Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease.

Previous studies have suggested that enlarged perivascular spaces (EPVSs) are potential radiological markers of cerebral ischemia in moyamoya disease (MMD). However, serial changes in EPVSs after surgical revascularization have not yet been clarified. We aimed to elucidate the postoperative changes in EPVSs in adult patients with MMD, clinical and radiological factors affecting the number of EPVSs, and the degree of postoperative changes. We counted the EPVSs in the centrum semiovale in each hemisphere on a T2-weighted MRI performed before surgery. EPVSs were quantified 3 months and 2 years after combined bypass surgery in surgically treated patients and compared with the number of EPVSs before surgery. We performed multivariate logistic regression analysis to identify the clinical and radiological factors associated with the number of EPVSs. This study included 120 hemispheres of 65 adults with MMD. Older age (P < 0.01), posterior cerebral artery (PCA) involvement (P < 0.01), and cerebral blood flow (CBF) impairment (P = 0.02) were significantly associated with a large number of EPVSs. The number of EPVSs markedly decreased at 3 months and 2 years after surgery compared with that before surgery (P < 0.01). PCA involvement (P = 0.04) and CBF impairment (P = 0.02) were independent predictors of the regression of EPVSs after surgery. The number of EPVSs in the centrum semiovale was closely associated with age, PCA involvement, and CBF impairment in adult patients with MMD, which remarkably regressed after surgical revascularization, especially in the hemispheres with PCA involvement and CBF impairment. EPVSs are reversible radiological markers reflecting impaired cerebral hemodynamics in adult patients with MMD.

Reversible sulcal fluid-attenuated inversion recovery hyperintensity after combined bypass surgery for moyamoya disease - A "crevasse" sign.

Background: Transient fluid-attenuated inversion recovery (FLAIR) hyperintensity is often observed on the operated brain surface after direct or combined bypass surgery for moyamoya disease, but its pathophysiology and clinical significance are still obscure. This study was aimed to clarify the underlying mechanism and clinical significance. Methods: This prospective study included 106 hemispheres of 61 patients with moyamoya disease and analyzed their radiological findings before and after combined bypass surgery. This study also included 11 patients who underwent superficial temporal artery to middle cerebral artery anastomosis for occlusive carotid artery diseases as the controls. Magnetic resonance imaging examination was serially repeated, and cerebral blood flow was measured before and after surgery. Signal intensity ratio (SIR) in the cortical sulci and cortex to the adjacent white matter on FLAIR images was calculated, and the postoperative SIR changes were semi-quantitatively evaluated to assess the temporal profile of postoperative FLAIR hyperintensity. Results: Postoperative FLAIR hyperintensity occurred within the cortical sulci on the operated hemispheres in all moyamoya patients but not in patients with occlusive carotid artery diseases. SIR values started to increase immediately after surgery, peaked at about 4-fold at 4-13 days post-surgery, then declined, and recovered to baseline values over 28 days or later. The magnitude of this phenomenon was proportional to the severity of cerebral ischemia but not to postoperative hyperperfusion. Conclusion: Reversible sulcal FLAIR hyperintensity specifically occurs in the operated hemispheres after direct bypass surgery for moyamoya disease. This "crevasse sign" may represent the mixture of the extensive leakage of oxygen and proteins from the pial arteries into the CSF.

Frequency, Characteristics, and Preventability of Adverse Drug Reactions in Perioperative Neurosurgery: Analysis Over 11 Years.

OBJECTIVE: Despite the importance of adverse drug reactions (ADRs), little is known about their role in perioperative neurosurgery. This study aimed to determine the prevalence of ADRs in perioperative neurosurgery and clarify the characteristics, severity, preventability, and risk factors of ADRs. METHODS: Data for all patients who underwent neurosurgical procedures over an 11-year period were analyzed. During the study period, 3648 surgical procedures were performed for 2695 patients. Demographic and clinical information documented included medical history, allergic history, diagnosis, surgical method, suspected drugs, concomitant medications, and drug details. Multivariate logistic regression analyses were performed to identify independent parameters that were correlated with ADRs. RESULTS: In total, 467 ADRs (18.3% ADRs/all neurosurgical procedures) were experienced by 401 patients. Anticonvulsants were associated with the highest number of ADRs (16.0%), followed by antibiotics (14.7%). Patients with ADRs were older than patients without ADRs (P < 0.01). The total number of drugs in patients with ADRs was 8.8 ± 3.6, compared to 5.2 ± 2.4 for patients without ADRs (P < 0.01). There were no significant differences in sex, allergic history, severe renal dysfunction (estimated glomerular filtration rate < 30 ml/min/1.73 m2), hypertension, diabetes, urgency of surgery, and type of surgery. Multivariate analysis showed that a high total number of drugs (odds ratio=3.2; 95% confidence interval 1.9-5.1) and older age (odds ratio=2.1; 95% confidence interval 1.3-3.8) were independent risk factors for ADRs. CONCLUSIONS: The frequency of suspected and severe ADRs was higher than expected. Polypharmacy and older age were independent risk factors for ADRs in perioperative neurosurgery. To decrease ADRs during perioperative neurosurgery, polypharmacy must be discouraged, especially among older adult patients.

Association between Pericarotid Fat Density and Positive Remodeling in Patients with Carotid Artery Stenosis.

Background/Objectives: The underlying mechanism of the potential involvement of inflammatory crosstalk between pericarotid fat and vascular layers in atherosclerosis pathogenesis is unclear. We investigated the association between pericarotid fat density and positive remodeling and inflammatory markers in carotid stenosis. We hypothesized that pericarotid fat density might serve as a marker of plaque inflammation in a clinical setting. Methods: We evaluated the stenosis degree and pericarotid fat density in 258 patients with carotid plaques. Plaque composition was examined, and the correlation between pericarotid fat density and expansive remodeling was investigated. Pearson's product-moment correlation coefficient was used to examine the relationship between pericarotid fat density and the expansive remodeling ratio. We also evaluated the relationship of pericarotid fat density with plaque composition, degree of stenosis, and macrophage and microvessel counts by. The subgroup analysis compared these factors between symptomatic mild carotid stenosis. Results: The pericarotid fat density was -63.0 ± 11.1 HU. The carotid fat densities were -56.8 ± 10.4 HU in symptomatic and -69.2 ± 11.4 HU in asymptomatic lesions. The pericarotid fat density values in intraplaque hemorrhage, lipid-rich necrotic core, and fibrous plaque were -51.6 ± 10.4, -59.4 ± 12.8, and -74.2 ± 8.4 HU, respectively. Therefore, the expansive remodeling ratio was 1.64 ± 0.4. Carotid fat density and expansive remodeling ratio were correlated. Immunohistochemistry showed high macrophage and microvessel levels (143.5 ± 61.3/field and 121.2 ± 27.7/field, respectively). In symptomatic mild carotid stenosis, pericarotid fat density was correlated with other inflammatory factors. The pericarotid fat density and expansive remodeling ratio (2.08 ± 0.21) were high in mild stenosis (-50.1 ± 8.4 HU). Conclusions: Pericarotid fat and intraplaque components were well correlated. Carotid fat density may be a marker of plaque inflammation in carotid plaques.

Intraoperative monitoring of cerebrospinal fluid gas tension and pH before and after surgical revascularization for moyamoya disease.

Background: This study aimed to directly measure cerebrospinal fluid (CSF) gas tensions and pH before and after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis for moyamoya disease. Methods: This study included 25 patients with moyamoya disease who underwent STA-MCA anastomosis combined with indirect bypass onto their 34 hemispheres. About 1 mL of CSF was collected before and after bypass procedures to measure CSF partial pressure of oxygen (PCSFO2), CSF partial pressure of carbon dioxide (PCSFCO2), and CSF pH with a blood gas analyzer. As the controls, the CSF was collected from 6 patients during surgery for an unruptured cerebral aneurysm. PCSFO2 and PCSFCO2 were expressed as the ratio to partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2), respectively. Results: PCSFO2/PaO2 was 0.79 ± 0.14 in moyamoya disease, being lower than 1.10 ± 0.09 in the controls (P < 0.0001). PCSFCO2/PaCO2 was 0.90 ± 0.10 in moyamoya disease, being higher than 0.84 ± 0.07 in the controls (P = 0.0261). PCSFO2/PaO2 was significantly lower in pediatric patients than in adult patients and in the hemispheres with reduced cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide than in those with normal CBF but reduced CVR. STA-MCA anastomosis significantly increased PCSFO2/PaO2 from 0.79 ± 0.14 to 0.86 ± 0.14 (P < 0.01) and reduced PCSFCO2/PaCO2 from 0.90 ± 0.10 to 0.69 ± 0.16 (P < 0.0001). There was no difference in CSF pH between moyamoya disease and the controls. Conclusion: PCSFO2/PaO2 was significantly lower in moyamoya disease than in the controls. Its magnitude was more pronounced in pediatric patients than in adult patients and depends on the severity of cerebral ischemia. STA-MCA anastomosis carries dramatic effects on CSF gas tensions in moyamoya patients. CSF may be a valuable biomarker to monitor the pathophysiology of cerebral ischemia/hypoxia in moyamoya disease.

The BHLHE40‒PPM1F‒AMPK pathway regulates energy metabolism and is associated with the aggressiveness of endometrial cancer.

BHLHE40 is a basic helix-loop-helix transcription factor that is involved in multiple cell activities including differentiation, cell cycle, and epithelial-to-mesenchymal transition. While there is growing evidence to support the functions of BHLHE40 in energy metabolism, little is known about the mechanism. In this study, we found that BHLHE40 expression was downregulated in cases of endometrial cancer of higher grade and advanced disease. Knockdown of BHLHE40 in endometrial cancer cells resulted in suppressed oxygen consumption and enhanced extracellular acidification. Suppressed pyruvate dehydrogenase (PDH) activity and enhanced lactated dehydrogenase (LDH) activity were observed in the knockdown cells. Knockdown of BHLHE40 also led to dephosphorylation of AMPKα Thr172 and enhanced phosphorylation of pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) Ser293 and lactate dehydrogenase A (LDHA) Tyr10. These results suggested that BHLHE40 modulates PDH and LDH activity by regulating the phosphorylation status of PDHA1 and LDHA. We found that BHLHE40 enhanced AMPKα phosphorylation by directly suppressing the transcription of an AMPKα-specific phosphatase, PPM1F. Our immunohistochemical study showed that the expression of BHLHE40, PPM1F, and phosphorylated AMPKα correlated with the prognosis of endometrial cancer patients. Because AMPK is a central regulator of energy metabolism in cancer cells, targeting the BHLHE40‒PPM1F‒AMPK axis may represent a strategy to control cancer development.

Clinical Significance of Carotid Endarterectomy and Carotid Artery Stenting in Older Patients Over 80.

As the average life expectancy increases, neurosurgeons are likely to encounter patients aged 80 years and above with carotid stenosis; however, whether old age affects clinical post-treatment outcomes of carotid endarterectomy (CEA) or carotid artery stenting (CAS) remains inconclusive. Thus, this study aimed to evaluate the outcomes following CEA or CAS in patients aged 80 years and above. This study included older over 80 years (n = 34) and younger patients (<80 years; n = 222) who underwent CEA or CAS between 2012 and 2022. All of them were followed up for a mean of 55 months. All-cause mortality, the incidence of vascular events, ability to perform daily activities, and nursing home admission rates were assessed. During follow-up periods, 34 patients (13.3%) died due to coronary artery disease, malignancy, and pneumonia, and the incidence was significantly higher in the elderly group than in the younger group (P = 0.03; HR, 3.01; 95% CI, 1.53-5.56). The incidence of vascular events did not differ between the older group (29.5%) and the younger group (26.9%, P = 0.58); however, the incidence was significantly higher in patients with high-intensity plaques than in those without that (P = 0.008; HR, 2.83, 95%CI, 1.27-4.87). The decline in the ability to perform daily activities and increased nursing home admission rates were high in elderly patients (P < 0.01). Although the mortality rate was higher in the elderly group, subsequent vascular events were comparable to that in the younger group. The results suggest that CEA and CAS are safe and useful treatments for carotid stenosis in older patients, especially to prevent ipsilateral ischemic stroke.

Intracerebral Hematoma in Patients With Impella Ventricular Assist Device Placement for Cardiogenic Shock: Report of Three Cases.

Despite the clear benefits of Impella in patients with cardiogenic shock, bleeding is a possible complication. Herein, we report three cases of intracerebral hemorrhage in patients with Impella implantation for cardiogenic shock, which were treated with hematoma evacuation. We present the clinical features, diagnosis, and management (hematoma evacuation) of patients with the Impella device (Abiomed, Danvers, Massachusetts) who developed intracerebral hemorrhage. Case one was a 56-year-old man who presented with chest pain and loss of consciousness, was diagnosed with acute myocardial infarction, and underwent urgent percutaneous coronary intervention and Impella placement. After eight days, the patient developed anisocoria. Computed tomography revealed a left intracerebral hemorrhage. An emergency hematoma evacuation was successfully performed (intraoperative blood loss: 2600 mL). Case two was a 54-year-old male who presented with persistent chest pain and loss of consciousness, was diagnosed with acute myocardial infarction, and underwent an emergency percutaneous coronary intervention with Impella implantation and venoarterial extracorporeal membrane oxygenation. The patient developed intracerebral hemorrhage after 26 days. Hematoma evacuation was successfully performed (intraoperative blood loss: 380 mL). Case three was a 52-year-old male who presented with dyspnea and hypotension, was diagnosed with dilated cardiomyopathy, and underwent Impella implantation and venoarterial extracorporeal membrane oxygenation, followed by which the patient developed subcortical hematoma. An emergency hematoma evacuation was performed (intraoperative blood loss: 3205 mL). The patient died 14 days after admission. Intracerebral hemorrhage is a potential cause of morbidity associated with Impella placement. Although hematoma evacuation is optimal, the bleeding tends to increase.

Effects of superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis on the cerebrospinal fluid gas tensions and pH in hemodynamically compromised patients.

PURPOSE: This study was aimed to directly measure cerebrospinal fluid (CSF) gas tensions and pH before and after STA-MCA anastomosis for occlusive carotid artery diseases to investigate its direct effects on the ischemic brain. METHODS: This study included 9 patients who underwent STA-MCA anastomosis on the basis of CBF studies. About 1 mL of CSF was collected before and after bypass procedures, and CSF pH, CSF PO2, and CSF PCO2 were measured with a blood gas analyzer. As the controls, the CSF was collected from 6 patients during surgery for unruptured cerebral aneurysm. CSF PO2 and CSF PCO2 were expressed as the ratio to PaO2 and PaCO2, respectively. RESULTS: Before bypass procedure, CSF PO2/PaO2 was 0.88 ± 0.16, being lower than the controls (1.10 ± 0.09; P = 0.005). CSF PCO2/PaCO2 was 0.93 ± 0.13, being higher than the controls (0.84 ± 0.06; P = 0.039). Ipsilateral-to-contralateral CBF ratio had a positive correlation with CSF PO2/PaO2 (P = 0.0028) but a negative correlation with the CSF PCO2/PaCO2 (P = 0.0045). STA-MCA anastomosis increased CSF pH from 7.402 ± 0.133 to 7.504 ± 0.126 (P = 0.0011) and CSF PO2/PaO2 from 0.88 ± 0.16 to 1.05 ± 0.26 (P = 0.018) but decreased CSF PCO2/PaCO2 from 0.93 ± 0.13 to 0.70 ± 0.17 (P = 0.0006). CONCLUSION: The severity of cerebral ischemia before surgery is intensely reflected in the gas tensions and pH of the CSF. STA-MCA anastomosis carries dramatic effects on CSF gas tensions and pH in hemodynamically compromised patients. CSF would be a valuable surrogate biomarker to monitor the severity of cerebral ischemia.

Decision-making for Subsequent Therapy for Patients With Recurrent or Advanced Endometrial Cancer Based on the Platinum-free Interval.

OBJECTIVE: The aim of this study was to evaluate the progression-free survival (PFS) and overall response rate (ORR) of patients with recurrent endometrial cancer (REC) or advanced endometrial cancer (AEC) retreated with platinum-containing chemotherapy (PCC) based on the platinum-free interval (PFI). We compared our results with those reported in the KEYNOTE-775 study (that used pembrolizumab plus lenvatinib). METHODS: A retrospective analysis was conducted of 65 patients with REC or AEC retreated with PCC between 2005 and 2020 at our hospital. Various clinicopathologic variables were analyzed: (1) age, (2) performance status, (3) histology, (4) history of pelvic irradiation in the adjuvant setting, (5) PFI, (6) chemotherapy regimen, (7) PFS and overall survival after retreatment with PCC, and (8) best ORR. Survival analyses were performed using Kaplan-Meier curves and log-rank tests. RESULTS: The best ORR and PFS were 43.3% and 9.5 months, respectively, in patients with REC/AEC with a PFI ≥6 months. These results were comparable with those of patients treated with pembrolizumab and lenvatinib. The best ORR and PFS of patients with a PFI of <6 months appeared to be inferior to those of patients treated with pembrolizumab plus lenvatinib. CONCLUSIONS: Pembrolizumab plus lenvatinib seems to be a better treatment choice for patients with REC or AEC with a PFI of <6 months. For a PFI of ≥6 months, pembrolizumab plus lenvatinib or PCC can be used depending on the degree of residual side -effects associated with cytotoxic agents.

Coil embolization for post-bypass aneurysm of middle meningeal artery for moyamoya disease - preservation of transdural anastomosis.

Background: Middle meningeal artery (MMA) pseudoaneurysm following revascularization surgery for moyamoya disease (MMD) is rare. Case Description: Here, a 29-year-old man presented with an MMA pseudoaneurysm after he underwent revascularization surgery (superficial temporal artery-to-middle cerebral artery bypass and encephalo-duro-myoarterio-pericranial synangiosis) for hemorrhagic MMD. At 3 months post-surgery, digital subtraction angiography showed a pseudoaneurysm in the right MMA. Transdural anastomosis to the parietal and occipital lobes was opacified at the distal MMA of the pseudoaneurysm. Intra-aneurysmal coil embolization was performed for preservation of transdural anastomosis. The postoperative course was uneventful. At 1 month post-embolization, angiography revealed an entirely occluded pseudoaneurysm. Conclusion: An increase in blood flow in the MMA due to bypass surgery may accelerate aneurysm development by increasing the hemodynamic stress. This case suggested that intra-aneurysmal embolization may be a potential treatment.

Endoscopic third ventriculostomy for patients with Blake's pouch cyst with adult-onset hydrocephalus: Importance of improved cerebrospinal fluid flow in the prepontine cistern - A case report.

Background: Blake's pouch cyst (BPC) is a posterior fossa cystic malformation that commonly occurs in children with rare adult onset. Herein, we report a case of adult onsets BPC. Case Description: A 61-year-old man presented with gait and cognitive disturbance. Preoperative magnetic resonance imaging (MRI) revealed scarring in the prepontine cistern, and cine phase-contrast MRI revealed no pulsation. Endoscopic third ventriculostomy (ETV) was performed with opening the scarring in the prepontine cistern. Postoperative cine phase-contrast MRI revealed that cerebrospinal fluid (CSF) flow in the prepontine cistern improved, resolving the patient's symptoms. Conclusion: We report a case of adult-onset BPC. The mechanism by which is becomes symptomatic is still unclear. We opened the scar in prepontine cistern in addition to ETV with good results. In this report, we discussed the importance of the improvement in CSF dynamics in the prepontine cistern.

Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE).

BACKGROUND: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. METHODS: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0-1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. RESULTS: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24-20.6]; P=0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P=0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62-30.7]; P=0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. CONCLUSIONS: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: UMIN000006640.

Tumor-derived ARHGAP35 mutations enhance the Gα13-Rho signaling axis in human endometrial cancer.

Dysregulated G protein-coupled receptor signaling is involved in the formation and progression of human cancers. The heterotrimeric G protein Gα13 is highly expressed in various cancers and regulates diverse cancer-related transcriptional networks and cellular functions by activating Rho. Herein, we demonstrate that increased expression of Gα13 promotes cell proliferation through activation of Rho and the transcription factor AP-1 in human endometrial cancer. Of interest, the RhoGTPase activating protein (RhoGAP), ARHGAP35 is frequently mutated in human endometrial cancers. Among the 509 endometrial cancer samples in The Cancer Genome Atlas database, 108 harbor 152 mutations at 126 different positions within ARHGAP35, representing a somatic mutation frequency of 20.2%. We evaluated the effect of 124 tumor-derived ARHGAP35 mutations on Gα13-mediated Rho and AP-1 activation. The RhoGAP activity of ARHGAP35 was impaired by 55 of 124 tumor-derived mutations, comprised of 23 nonsense, 15 frame-shift, 15 missense mutations, and two in-frame deletions. Considering that ARHGAP35 is mutated in >2% of all tumors, it ranks among the top 30 most significantly mutated genes in human cancer. Our data suggest potential roles of ARHGAP35 as an oncogenic driver gene, providing novel therapeutic opportunities for endometrial cancer.

Acute subdural hematoma in an infant with a biphasic clinical course and late reduced diffusion.

Background: Bright tree appearance (BTA) is a characteristic finding on diffusion-weighted magnetic resonance (MR) imaging with transient high intensity in the white matter. BTA is characteristic of infants with acute encephalopathy with biphasic seizures, but it has also been reported in head trauma cases. In this report, we describe an infant case of traumatic brain injury that demonstrated a biphasic clinical course and late reduced diffusion (TBIRD). Case Description: A 5-month-old boy suffered from head trauma and developed coma and seizures. Computed tomography scans revealed acute subdural hematoma on the right side. He underwent an emergency operation to remove the hematoma but subsequently had seizure clusters for three days. Diffusion-weighted MR imaging revealed BTA in the right cerebral hemisphere. He was treated with antiepileptic agents and fully recovered to pre-injury condition, and MR imaging no further revealed any BTA 20 days after head trauma. He developed no complications at the 10-month postoperative follow-up. Conclusion: We reported a case of TBIRD following head trauma in the infant. The pathogenesis remains unclear, but we consider the possibility of biphasic seizures in infant head trauma cases, and we should appropriately administer the anticonvulsants and carefully check for MR imaging.

Therapeutic strategy of severe circular calcified carotid plaque with hemodynamic impairment: A patient treated by carotid endarterectomy following balloon angioplasty to prevent hyperperfusion.

Background: Cerebral hyperperfusion syndrome (HPS) is a serious complication. Recently, staged angioplasty has been reported as an effective strategy to avoid HPS. Severe calcification has been reported as contraindication of carotid artery stenting (CAS). In these cases, carotid endarterectomy (CEA) might be an alternative second stage treatment. We present a case of severe circular calcified plaque with hemodynamic impairments, treated with CEA following percutaneous transluminal angioplasty (PTA) to prevent HPS. Case Description: A 77-year-old woman presented with severe stenosis at the proximal left internal carotid artery. A CT scan of the neck demonstrated circular calcification. 123I-iodoamphetamine single-photon emission computed tomography (123I-IMP SPECT) showed reductions in cerebral blood flow (CBF) and cerebral vascular reserve in the left hemisphere. Staged therapy was subsequently performed as this patient had a high risk of HPS after conventional CAS or CEA. In the first stage, PTA was performed under local anesthesia. Two days after the procedure, 123I-IMP SPECT revealed improvements in CBF. There were no neurological morbidities. CEA was then performed under general anesthesia 7 days later, for the second stage. We found a calcified plaque with a large thrombus at its proximal end. A hematoxylin-eosin stain of the thrombus showed mostly intact and partially lytic blood cells. Postoperative 123I-IMP SPECT revealed CBF was improved, with no hyperperfusion immediately and 2 days after CEA. The patient was discharged with no neurological deficits. Conclusion: CEA following PTA for severe circular calcified plaque can be an alternative treatment strategy to prevent HPS. A disadvantage is the formation of thrombi. Early CEA should be considered if thrombus formation is suspected.

Prognostic impact of adding bevacizumab to carboplatin and paclitaxel for recurrent, persistent, or metastatic cervical cancer.

OBJECTIVE: Recent randomized phase III trial has shown significant benefit in overall survival (OS) for patients with advanced cervical cancer by adding bevacizumab to conventional chemotherapy. The aim of this study was to evaluate the prognostic impact for Japanese recurrent, persistent, or metastatic cervical cancer patients where bevacizumab was added to paclitaxel plus carboplatin. MATERIALS AND METHODS: A retrospective analysis was performed on 90 patients with recurrent, persistent, or metastatic cervical cancer mainly treated by paclitaxel plus carboplatin between 2005 and 2019 at our hospital. Data for the following clinicopathological variables were analyzed: (1) bevacizumab use; (2) histology; (3) disease presentation; (4) performance status; (5) prior chemotherapy containing platinum agent; (6) pelvic disease; (7) prior pelvic radiotherapy; (8) location of target lesions. Survival analysis was performed using Kaplan-Meier curves, log-rank tests, Wilcoxon tests, and Cox proportional hazards models combined with propensity score matching. RESULTS: Adding bevacizumab to paclitaxel plus carboplatin showed significantly increased complete response to compared with that of non-users. In a Cox regression hazard model, bevacizumab use tended to show better OS though without statistically significance. After propensity score matching, adding bevacizumab to paclitaxel plus carboplatin showed a significant better OS by univariate analysis using Wilcoxon test, not by log-rank test. CONCLUSION: Adding bevacizumab to paclitaxel plus carboplatin showed a limited prognostic impact for recurrent, persistent or advanced cervical cancer patients in the real world. Further effective second-line treatments are needed to prolong OS of patients with recurrent, persistent or advanced cervical cancer.

Usefulness of Orbitocranial Approach in Neck Clipping of Aneurysms Arising from Middle Cerebral Artery Proximal to the Limen Insulae: A Case Series.

BACKGROUND: Neck clipping of the aneurysms arising from the middle cerebral artery (MCA) proximal to the limen insulae is often difficult because of difficulties in securing a bright and wide operative field to observe the aneurysms and surrounding structures, such as the anterior perforated substance, lenticulostriate arteries, and early frontal branch. Our objective was to determine the usefulness of the orbitocranial approach in neck clipping of the aneurysms arising from the MCA proximal to the limen insulae. METHODS: This prospective study included 7 patients who underwent neck clipping of aneurysms arising from the MCA proximal to the limen insulae through the orbitocranial approach. In addition to conventional pterional craniotomy, the superiolateral orbital rim was resected with a 1-piece fashion. Its procedures, complications, and outcomes were reviewed. RESULTS: Removal of the superolateral orbital rim facilitated a bright and wide observation from the skull base side. It was much easier to identify the anterior perforated substance, lenticulostriate arteries, and early frontal branch around the aneurysm through the orbitocranial approach than through the conventional pterional approach. Neck clipping could be performed completely and safely in all cases. CONCLUSIONS: The orbitocranial approach to aneurysms arising from the MCA proximal to the limen insulae provides us a bright and wide operative field compared with the conventional pterional approach, which is useful to secure complete and safe neck clipping by avoiding cerebral contusion and unexpected obstruction of the early frontal branch.

Impact of system approach and personal performance on preventable morbidity and mortality events in neurosurgery patients.

PURPOSE: Adverse events in neurosurgery are a serious problem. The approach for seeking solutions for adverse events has shifted from a personal approach to a systemic approach. However, to some extent, preventable morbidity events could be related to personal performance. This study aimed to clarify the impact of personal performance and systematic failure on the occurrence of morbidity and mortality events in neurosurgery patients. METHODS: All morbidity and mortality conference data stored within our department over a 9-year period were analyzed. There were 4580 admitted patients and 3262 surgical procedures performed. We performed a three-step classification of morbidity and mortality events based on the possibility of prevention, root of the event, and personal or systemic issues. RESULTS: As a result of the first step, 214 preventable and 278 unpreventable events were identified. Of the preventable events, two mortality and 212 morbidity events were analyzed. In the second step, 155 (72.4%), 34 (15.9%), 13 (6.1%), and 12 (5.6%) events were categorized as technical complications, critical events, judgment errors, and human factors, respectively. There were 179 events (83.6%) classified as personal performance issues and 35 events (16.4%) as systemic issues. The ratio of personal performance to systemic issues varied widely, with significant differences among the four categories (P < 0.01). CONCLUSIONS: Among neurosurgery patients who have preventable morbidity, issues related to personal performance were more frequent than systemic issues. Efforts to improve systems should be unwavering. However, the personal responsibility of neurosurgeons to avoid preventable complications should not be ignored.

Thin calcification (< 2 mm) can highly predict intraplaque hemorrhage in carotid plaque: the clinical significance of calcification types.

PURPOSE: Calcification pathogenesis and the relationship between calcification and plaque composition remain unclear. This study explored the calcification characteristics of vulnerable plaques, especially focusing on calcification thickness, using computed tomography angiography and magnetic resonance plaque imaging. METHODS: Demographic, computed tomography angiography, and magnetic resonance plaque imaging data were acquired from 178 patients with 229 lesions diagnosed with carotid stenosis. The calcification types were categorized by calcification thickness. We evaluated their features, including the anatomical location and the plaque composition compared with MR plaque imaging, and clarify the clinical characteristics. Furthermore, an immunohistochemical subgroup analysis was performed on 84 lesions treated with carotid endarterectomy. RESULTS: The result of the ROC analysis suggested the threshold between symptomatic and asymptomatic calcification was 2.04 mm (AUC;0.841, 95%CI; 0.771-0.894). Calcification with ≥ 2 mm thickness was classified as thick calcification and < 2 mm thickness as thin calcification. Multivariate analysis suggested the prevalence of symptomatic patients in the thin calcification group was significantly higher than others (P = 0.01; odds ratio, 4.1; 95% confidence interval 2.8-7.2). Plaques with thin calcification were associated with plaque with intraplaque hemorrhage (P < 0.01). The interobserver reliability (κ) of calcification type was 0.962 (95% confidence interval, 0.941-0.988). Immunohistochemical analysis demonstrated that the numbers of CD68-positive cells and CD31-positive microvessels in shoulder lesions were significantly higher in the thin calcification group than in the non-thin group (both P < 0.01). CONCLUSIONS: Thin calcification was associated with plaques with intraplaque hemorrhage and had different clinical implications than thick calcification.