5-aminolevulinic acid-guided endoscopic biopsy with violet light-emitting diode flashlight in malignant glioma: Technical note.

Background: 5-aminolevulinic acid (5-ALA) photodynamic diagnosis (PDD) has enabled better identification of malignant tumor cells and real-time intraoperative guidance. Here, we report a reasonable procedure for 5-ALA-guided endoscopic biopsy with a violet light-emitting diode (LED) flashlight for deep-seated malignant gliomas. Methods: A 63-year-old man presented with a headache and left upper homonymous quadrantanopia. Imaging studies showed atypical lesions with non-significant and partial contrast enhancement in the right deep temporo-occipital lobe. An endoscopic biopsy was performed under the guidance of 5-ALA PDD with a violet LED flashlight. Results: The tumor tissues, which were difficult to distinguish from normal brain parenchyma under white light, were positive for 5-ALA fluorescence. The histopathological diagnosis was astrocytoma (the World Health Organization grade 3). The patient underwent adjuvant chemoradiation therapy. Headache and anopia improved, and no recurrence was observed at 12 months follow-up. Conclusion: This technique of neuroendoscopic biopsy guided by 5-ALA PDD fluorescence with a violet LED flashlight may allow a safe and accurate diagnosis of deep-seated malignant gliomas.

Efficacy and Safety of Switching from Sitagliptin to Ipragliflozin in Obese Japanese Patients with Type 2 Diabetes Mellitus: A Single-Arm Multicenter Interventional Study.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors have limited efficacy in improving glycemic control for obese Japanese patients with type 2 diabetes mellitus. Sodium-glucose co-transporter 2 inhibitors are recommended for use in patients with type 2 diabetes with obesity. Nevertheless, there has been no previously published study on the effect of switching from dipeptidyl peptidase-4 inhibitors to sodium-glucose co-transporter 2 inhibitors on the systemic and organic effects in obese Japanese patients with type 2 diabetes. OBJECTIVES: We evaluated the efficacy and safety of switching from sitagliptin to ipragliflozin for 24 weeks in obese Japanese patients with inadequately controlled type 2 diabetes. METHODS: Fifty-one obese patients with type 2 diabetes (body mass index > 25 kg/m2) treated with sitagliptin (50 mg) and metformin but with inadequate glycemic control (glycosylated hemoglobin [HbA1c] > 7.5% and < 9.0%) were enrolled. After a 4-week observation period, sitagliptin was switched to ipragliflozin (50 mg) for 24 weeks. The primary outcome was the change in HbA1c from baseline to the end of treatment. The secondary outcomes were changes in clinical characteristics and other biochemical variables. RESULTS: Fifty-one patients with an average HbA1c of 8.37 ± 0.48% and body mass index of 28.8 ± 3.8 kg/m2 were enrolled. Fifty patients completed the study, one patient stopped ipragliflozin at 4 weeks because of the development of hyperosmolar hyperglycemic syndrome. No significant change in HbA1c from baseline to the end of treatment was observed (- 0.02 ± 0.75%). However, fasting plasma glucose was reduced (- 16.2 ± 28.4 mg/dL, p < 0.001), and biochemical variables associated with insulin resistance, oxidative stress, and hepatic and renal functions showed significant improvements. No severe adverse effects were observed, except in the one aforementioned case. CONCLUSIONS: Switching from sitagliptin to ipragliflozin did not alter HbA1c in obese patients with type 2 diabetes, while improving parameters related to organ homeostasis. These data provide novel information useful for selecting oral anti-diabetic agents for patients with type 2 diabetes with obesity, a risk factor for developing various complications of diabetes. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials identifier: jRCT#031190022.

Treatment of new-onset primary central nervous system lymphoma in elderly patients using RMPV chemotherapy: a single-institution experience.

The prognosis of primary central nervous system lymphoma (PCNSL) in the elderly remains poor. We aimed to evaluate the outcome of rituximab, methotrexate, procarbazine, and vincristine (RMPV) chemotherapy in elderly patients with new-onset PCNSL. Twenty-eight patients aged ≥ 70 years treated for PCNSL between 2010 and 2020 were examined retrospectively. Nineteen patients received RMPV and nine did not qualify. Patients received five to seven cycles of RMPV plus response-adapted whole-brain radiotherapy (WBRT) and cytarabine. Ten of the 19 patients who received RMPV (52.6%) completed the induction, but only four patients (21.1%) completed RMPV chemotherapy, WBRT 23.4 Gy, and cytarabine. Median progression-free survival (PFS) and overall survival (OS) in the RMPV group was 54.4 and 85.0 months, respectively. Both PFS and OS were significantly longer in patients who received RMPV chemotherapy than in those who did not, and in patients who started but did not complete RMPV than in those who did not receive RMPV. Patients who received incomplete RMPV tended to have a favorable prognosis. Initial treatment with RMPV chemotherapy was effective in elderly patients with PCNSL. Adjusting the number of courses of RMPV may improve the prognosis of elderly patients with PCNSL, but further verification is necessary.

Impact of immediate general anesthesia in the emergency room on prevention of rebleeding after subarachnoid hemorrhage.

BACKGROUND: Aneurysm rebleeding is fatal in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate whether immediate general anesthesia (iGA) management in the emergency room, upon arrival, prevents rebleeding after admission and reduces mortality following aSAH. METHODS: The clinical data of 3033 patients with World Federation of Neurosurgical Societies (WFNS) grade 1, 2, or 3 aSAH from the Nagasaki SAH Registry Study between 2001 and 2018 were retrospectively analyzed. iGA was defined as sedation and analgesia using intravenous anesthetics and opioids combined with intubation induction. We calculated crude and adjusted odds ratios to evaluate the associations between iGA and the risk of rebleeding/death using multivariable logistic regression models with fully conditional specification for multiple imputations. In the analysis of the relationship between iGA and death, we excluded patients with aSAH who died within 3 days after the onset of symptoms. RESULTS: Of the 3033 patients with aSAH who met the eligibility criteria, 175 patients (5.8%) received iGA (mean age, 62.4 years; 49 were male). Heart disease, WFNS grade, and lack of iGA were independently associated with rebleeding in the multivariable analysis with multiple imputations. Among the 3033 patients, 15 were excluded due to death within 3 days after the onset of symptoms. After excluding these cases, our analysis revealed that age, diabetes mellitus, history of cerebrovascular disease, WFNS grade, Fisher grade, lack of iGA, rebleeding, postoperative rebleeding, no shunt operation, and symptomatic spasm were independently associated with mortality. CONCLUSIONS: Management by iGA was associated with a 0.28-fold decrease in the risks of both rebleeding and mortality in patients with aSAH, even after adjusting for the patient's history of diseases, comorbidities, and aSAH status. Thus, iGA can be a treatment for the prevention of rebleeding before aneurysmal obliteration treatment.

Solicitation matters: Cultural differences in solicited and unsolicited support provision.

Two studies aimed to examine cultural differences in social support provision, with or without solicitation, in Japan and the United States (US). In Study 1, we replicated a previous study with Japanese university students. We found that the Japanese participants did not provide social support when it was not solicited, as compared with when it was solicited. Furthermore, in Study 2, participants were asked to respond to a questionnaire regarding a hypothetical stressful situation experienced by a close other and to indicate their willingness to provide support. We confirmed our hypothesis that Japanese participants hesitate to provide unsolicited support to close others (such as family members or close friends), even when they recognize that the close others are in need, whereas the American participants do not hesitate to provide such support. Contrastingly, regarding solicited support, the Japanese and Americans were equally ready to provide support, as hypothesized. The cultural difference in social support resides in the provision of unsolicited support. These results suggest that differences in culturally appropriate responses to needy people are responsible for the difference in the provision of unsolicited vs. solicited social support.

Ruptured basilar artery perforator aneurysm: a novel mechanism of pure subarachnoid hemorrhage in moyamoya disease. Illustrative case.

BACKGROUND: Pure subarachnoid hemorrhage (SAH) in patients with moyamoya disease is a rare occurrence. Three underlying mechanisms have been described previously, except for ruptured aneurysm of the circle of Willis. Herein, the authors describe a novel mechanism: rupture of a perforator aneurysm in moyamoya disease. OBSERVATIONS: A 51-year-old man experienced sudden onset of severe headache and vomiting. Computed tomography showed diffuse SAH. Digital subtraction angiography (DSA) showed unilateral moyamoya disease without remarkable etiology of SAH. The patient underwent conservative management with antihypertensive agents. The second DSA on day 17 revealed a slow-filling aneurysm emerging from the basilar top perforating artery. The diagnosis of SAH due to unknown origin was changed to ruptured basilar artery perforator aneurysm (BAPA). The third follow-up DSA on day 159 revealed the resolution of BAPA. LESSONS: In the case of pure SAH, it is crucial to consider the possibility of perforator aneurysms due to hemodynamic stress caused by moyamoya disease. Repeated DSA is essential for detecting the lesion.

Of Mice and Culture: How Beliefs About Knowing Affect Habits of Thinking.

Recent research suggests that individuals from East Asian and Western cultures differ in the degree to which they hold a folk world view known as naïve dialecticism, which is characterized by tolerance for contradiction, expectation of change, and cognitive holism. The current research utilizes the Mouse Paradigm to investigate the dynamic nature of naïve dialecticism in real time by measuring individuals' fluctuations in judgment during the process of contemplation. The results showed cultural differences in dynamic measures of evaluation process: Japanese participants took more time to stabilize their thought and showed more fluctuations in their judgment than American participants. These cultural differences were fully mediated by individual differences in levels of naïve dialecticism as measured by the level of dialectical self-views. Implications for cultural psychology and the psychology of dialectical thinking are discussed.

Impact of Pre-operative Embolization With Onyx for Brain Arteriovenous Malformation Surgery.

Objective: To clarify the safety and efficacy of pre-operative embolization using Onyx liquid embolic agent (Onyx; ev3) compared with N-butyl cyanoacrylate (NBCA; Cordis Neurovascular, Inc.) or coils in cerebral arteriovenous malformation (AVM) surgery. Methods: This was a retrospective review of a prospectively collected clinical database of brain AVMs treated at our institute from January 2005 to March 2021. A total of 38 consecutive patients who underwent AVM resection after pre-operative embolization were included. Based on pre-operative embolization materials, the patients were divided into the pre-Onyx group (n = 16), in which NBCA or coils were used for embolization, and the Onyx group (n = 22). Patient characteristics and treatment results were compared between the two groups. Results: Patient characteristics were comparable between the two groups in terms of age, sex, and rupture status. While the Spetzler-Martin grade was also similar between the two groups, the location of the AVM nidus in the eloquent area was slightly higher in patients in the Onyx group (72.7%) than in patients in the pre-Onyx group (43.8%) (P = 0.09). The embolization rate was higher in the pre-Onyx group (mean: 63.0%; range: 12.7-100%) than in the Onyx group (mean: 50.0%; range: 15.8-100%), but the difference was not statistically significant (P = 0.06). The time needed for surgical removal was shorter in the Onyx group (mean: 354.8 min; range: 144-884 min) than in the pre-Onyx group (mean: 457.9 min; range: 240-1,294 min); however, this difference was not statistically significant (P = 0.13). The amount of intraoperative bleeding was significantly lower in the Onyx group (mean: 129.8 ml; range: 20-540 mL) than in the pre-Onyx group (mean: 448.8 mL; range: 120-1,550 ml) (P = 0.0008). The surgical complication rates were comparable between the two groups (pre-Onyx group, 18.8%; Onyx group, 4.5%; P = 0.29). Conclusions: Pre-operative embolization with Onyx can significantly reduce the amount of intraoperative bleeding in AVM resection and may contribute to safe AVM surgery.

A Spontaneous Extracranial Internal Carotid Artery Dissection with Autosomal Dominant Polycystic Kidney Disease: A Case Report and Literature Review.

Background and Objectives: Non-cystic manifestation of autosomal dominant polycystic kidney disease (ADPKD) is an important risk factor for cerebral aneurysms. In this report, we describe a rare spontaneous internal carotid artery (ICA) dissection in a patient with ADPKD. Observations: A 38-year-old woman with a history of ADPKD and acute myocardial infarction due to coronary artery dissection experienced severe spontaneous pain on the left side of her neck. Magnetic resonance imaging (MRI) revealed a severe left ICA stenosis localized at its origin. Carotid plaque MRI showed that the stenotic lesion was due to a subacute intramural hematoma. Close follow-up by an imaging study was performed under the diagnosis of spontaneous extracranial ICA dissection, and spontaneous regression of the intramural hematoma was observed uneventfully. Conclusions: When patients with a history of ADPKD present with severe neck pain, it is crucial to consider the possibility of a spontaneous ICA dissection. A carotid plaque MRI is beneficial in the differential diagnosis. Conservative management may benefit patients without ischemic symptoms.

Hematoma expansion caused by trapped cerebrospinal fluid in subacute phase intracerebral hemorrhage: A case report.

Background: Although hematoma expansion (HE) is caused by active bleeding in patients with intracranial hemorrhage in most cases, cerebrospinal fluid (CSF) trapped in the hematoma cavity is not a well-known cause of HE. Case Description: We present a case of subcortical hemorrhage in an 80-year-old woman who experienced neurological deterioration in the subacute phase because of HE caused by CSF pooling in the hematoma cavity. The patient was transferred to our hospital from a previous hospital for surgical treatment because the consciousness disturbance was likely caused by the perihematomal edema that occurred 4 days after onset. Head computed tomography (CT) at admission to our hospital showed a blend sign, and a part of the low-density area of the hematoma was enlarged compared with the CT at admission to the previous hospital. Although the hematoma was located adjacent to the lateral ventricle, no intraventricular hemorrhage was observed. Emergent hematoma evacuation was performed, and intraoperative findings indicated that the enlarged hematoma cavity was caused by CSF pooling. The patient's postoperative course was uneventful. She was transferred to a rehabilitation hospital 16 days after admission to our hospital. Conclusion: Hematomas adjacent to the ventricle and showing a blend sign can expand in the subacute phase because of the trapped CSF.

Real-world use of enzalutamide in men with nonmetastatic castration-resistant prostate cancer in Japan.

BACKGROUND: The purpose of the study is to evaluate real-world effectiveness and safety of enzalutamide in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) in Japan. METHODS: This was a retrospective evaluation of medical records from men in Japan who started enzalutamide treatment from November 1, 2014, to March 31, 2018, and received androgen deprivation therapy throughout. The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included PSA response rate, time to first use of new antineoplastic therapy, time to first use of cytotoxic chemotherapy, and enzalutamide treatment duration. An exploratory analysis of metastasis-free survival (MFS) was also performed. Adverse events (AEs) were analyzed to assess safety. RESULTS: Based on data from medical records of 205 men in Japan, median time to PSA progression was 27 months (95% confidence interval [CI] 19-not reached [NR]), with 82.5% and 52.0% of men achieving PSA response rates of ≥ 50% and ≥ 90%, respectively. Median time to first use of new antineoplastic therapy was 36 months (95% CI 27-NR) and median enzalutamide treatment duration was 13 months (interquartile range: 7-24). Median time to first use of cytotoxic chemotherapy was NR (95% CI 41-NR). Median MFS was 29 months (95% CI 23-35). In total, 51.7% of men experienced AEs, with malaise (18.5%), decreased appetite (10.7%), and nausea (4.9%) the most frequently reported. CONCLUSIONS: This is the first study to demonstrate the real-world effectiveness and safety of enzalutamide in men with nmCRPC in Japan, further informing healthcare providers about available treatment options for this patient population.

Stem Cell Therapy for Acute/Subacute Ischemic Stroke with a Focus on Intraarterial Stem Cell Transplantation: From Basic Research to Clinical Trials.

Stem cell therapy for ischemic stroke holds great promise for the treatment of neurological impairment and has moved from the laboratory into early clinical trials. The mechanism of action of stem cell therapy includes the bystander effect and cell replacement. The bystander effect plays an important role in the acute to subacute phase, and cell replacement plays an important role in the subacute to chronic phase. Intraarterial (IA) transplantation is less invasive than intraparenchymal transplantation and can provide more cells in the affected brain region than intravenous transplantation. However, transplanted cell migration was reported to be insufficient, and few transplanted cells were retained in the brain for an extended period. Therefore, the bystander effect was considered the main mechanism of action of IA stem cell transplantation. In most clinical trials, IA transplantation was performed during the acute and subacute phases. Although clinical trials of IA transplantation demonstrated safety, they did not demonstrate satisfactory efficacy in improving patient outcomes. To increase efficacy, increased migration of transplanted cells and production of long surviving and effective stem cells would be crucial. Given the lack of knowledge on this subject, we review and summarize the mechanisms of action of transplanted stem cells and recent advancements in preclinical and clinical studies to provide information and guidance for further advancement of acute/subacute phase IA stem cell transplantation therapy for ischemic stroke.

Characteristics of aneurysmal subarachnoid hemorrhage associated with rheumatic disease.

Spontaneous subarachnoid hemorrhage (SAH) occurs due to intracranial aneurysm rupture in most cases. Rheumatic disease may cause vessel wall inflammation, which can increase the risk of rupture. However, the characteristics of SAH with rheumatic disease are unknown. This study aimed to evaluate SAH features in patients with rheumatic disease. We retrospectively analyzed clinical data of 5066 patients from the Nagasaki SAH Registry Study who had been diagnosed with aneurysmal SAH between 2001 and 2018. We evaluated the SAH characteristics in patients with rheumatic disease using multivariable logistic regression analysis. In total, 102 patients (2.0%, 11 men and 91 women, median age 69.0 [57.0-75.5]) had rheumatic disease. In these patients, univariate logistic regression analysis showed that sex, hypertension, family history of SAH, smoking history, World Federation of Neurosurgical Societies grade on admission, aneurysm size, multiple aneurysms, treatment, and symptomatic spasms were associated with SAH. Multivariable logistic regression analysis showed that characteristics independently associated with SAH in rheumatic disease were female sex (odds ratio [OR] 3.38; 95% confidence interval [CI] 1.81-6.93, P < 0.001), hypertension (OR 0.60; 95% CI 0.40-0.90, P = 0.012), family history of SAH (OR 0.18; 95% CI 0.01-0.80, P = 0.020), small ruptured aneurysms (OR 1.50; 95% CI 1.02-2.24, P = 0.048), and multiple aneurysms (OR 1.69; 95% CI 1.09-2.58, P = 0.021) in comparison with SAH without rheumatic disease. In conclusion, SAH in patients with rheumatic disease was characterized by small multiple aneurysms, regardless of the low incidence of hypertension and family history of SAH.

A Case of Cerebral Hyperperfusion Showing Unique Characteristics on Susceptibility-weighted MR Imaging after Carotid Endarterectomy.

Cerebral hyperperfusion syndrome (CHS) is a potentially devastating complication of carotid endarterectomy (CEA). Early detection and treatment of hyperperfusion are important before the condition develops into CHS. We herein present a case involving a 65-year-old female with severe right internal carotid artery (ICA) stenosis, who experienced hyperperfusion after right CEA. During the postoperative course, changes in the resting cerebral blood flow (rCBF) were evaluated using single-photon emission computed tomography (SPECT), and were found to correlate with the changes in the signal intensity of cortical arteries, cortical veins, and perilateral ventricular veins of the right middle cerebral artery (MCA) territory on susceptibility-weighted imaging (SWI). SWI showed a prominent hyperintensity of cortical arteries in the right MCA territory at postoperative day 1 (POD1), but the hyperintensity gradually decreased over time and became indistinct by POD48. As for cortical veins and perilateral ventricular veins, SWI showed an increased signal intensity of these veins during the peak of rCBF on POD1, but later, the signal intensity decreased as rCBF decreased on POD5. The signal intensity of cortical veins and perilateral ventricular veins finally returned to normal on POD9. Those SWI findings could be related to an impairment of cerebral autoregulation and the resulting hyperperfusion. SWI could be potentially useful as an additional tool in the evaluation of hyperperfusion.

Hypointensity of draining veins on susceptibility-weighted magnetic resonance images might indicate normal venous flow and a lower risk of intracerebral hemorrhage in patients with intracranial arteriovenous shunt(s).

Patients with intracranial arteriovenous shunt(s) have a risk of intracerebral hemorrhage (ICH). We investigated the signal intensity of draining veins on susceptibility-weighted imaging (SWI) and the status of venous drainage shown by digital subtraction angiography (DSA). We then evaluated whether the signal intensity of draining veins on SWI is related to normal venous flow (NVF) and/or ICH. We analyzed SWI and DSA in 10 consecutive patients with intracranial arteriovenous shunt(s). Opacification of draining veins in the normal venous phase by DSA was judged as NVF. We evaluated the relationship between the intensity of draining veins on SWI and the presence of NVF before and after treatment. The relationship between the intensity of draining veins on SWI and the presence of ICH surrounding the draining veins was also evaluated. Of 10 patients with untreated arteriovenous shunt(s), two had arteriovenous malformation and eight had a dural arteriovenous fistula with cortical venous reflux. We analyzed 26 draining veins before treatment. In preoperative analysis, draining veins with hypointensity were significantly more likely to show NVF than were draining veins with isointensity or hyperintensity (45.5% vs. 0.0%, P = 0.007). While 69.2% of the areas surrounding draining veins with isointensity or hyperintensity showed ICH, no veins with hypointensity showed ICH (P = 0.011, odds ratio 0.036; 95% confidence interval 0.0017-0.80). In conclusion, draining veins with hypointensity on SWI may contain NVF, despite arteriovenous shunting. The areas surrounding these veins might have a lower risk of ICH because of less venous hypertension.

A long side chain imidazolium-based graft-type anion-exchange membrane: novel electrolyte and alkaline-durable properties and structural elucidation using SANS contrast variation.

Newly designed styrylimidazolium-based grafted anion-exchange membranes (StIm-AEMs), in which imidazolium ionic groups are attached to styrene at the far side from the graft chains, were prepared by radiation-induced graft polymerization of p-(2-imidazoliumyl) styrene onto poly(ethylene-co-tetrafluoloethylene) (ETFE) films, followed by N-alkylation and ion-exchange reactions. StIm-AEM having an ion exchange capacity (IEC) of 0.54 mmol g-1 with a grafting degree (GD) of ∼18%, possesses practical conductivity (>50 mS cm-1) even with a very low water uptake (∼10%) and high stability over 600 h in a 1 M KOH solution at 80 °C. There exists a critical IEC (IECc) in the range of 0.7-0.8 mmol g-1 over which the membrane showed high water uptake, which resulted in pronounced susceptibility to hydrolysis. Using small-angle neutron scattering technique with a contrast variation method, we found the hydrophilic phase in StIm-AEMs with IECs lower and higher than IECc shows "reverse-micelles" with water domains dispersed in the polymer matrix and "micelles" with graft polymer aggregates dispersed in the water matrix, respectively. The further analysis of micelle structures using the hard-sphere liquid model and Porod limit analysis reveals that the interfacial structures of ionic groups are essential for the electrochemical properties and durability of StIm-AEMs. In addition, StIm-AEM with an IEC of 0.95 mmol g-1 and the maximum power density of 80 mW cm-2 in the hydrazine hydrate fuel cell test, exhibited long-term durability under constant current (8.0 mA) up to 455 h, which, thus far, is the best durability at 80 °C for platinum-free alkaline-type liquid fuel cells.

Correction to: Intra-Arterial Transplantation of Low-Dose Stem Cells Provides Functional Recovery Without Adverse Effects After Stroke.

The original version of this article unfortunately contained an error in affiliation of Yuhtaka Fukuda.

Surgical Venous Drainage Disconnection from Cavernous Sinus Dural Arteriovenous Fistula and Ruptured Varix.

BACKGROUND: Cavernous sinus dural arteriovenous fistulas (CS dAVFs) occasionally behave aggressively (e.g., intracranial hemorrhage, venous infarction, seizures) depending on the drainage flow and presence of a collateral route of cortical or basal cerebral venous drainage. When a CS dAVF with aggressive behavior is encountered, a radical cure is required to avoid catastrophic deficits. However, conventional transvenous cavernous sinus (CS) embolization via the inferior petrosal sinus does not always achieve shunt obliteration. We herein report a case of surgical venous drainage disconnection in an 83-year-old woman with a CS dAVF. CASE DESCRIPTION: The patient presented with coma and anisocoria due to intracranial hemorrhage. Because of the patient's critical condition, we had no choice but to perform emergency decompressive craniectomy and hematoma evacuation without detailed preoperative hemodynamic information obtained by digital subtraction angiography. Postoperative digital subtraction angiography showed a CS dAVF with retrograde venous drainage of the deep middle cerebral vein (DMCV) and varix formation in the affected DMCV, causing hemorrhagic episodes. Five days after admission, the patient's neurologic state worsened because of rebleeding from the varix, which had increased in size. The percutaneous transvenous approach failed because of compartmentalization within the CS. Open surgery was performed; the deep vasculature was exposed by the transsylvian approach, and the arterialized DMCV was permanently clipped at its proximal segment with disconnection from the venous varix and fistulous point. Shunt obliteration was successfully achieved. CONCLUSIONS: Surgical venous drainage disconnection from the fistulous point may be an alternative radical therapy for CS dAVFs with aggressive behaviors.

Open-Label Study to Assess the Efficacy of Ipragliflozin for Reducing Insulin Dose in Patients with Type 2 Diabetes Mellitus Receiving Insulin Therapy.

BACKGROUND AND OBJECTIVE: To avoid insulin-induced hypoglycemia and weight gain, the minimum dose of insulin should be used. In this study, therefore, we examined insulin dose reduction by ipragliflozin add-on therapy in Japanese patients with type 2 diabetes mellitus treated with long-acting basal insulin. METHODS: In this multicenter, open-label study, patients received one ipragliflozin 50-mg tablet once daily in combination with basal insulin for 24 weeks. The primary efficacy endpoint was the change and percent change in insulin dose from baseline to Week 24. Secondary efficacy endpoints included changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), glycoalbumin, cholesterol, leptin, adiponectin, C-peptide, glucagon, body weight, and blood pressure, and number of patients achieving withdrawal of insulin at the end of treatment (EOT). Treatment-emergent adverse events (TEAEs) were evaluated for safety. RESULTS: In total, 114 patients were screened, 103 were registered, and 97 completed the study. The mean age was 59 years and 72.8% of patients were male. The mean change in insulin dose from baseline at Week 24 was - 6.6 ± 4.4 units/day (p < 0.001); the mean percent change was - 29.87%. HbA1c, FPG, glycoalbumin, glucagon levels, body weight, and blood pressure significantly decreased from baseline to EOT (p < 0.05). Cholesterol, leptin, and adiponectin were unaffected. One patient was able to stop insulin treatment at Week 16. The incidence of TEAEs was 60.2%. Hypoglycemia (10.7%) and pollakiuria (13.6%) were the most common drug-related TEAEs. Conclusions Once-daily 50-mg ipragliflozin enabled a 30% dose reduction of insulin by Week 24 compared with baseline. No major safety concerns were raised. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02847091).