Search

Thyrotropin-secreting pituitary adenoma (TSHoma) is rare but occasionally causes cardiovascular complications such as atrial fibrillation (AF) due to hyperthyroidism. Graves' disease (GD) is a common hyperthyroid condition often associated with subclinical AF. Some reports have shown echocardiographic changes in patients with GD. We aimed to evaluate the preoperative cardiac function in patients with TSHomas and compared the results among patients with TSHomas and GD and control subjects. Patients with TSHomas (n = 6) and GD (n = 20) were compared with control subjects with normal cardiac function (n = 20) based on echocardiographic findings. The average age, sex, and proportions of patients with a history of diabetes mellitus and hypertension were equal in each group, and the AF prevalence was matched in patients with TSHomas and GD. The values of left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), left ventricular ejection fraction (LVEF), and left atrial diameter (LAD) were used to assess cardiac function. In echocardiography, LAD showed a significant difference between patients with TSHomas and control subjects (p = 0.026). The mean LAD values were 36.9 ± 7.1, 38.2 ± 8.9, and 28.7 ± 3.9 mm for patients with TSHomas and GD and control subjects, respectively. There were no significant differences in other echocardiographic parameters among the groups. Before treatment, serum thyroid hormone levels (free triiodothyronine and thyroxin) were not significantly different among patients with TSHomas and GD. We found that patients with TSHomas or GD had enlarged LADs. This finding suggests that AF may be more hidden in patients with TSHomas than previously reported.

Water not only exists in the ventricles and cisterns but is also contained in the cerebral parenchyma. Water movement in most tissues has been described to be mediated by water channels since the discovery of these channels(aquaporins: AQPs). As to the intracranial situation, AQP-1 is abundantly expressed in the epithelial cells of the choroid plexus. AQP-4 is also enriched in the ependyma, endfeet of astrocytes at the blood-brain barrier, and glia limitans. AQP-4 is involved in cerebrospinal fluid(CSF)absorption, while AQP-1 is involved in CSF production. Impairment of CSF absorption through AQP-4 is considered to be caused by an inflammatory mechanism and finally leads to the development of hydrocephalus. Recently, the glymphatic system was recognized as an intracranial lymphatic system and hypothesized to be involved in CSF absorption and waste removal into the CSF. Disturbances of this glymphatic system may induce Alzheimer's disease and idiopathic normal-pressure hydrocephalus. Although the mechanism of CSF production in the epithelial cells of the choroid plexus remains to be elucidated, the existence of glycolysis leading to the facilitation of AQP-1 expression is considered a key point in CSF production.

Background Aquaporin (AQP) 1 expression has been linked with tumor malignancy but its role in glioblastoma (GBM), a lethal glioma, remains to be clarified. Methods AQP1 expression was examined in 33 human GBM specimens by immunohistochemistry. GBM cells (U251 and U87) that stably express AQP1 were established and used for cellular proliferation, migration, invasion, and vascular tube formation assays. The GeneChip assay was used to identify differentially expressed genes in AQP1‐expressing cells. Results AQP1 was expressed only in tumor cells. AQP1 dose‐dependently accelerated cell migration and invasion, but not proliferation, in GBM cell lines. AQP1 also upregulated cathepsin B, focal adhesion kinase and activities of matrix metalloproteinase 9. AQP1 in GBM cells induced wall thickness of ECV304, vascular endothelial cells, in a contact‐dependent manner. Downregulation of thrombospondin type 1 domain containing 7A (THSD7A) was identified in AQP1‐expressing GBM cells in vitro, and was negatively correlated with AQP1 expression in human GBM specimens. Conclusion AQP1 is involved in tumor malignancy by facilitating the migration and invasion of GBM cells, and promoting the formation of vascular beds that are characteristic of GBM by downregulating THSD7A., We examined whether AQP1 could enhance the malignant properties of GBM in vitro, including cell proliferation, migration, invasion, and blood vessel‐like tube formation. AQP1 is involved in tumor malignancy by facilitating the migration and invasion of GBM cells, and promoting the formation of vascular beds that are characteristic of GBM by downregulating THSD7A.

Cancer stem cells are associated with chemoresistance and rapid recurrence of malignant tumors, including glioblastoma (GBM). Although temozolomide (TMZ) is the most effective drug treatment for GBM, GBM cells acquire resistance and become refractory to TMZ during treatment. Therefore, glioma stem cell (GSC)-targeted therapy and TMZ-enhancing therapy may be effective approaches to improve GBM prognosis. Many drugs that suppress the signaling pathways that maintain GSC or enhance the effects of TMZ have been reported. However, there are no established therapies beyond TMZ treatment currently in use. In this study, we screened drug libraries composed of 1,301 existing drugs using cell viability assays to evaluate effects on GSCs, which led to selection of kenpaullone, a kinase inhibitor, as a TMZ enhancer targeting GSCs. Kenpaullone efficiently suppressed activity of glycogen synthase kinase (GSK) 3β. Combination therapy with kenpaullone and TMZ suppressed stem cell phenotype and viability of both GSCs and glioma cell lines. Combination therapy in mouse models significantly prolonged survival time compared with TMZ monotherapy. Taken together, kenpaullone is a promising drug for treatment of GBM by targeting GSCs and overcoming chemoresistance to TMZ.

Objectives The aim of this study was to evaluate the impact of the J-CTO score on long-term target lesion revascularization (TLR) after successful native chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). Background We previously reported that the J-CTO score could be used to stratify the lesion complexity and procedural success rate in CTO lesions. Methods We evaluated the prognostic significance of a high J-CTO score for long-term TLR rate in the J-CTO Registry. Results In the 425 lesions of 408 patients who underwent successful CTO-PCI during a median follow-up of 63.0 (interquartile range: 21.2-72.9) months in the J-CTO Registry, the cumulative incidence of TLR of lesions with a J-CTO score ≥ 2 (n = 216) was significantly higher than in those with a J-CTO score ≤ 1 (n = 209) (27.0 versus 19.4% at 5 years, respectively, P = 0.04). Among 323 lesions of 309 patients with a complete 5-year follow-up, the rate of TLR was 28% (n = 91). A J-CTO score ≥ 2 was independently associated with a higher risk of TLR (odds ratio, 1.73; 95% confidence interval, 1.01-2.99, P = 0.048) even after adjustment for clinically relevant baseline factors. Conclusions Patients with high J-CTO score lesions had a higher 5-year risk of TLR.

Objective Pituitary macroadenomas extend into the extrasellar space, such as the sphenoid sinus, cavernous sinuses, and suprasellar region. However, factors that regulate the direction of their extensions into the surrounding anatomical structures remain unknown. Methods This retrospective study included 162 patients who were treated for pituitary adenomas that had maximum diameters greater than 20 mm. According to the direction of adenoma extension, patients were divided into 4 groups: group A, inferior into the sphenoid sinus; group B, lateral into the cavernous sinus; group C, suprasellar region with enlarged sella turcica; and group D, supraellar region without enlarged sella turcica. Several anatomical structures surrounding the sella turcica were evaluated statistically, and multivariate logistic regression analysis was performed if the structures met the determining factors of adenomas extensions. Results The maximum diameter of adenomas was significantly larger in groups A and D. The maximum diameter of the diaphragmatic foramen was largest in group C (19.3 mm) and was significantly narrower in groups B (12.7 mm) and D (12.5 mm). Intrasphenoid septation, attached on the midline of the sella turcica, was observed most frequently in group D (78.6%) and was not detectable in group A (0%). Extension into the cavernous sinus, classified as dural discontinuity, was highly prevalent in group B (80.0%) and was uncommon in group C (12.3%). Erosion of the posterior clinoid process was most apparent in group B (92.0%). Conclusions The integrity of the sella dura and the intrasphenoid septation can regulate adenoma extension by encouraging their growth towards paths of least resistance.

Traumatic retroclival epidural hematoma is rare. It is more common in pediatrics than in adults. Although it has been known that these cases are frequently associated with abducens nerve palsy, internal carotid artery stenosis is rarely found with those hematomas. An 8-year-old girl was transferred to our hospital following a traffic accident. She had clear consciousness with right abducens nerve palsy. Computed tomography revealed the left side of both retroclival hematoma without clival fracture and subarachnoid hemorrhage at the Sylvian fissure. She also had a fracture of left femoral neck and ipsilateral lung contusion. Magnetic resonance imaging revealed a retroclival hematoma located in the epidural space and severe stenosis of left internal carotid artery (ICA) from the cavernous to supraclinoid portion without evidence of brain contusion. She was managed conservatively, and her right abducens nerve palsy recovered completely without deterioration of other neurological findings. Neuroradiological findings suggested this ICA stenosis as traumatic dissection. She was discharged home 2 months after the traffic accident. Retroclival epidural hematoma without clival fracture associated with ipsilateral ICA stenosis is extremely rare. Although the exact mechanism of the ICA stenosis remains unclear, cerebral vascular events should be considered in the cases with traumatic retroclival hematoma.

Oculomotor nerve palsy (ONP) occasionally occurs in cases of pituitary apoplexy (PA) associated with pituitary adenoma, but its mechanism remains unclear. Intracranial nerves are clearly visualized by fast-imaging employing with steady-state acquisition (FIESTA). Here, we assessed the oculomotor nerve compression in patients with PA associated with pituitary adenoma using FIESTA. Twenty-eight cases of PA, with or without ONP, were retrospectively reviewed. All patients had undergone preoperative FIESTA. Two neuroradiologists, unaware of the patient’s clinical symptoms, evaluated the presence and location of oculomotor nerve compression due to the tumor. Thirteen of the twenty-eight PA cases were associated with ONP. Tumor size and degree of cavernous sinus invasion were not significantly different between the ONP and non-ONP groups. Even in the ONP group, 8/13 (62%) tumors did not show cavernous sinus invasion. Via FIESTA, the presence of oculomotor nerve compression was confirmed in 11/13 (85%) and 5/15 (33%) cases in the ONP and non-ONP groups, respectively (p = 0.008). The radiologists’ diagnoses of laterality of nerve compression (right or left) were consistent with the patient’s affected eye. In the ONP group, the location of the nerve compression was located at the entry point to the cavernous sinus, the so-called oculomotor triangle, in 9/11 (82%) cases and intra cavernous sinus in 2/11 (18%) cases. Compression at the oculomotor triangle is considered the main cause of ONP with PA in pituitary adenomas.

金沢大学附属病院脳神経外科, Background and purpose: Hemodynamic impairments are considered risk factors of cerebral hyperperfusion after carotid artery stenting (CAS); measurement by Single-photon emission computed tomography (SPECT) using a subjective region of interest (ROI) method lacks consistency and reproducibility. Materials and methods: The present study compared objective perfusion analysis (stereotactic extraction estimation [SEE] method) with the ROI method for preoperative SPECT to predict the hyperperfusion phenomenon (HPP) after CAS. Preoperative resting asymmetry index (cerebral blood flow [CBF] ratio from the affected to unaffected hemisphere) and cerebrovascular reactivity (CVR) to acetazolamide were measured by N-isopropyl-p-[123I]-iodoamphetamine SPECT using the SEE and ROI method in 84 patients. CBF was also measured the day after CAS. Perfusion data with the highest area under the curve (AUC) by receiver-operating characteristic (ROC) analysis was considered a perfusion risk factor of HPP. Multivariate analyses for clinical characteristics and perfusion risk factors were performed to determine predictors of HPP. Results: The HPP was observed in 10 patients (11.9%). Female sex, contralateral stenosis, and degree of stenosis were significantly associated with HPP development on univariate analysis, and symptomatic stenosis was not found to be a significant factor. On SPECT analysis, CVR in the MCA area by SEE method had the highest AUC (0.981). Multivariate analysis showed that CVR in the MCA area was a significant predictor of HPP (P = 0.041). To predict hyperperfusion, the ROC curve of the CVR showed a cutoff value of –0.60%, sensitivity of 94.6%, and specificity of 100% (P < 0.001). Conclusions: Objective SEE method had better a predictive capability than ROI method to identify risk of hyperperfusion after CAS. © 2018 Elsevier Masson SAS, Embargo Period 12 months

Elderly patients with acromegaly who have comorbidities may increasingly encounter perioperative complications; however, little data are available on the risks and outcomes of surgical treatment in these patients. We aimed to analyze and compare the results of transnasal transsphenoidal surgery (TTS) in elderly and younger patients.Eighty-seven consecutive patients with acromegaly who underwent TTS were included. We divided the patients into elderly (≥65 years) and younger (65 years) groups and compared clinical characteristics, anesthesia risk, and surgical outcomes in these 2 groups.The 87 patients included 24 (27.6%) in the elderly group and 63 (73.4%) in the younger group. Preoperative endocrinologic and radiologic assessments showed no significant differences between the 2 groups. Although a grade 3 American Society of Anesthesiologists Physical Status classification was more common in the elderly group (75% vs. 3%; P = 0.00001) owing to the severity of associated diseases, no significant between-group difference in perioperative complications was seen (17% vs. 6%; P = 0.142). Sixteen elderly patients and 45 younger patients achieved endocrinologic remission following surgery (67% vs. 71%; P = 0.426). The incidence rate of postoperative new pituitary deficit was similar in the elderly and younger groups (4% vs. 3%; P = 0.625). Approximately one-third of the elderly patients with diagnosed hypertension or diabetes mellitus tapered their medication after successful tumor removal.TTS can be considered a safe treatment for both younger and elderly patients with acromegaly. Successful tumor removal provided a significant improvement in comorbidities even in elderly patients with acromegaly.

Objectives It is well-known that Rathke’s cleft cysts (RCCs) infrequently cause headache, endocrinological dysfunction, and visual disturbance, and in rare cases, cause diabetes insipidus (DI). Although surgical evacuation of the cyst content can result in high rates of symptomatic improvement, not only the treatment efficacy but also the pathophysiology of DI with RCC are undetermined. The aim of this study is to elucidate the underlying mechanisms and outcomes of DI associated with RCCs. Patients and Methods We retrospectively studied 109 patients with RCCs treated at Kanazawa University Hospital between 2000 and 2016. Their age, sex, symptoms, endocrinological status, DI, visual disturbance, neuroradiological findings, pathological appearances, and pre-/post-operative hormone levels and status of anti-diuretic hormone replacements were assessed. Results Among 109 cases of RCCs, five cases (4.6%, 2 males and 3 females) manifested with DI as initial presentation were included. These five cases could be divided into two types: the acute type and the chronic type, based on the onset and duration of symptoms. Three acute onset cases presented with not only strong thirst but also sudden headaches without pituitary dysfunction, whereas the two chronic onset cases presented with chronic headaches and hypopituitarism. Pathological examination in the acute type revealed inflammatory cell infiltration into only the posterior lobe of the pituitary and disruption of the cyst wall adjacent to the posterior lobe, which might suggest RCC rupture. In contrast, the chronic type showed inflammatory cell infiltration into both the anterior and posterior lobes of the pituitary and thickened fibrosis beneath the cyst wall. Postoperatively, two cases of the acute type could be controlled with a smaller amount of 1-deamino-8-D-arginine vasopressin (DDAVP) than that required preoperatively, whereas no change was observed in the cases of the chronic type. Conclusion The cases of DI onset caused by RCCs could be divided into the acute type and the chronic type. In the chronic type, surgical treatment could not affect the status of DI. However, in acute type, urgent surgical intervention partially relieved DI.

It is unknown whether there is a threshold of creatine kinase (CK) or CK-MB affecting the subsequent mortality for post-discharge myocardial infarction (PDMI) after percutaneous coronary intervention. Current study sought to evaluate the impact of PDMI. The study population included 30,051 patients with successful coronary stenting and discharged alive in the pooled patient-level database of 4 Japanese studies (j-Cypher registry, CREDO-Kyoto PCI/CABG registry cohort-2, RESET, and NEXT). During 4.4 ± 1.4 year follow-up, 915 patients experienced PDMI (cumulative 5-year incidence of 3.6%). Among 466 patients with available peak CK ratio (peak CK/upper limit of normal), peak CK ratio (

Background: Ventricular fibrillation and atrial fibrillation are well-known arrhythmias in patients with Brugada syndrome. This study evaluated the characteristics of the atrial arrhythmogenic substrate using the signal-averaged electrogram (SAECG) in patients with Brugada syndrome. Methods: SAECGs were performed during normal sinus rhythm in 23 normal volunteers (control group), 21 patients with paroxysmal atrial fibrillation (PAF; PAF group), and 21 with Brugada syndrome (Brugada group). Results: The filtered P wave duration (fPd) in the control, Brugada, and PAF groups was 113.9 ± 12.9 ms, 125.3 ± 15.0 ms, and 137.1 ± 16.3 ms, respectively. The fPd in the PAF group was significantly longer compared to that in the control and Brugada groups (p

Radiation-induced glioma (RIG) is a rare secondary glioma. The tumors morphologically resemble their sporadically arising counterparts. Recently, the WHO classification of tumors of the central nervous system was revised to incorporate molecular biomarkers together with classic histological features. The status of molecular biomarkers in RIG, however, remains unclear. The objective of this study was to investigate if commonly accepted glioma-specific biomarkers are relevant in RIGs. Among 269 gliomas diagnosed as WHO grade 2, 3 and 4 in our institution, four were diagnosed as RIGs. Immunohistochemical (IHC) staining for isocitrate dehydrogenase 1 (IDH1), p53, alpha thalassemia/mental retardation syndrome X-linked (ATRX), and H3K27M, and direct DNA sequencing of IDH1/2, telomerase reverse transcriptase (TERT) promoter, Histone H3.3 (H3F3A) and B-Raf (BRAF) genes was performed. All tumor specimens were IDH1-, p53- and H3K27M-negative. The nuclei of tumor cells in all cases exhibited positive staining for ATRX. In direct DNA sequencing analysis, no IDH1, IDH2, TERT promoter, H3F3A or BRAF mutations were found in any of the cases. Our findings suggest that these characteristic glioma-associated molecular mutations may be rare events in RIGs. More RIGs need to be tested for analysis of molecular biomarkers to clarify the clinical and histopathological spectra of this tumor.

Introduction Endoscopic endonasal transsphenoidal surgery (EETS) is increasingly applied to treat tuberculum sellae meningiomas. However, if the tumor adheres firmly to the optic nerve, dissection of the interface between both structures should be prudent to preserve visual function. The purpose of this study was to investigate whether tumor adhesion to the optic nerve can be predicted preoperatively by fast imaging with steady-state acquisition (FIESTA). Methods Twenty-two patients with tuberculum sellae meningioma treated with EETS were retrospectively identified. Clinical characteristics, radiologic studies, intraoperative findings, and outcomes were reviewed from their clinical charts. Results Patients' symptoms included visual function impairment in 18 patients and headaches in 4 patients. Symptoms were resolved in 19 patients after operation. Preoperative radiologic evaluation was performed in 44sides (22 patients) of the interface between tumors and the optic nerves and showed absence of peritumoral hyperintensity on FIESTA in 7 sides in 7 patients. In 5 of the 7 sides, tumor dissection was complicated by firm adhesion to the optic nerves. Among these cases, visual functions were unchanged in 1 patient after complete removal of the adhesion but substantially improved in 3 patients after partial resection. In the remaining 37 sideswith preoperative peritumoral hyperintensity, noadhesion was found between both structures intraoperatively. Conclusions Absence of peritumoral hyperintensity between tuberculum sellae meningioma and the optic nerve on FIESTA may indicate firm adhesion at the interface, severely complicating complete removal. Preoperative recognition of this adhesion is important for safe tumor removal and preservation of visual functions. © 2017 Elsevier Inc., Embargo Period 12 months

Purpose: Although hemorrhage within pituitary adenomas frequently exacerbates the symptoms, there are many grades of severity. Moreover, the contributing factors for symptom severity are still controversial. Methods: This retrospective study included 82 patients who underwent transsphenoidal surgery for pituitary adenomas with intratumoral hemorrhage. The grades of preoperative symptoms were classified into group A, asymptomatic or minor symptoms; group B, moderate symptoms sufficient for complain; and group C, severe symptoms disturbing daily life. Results: The hemorrhage volume within an adenoma was significantly higher in group C (92.6%) than in groups A (48.6%) and B (58.7%). Both headache and diplopia were dominant in group C, occurring in 72.2% and 27.8% of the patients, respectively. In group C, there was no significant difference in frequency between adenoma extensions into the sphenoid sinus (0%) and involvement of the cavernous sinus of Knosp grade 4 (0%), and extensions into the suprasellar region were not common (38.9%). The most distinctive feature was that “no extrasellar extension” was found only in group C (41.2%), and “multidirectional extension” was not detected in this group (0%). Multiple regression analysis revealed that the most powerful determining factors were the high frequencies of intratumoral hemorrhage and lack of extrasellar and multidirectional extensions. Conclusion: Rapid volume expansion of a hematoma and lack of extension or unidirectional extension might lead to significant compression of the sellar and surrounding structures. Of note, the integrity of the sellar dura might contribute to the acute onset of symptom manifestations caused by hemorrhage in pituitary adenomas. © 2017 Springer Science+Business Media, LLC, Embargo Period 12 months

Purpose: To analyze the clinical characteristics of acromegalic patients with empty sella (ES, herniation of the subarachnoid space within the sella turcica) and the impact of ES on transsphenoidal surgery in such patients. Methods: Seventy-eight patients, newly diagnosed with acromegaly who underwent transsphenoidal surgery were included. ES was defined as the pituitary gland and adenoma occupying less than 50% of the sella turcica on midsagittal magnetic resonance (MR) imaging. Results: Twelve patients (15.4%), predominantly female (10 women, p = .047), had ES in preoperative MR imaging. ES patients had smaller mean tumor diameter (6.3 mm) than non-ES patients (11.2 mm, p = .001). In preoperative MR imaging, occult adenoma was found in three (25%) ES and three (4.5%) non-ES patients (p = .044). Intraoperative cerebrospinal fluid (CSF) leakage was more frequent in the ES patients than in the non-ES patients (58.3 vs. 25.8%, p = .024). This led to an increased rate of sellar floor reconstruction using abdominal fat and/or postoperative lumber drainage in the ES patients (ES: 41.7 vs. non-ES: 16.7%, p = .063). Endocrinological remission after surgery was more frequent in the non-ES patients (72.7%) than in the ES patients (58.3%) (p = .248). Conclusions: Co-existence of acromegaly with ES is not rare, and is associated with occult adenoma, intra/postoperative CSF leakage, and a worse endocrinological outcome after transsphenoidal surgery; although, the underlying mechanism remains unclear. © 2017 Springer Science+Business Media New York, Embargo Period 12 months

Objectives The fractional flow reserve (FFR) is an index of the severity of coronary stenosis that has been clinically validated in several studies. The instantaneous wave-free ratio (iFR) and the resting distal coronary artery pressure/aortic pressure (Pd/Pa) are nonhyperemic pressure-derived indices of the severity of stenosis. This study sought to examine the diagnostic accuracy of the iFR and resting Pd/Pa with respect to hyperemic FFR. Methods Following an intracoronary injection of papaverine, the iFR, resting Pd/Pa, and FFR were continuously measured in 123 lesions in 103 patients with stable coronary disease. Results The iFR and resting Pd/Pa values were strongly correlated with the FFR (R=0.794, p0.89 and a Pd/Pa value of >0.92 were defined as double-negative lesions. In these 109 lesions, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.3%, 82.9%, 75.0%, 95.1%, and 86.2%, respectively. Conclusion This analysis demonstrated that the iFR and resting Pd/Pa were strongly correlated with the FFR and that the diagnostic accuracy of the iFR was similar to that of the resting Pd/Pa. The diagnostic accuracy can be improved with the use of both the iFR and the resting Pd/Pa.

Background There is a lack of information on the natural history of asymptomatic carotid artery stenosis (AsymCS) associated with cardiovascular diseases that require surgery. The aim of this study was to investigate risk factors for postoperative ipsilateral ischemic stroke and all-cause mortality after cardiovascular surgery in patients with AsymCS. Methods Among 2158 patients who underwent cardiovascular surgery, 150 patients with AsymCS who didn't undergo carotid revascularization were included. The relationships between preoperative factors, including carotid intraplaque hemorrhage (IPH), and postoperative ipsilateral ischemic stroke and all-cause mortality were analyzed retrospectively. Results During the median follow-up of 1087 days of 150 patients with 19 IPH, 12 (8.0%) and 21 (14.0%) encountered ipsilateral infarction and all-cause mortality, respectively. Multivariable Cox regression analyses indicated that IPH was significantly predictive of both ipsilateral infarction (hazard ratio [HR] 21.31, 95% confidence interval [CI], 4.98–91.17; P ≤.001) and all-cause mortality (HR 4.64, 95% CI, 1.61–13.34; P = .004). Another significant factor was peak systolic velocity for ipsilateral infarction with the cutoff velocity of 227 cm/s by the receiver-operating characteristic curve. Conclusions In this cohort of patients with AsymCS undergoing cardiovascular surgery, IPH had a close connection with a high risk of both postoperative ischemic stroke and mortality after cardiovascular surgery.

Objective Removal of pineal region tumors, which are deeply placed and encircled by intricate neurovascular structures, is challenging to neurosurgeons. The aim of this study was to present our experience with the exclusive endoscopic occipital transtentorial approach (EEOTA) used for removal of pineal region tumors. Methods A retrospective review was performed of patients who underwent surgery using the EEOTA to remove pineal region tumors from May 2016 to August 2018. The details of the EEOTA procedure were confirmed. Results Five patients underwent surgery via the EEOTA for treatment of pineal region tumors. In all cases, it was possible to perform the EEOTA less invasively through a keyhole craniotomy approximately 2.0–2.5 cm in size. The EEOTA produced an excellent view and provided natural and automatic orientation. There was essentially no blind spot in this procedure, even for the floor or ipsilateral wall of the third ventricle. Gross total resection was achieved in 4 cases. In the patient with atypical teratoid rhabdoid tumor, we abandoned gross total resection because of a hardened adhesion to the tectum and the great cerebral vein and its tributaries. Two patients presented with transient upper gaze palsy immediately after surgery but experienced complete recovery during the follow-up period. Conclusions The EEOTA is a very promising technique for removal of pineal region tumors and has the potential for extensive and routine application for surgeons familiar with endoscopic surgery.

Hypophysial and hypothalamic dysfunction caused by craniopharyngioma is a serious problem despite the progress of surgical approaches and techniques. Perifocal edema induced by craniopharyngioma could be speculated as a potential factor resulting in pre- and post-operative hypophysial and hypothalamic dysfunction, as well as, their anatomical involvement. Medical records of 54 patients with craniopharyngioma were retrospectively reviewed. The edema was characterized by a hyperintense area in magnetic resonance imaging, being classified into no edema (group A), only adjacent to the tumor (group B), and extending to the internal capsule or the optic tract (group C). Age, sex, tumor diameter, presence of cyst, hydrocephalus, intracranial pressure (ICP) elevation, visual function impairment, hypopituitarism, diabetes insipidus, memory disturbance, and obesity were investigated. The occurrence rate of edema was found more frequently in adults (73.7%) than in children (25.0%). The peritumoral edema grading system had an excellent correlation with the degree of hypothalamic involvement graded by the Puget’s system. Pre-operative ICP elevation was significantly detected in group C when compared with the other groups. In adults patients, group C was significantly associated with the occurrence of hydrocephalus both in pre- and post-operatively. Pre- and post-operative hypothalamic dysfunction, including diabetes insipidus, memory disturbance, and obesity, were highest in group C. Hypothalamic dysfunctions greatly influence the quality of daily living following craniopharyngioma surgery. The grading of perifocal edema’s extension could be a new index suggesting pre- and post-operative hypothalamic dysfunction caused by craniopharyngioma in addition to their anatomical involvement.

金沢大学医薬保健研究域医学系, Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin (Oxt -/-, Cd38 -/-) or its receptor (Oxtr -/-) fail to nurture. Normal maternal behaviour is restored by peripheral oxcytocin replacement in Oxt -/- and Cd38 -/-, but not Oxtr -/- mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Ager -/- male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in Ager -/- mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding., 30820471

Background Rathke cleft cysts (RCCs) arise from the remnant of Rathke pouch and are usually found in the intermediate lobe. In most cases, RCCs remain intrasellar and extend into the suprasellar region. Rarely, they emerge entirely into the suprasellar cistern—entirely suprasellar Rathke cleft cyst (ESSRCC). Methods We retrospectively reviewed medical records of 7 patients (5.5%) with ESSRCC among 128 patients with a diagnosis of RCC from January 1994 to September 2018. Of RCC cases, 70 were treated surgically. Patient age and sex, symptoms, magnetic resonance imaging findings, cyst diameter, presence of preoperative or postoperative hypopituitarism, operative procedures and complications, and functional outcomes at the final follow-up were investigated. Results All patients with ESSRCC were women with mean age 45.7 years (range, 29–69 years) at diagnosis. All patients experienced headache, mainly in the retro-orbital region. Mean ESSRCC diameter was 9.9 mm (range, 6–14 mm). Most cases exhibited hyperintensity on both T1-weighted and T2-weighted imaging. The endoscopic endonasal transtuberculum sellae approach relieved headache effectively and safely in 5 patients. Postoperative endocrinologic functions were almost entirely preserved. No patient experienced recurrence during the follow-up period. Conclusions RCCs should be considered in the differential diagnosis of suprasellar cysts. The endoscopic endonasal transtuberculum sellae approach has an advantage in visualizing these lesions owing to the direction of light from the endoscope. Headache could be treated effectively with the endoscopic endonasal transtuberculum sellae approach without recurrence of cysts or pituitary dysfunction.

Introduction: Symptomatic Rathke cleft cysts (RCCs) are rarely detected in neuroradiological screening and are less commonly found in children than in adults. However, when RCCs are observed in children, it is important to carefully distinguish a RCC from a cystic craniopharyngioma (CP) even if surgically treated or conservatively followed up. Methods: We conducted a retrospective review of clinical data from 11 patients with symptomatic RCCs whose ages were under 18 years and compared the data with data from 15 age- and sex-matched patients with cystic CP who were treated at our institute. Results: The mean age of the patients with RCCs was 12.2 years (range, 6–18). There were six males and five females. As initial symptoms, nine patients presented with headache, while two each had impaired visual function, diabetes insipidus, and activity loss. The 14 patients with CP suffered from impaired visual function. Magnetic resonance imaging (MRI) mainly showed hyperintensity on T1-weighted images (WIs) and hypointensity on T2-WI in patients with RCC. However, patients with CP had characteristic hyperintensity on T2-WI. The average maximum diameter of the RCCs was 19.0 mm on average (range, 8–33 mm). The RCCs were thus significantly smaller than CPs (34.9 mm; range, 21–54 mm). The RCCs were usually oval or dumbbell-shaped and regular in appearance, while the larger CPs were lobular and irregular. A preoperative endocrinological evaluation revealed insufficiencies in four axes in five patients with RCC. Postoperative endocrinological status improved in three patients, remained unchanged in three, and worsened in one. The gonadotropin axis was damaged in a majority (nine) of the patients with CP preoperatively. Postoperative evaluation revealed deficits in five axes in 14 patients with CP, which is a significantly different trend than observed in patients with RCC. Eight patients underwent surgical procedures (transsphenoidal surgery (TSS) in four, craniotomy in four). Two of these patients experienced a recurrence of the cysts. One of these patients subsequently underwent two craniotomies followed by radiation and other underwent TSS. Among the three conservatively treated patients, two experienced a transient worsening of their symptoms along with cyst enlargement. However, none of the three conservatively treated patients required an operation. Conclusions: When RCCs become symptomatic in children, the most common symptom they lead to is headache. The cysts are commonly small, regular, and oval in shape. Hypointensity of cyst contents on MRI is a characteristic of RCCs, which distinguishes them from CPs. Surgical intervention can be effective and lead to the relief of symptoms without a high rate of complications. However, there seems to be a relatively high recurrence rate following surgery. Thus, if the patient’s symptoms remain minor, the surgical treatment option should be used only when prudent, as the patient’s symptoms may improve over time. © 2016 Springer-Verlag Berlin Heidelberg, In Press / Embargo Period 12 months

Objectives It is important to identify and maintain a midline orientation during endoscopic transsphenoidal surgery (ETSS) for sellar lesions to prevent critical injury to the internal carotid artery. Therefore, the preoperative neuroradiological assessment of the bony structures in the sphenoid sinus, including the septum attachment to the sellar floor and its surrounding structures, is essential. It has been reported that the midline filum of the sellar dura can function as a useful intraoperative orientation guide during ETSS. However, the relationship between the midline dural filum and the intrasinus bony structures, such as the sellar floor, the intrasinus septation and the ossification, remains unclear and the mechanisms underlying development of the midline dural filum have also not yet been explored. Methods This retrospective study included 160 patients undergoing ETSS to assess both the midline dural filum and the intrasinus bony structures, using video recording reviews. The intrasinus septum and the ossification in the sphenoid sinus were evaluated on the computed tomography images of the bone window. Results A midline dural filum was identified in 66 (41.3%) of 160 patients. Attachment of the septum to the sellar midline was found in 61 (39.4%) of 155 patients, after excluding 5 patients with the conchal type of sphenoid sinus, 55 (90.2%) of 61 patients with a septum on the midline and only 6 (6.4%) of the remaining 94 patients without a septum on the midline had a midline dural filum. The relationship between a midline dural filum and a septum on midline was statistically significant (p < 0.001), regardless of the number of intrasphenoidal septa. In terms of the types of sphenoid sinus, the midline dural filum was predominantly detected in patients where ossification extended over the midline filum. In patients with the sellar type of sphenoid sinus, 49 (36.0%) of 136 had a midline dural filum, meanwhile, 16 (84.2%) of 19 patients with the pre-sellar type (p = 0.039) and all 5 patients (100%) with the choncal type harbored a midline dural filum (p < 0.001). Conclusion This study clearly verified the importance of the midline dural filum in a large series and evaluated the obvious relationship between the midline dural filum and the bony structures on the sellar floor. Our results strongly suggest that, during developing of the midline dural filum, the sellar dura becomes tethered to the bony elements attached to the sellar surface, such as the septum on the midline and the ossification in both the pre-sellar and the conchal type of sphenoid sinus. © 2016 Elsevier B.V. All rights reserved., Embargo Period 12 months

Purpose Acromegaly is a systemic disease which causes multiple bony alterations. Some authors reported that acromegalic patients have risk factors for an intraoperative vascular injury due to the specific anatomical features of their sphenoid sinus. The objective of our study was to analyze the anatomic characteristics of sphenoid sinus in acromegalic patients compared with controls, by evaluation of computed tomography (CT) findings. Methods We examined 45 acromegalic (acromegaly group) and 45 non-acromegalic patients (control group) with pituitary adenomas who were matched for sex, age, height, tumor size, and cavernous sinus invasion (Knosp grade). Preoperative CT of the pituitary region including the sphenoid sinus was used to evaluate the following anatomic characteristics: type of sphenoid sinus (sellar or pre-sellar/conchal); intrasphenoid septa (non/single or multiple); carotid artery protrusion; carotid artery dehiscence; intercarotid distance. Results Sixteen acromegalic patients (35.5 %) and 6 controls (13.3 %) had carotid artery protrusion. Additionally, 10 acromegalic patients (22.2 %) and 3 controls (6.6 %) had carotid artery dehiscence. Carotid artery protrusion and dehiscence were more frequent in the acromegaly group than in control group (p = 0.013 and 0.035, respectively). Other anatomic characteristics (type of sphenoid sinus, intrasphenoid septa, and intracarotid distance) showed no significant differences between acromegaly and control groups. Conclusions Our study suggests that carotid artery protrusion and dehiscence occur more frequently among acromegalic patients, compared with non-acromegalic patients. It is important for surgeons to be aware of these anatomic variations to avoid vital complications, such as carotid injuries, during surgery.

Obstructive hydrocephalus is the most common complication of intracranial germ cell tumors (IGCTs). Although ventriculoperitoneal shunts (VPSs) were previously used for treating this condition, they have recently been replaced by endoscopic third ventriculostomy (ETV), as the latter can avoid various complications caused by a VPS and can preserve physiological cerebrospinal fluid (CSF) dynamics. Therefore, if a VPS malfunctioned in patients who had previously been treated for IGCTs, it seems reasonable to consider removing the problematic VPS, followed by ETV, as long as magnetic resonance imaging reveals third ventricle floor ballooning and the cause of obstruction in the ventricular system, which are indicators for ETV. Here, we present the cases of three patients who underwent simultaneous removal of malfunctioning VPSs and ETV, more than 20 years (range 20–27 years) after initial treatment for IGCT and relevant obstructive hydrocephalus. Despite a relatively long shunt dependency, their obstructive hydrocephalus was well-managed by ETV, probably because CSF absorptive capacity remained intact after IGCT ablation by radio-chemotherapy. Patients with previously treated IGCTs can thus be released from the need for a VPS, regardless of long-term shunt dependency.

AIMS We investigated the impact of the J-CTO score, a pre-procedural risk score for successful guidewire crossing within 30 minutes through chronic total occlusion (CTO) lesions, on procedural and midterm clinical outcomes in terms of target lesion revascularisation (TLR) after CTO recanalisation. METHODS AND RESULTS The primary endpoint of this substudy was midterm TLR. The net midterm success rate was calculated by multiplying the lesion success rate by the TLR-free survival rate. The initial lesion success rates according to the J-CTO score categories of 0, 1, 2, and ≥3 were 97.0%, 92.1%, 86.5%, and 73.6%, respectively (p

Of the erythropoietin-producing human hepatocellular receptors (Ephs), EphB4 has recently emerged as a potential target in several cancers due to its roles in modified cell migration and invasion. As little is known about the roles of EphB4 in glioma, we sought to investigate its function in glioma by in vitro cell migration and invasion assays, immunoblotting and immunostaining. EphB4 was expressed in glioma cell lines and stem-like cell lines. The stimulation of glioma cells with ephrin-B2, the sole ligand of EphB4, conducted EphB4 phosphorylation and suppressed migration and invasion that downregulation of EphB4 using small interfering RNA abrogated. The stimulation also suppressed the phosphorylation of Akt. We confirmed by immunostaining that EphB4-positive cells existing only in the tumor core, whereas ephrin-B2-positive cells widespread in both the tumor core and the invasive area signifying that EphB4-ephrin-B2 reaction occurred only at the tumor core. Taken together, our data suggest that ephrin-B2-dependent EphB4 phosphorylation acts as an anchoring signal to reduce the malignancy by inhibiting Akt phosphorylation in the glioma core, whereas the scarcity of signaling in the tumor periphery promotes invasion into the surrounding brain.

A 43-year-old woman with an 8-year history of diabetes, hypertension, and dyslipidemia presented with amenorrhea and convulsion. Her MRI scan revealed a 3.5-cm T2-hyperintense pituitary macroadenoma with suprasellar extension to the frontal lobe and bilateral cavernous sinus invasion. Her serum levels of GH and insulin-like growth factor-I (IGF-I) were elevated to 9.08 ng/mL (normal range

Background Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI). Methods and results In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06) Conclusion Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI. Trial registration CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.

Background Coronary computed tomography angiography (CCTA) not only provides information regarding luminal stenoses but also allows for visualization of mural atheromatous changes (coronary plaques). Objective We sought to elucidate whether plaques seen on CCTA enable prediction of 2-year outcomes in patients with suspected and known coronary artery disease (CAD). Methods Of 3015 patients who underwent CCTA, the images and 2-year clinical courses of 2802 patients were independently analyzed. The primary endpoint was the composite of all-cause death and acute coronary syndrome. Results During the 2-year observation period, 49 (1.7%) patients developed the primary outcome. The 2-year rates of the primary outcome in the normal (n = 515, no mural lesions), calcium (n = 654, calcified lesion alone), and plaque groups (n = 1633, presence of noncalcified or partially calcified plaques) were 0.2%, 2.0%, and 2.1%, respectively (P = 0.0028). Adverse plaque features such as low attenuation, positive remodeling, spotty calcification, and the napkin-ring sign (low-attenuation core with a higher-attenuation rim) were assessed by an independent core laboratory. Stepwise multivariate Cox proportional hazard analysis showed that a plaque with two or more characteristics (adjusted hazard ratio, 1.98; 95% confidence interval, 1.09–3.60; P = 0.0254), age of ≥67 years (mean), statin treatment after CCTA, and obstructive stenosis remained independent predictors of the primary outcome. Conclusions Plaque imaging in CCTA has predictive value for the 2-year outcome and is a useful identifier for high-risk patients among those with known and suspected CAD.

Introduction Chiari malformation type I (CM-I) is a well-known hindbrain disorder in which the cerebellar tonsils protrude through the foramen magnum. The soft tissues, including the transverse ligament and the tectorial membrane at the retro-odontoid space, can compress the cervicomedullary junction if they become hypertrophic. Methods Twenty-two symptomatic patients with CM-I (aged 5–19 years) were treated between 2007 and 2017 at our institute. The retro-odontoid soft tissue was evaluated using T2-weighted magnetic resonance imaging. Anteroposterior (AP) distances and craniocaudal distances of the soft tissue were measured in patients with CM-I and 48 normal control children. Modified clivoaxial angles were also evaluated as the index of ventral compression of the cervicomedullary junction. Results Of the 18 patients treated with foramen magnum decompression, 16 patients improved postoperatively, whereas the condition of 2 remained unchanged. The AP distances in the CM-I group (6.0 mm) were significantly larger than those in the control group (3.5 mm), whereas there were no apparent differences in the craniocaudal distances. Modified clivoaxial angles were obviously smaller in the CM-I group (131.5°) than in the control group (146.9°). Moreover, the AP distances were significantly reduced postoperatively (5.5 mm), although the other parameters did not change significantly. Conclusions The retro-odontoid soft tissue in symptomatic patients with CM-I can be hypertrophic enough to compress the cervicomedullary junction ventrally even if there are no combined osseous anomalies. Foramen magnum decompression works to reduce the hypertrophic changes significantly, suggesting that downward tonsil movement might participate in hypertrophic soft tissue formation at the retro-odontoid space.

The influence of antiplatelet therapy discontinuation on the incidence of stent thrombosis, especially very late stent thrombosis, after drug-eluting stent implantation has not been yet fully addressed.Relationship between antiplatelet therapy discontinuation and stent thrombosis up to 5years was evaluated in 12,812 consecutive patients undergoing sirolimus-eluting stents (SES) implantation in the j-Cypher registry. Data on status of antiplatelet therapy during follow-up were collected prospectively.Median follow-up interval was 1699days (interquartile range, 1184-1928days). Incidences of definite stent thrombosis were 0.34% at 30days, 0.55% at 1year, and 1.6% at 5years. Dual antiplatelet therapy was maintained in 97.4%, 63%, and 43.9% of patients at 30days, 1year, and 5years, respectively. The rates of stent thrombosis in patients who discontinued both thienopyridine and aspirin were significantly higher in the time intervals of 31-365days, 2-3years and 3-4years, and tended to be higher in the time intervals of 1-2years and 4-5years than those in patients who continued both (31-365days: 1.26% versus 0.2%, P0.001; 1-2years: 0.59% versus 0.15%, P=0.06; 2-3years: 1.35% versus 0.2%, P=0.004; 3-4years: 1.09% versus 0.25%, P=0.0496; 4-5years: 1.35% versus 0.43%, P=0.17). Patients who discontinued either thienopyridine or aspirin only did not have an excess of stent thrombosis in any time intervals.In conclusion, discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine or aspirin only, was associated with an increased incidence of late and very late stent thrombosis up to 5years after SES implantation.

Background Headache frequently occurs in patients with pituitary adenoma and is reported in large as well as small adenomas. However, the exact mechanism of headache derived from pituitary adenoma remains unknown. Objective To evaluate the contribution of intrasellar pressure (ISP) to headache manifestation by using intraoperative ISP measurement. Methods The records of 108 patients who had first-time transsphenoidal surgery for pituitary adenoma were reviewed retrospectively. Measurement of intraoperative ISP was undergone using intracranial pressure monitoring sensors and compared with radiological assessment. Results Among 30 patients with headache, 29 (96.7%) presented with significant headache (Headache Impact Score-6, 50 or greater). Intraoperative ISP measurement was conducted successfully in all cases, and revealed higher ISP in patients with headache (35.6 ± 9.2 mm Hg) than in those without headache (15.8 ± 5.2 mm Hg). The ISP reduction after sella floor decompression was greater in patients with headache than that in patients without headache. In patients with headache, the frequency of invasion into the cavernous sinus or sphenoid sinus was significantly lower, and the diameter of the foramen at the diaphragm sellae was narrower. In addition, intratumoral cyst or hematoma was more common in patients with headache. Postoperatively, headache was either diminished or improved in 28 patients (93.3%). Conclusion Headache in patients with pituitary adenomas associated with ISP elevation, results from compromised dural integrity at the sella and intratumoral hemorrhage. The increased stretch force of the sella dura may be a notable etiology of headache in patients with pituitary adenoma.

Objective Measuring the fractional flow reserve (FFR) requires the induction of coronary hyperemia, usually with adenosine, adenosine triphosphate (ATP), or papaverine. However, adenosine can induce rhythmic complications, and intracoronary boluses of papaverine that prolong the QT interval can cause ventricular tachycardia. Injection of contrast media, which is routinely performed to validate the FFR guidewire placement, also induces hyperemia and may be an alternative method of measuring the FFR. We evaluated the diagnostic accuracy of the FFR after contrast hyperemia (FFRcont) compared to FFR evaluated after intracoronary papaverine (FFRpp). Methods This study included 109 lesions in 93 patients (mean age 70.4±8.7 years) with stable coronary disease. The FFR was measured as follows: 1) baseline pressure value; 2) FFRcont after intracoronary contrast injection (iopamidol, 8 mL for left coronary artery [LCA] or 6 mL for right coronary artery [RCA]); 3) FFRpp after intracoronary injection of papaverine (12 mg for LCA or 8 mg for RCA). Results FFRcont values were strongly correlated with FFRpp (R=0.940, p

Objective The optimal medication therapies are recommended in patients with coronary artery disease even after the coronary revascularization. However, the information of optimal medical therapy in dialysis population is scant. We assessed the efficacy of statin on the clinical outcomes after Sirolimus-eluting stent (SES) implantation in patients with and without dialysis. Methods and Results We analyzed date from 843 consecutive patients who successfully treated with SES in our institution between August 2004 and November 2006. Among patients, 96 patients (11.4%) were undergoing dialysis. In non-dialysis patients, 405 patients (54%) were treated with statin at hospital discharge. In dialysis patients, only 16 patients (17%) were treated with statin. In non-dialysis patients, mortality rate was significantly lower in patients treated with statin than those without statin (4.4% vs. 13.9%, p

Objective Very late stent thrombosis (VLST) remains an unresolved problem, and recent reports have indicated that VLST onset can occur in patients treated with both drug-eluting stents (DES) and bare metal stents (BMS). We evaluated the causes of VLST using optical coherence tomography (OCT). Methods OCT was performed in 22 patients (12 DES-treated patients, 10 BMS-treated patients). Because two instances of VLST occurred simultaneously in one case in the DES group, the DES group comprised 13 lesions, while the BMS group comprised 10 lesions. All struts were counted in each frame, and the proportion of uncovered or malapposed struts was calculated based on the overall number of struts in the stent. Results The interval from stent implantation to VLST onset was significantly longer in the BMS group. The proportion of uncovered struts and the ratio of malapposed struts were significantly higher in the DES group than in the BMS group. The OCT analysis demonstrated intimal hyperplasia or intimal disruption in all patients in the BMS group. However, in the DES group, severe hyperplasia and/or neoatherosclerosis was observed in only eight lesions (61.5%), while uncovered and malapposed struts were involved in the other lesions. Conclusion In most BMS-treated lesions, it appeared that VLST was caused by the occurrence of neoatherosclerosis after stent implantation. The causes of VLST in DES-treated lesions are more various and complicated than those observed for BMS-treated lesions.

The current development of serological biomarkers allows detection of smaller myocardial necrosis and early acute myocardial infarction (AMI). We evaluated the relevance of the heart-type fatty acid binding protein (H-FABP) assay, which has recently been approved in Japan, for early diagnosis of AMI as compared with the sensitive troponin assay.This is an observational study in a single center. From 2010 July to 2011 January, 114 patients who presented with symptoms suggestive of AMI were enrolled.AMI was adjudicated in 45 patients (40%). The diagnostic accuracy of measurements obtained at presentation for AMI, as quantified by the area under the receiver-operating-characteristic curve (AUC), was significantly lower with H-FABP assay than the sensitive troponin assay [AUC for H-FABP, 0.59; 95% confidence interval (CI) 0.48-0.70; and for troponin I, 0.89; 95% CI, 0.83-0.94; P.0001]. Among patients who presented within 2h after the onset of chest pain, the AUC for H-FABP was even low as compared with sensitive troponin (0.55; 0.39-0.72 vs. 0.89; 0.80-0.98, p0.001). The clinical sensitivity for the diagnosis of AMI with the cutoff point of 99 th percentile was similar in both assays (81% and 81%, respectively), however, the specificity was extremely low in the H-FABP assay as compared with sensitive troponin assay (19% and 79%, respectively).The measurement of H-FABP in 114 consecutive patients with chest pain suggestive of AMI showed no improvement of diagnosis for early AMI as compared with the current sensitive troponin assay because of its extremely low specificity.

Diabetes insipidus (DI) remains a complication of transsphenoidal surgery (TSS) for sellar and parasellar tumors. Antidiuretic hormone (ADH) appears as hyper intensity (HI) in the pituitary stalk and the posterior lobe of the pituitary gland on T1-weighted magnetic resonance (MR) imaging. Its disappearance from the posterior lobe occurs with DI, indicating a lack of ADH. The appearance of HI in the pituitary stalk indicates disturbances in ADH transport. This retrospective study included 172 patients undergoing TSS for sellar tumors at our institute from 2006 to 2014. Sequential T1-weighted MR images without enhancement were evaluated for HI in the pituitary stalk and the posterior lobe to assess the localization of ADH before and at intervals after TSS. DI was assessed pre- and postoperatively. HI in the pituitary stalk showed the following morphology: (1) ovoid in the distal end of the pituitary stalk (group A), (2) linear in the distal part of the pituitary stalk (group B), (3) linear in the whole pituitary stalk (group C). Preoperative DI occurred in 6 patients (3.5 %) with no HI observed in the posterior lobe. Postoperative DI was transient in 82 patients (47.7 %), and permanent in 11 (6.4 %). One week after surgery, HI was absent in the posterior lobe in 74 patients (43.0 %), and present in the pituitary stalk in 99 patients (57.6 %); both were significantly correlated with postoperative DI (p

Background Generally, newly progressed coronary lesions (NPCLs) are considered to be composed of lipid-rich plaques. In case of vulnerable plaque rupture, they may quickly become culprit lesions responsible for acute coronary syndromes. Methods Between September 2011 and September 2015, 2034 patients underwent scheduled follow-up coronary angiography (CAG) after percutaneous coronary intervention (PCI) in Tsuchiya General Hospital. Patients with NPCLs found by CAG during the follow-up period were evaluated by optical coherence tomography (OCT). NPCLs were defined as the lesions with less than 50% diameter stenosis, which progressed to more than 75% diameter stenosis within 3years after the previous CAG. Patients with restenosis after PCI were excluded. We compared OCT findings of NPCLs between symptomatic and asymptomatic patients. Results The follow-up CAG showed NPCLs in 64 patients (3.2%). OCT revealed fibrous plaque in 42 patients (65.6%) and thin-cap fibroatheroma in one patient. Thirteen patients had chest symptoms for one month before CAG and the remaining 51 patients were asymptomatic. The prevalence of fibrous plaque and intimal disruption or plaque rupture were not significantly different between symptomatic and asymptomatic patients (61.5% vs. 66.7%, p=0.752 and 30.8% vs. 11.8%, p=0.213, respectively). However, thrombi were more frequently observed in symptomatic patients (61.5% vs. 13.7%, p Conclusions The majority of NPCLs found in asymptomatic patients at follow-up CAG were not vulnerable; however, those found in symptomatic patients might be vulnerable. In clinical practice, NPCLs found in asymptomatic patients should be evaluated for functional severity of stenosis in order to determine the need for coronary revascularization.

// Takuya Furuta 1 , Hemragul Sabit 1 , Yu Dong 1 , Katsuyoshi Miyashita 1 , Masashi Kinoshita 1 , Naoyuki Uchiyama 1 , Yasuhiko Hayashi 1 , Yutaka Hayashi 1 , Toshinari Minamoto 2 , Mitsutoshi Nakada 1 1 Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan 2 Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan Correspondence to: Mitsutoshi Nakada, email: mnakada@med.kanazawa-u.ac.jp Keywords: glioblastoma, GSK3β, drug repositioning, translational research, clinical study Received: May 11, 2016 Accepted: January 25, 2017 Published: February 09, 2017 ABSTRACT Background: Glycogen synthase kinase (GSK)-3β has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3β activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ). Materials and Methods: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3β in the primary tumor. GBM cells and a mouse model were examined for the effects of GSK3β-inhibitory drugs, cimetidine, lithium, olanzapine, and valproate. The safety and efficacy of the cocktail of these drugs (CLOVA cocktail) in combination with TMZ were tested in the mouse model and in a clinical study for recurrent GBM patients. Results: Activation of GSK3β in the tumor inversely correlated with patient survival as an independent prognostic factor. CLOVA cocktail significantly inhibited cell invasion and proliferation. The patients treated with CLOVA cocktail in combination with TMZ showed increased survival compared to the control group treated with TMZ alone. Conclusions: Repositioning of the GSK3β-inhibitory drugs improved the prognosis of refractory GBM patients with active GSK3β in tumors. Combination of CLOVA cocktail and TMZ is a promising approach for recurrent GBM.

This report describes a case of subacute stent thrombosis (SAT) after drug-coated balloon (DCB). A 79-year-old male was investigated for stable angina. An in-stent restenosis (ISR) lesion was detected by coronary angiography. A skin reaction related to the anti-platelet agent thienopyridine was also observed at this time. Therefore, DCB was used to treat the ISR lesion under single anti-platelet therapy (aspirin). However, 3 days after percutaneous coronary intervention, SAT occurred. OCT did not reveal the underlying cause of SAT. Further data are needed to clarify the optimal duration of dual anti-platelet therapy after DCB.

Background— Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization. Methods and Results— Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES ( P noninferiority P superiority =0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P =0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, P noninferiority P superiority =0.24) at 278±63 days after index stent implantation. Conclusions— One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01035450.

Aims To investigate the clinical outcomes of paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) in patients on dialysis. Methods and results Between May 2004 and December 2008, 95 patients on dialysis with 124 lesions were treated with PES alone, and were compared to 184 patients on dialysis with 244 lesions treated with SES alone, retrospectively. One-year major adverse cardiac event (MACE) including stent thrombosis, target lesion revascularisation (TLR), myocardial infarction (MI) and cardiac death were compared. Baseline characteristics were similar except for previous CABG (p = 0.02) and reference vessel diameter (p = 0.04). During hospitalisation, all cause death was more frequently observed in the PES group (p = 0.004). In-hospital MACE was not significantly different (p = 0.8). The incidence of 1-year MACE in the PES group was lower than that in the SES group (14.7%, 28.3%, p = 0.04), mainly due to the reduction of TLR (11.6%, 25.0%, p = 0.03). Rates of stent thrombosis (0%, 2.7%, p = 0.1), MI (1.1%, 3.8%, p = 0.2), and cardiac death (3.2%, 4.4%, p = 0.6) were not significantly different. Conclusions PES appears to be more efficient in reducing angiographic and clinical restenosis in dialysis patients compared with SES.

Late-onset idiopathic aqueductal stenosis (LIAS) has been recognized as one of the clinical entities of adulthood hydrocephalus for decades, although there have been no radiological reports that show normal ventricular systems before the development of LIAS. We present here an adolescent case of LIAS with a previously normal ventricular system on magnetic resonance imaging (MRI). A 17-year-old boy had been suffering from chronic headaches and mild intellectual disability (MID) since he became a teenager, and this had prevented him from leading an ordinary school life. MRIs on admission showed triventriculomegaly from the aqueductal stenosis that had not been detected on previous MRIs, at least until the age of 6. An endoscopic third ventriculostomy was successfully performed, which improved both the headache and the MID. The developmental mechanism of LIAS remains unclear, although the membranous ependymal-like tissue observed in the aqueduct suggested the preceding existence of an inflammatory process around this region. To the best of our knowledge, this case was noteworthy because the development of LIAS was clearly demonstrated on MRI for the first time.

Aims Long-term outcomes after sirolimus-eluting stent (SES) implantation in haemodialysis (HD) patients have remained controversial. We investigated the impact of HD on outcomes after SES implantation. Methods and results We analysed the data on 2050 patients who underwent SES implantation in a multi-centre prospective registry in Japan. Three-year clinical outcomes were compared between the HD group ( n = 106) and the non-haemodialysis (NH) group ( n = 1944). At the 3 year clinical follow-up, the rates of unadjusted cardiac mortality (HD: 16.3 vs. NH: 2.3%) and target-lesion revascularization (TLR) (HD: 19.4 vs. NH: 6.6%) were significantly higher in the HD group than the NH group ( P < 0.001). Although HD group had a numerically higher stent thrombosis rate, the difference in stent thrombosis between the two groups (HD: 2.0 vs. NH: 0.7%) did not reach statistical significance. Using Cox's proportional-hazard models with propensity score adjustment for baseline differences, the HD group had higher risks of TLR [HD: 16.3 vs. NH: 6.1%; hazard ratio, 2.83; 95% confidence interval (CI): 1.62–4.93, P = 0.0003] and cardiac death (HD: 12.3 vs. NH: 2.3%; hazard ratio, 5.51; 95% CI: 2.58–11.78, P < 0.0001). The consistent results of analyses, whether unadjusted or adjusted for other baseline clinical and procedural differences, identify HD as an independent risk factor for cardiac death and TLR. Conclusions Percutaneous coronary intervention with SES in HD patients has a higher incidence of repeat revascularization and mortality compared with those in NH patients. Haemodialysis appears to be strongly associated with mortality and repeat revascularization even after SES implantation.

A retro-odontoid pseudotumor (ROP) is commonly associated with atlantoaxial subluxation (AAS). Here, we report a patient with ROP but without AAS. The patient was a 72-year-old man who did not have a history of rheumatoid arthritis or trauma to the head and neck. The patient was admitted to our hospital with gait disturbance, progressive motor weakness in both upper extremities and sensory disturbance in all four extremities. MRI showed a retro-odontoid mass with severe compression of the cervical spinal cord. A CT scan showed spondylotic changes in C5, C6, and C7 and bilateral facet fusion between C3 and C4. Dynamic radiography showed no evidence of AAS; there was loss of mobility at C2-C7 and excessive mobility at C1. Intraoperative pathological examination revealed that the lesion was a pseudotumor; therefore, posterior C1-C2 fixation was performed. MRI performed 6 months after the operation revealed that the pseudotumor was markedly reduced. To the best of our knowledge, patients with ROP without AAS are uncommon.

Background It is unknown whether adenosine triphosphate disodium (ATP) administration during primary percutaneous coronary intervention (PCI) is useful in anterior acute myocardial infarction (AMI). Methods The study was a prospective, non-randomized, open-label trial. Primary PCI was successfully performed in 204 consecutive patients with first anterior AMI. ATP at a mean dose of 117 μg/kg/min for 45 min on an average was infused intravenously during PCI in 100 patients (Group 1). In the other 104 patients, normal saline was administered (Group 2). ST-segment resolution (STR) was estimated 90 min after recanalization. The no-reflow ratio was measured 2 weeks later, using intravenous myocardial contrast echocardiography. Left ventricular ejection fraction (LVEF), LV regional wall motion (LVRWM), and LV end-diastolic volume index (LVEDVI) were measured 6 months later. Results Baseline patient characteristics of the two groups were similar, including TIMI risk scores. Significant STR (≧50% resolution compared to baseline) (66% versus 50%; Group 1 versus Group 2, p =0.02), no-reflow ratio (24% versus 34%, indicated by mean values, p =0.02), LVEF (61% versus 55%, p =0.0007), LVRWM (−1.56 versus −2.05, using the SD/chord, p =0.0001), and LVEDVI (60 ml/m 2 versus 71 ml/m 2 , p =0.0007) were significantly better in Group 1, and the no-reflow ratio, LVEF, LVRWM and LVEDVI were significantly better in ATP-administered patients, regardless of antecedent angina or advanced age. ATP Administration was consistently identified as a significant determinant for STR, no-reflow ratio, LVEF, LVRWM, and LVEDVI. Conclusions Intravenous ATP administration during reperfusion is an independent determinant of STR and the no-reflow ratio, and LVEF, LVRWM, and LVEDVI at 6 months after primary PCI.