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

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

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

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

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

BACKGROUND: Surgical clipping of anterior communicating artery (ACoA) aneurysms remains challenging due to their complex anatomy. Anatomical risk factors for ACoA aneurysm surgery require further elucidation. The aim of this study is to investigate whether proximity of the midline perforating artery, subcallosal artery (SubCA), and associated anomaly of the ACoA complex affect functional outcomes of ACoA aneurysm surgery. METHODS: A total of 92 patients with both unruptured and ruptured ACoA aneurysms, who underwent surgical clipping, were retrospectively analyzed from a multicenter, observational cohort database. Association of ACoA anatomy with SubCA origin at the aneurysmal neck under microsurgical observation was analyzed in the interhemispheric approach subgroup (n = 56). Then, we evaluated whether anatomical factors associated with SubCA neck origin affected surgical outcomes in the entire cohort (both interhemispheric and pterional approaches, n = 92). RESULTS: In the interhemispheric approach cohort, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was stratified to have the highest probability of the SubCA neck origin by a decision tree analysis. Then, among the entire cohort using either interhemispheric or pterional approach, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was significantly associated with poor functional outcomes by multivariable logistic regression analysis (OR 6.76; 95% CI 1.19-38.5; p = 0.03) as compared with A1 symmetry group in the acute subarachnoid hemorrhage settings. CONCLUSION: Combination of A1 asymmetry and larger aneurysmal size was significantly associated with SubCA aneurysmal neck origin and poor functional outcomes in ACoA aneurysm surgery. Interhemispheric approach may be proposed to provide a wider and unobstructed view of SubCA for ACoA aneurysms with this high-risk anatomical variant.

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

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

Alteration and Stability of Complex Macromolecular Amino Acid Precursors in Hydrothermal Environments.

The early Solar System comprised a broad area of abiotically created organic compounds, including interstellar organics which were integrated into planetesimals and parent bodies of meteorites, and eventually delivered to the early Earth. In this study, we simulated interstellar complex organic compounds synthesized by proton irradiation of a gas mixture of CO, NH3, and H2O, which are known to release amino acids after acid hydrolysis on the basis of Kobayashi et al. (1999) who reported that at the first stage of chemical evolution, the main compounds formed abiotically are complex organic compounds with high molecular weights. We examined their possible hydrothermal alteration and stabilities as amino acid precursors under high temperature and pressure conditions simulating parent bodies of meteorites by using an autoclave. We reported that all samples treated at 200-300 °C predominantly released glycine and alanine, followed by α-aminobutyric acid, and serine. After heating, amino acid concentrations decreased in general; however, the recovery ratios of γ-aminobutyric acid increased with temperature. The interstellar complex organic analog could maintain as amino acid precursors after being treated at high temperature (200-300 °C) and pressure (8-14 MPa). However, the molecular structures were altered during heating to form organic compounds that are more stable and can survive in elevated hydrothermal conditions.

[Recurrent High-grade Astroblastoma Treated with Stereotactic Radiotherapy:A Case Report].

INTRODUCTION: Astroblastoma is a rare, supratentorial glial tumor, occurring predominantly in children and young adults. However, treatment strategies have not yet been established for this rare disease. CASE PRESENTATION: A 6-year-old boy presented with headache and nausea. CT and MRI revealed a left frontal mass lesion with slight edema and macrocalcifications. Gross tumor resection was performed. Histological examination found neoplastic cells with astroblastic characteristics, and a striking perivascular array of pseudorosettes. The final diagnosis was high-grade astroblastoma. MRI 13 months after surgery suggested local recurrence, and an enlargement was found 3 months later. Stereotactic radiotherapy(SRT)was performed. MRI after SRT showed enhanced cyst formation around the tumor bed, suggesting tumor recurrence. However, 11C-methionine positron emission tomography(PET)revealed radiation necrosis. The last follow-up MRI 15 months after SRT showed no further recurrence. CONCLUSION: Astroblastoma is rare, therefore, no optimal management is known. SRT may be effective to treat recurrent astroblastomas. 11C-methionine PET/CT was useful to differentiate metastatic disease from radiation necrosis.

[Preliminary Experience of a Biplane Flat Panel and Tailor-made Operating Table-equipped Hybrid Operating Room].

A hybrid operating room(Hybrid OR), where operative equipment and flat panel angiography are both available, is becoming common for complex cerebrovascular surgery. However, the current Hybrid OR remains suboptimal as it is not cost-effective and contains uncomfortable operating beds, and a single-plane flat panel. Therefore, we introduced a novel Hybrid OR system, which has a biplane flat panel detector and three mutually exchangeable tailor-made operating beds. In this article, we report our preliminary experience of this novel Hybrid OR, focusing on improved cost-effectiveness by the availability of diagnostic angiography and standard endovascular surgery, optimal selection of three different types of operating beds, and procedural workflow in individual hybrid cerebrovascular surgery.

CD146 is highly expressed in glioma stem cells and acts as a cell cycle regulator.

INTRODUCTION: CD146 is highly expressed in various malignant tumors and contributes to their malignancy phenotype, which involves metastatic and tumorigenic activity. However, studies on the expression and function of CD146 in brain tumors are limited. METHODS: We over-expressed or knocked-down CD146 in both conventionally cultured glioma cells and tumor spheres (TS). The distribution of glioma cells and their stem cells in different cell cycle phases was analyzed by flow cytometry using the stem cell marker CD133 and the glial precursor marker A2B5. CD146 expression was immunohistochemically examined in glioma tissues. RESULTS: The majority of glioma stem cells (GSCs) expressing CD133 were also CD146-positive. CD146 knockdown in GSCs significantly compromised cell growth. Cell cycle analysis revealed that most of the CD146 and CD133 double-positive cells were in the G2/M phase. Ectopic expression of CD146 in parental glioma cells resulted in cell cycle arrest of most differentiated cells in G0/G1 phase. In contrast, ectopic expression of CD146 in GSCs resulted in an increase in the number of CD133-positive cells in the G2/M phase. Furthermore, CD146 knockdown reduced the number of CD133-positive cells in the G2/M phase, which was consistent with effects of cell growth inhibition. Immunohistochemical analysis revealed that CD146 expression was significantly upregulated in World Health Organization (WHO) Grade III and IV glioma and positively correlated with CD133 expression. CONCLUSIONS: CD146 is mainly expressed in dividing GSCs and may be a potential target for eradicating glioma stem cells.

Impact of Upper Limb Function and Employment Status on Return to Work of Blue-Collar Workers after Stroke.

BACKGROUND AND PURPOSE: Return to work (RTW) after stroke is the ultimate goal of the working population to achieve economic independence and well-being. Previous studies have reported lower RTW rates of blue-collar workers versus white-collar workers. Thus, investigating predictive factors for RTW of blue-collar workers is meaningful to improve RTW after stroke. Here, we investigate the physical, cognitive, and social factors associated with the RTW of blue-collar workers after stroke. METHODS: Poststroke rehabilitation data for 71 patients aged 15-64 years who had been active blue-collar workers at stroke onset were analyzed from a single-center observational cohort database. Baseline characteristics, social background factors, and quantitative assessments of the upper limb, lower limb, and cognitive functions at discharge were analyzed to identify any association with RTW. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value of continuous valuables with significant associations. RESULTS: Functional upper limb represented by an increasing Simple Test for Evaluating hand Function (STEF) score was independently associated with RTW of blue-collar workers by multivariable logistic regression analysis (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.14; p = .017). Correlation with self-employment status was also significant compared to that with employee status (OR, 185; 95% CI, 1.05-32400; p = .048). The cutoff value of the 100-point scale STEF to discriminate between RTW and non-RTW was 82. CONCLUSIONS: Functional upper limb and self-employment status were independent predictors for the RTW of blue-collar workers after stroke.

"Clip Anchor-Assisted Coil Embolization" for Endovascular Parent Artery Occlusion of Intracranial Traumatic Aneurysm.

Traumatic cerebral aneurysms are histologically dissecting aneurysms or pseudoaneurysms, thus requiring parent artery occlusion for cure. Combination of endovascular parent artery occlusion and extracranial-intracranial bypass is considered optimal to obtain complete obliteration of the aneurysm and to avoid hemodynamic hypoperfusion. However, endovascular parent artery occlusion of the supraclinoid internal carotid artery (ICA) is at risk of ischemic complications due to distal coil protrusion to adjacent perforating arteries or distal embolism of the thrombi generated in the coil mass. A 20-year-old man presented with progressive left optic neuropathy following motor vehicle accident. Radiological examination revealed left supraclinoid ICA aneurysmal formation with dissecting change. We treated this traumatic supraclinoid ICA aneurysm by combination of endovascular parent artery occlusion and high-flow bypass in the hybrid operating room. An aneurysmal clip was applied on the ICA just distal to the aneurysm prior to coil embolization, and worked as a scaffold for subsequent filling coils and as a blockade for the distal emboli. This "clip anchor-assisted coil embolization" technique resulted in optimal parent artery occlusion for the traumatic aneurysm of the supraclinoid ICA with minimal risks of residual blood flow, intraoperative rupture, and thromboembolic complications.

[Failed Surgical Clipping of a Posterior Communicating Artery Aneurysm with Oculomotor Nerve Palsy due to Ventricular Tachycardia:Validity of Endovascular Coiling in the Hybrid Operating Room].

Unruptured posterior communicating artery aneurysms with oculomotor nerve palsy are at high risk of rupture, and early intervention is recommended to prevent aneurysm bleeding and to improve oculomotor function. Both surgical clipping and endovascular coiling are available, and either of them is applied according to the anatomical condition and patient's comorbidity. In this article, we describe a case of an unruptured posterior communicating artery aneurysm with oculomotor nerve palsy, which was initially treated with surgical clipping. Owing to ventricular tachycardia during surgery, the craniotomy was discontinued and switched to endovascular coiling. In this operation, use of a hybrid operating room for coiling enabled adequate heparinization and immediate recraniotomy to prevent ischemic and hemorrhagic complications, respectively.

Extradural Anterior Clinoidectomy and Optic Canal Unroofing for Paraclinoid and Basilar Aneurysms: Usefulness of a No-Drill Instrumental Method.

The authors describe extradural anterior clinoidectomy without the use of a high-speed drill or ultrasonic device to clip paraclinoid and basilar aneurysms, which can eliminate potential complications related to traditional power drilling or ultrasonic device use. This method involves four steps: (1) partial osteotomy of the sphenoid wing at the superior orbital fissure (SOF); (2) peeling of the dura propria of the temporal lobe from the inner cavernous membrane of the SOF; (3) isolation and resection of the exposed meningo-orbital band to expose the superolateral aspect of the anterior clinoid process (ACP); and (4) piecemeal rongeuring of ACP and the roof of the optic canal. The entire procedure was performed using surgical instruments, including micro-rongeurs, a fine Kerrison punch, and micro-dissectors. Subsequently, intradural neck clipping was performed. Twenty consecutive patients with paraclinoid and basilar aneurysms successfully underwent clipping after this non-drill extradural clinoidectomy. Minor morbidity was noted in two patients (cerebrospinal fluid leakage in one and transient oculomotor palsy in the other). The non-drill method is a simple, easy, safe, and quick alternative to traditional power drilling in extradural clinoidectomy, and this method can avoid morbidity related to direct mechanical/thermal injury of important neurovascular structures.

Flexible endoscopically assisted evacuation of acute and subacute subdural hematoma through a small craniotomy: preliminary results.

BACKGROUND: The first choice to treat acute subdural hematoma (SDH) is a large craniotomy under general anesthesia. However, increasing age or comorbid burden of the patients may render invasive treatment strategy inappropriate. These medically frail patients with SDH may benefit from a combination of small craniotomy and endoscopic hematoma removal, which is less invasive and even available under local anesthesia. Although hematoma evacuation with a rigid endoscope for acute or subacute SDHs has been reported in the literature, use of a flexible endoscope may have distinct advantages. In this article, we attempted to clarify the utility of small craniotomy evacuation with a flexible endoscope for acute and subacute SDH in the elderly patients. METHOD: Between November 2013 and September 2016, a total of 17 patients with acute SDH (15 patients), subacute SDH (1 patient), or acute aggravation of chronic SDH (1 patient) underwent hematoma evacuation with a flexible endoscope at our hospital and were enrolled in this retrospective study. Either under local or general anesthesia, the SDH was removed with a flexible suction tube with the aid of the flexible endoscope through the small craniotomy (3 × 4 cm). Hematoma evacuation rate, improvement of clinical symptoms, and procedure-related complications were evaluated. RESULTS: Hematoma evacuation rate was satisfactory, and statistically significant clinical improvement was observed in postoperative Glasgow Coma Scale in all cases compared to the preoperative assessment. No procedure-related hemorrhagic complications were observed. CONCLUSIONS: The results reported here suggest that small craniotomy evacuation with a flexible endoscope is a safe, effective, and minimally invasive treatment for acute and subacute SDH in selected cases.

Asymptomatic Carotid T1-High-Intense Plaque as a Risk Factor for a Subsequent Cerebrovascular Ischemic Event.

BACKGROUND: Intraplaque hemorrhage, detected as a high-signal intensity on carotid MRI, is also strongly associated with ischemic events in symptomatic patients. However, in asymptomatic patients, the relationship of the T1-high intense plaque and the subsequent stroke is not clear. The aim of this study is to test the hypothesis that asymptomatic carotid T1-high intense plaque is a risk factor for a subsequent cerebrovascular ischemic event. METHODS: Of the 1,353 consecutive patients, who underwent head and carotid MRI as part of their annual medical check-up, the imaging quality of 13 was poor and 150 did not present for follow-up examination, thus leaving 1,190 subjects for evaluation. Of the 1,190 patients, 96 patients had findings of high-signal intensity on carotid MRI and 1,094 patients did not. Cerebrovascular events were retrospectively evaluated. RESULTS: During a mean follow-up period of 53 months, 4 patients with high-signal intensities on carotid MRI (4%) and 3 with no findings (0.3%) had a cerebrovascular ischemic event, with the occurrences significantly higher in the high-signal-intensity group. (p < 0.01) Cox regression analysis indicated that the presence of the high-intense plaque on carotid MRI (hazard ratio [HR] 4.2; 95% CI 1.0-17.1; p = 0.04), age (HR 1.1; 95% CI 1.0-1.2; p = 0.003), and diabetes mellitus (HR 7.2; 95% CI 1.8-27.4; p = 0.004) were associated with the occurrence of subsequent ischemic cerebrovascular events. CONCLUSIONS: Asymptomatic carotid T1-high-intense plaque might be a potential high-risk factor for a subsequent cerebrovascular ischemic event.

Histological Examination of Trousseau Syndrome-Related Thrombus Retrieved Through Acute Endovascular Thrombectomy: Report of 2 Cases.

The mechanism of thrombus formation in Trousseau syndrome remains unclear. The purpose of this study was to investigate specific pathological findings of the thrombi in Trousseau syndrome. The authors report on 2 cases of thrombi in Trousseau syndrome from large cerebral vessels removed by endovascular therapy and compared with thrombi in atherosclerosis or cardiac embolism. The first patient, a 67-year-old man, was transferred to our hospital for sudden onset consciousness disturbance and tetraparesis. He had been diagnosed with stage IV lung cancer. The magnetic resonance (MR) angiography demonstrated basilar artery occlusion. An endovascular thrombectomy was performed. The second patient, an 84-year-old woman, was transferred to our hospital for sudden onset motor aphasia and right-sided motor weakness. She has a history of stage IV pancreatic body cancer. The MR angiography demonstrated left middle cerebral artery occlusion. An endovascular thrombectomy was performed for the floating thrombus. Macroscopic findings of retrieved thrombi were observed immediately after thrombectomy. The thrombi in Trousseau syndrome were white in color and solid against manual compression, whereas thrombi from other causes were red and fragile. In terms of microscopic findings, the thrombi in Trousseau syndrome mainly contained fibrin. On the other hand, thrombi associated with atherosclerosis or cardiac embolism had smaller area of fibrin with a considerable amount of red and white blood cells. The thrombi in Trousseau syndrome, which caused occlusion of large cerebral vessel, almost exclusively consisted of fibrin.

[Indocyanine Green Videoangiography-Guided Target Bypass for Surgical Trapping of Distal Middle Cerebral Artery Aneurysm:A Technical Case Report].

Intraoperative indocyanine green(ICG)videoangiography is simple, less invasive, and enables real-time observation of hemodynamics during neurovascular surgery. In this article, we describe a case of ruptured distal middle cerebral artery aneurysm, which was unclippable and required parent artery occlusion with extracranial-intracranial bypass. Under temporary clipping of the proximal vessel, ICG videoangiography demonstrated the proper target vessel for bypass through delayed and retrograde filling of the dye. In this operation, ICG videoangiography contributed to simpler and less invasive procedures, by avoiding dissection of the tight cerebral fissure and intraoperative angiography.

Reflux of Anterior Spinal Artery Predicts Recurrent Posterior Circulation Stroke in Bilateral Vertebral Artery Disease.

BACKGROUNDS AND PURPOSE: Predictive value of reflux of anterior spinal artery for recurrent posterior circulation ischemia in bilateral vertebral arteries steno-occlusive disease was evaluated. METHODS: We retrospectively reviewed 55 patients with symptomatic posterior circulation stroke caused by bilateral stenotic (>70%) lesions of the vertebral artery. We investigated any correlation of clinical and angiographic characteristics including collateral flow patterns, with recurrent stroke. Risk factors for poor 3-month functional outcome were also evaluated. RESULTS: Recurrent posterior circulation stroke was observed in 15 (27.3%) patients. Multivariable analysis using Cox proportional hazards model showed anterior spinal artery reflux as a significant risk factor for stroke recurrence (adjusted hazard ratio, 19.3 [95% confidence interval, 5.35-69.9]; P<0.001). Anterior spinal artery reflux was also correlated with poor functional outcome (modified Rankin Scale score, 3-6; adjusted odds ratio, 7.41 [95% confidence interval, 1.24-44.4]; P=0.028). CONCLUSIONS: In patients with symptomatic bilateral vertebral artery occlusive disease, anterior spinal artery reflux predicted recurrent posterior circulation stroke and poor functional outcome.

[De novo distal superior cerebellar artery aneurysm after embolization of a ruptured aneurysm at the bifurcation of the contralateral basilar and superior cerebellar arteries].

The formation of de novo aneurysms in the posterior fossa after successful treatment of a previous aneurysm in the same fossa is rare. Here we describe a case of a de novo generated aneurysm at the distal superior cerebellar artery(SCA)7 years after the successful obliteration of an aneurysm at the contralateral basilar artery(BA)-SCA bifurcation. The treatment of the original posterior fossa aneurysm may lead to hemodynamic changes that may contribute to the formation of a de novo aneurysm at another vulnerable point in the posterior fossa circulation. We conclude that a close surveillance is required after the initial treatment of posterior fossa aneurysms in order to detect the possible formation of de novo aneurysms.

Endovascular treatment of sphenoid wing dural arteriovenous fistula with pure cortical venous drainage.

Curative endovascular treatment of sphenoid wing dural arteriovenous fistula (dAVF) with pure cortical venous drainage is challenging because of its rarity, lack of accessible dural sinus for transvenous embolization (TVE), and proximity of skull base vital regions. Direct surgery to disconnect venous reflux has been favored. We report the curative endovascular treatment of two sphenoid wing dAVFs with pure cortical venous drainage. One patient revealed complete obliteration of dAVF by a single session of transarterial embolization (TAE). As part of strategic TAE for this complex dAVF, we used a novel approach to create a complete flow-arrest condition in which coils and an occlusion balloon were combined. A liquid agent was then injected across the pathological fistula and into the parent venous apparatus, thereby occluding the lesion. The other patient was treated with percutaneous TVE after TAE was unsuccessful. With a specific strategy and appropriate devices, the microcatheter was successfully introduced through sigmoid sinus, transverse sinus, superior sagittal sinus, and refluxing cortical vein by puncture of the jugular vein. Coils were deployed at the venous side of the fistula, resulting in successful obliteration of the dAVF. Sphenoid wing dAVF with pure cortical venous drainage could be curable by endovascular treatment with proper strategy and instruments when anatomical condition permits.