, we suspected MCN-EN in these 105 patients, 50 of whom are our study subjects. Their treatment outcomes were assessed at the time of discharge and at follow-up visits. MCN-EN was diagnosed in 50 of the 383 patients (13.1%) and they were hospitalized. In 43 (11.2%), MCN-EN was associated with other diseases (superior cluneal nerve entrapment, n = 21, sacroiliac joint pain, n = 9, other, n = 13). At the time of discharge, the symptoms of patients with LBP due to MCN-EN were significantly improved by repeat MCN blocks. In 7 of the 383 patients (1.8%), LBP was improved by only MCN blocks; 5 of them had reported leg symptoms in the dorsal part of the thigh. After discharge, 22 of the 50 hospitalized patients required no additional treatments after 2–5 blocks; 19 required only conservative treatment, and 9 underwent microsurgical release of the MCN. We confirmed MCN-EN in 50 of 105 patients admitted for intractable LBP. Repeat MCN blocks were effective in 22 patients; 19 required additional conservative treatment, and 9 underwent surgery. Buttock pain radiating to the posterior thigh was an MCN-EN symptom that has been diagnosed as pseudo-sciatica. Before subjecting patients with intractable LBP to surgery, the presence of MCN-EN must be ruled out.

Lumbar disc herniation (LDH) elicits low back pain (LBP) and lower-limb symptoms. Paralumbar spine disease (PLSD), for example, superior cluneal nerve/middle cluneal nerve entrapment (SCN-EN, MCN-EN) and sacroiliac joint pain (SIJ), may be attributable to LDH whose treatment may not ameliorate their symptoms. We treated LDH patients and addressed their coexisting PLSDs. We retrospectively analyzed the effects of targeted block therapy for PLSD in 47 patients with LDH. They were 23 men and 24 women ranging in age from 21 to 79 years. They were seen between August 2014 and October 2018, within 3 weeks of LDH onset. PLSD was diagnosed based on the symptoms of patients whose pain was not controlled by oral medications. The treatment outcome was assessed by comparing the numerical rating scale (NRS) and the Roland-Morris Disability Questionnaire (RDQ) score recorded before and 2 weeks after last block treatment. Of the 47 patients with LDH, 2 suffered no LBP and 30 reported tenderness in the low back. We performed block therapy in 13 patients; 9 (19.1%) had concurrent PLSD and experienced pain relief. Their NRS improved from 8.1 ± 1.8 before- to 1.3 ± 0.9 after treatment; their RDQ score fell from 11.2 ± 6.0 to 0.9 ± 1.2 (both, p < 0.01). In an LDH patient with MCN-EN alone, MCN neurolysis was performed 2 weeks after a single MCN block proved to be only transiently effective. Paralumbar diseases may coexist in patients with LDH; treatment of the former may alleviate their LBP.

Background Long‐term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high‐risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23–0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26–0.91) were lower in DAPT than SAPT, whereas the risk of severe or life‐threatening bleeding (HR, 0.72; 95% CI, 0.12–4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01995370.

Background Numerous studies have demonstrated attentional control difficulties and high avoidance coping in patients with anorexia nervosa. Attention is a critical coping resource because it enables individuals to demonstrate self-control and complete goal-directed behaviours. Aims We aimed to examine whether attentional control difficulty is related to high avoidance coping, and investigate the neural underpinnings of attentional control difficulties in individuals with anorexia nervosa. Method Twenty-three patients with anorexia nervosa and 17 healthy controls completed questionnaires that assessed attention and coping, and underwent functional magnetic resonance imaging while performing a go/no-go task. Results Patients with anorexia nervosa showed weaker attentional control, higher omission error rates and higher avoidance coping compared with healthy controls. Attentional control difficulty was associated with higher avoidance coping in both groups. Functional magnetic resonance imaging analysis showed less deactivation in regions representing internal mental processing, such as the praecuneus, cuneus and left lingual gyrus, during the no-go condition. Moreover, weakened deactivation of the left lingual gyrus was associated with higher commission error rate in the anorexia nervosa group. Conclusions Our results suggest that patients with anorexia nervosa may have difficulty in maintaining attention to external ongoing events because of disturbance from internal self-related thought, and support the notion that attentional control difficulties underlie the frequent use of avoidance coping in anorexia nervosa.

Although dual antiplatelet therapy with aspirin and clopidogrel reduces early recurrence of ischaemic stroke, with long-term use this type of therapy is no longer effective and the risk of bleeding increases. Given that cilostazol prevents stroke recurrence without increasing the incidence of serious bleeding compared with aspirin, we aimed to establish whether dual antiplatelet therapy involving cilostazol is safe and appropriate for long-term use.In a multicentre, open-label, randomised controlled trial across 292 hospitals in Japan, patients with high-risk non-cardioembolic ischaemic stroke identified on MRI were randomly assigned to two groups in a 1:1 ratio to receive monotherapy with either oral aspirin (81 or 100 mg, once per day) or clopidogrel (50 or 75 mg, once per day) alone, or a combination of cilostazol (100 mg, twice per day) with aspirin or clopidogrel. Randomisation was done centrally (using block randomisation with a block size of six per each participating hospital) through a web-based registration system and was done by EPS Corporation. The patients were required to have at least 50% stenosis of a major intracranial or extracranial artery or two or more of the vascular risk factors. Trial medication was continued for half a year or longer, for a maximum of 3·5 years. The primary efficacy outcome was the rate of first recurrence of symptomatic ischaemic stroke. Safety outcomes were severe or life-threatening bleeding; any adverse events; serious adverse events; and any bleeding events. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the as-treated population. This trial was registered with ClinicalTrials.gov (number NCT01995370) and UMIN Clinical Trials Registry (number 000012180).Participants were recruited from Dec 13, 2013, to March 31, 2017. 932 patients assigned to the dual therapy group and 947 patients assigned to the monotherapy group were included in the intention-to-treat analysis. The trial was stopped after the enrolment of 1884 patients of an anticipated 4000 patients because of the delay in recruitment. Ischaemic stroke recurred in 29 (3%) of 932 patients (annualised rate 2·2%) on dual therapy including cilostazol and 64 (7%) of 947 patients (annualised rate 4·5%) on monotherapy during a median 1·4 years follow-up (hazard ratio [HR] 0·49, 95% CI 0·31-0·76, p=0·0010). Severe or life-threatening bleeding occurred in eight patients (annualised rate 0·6%) on dual therapy and 13 patients (annualised rate 0·9%) on monotherapy (HR 0·66, 95% CI 0·27-1·60, p=0·35). Occurrence of any type of adverse event was similar between the groups (255 [28%] of 910 patients in the dual therapy group vs 219 [24%] of 921 patients in the monotherapy group); as was occurrence of serious adverse events (87 [10%] vs 142 [15%]) and bleeding events (38 [4%] vs 33 [4%]). Gastrointestinal bleeding, which affected nine (1%) of 910 patients in the monotherapy group and nine (1%) of 921 patients in the dual therapy group, was the most common type of bleeding.The combination of cilostazol with aspirin or clopidogrel had a reduced incidence of ischaemic stroke recurrence and a similar risk of severe or life-threatening bleeding compared with treatment with aspirin or clopidogrel alone in patients at high risk for recurrent ischaemic stroke.Otsuka Pharmaceutical.

ObjectiveThe clinical phenotype of gambling disorder (GD) is suggestive of changes in brain regions involved in reward and impulse suppression, notably the striatum. Studies have yet to characterize striatal morphology (shape) in GD and whether this may be a vulnerability marker.AimsTo characterize the morphology of the striatum in those with disordered gambling (at-risk gambling and GD) versus controls.MethodIndividuals aged 18–29 years were classified a priori into those with some degree of GD symptoms (at-risk gambling and GD) or controls. Exclusion criteria were a current mental disorder (apart from GD), history of brain injury, or taking psychoactive medication within 6 weeks of enrollment. History of any substance use disorder was exclusionary. Participants completed an impulsivity questionnaire and structural brain scan. Group differences in volumes and morphology were characterized in subcortical regions of interest, focusing on the striatum.ResultsThirty-two people with GD symptoms (14 at-risk and 18 GD participants) and 22 controls completed the study. GD symptoms were significantly associated with higher impulsivity and morphological alterations in the bilateral pallidum and left putamen. Localized contraction in the right pallidum strongly correlated with trait impulsivity in those with GD symptoms.ConclusionsMorphologic abnormalities of the striatum appear to exist early in the disease trajectory from subsyndromal gambling to GD and thus constitute candidate biological vulnerability markers, which may reflect differences in brain development associated with trait impulsivity. Striatal morphology and associated impulsivity might predispose to a range of problematic repetitive behaviors.

Sacroiliac joint (SIJ)-related pain is associated with low back- and buttock pain and the SIJ score is diagnostically useful because it helps to differentiate between SIJ-related pain and pain due to other factors such as lumbar disc herniation and lumbar spinal canal stenosis. Middle cluneal nerve (MCN) entrapment (MCN-E) can produce pain involving the lower back and buttocks. Therefore, the origin of the pain must be identified. We successfully treated patients with a high SIJ score whose pain was attributable to MCN-E. Between August 2016 and June 2017, we treated 40 patients with non-specific low back pain. Among them, 18 (45%) presented with a positive SIJ score. Although SIJ treatment was unsuccessful in 4 of these patients, they responded to MCN-E treatment. All 4 patients reported tenderness at the site of the sacrotuberous ligament (STL); 3 were positive for the one-finger test and experienced pain while sitting in a chair. The effect of SIJ block was inadequate in the 4 patients. As they reported severe pain at the trigger point in the area of the MCN, we performed MCN blockage. It resulted in pain control. However, in 1 patient, the effect of MCN block was transient and required MCN neurolysis. At the last visit, our patients’ symptoms were significantly improved; their average numerical rating scale score fell from 8.3 to 1.0, their Roland-Morris Disability Questionnaire score fell from 12.8 to 0.3, and their average Japanese Orthopaedic Association score rose from 12.5 to 19.5. In patients with suspected SIJ-related pain, the presence of MCN-E must be considered when the effect of SIJ block is unsatisfactory.

Background Retroperitoneal high-grade serous carcinoma (HGSC) is extremely rare and the origin remains unclear. We present a case of retroperitoneal HGSC and coexisting serous tubal intraepithelial carcinoma (STIC), which is considered as the main origin of ovarian HGSC. We reviewed the available literature and discussed about the origin of this rare disease. Case presentation A 58-year-old female with a 93 × 65 × 62 mm-solid tumor with a cystic part was located immediately dorsal to the rectum underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy, and en bloc resection of the retroperitoneal tumor together with lower anterior resection of the rectum. Histological diagnosis was retroperitoneal HGSC and STIC at the right fallopian tube. Two deleterious somatic mutations in TP53 and BRCA2 genes were shared between retroperitoneal HGSC and STIC. Conclusions In addition to clinical features in the previous reports, our genetic findings suggest the origin of retroperitoneal HGSC might be STIC.

The need for closure (NFC), a desire for a firm answer and less ambiguity, has a key role in cognitive flexibility in typical development (TD) populations. This study investigated this motivational construct and its relation to cognitive inflexibility in autism spectrum disorder (ASD). Compared with individuals with TD, those with ASD reported higher levels in preference for predictability and closed-mindedness and lower levels in decisiveness. These NFC facets were significantly associated with cognitive flexibility in ASD as well as TD groups. The study findings provide further insights into the motivational underpinnings of flexible behavior in ASD.

Background: Middle cluneal nerve entrapment neuropathy (MCN-EN) is a known cause of low back pain (LBP). Here, we succeeded in treating a patient with a lumbar disc herniation who actually had MCN-EN with a nerve block and neurolysis. Case Description: A 52-year-old female presented with severe left lower back and lateral thigh pain making it difficult to walk. The lumbar MRI revealed a disc herniation on the left at the L5/S1 level. On palpation, we identified a trigger point on the buttock where the MCN penetrates the long posterior sacroiliac ligament between the posterior superior and inferior iliac spine. Two left-sided MCN blocks, followed by the left MCN neurolysis procedure, were performed under local anesthesia. At the last follow-up, 10 months after surgery, the LBP has not recurred, and she requires no medications for pain control. Conclusion: Here, a patient with a left-sided L5S1 disc herniation and low back/leg pain was successfully treated for MCN-EN with nerve block followed by neurolysis.

IntroductionAnorexia nervosa is a refractory psychiatric disorder with a mortality rate of 5.9% and standardised mortality ratio of 5.35, which is much higher than other psychiatric disorders. The standardised mortality ratio of bulimia nervosa is 1.49; however, it is characterised by suicidality resulting in a shorter time to death. While there is no current validated drug treatment for eating disorders in Japan, cognitive–behavioural therapy (CBT) is a well-established and commonly used treatment. CBT is also recommended in the Japanese Guidelines for the Treatment of Eating Disorders (2012) and has been covered by insurance since 2018. However, the neural mechanisms responsible for the effect of CBT have not been elucidated, and the use of biomarkers such as neuroimaging data would be beneficial.Methods and analysisThe Eating Disorder Neuroimaging Initiative is a multisite prospective cohort study. We will longitudinally collect data from 72 patients with eating disorders (anorexia nervosa and bulimia nervosa) and 70 controls. Data will be collected at baseline, after 21–41 sessions of CBT and 12 months later. We will assess longitudinal changes in neural circuit function, clinical data, gene expression and psychological measures by therapeutic intervention and analyse the relationship among them using machine learning methods.Ethics and disseminationThe study was approved by The Ethical Committee of the National Center of Neurology and Psychiatry (A2019-072). We will obtain written informed consent from all patients who participate in the study after they had been fully informed about the study protocol. All imaging, demographic and clinical data are shared between the participating sites and will be made publicly available in 2024.Trial registration numberUMIN000039841

Aim We aimed to evaluate regional disparities in the proportion of the three main laparoscopic surgeries for benign gynecological diseases among 47 prefectures in Japan and their correlation with the number of laparoscopy-qualified gynecologists per population. Methods In this retrospective ecological study, we collected the data of patients from 47 prefectures in 2017 using "The National Database of Health Insurance Claims and Specific Health Checkups of Japan" Open Data from the Ministry of Health, Labor and Welfare in Japan. The primary outcome of the study was the proportion of laparoscopic surgeries conducted for benign gynecologic diseases (hysterectomy, myomectomy and surgery for the benign ovarian diseases). The main exposure was the number of laparoscopy-qualified gynecologists per 100 000 females. Results The average proportion of laparoscopic hysterectomies, myomectomies and surgeries for the benign ovarian disease were 38% (standard deviation (SD) 16, range 12-74), 48% (SD 18, range 9-81) and 60% (SD 11, range 36-79), respectively. Multiple regression analysis showed a significant correlation between the number of laparoscopy-qualified gynecologists per 100 000 females and the proportion of the three main laparoscopic surgeries. Conclusion There are obvious regional disparities in the proportion of the three main laparoscopic procedures for benign gynecological diseases among 47 prefectures. The number of laparoscopy-qualified gynecologists correlated significantly with these regional disparities. The academic society should monitor these regional disparities and make an effort to reduce these regional disparities by increasing laparoscopy-qualified gynecologists in areas where the widespread use of laparoscopic techniques is lagging.

ARID1A loss-of-function mutation accompanied by a loss of ARID1A protein expression is considered one of the most important driver events in endometriosis-associated ovarian cancer. Although our recent genomic study clarified that ARID1A loss-of-function mutations were detected in 13% of ovarian endometriosis, an association between the ARID1A mutation status and ARID1A protein expression in ovarian endometriosis remains unclear. We performed immunohistochemical staining for ARID1A in 78 ovarian endometriosis samples and 99 clear cell carcinoma samples. We revealed that not only 70 endometriosis samples without ARID1A mutations but also eight endometriosis samples with ARID1A loss-of-function mutations retained ARID1A protein expression. On the other hand, most of clear cell carcinomas with ARID1A loss-of-function mutations showed a loss of ARID1A protein expression. In particular, clear cell carcinoma samples which harbor multiple ARID1A loss-of-function mutations or both a single ARID1A loss-of-function mutation and ARID1A allelic imbalance lost ARID1A protein expression. However, ARID1A protein expression was retained in seven clear cell carcinomas with ARID1A loss-of-function mutations. These results suggest that a single ARID1A loss-of-function mutation is insufficient for ARID1A loss in ovarian endometriosis and some clear cell carcinoma. Further driver events may be needed for the malignant transformation of ovarian endometriosis with ARID1A loss-of-function mutations.

Background Surgery for idiopathic tarsal tunnel syndrome (TTS) is of limited effectiveness or ineffective. Using indocyanine green video angiography (ICG-VA), we treated idiopathic TTS by posterior tibial artery (PTA) decompression from the posterior tibial nerve (PTN) and evaluated postoperative patency of the PTA. Methods We treated 12 patients (12 feet) with idiopathic TTS by PTA decompression from the PTN and transposed its location. Age range of patients was 70–87 years (mean 77.9 years); all patients were operated on under local anesthesia. After a 2-cm skin incision, the flexor retinaculum was resected, and the PTA was decompressed from the PTN. It was then sutured to the flexor retinaculum for decompression and to prevent compression recurrence. ICG-VA was used to confirm the absence of PTA flow disturbance and to inspect the vasa nervorum of the PTN. Results We encountered no intraoperative or postoperative complications. Postoperatively, ICG-VA confirmed blood flow in the PTA and intactness of the vasa nervorum in all cases. One patient required adjustment of PTA position. All patients reported symptom improvement. Conclusions Our surgical method of treating idiopathic TTS under ICG-VA monitoring is simple, safe, and effective.

Aim This study aimed to investigate the trends in overall hysterectomy and other alternative therapies for benign uterine diseases per population aged 40-54 years in Japan. Methods We conducted a national representative cohort study in Japan. We obtained data from 'The National Database of Health Insurance Claims and Specific Health Checkups of Japan' Open Data. The primary outcome was the number of overall hysterectomies for benign gynecologic diseases per population aged 40-54 years, from 2014 to 2017 in Japan. The secondary outcome was the number of alternative surgical and drug therapies to hysterectomy per population. We also analyzed the correlation between the number of laparoscopy-qualified gynecologists and the number of overall hysterectomies per population among 47 prefectures in 2017. Results The number of overall hysterectomies for benign gynecological diseases per 100 000 females aged 40-54 years gradually increased from 320 in 2014 to 344 in 2017 (7.5% increase overall). Moreover, there was a significant increase in the use of levonorgestrel intrauterine systems. We could not explain the reason for this increase in the rate of overall hysterectomies by summarizing the increase or decrease of alternative therapies to hysterectomy. Multiple regression analysis showed a significant correlation between the number of laparoscopy-qualified gynecologists and the number of overall hysterectomies among 47 prefectures. Conclusion Despite the spread of alternative therapies to hysterectomy, there was an increasing trend for overall hysterectomies in Japan. The reason was not clear but may be related to the spread of laparoscopic hysterectomy.

Background: Outcomes of stroke with cancer-related coagulopathy (Trousseau syndrome) is predominantly attributed to cancer managements; however, stroke management by anticoagulants can contribute to the best supportive care. We aimed to find predictors of the outcome by multivariate analysis, including machine-learning (ML) based feature-engineering. Methods: A single-center retrospective study using a prospective cohort was conducted between April 2011 and June 2019. Out of the cumulative total of 110 acute ischemic stroke patients with malignancy, 65 were treated with anticoagulants, including warfarin (n=19), non-vitamin K dependent oral anticoagulants (NOAC, n=40), or subcutaneous heparin injections (n=6). Cancer-related coagulopathy was defined by elevated blood D-dimer levels at the onset of stroke with malignancy. The incidence of stroke recurrence was analyzed using 40 variables by logistic regression (LR) and in-house ML programs. Results: Out of 65 instances of the cancer-related stroke, 12 (18.5%) stroke recurrences were observed during 455 ± 70 days (mean, SEM). The stroke subtypes were cardioembolism (n=2), stroke with undetermined etiology (n=23) or other determined etiology (cancer-related coagulopathy, n=40). Multivariate LR revealed significant predictors of stroke recurrence, including NOAC usage and stroke subtype. Whereas, combination of forward stepwise selection and Naïve-Bayes (NB) or support vector machine found the blood D-dimer level as an additional important predictor. Input the D-dimer level in addition to NOAC usage and stroke subtype yielded the best area under the curve (AUC) for either of LR or NB compared to input warfarin or heparin usage. AUC for the LR for these 3 variables was better than that for NB. Conclusion: This study suggests the incidence of stroke recurrence is high in this clinical situation. NOAC usage, stroke subtype, and blood D-dimer level at the onset of stroke have predictive value of the outcome.

OBJECTIVEThe etiology of low-back pain (LBP) is heterogeneous and is unknown in some patients with chronic pain. Superior cluneal nerve entrapment has been proposed as a causative factor, and some patients suffer severe symptoms. The middle cluneal nerve (MCN) is also implicated in the elicitation of LBP, and its clinical course and etiology remain unclear. The authors report the preliminary outcomes of a less invasive microsurgical release procedure to address MCN entrapment (MCN-E).METHODSThe authors enrolled 11 patients (13 sites) with intractable LBP judged to be due to MCN-E. The group included 3 men and 8 women ranging in age from 52 to 86 years. Microscopic MCN neurolysis was performed under local anesthesia with the patient in the prone position. Postoperatively, all patients were allowed to walk freely with no restrictions. The mean follow-up period was 10.5 months. LBP severity was evaluated on the numerical rating scale (NRS) and by the Japanese Orthopaedic Association (JOA) and the Roland-Morris Disability Questionnaire (RDQ) scores.RESULTSAll patients suffered buttock pain, and 9 also had leg symptoms. The symptoms were aggravated by standing, lumbar flexion, rolling over, prolonged sitting, and especially by walking. The numbers of nerve branches addressed during MCN neurolysis were 1 in 9 patients, 2 in 1 patient, and 3 in 1 patient. One patient required reoperation due to insufficient decompression originally. There were no local or systemic complications during or after surgery. Postoperatively, the symptoms of all patients improved statistically significantly; the mean NRS score fell from 7.0 to 1.4, the mean RDQ from 10.8 to 1.4, and the mean JOA score rose from 13.7 to 23.6.CONCLUSIONSLess invasive MCN neurolysis performed under local anesthesia is useful for LBP caused by MCN-E. In patients with intractable LBP, MCN-E should be considered.

Aim Echo-planar imaging is a common technique used in functional magnetic resonance imaging (fMRI); however, it suffers from image distortion and signal loss because of large susceptibility effects that are related to the phase-encoding direction of the scan. Despite this relation, the majority of neuroimaging studies has not considered the influence of phase-encoding direction. Here, we aimed to clarify how phase-encoding direction can affect the outcome of an fMRI connectivity study of schizophrenia (SCZ). Methods Resting-state fMRI using anterior to posterior (A-P) and posterior to anterior (P-A) directions was used to examine 25 patients with SCZ and 37 matched healthy controls (HC). We conducted a functional connectivity (FC) analysis using independent component analysis and performed three group comparisons: (i) A-P versus P-A (all participants); (ii) SCZ versus HC for the A-P and P-A datasets; and (iii) the interaction between phase-encoding direction and participant group. Results The estimated FC differed between the two phase-encoding directions in areas that were more extensive than those where signal loss has been reported. Although FC in the SCZ group was lower than that in the HC group for both directions, the A-P and P-A conditions did not exhibit the same specific pattern of differences. Further, we observed an interaction between participant group and the phase-encoding direction in the left temporoparietal junction and left fusiform gyrus. Conclusion Phase-encoding direction can influence the results of FC studies. Thus, appropriate selection and documentation of phase-encoding direction will be important in future resting-state fMRI studies.

Study design Retrospective study (level of evidence=3). Purpose We examine the relationship between residual symptoms after discectomy for lumbar disc herniation and peripheral nerve (PN) neuropathy. Overview of literature Patients may report persistent or recurrent symptoms after lumbar disc herniation surgery; others fail to respond to a variety of treatments. Some PN neuropathies elicit symptoms similar to those of lumbar spine disease. Methods We retrospectively analyzed data for 13 patients treated for persistent (n=2) or recurrent (n=11) low back pain (LBP) and/or leg pain after primary lumbar discectomy. Results Lumbar re-operation was required for four patients (three with recurrent lumbar disc herniation and one with lumbar canal stenosis). Superior cluneal nerve (SCN) entrapment neuropathy (EN) was noted in 12 patients; SCN block improved the symptoms for eight of these patients. In total, nine patients underwent PN surgery (SCN-EN, n=4; peroneal nerve EN, n=3; tarsal tunnel syndrome, n=1). Their symptoms improved significantly. Conclusions Concomitant PN disease should be considered for patients with failed back surgery syndrome manifesting as persistent or recurrent LBP.

Supplemental digital content is available in the text., Objectives Cervical cancer is one of the most frequently diagnosed cancers in pregnancy. Our aim was to evaluate the safety and efficacy of abdominal radical trachelectomy (ART) for pregnant women with early-stage cervical cancer who strongly desire to preserve their pregnancies. Methods/Materials A retrospective observational study was performed for stage IB1 cervical cancer patients who underwent ART or radical hysterectomy (RH) at our hospital between February 2013 and June 2017. We compared differences in perioperative findings and oncologic outcomes among ART during pregnancy (ART-DP), ART, and RH groups. Results A total of 38 patients were included in this analysis. Six, 10, and 22 patients were assigned to the ART-DP, ART, and RH groups, respectively. There were no significant differences in the distribution of pathological TNM classifications, histology, tumor size, stromal invasion, and lymph-vascular space invasion among the 3 groups. The patients in the ART-DP group were younger than those in the RH group (P = 0.014). The ART-DP group was associated with more blood loss and prolonged surgery compared with the RH group (P = 0.017 and P = 0.014). The number of total lymph nodes in the ART-DP group was lower than that in the RH group (P = 0.036). However, there were no significant differences in age, surgical time, blood loss, or lymph node count between the ART-DP and ART groups. There were no significant differences in progression-free and overall survival times among the 3 groups, and no recurrence was observed in the ART-DP group. Conclusions Abdominal radical trachelectomy may be a tolerable treatment option for pregnant women with early-stage cervical cancer who strongly desire a baby.

Objective Some patients experience failed back surgery syndrome after lumbar spine surgery. We report the effect of additional treatments for paralumbar spine and peripheral nerve diseases addressing residual symptoms after surgery. Methods We enrolled 74 patients (59 men and 15 women; mean age 62.9 years) who had undergone lumbar posterior decompression surgery. Mean follow-up after initial surgery was 26.2 months (range, 13–48 months). We subsequently diagnosed paralumbar spine diseases, including superior cluneal nerve entrapment neuropathy with (n = 3) or without gluteus medius muscle pain (n = 4) and gluteus medius muscle pain alone (n = 5), and peripheral nerve diseases, including peroneal nerve entrapment neuropathy (n = 4) and tarsal tunnel syndrome (n = 1), based on persistent or recurring clinical symptoms and nerve block effects. Treatment outcomes were analyzed by comparing Roland-Morris Disability Questionnaire and Japanese Orthopaedic Association scores. Results Of 74 patients, 54 (73.0%) improved after initial lumbar surgery (group A), and 20 (27.0%) continued to experience symptoms or experienced symptom recurrence during follow-up (group B). In group B, 4 patients improved with conservative therapy, 11 underwent 1 additional surgical procedure, and 5 underwent >1 additional surgical procedures. After these additional treatments, clinical outcomes were recorded as good. At the last follow-up visit, there was no difference between group A and group B. Conclusions Of 74 patients who underwent lumbar spine surgery, 16 (21.6%) required additional surgery. To reduce the incidence of failed back surgery syndrome, concurrent diseases that may be masked by symptoms resulting from severe lumbar spine disease must be ruled out, as these diseases may become apparent after initial lumbar spine surgery.

Superficial peroneal nerve (S-PN) entrapment neuropathy (S-PNEN) is comparatively rare and may be an elusive clinical entity. There is yet no established surgical procedure to treat idiopathic S-PNEN. We report our surgical treatment and clinical outcomes. We surgically treated 5 patients (6 sites) with S-PNEN. The 2 men and 3 women ranged in age from 67 to 91 years; one patient presented with bilateral leg involvement. Mean post-operative follow-up was 25.3 months. We recorded their symptoms before- and at the latest follow-up visit after surgery using a Numerical Rating Scale and the Japan Orthopedic Association score to evaluate the affected area. We microsurgically decompressed the affected S-PN under local anesthesia without a proximal tourniquet. We made a linear skin incision along the S-PN and performed wide S-PN decompression from its insertion point at the peroneal tunnel to the peroneus longus muscle (PLM) to the point where the S-PN penetrated the deep fascia. One patient who had undergone decompression in the area of a Tinel-like sign at the initial surgery suffered symptom recurrence and required re-operation 4 months later. We performed additional extensive decompression to address several sites with a Tinel-like sign. All 5 operated patients reported symptom improvement. In patients with idiopathic S-PNEN, neurolysis under local anesthesia may be curative. Decompression involving only the Tinel area may not be sufficient and it may be necessary to include the area from the PLM to the peroneal nerve exit point along the S-PN.

Introduction: We studied the clinical and nerve pathological features in 6 patients whose low back pain (LBP) was relieved by superior cluneal nerve (SCN) neurectomy to determine whether nerve compression was the mechanism underlying this type of LBP. Methods: ALL 6 patients (7 nerves) underwent SCN neurectomy for intractable LBP. Their clinical outcomes and the pathological features of 7 nerves were reviewed. Results: All patients reported LBP relief immediately after SCN neurectomy. Pathological study of the 7 resected nerves showed marked enlargement, decreased myelinated fiber density, an increase in thinly myelinated fibers (n=2), perineurial thickening (n=5), subperineurial edema (n=4), and Renaut bodies (n=4). At the distal end of one enlarged nerve we observed a moderate reduction in the density, and marked reduction in the number, of large myelinated fibers. Discussion: The pathological findings and effectiveness of neurectomy suggest that in our patients, SCN neuropathy likely elicited LBP via nerve compression. This article is protected by copyright. All rights reserved.

Object Low back pain (LBP) attributable to fusion failure, implant failure, infection, malalignment, or adjacent segment disease may persist after lumbar fusion surgery (LFS). Superior cluneal nerve (SCN) entrapment neuropathy (SCNEN) is a clinical entity that can produce LBP. We report that SCNEN treatment improved LBP in patients who had undergone LFS. Methods Between April 2012 and August 2015, we treated 8 patients (4 men and 4 women ranging in age from 38 to 88 years; mean age, 69 years) with SCNEN for their LBP after LFS. Our criteria for the diagnosis of SCNEN included a trigger point over the posterior iliac crest 7 cm from the midline and numbness and radiating pain in the SCN area upon compression of the trigger point. Symptom relief was obtained in more than 75% of patients within 2 h of inducing a local nerve block at the trigger point in the buttocks. The mean postoperative follow-up period was 28 months (range, 9-54 months). Results LBP was unilateral in 3 and bilateral in 5 patients. The senior author (T.I.) operated all patients for SCNEN under local anesthesia because they reported recurrence of pain after the analgesic effect of repeat injections wore off. This led to a significant improvement of their LBP. Conclusions SCNEN should be considered in patients reporting LBP after LFS. Treatment of SCNEN may be a useful option in patients with failed back surgery syndrome after LFS.

Aim Anorexia nervosa (AN) includes the restricting (AN-r) and binge-eating/purging (AN-bp) subtypes, which have been reported to differ regarding their underlying pathophysiologies as well as their behavioral patterns. However, the differences in neural mechanisms of reward systems between AN subtypes remain unclear. The aim of the present study was to explore differences in the neural processing of reward and punishment between AN subtypes. Methods Twenty-three female patients with AN (11 AN-r and 12 AN-bp) and 20 healthy women underwent functional magnetic resonance imaging while performing a monetary incentive delay task. Whole-brain one-way analysis of variance was conducted to test between-group differences. Results There were significant group differences in brain activation in the rostral anterior cingulate cortex and right posterior insula during loss anticipation, with increased brain activation in the AN-bp group relative to the AN-r and healthy women groups. No significant differences were found during gain anticipation. Conclusion AN-bp patients showed altered neural responses to punishment in brain regions implicated in emotional arousal. Our findings suggest that individuals with AN-bp are more sensitive to potential punishment than individuals with AN-r and healthy individuals at the neural level. The present study provides preliminary evidence that there are neurobiological differences between AN subtypes with regard to the reward system, especially punishment processing.