Effectiveness of S-Shaping of the Tip of the FUBUKI Guiding Catheter to Match the Shape of the Cervical Internal Carotid Artery in Anterior Circulation Cerebral Aneurysm Embolization.

Objective: During cerebral aneurysm embolization of the anterior circulation, the guiding catheter (GC) should be placed as distally as possible in the cervical internal carotid artery (ICA) to secure the maneuverability of the microcatheter and distal access catheter. However, if the shape of the tip of the GC does not appropriately match the course of the ICA, blood stasis might occur. We investigated whether shaping the tip of the GC into an S-shape would allow more stable catheterization to the distal ICA than the conventional GC with an angled tip. Methods: We included patients with cerebral aneurysms of the anterior circulation who were treated at our institution from April 2019 to April 2021. First, we evaluated the cervical ICA course in these patients through cerebral angiography and classified the courses into type S, type I, and type Z. Then, we focused on the most frequently encountered type-S cervical ICA to investigate the forging effect of the GC tip into an S-shape. We evaluated the lateral view of the carotid angiograms to examine whether the catheter tip reached the foramen magnum (FM) without interrupting ICA blood flow. The effects of age, sex, side, a history of hypertension and smoking, and an S-shape modification of the GC tip on the outcome of GC placement were analyzed. Results: A total of 67 patients were included in this study. The tip of the GC was placed at the FM in 27 cases. Among these factors, only the S-shape modification was significantly associated with whether the GC could be placed at the level of the FM (p <0.0001). Conclusion: By forging the tip of the GC into an S-shape, the GC can be safely advanced to the distal part of the cervical ICA, which may contribute to the improved maneuverability of microcatheters.

Unmanageable Cerebrospinal Fluid Leakage With Eosinophilic Meningitis in a Gliadel Wafer Implant Patient.

Gliadel wafer implants (Eisai Inc., Woodcliff Lake, NJ, USA) have shown their efficacy in prolonging survival in patients with malignant gliomas. The safety of Gliadel wafers has also been reported; however, there is a certain risk of adverse events. We present a rare case of refractory cerebrospinal fluid (CSF) leakage with eosinophilic meningitis in a patient with glioblastoma who underwent tumor resection with Gliadel wafer implants. A 60-year-old man presented with a glioblastoma in the right temporal lobe. The patient underwent tumor resection with Gliadel wafer implants. During the postoperative course, the patient presented with intractable CSF leakage and the development of a pseudomeningocele. A delayed rise in blood and CSF eosinophil count (a few weeks after the primary operation) and positive drug-induced lymphocyte stimulation test (DLST) results against the Gliadel wafer led to the diagnosis of an allergic reaction to these implants. Removal of the Gliadel wafers resolved the eosinophilic reaction; however, the patient subsequently required a shunt procedure for persistent hydrocephalus. This case highlights the importance of investigating rare causes of refractory CSF leakage and hydrocephalus due to allergic reactions to Gliadel wafers. Delayed elevations of eosinophils in blood and CSF tests may lead to a diagnosis of eosinophilic meningitis. DLST against Gliadel wafers is also useful for diagnosis when it is available. To control the hydrocephalus, not only the shunt procedure but also wafer removal must be considered; however, patients with limited life expectancy are generally hesitant to undergo such additional procedures.

Differences in the Demographics and Clinical Characteristics between the Ossification of the Posterior Longitudinal Ligament and Ossification of the Ligamentum Flavum in Patients Who Underwent Thoracic Spinal Surgery for Compressive Myelopathy.

Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are related diseases associated with the ossification of spinal ligaments that can occasionally lead to thoracic myelopathy. We retrospectively analyzed the clinical data of 34 consecutive patients who underwent thoracic spinal surgeries for OPLL and/or OLF at our hospital between July 2010 and June 2022, and statistically compared data between patients with thoracic OPLL (TOPLL; n = 12) and those with thoracic OLF (TOLF; n = 22). The mean age of the TOPLL group was significantly lower than that of the TOLF group (53.7 vs. 68.4 years). The TOPLL group exhibited a greater female predominance than the TOLF group (58.3% vs. 18.2%). The median body mass index of the TOPLL group was significantly higher than that of the TOLF group (33.0 vs. 26.0 kg/m2). Patients with TOPLL significantly required instrumented fusion and repetitive surgical intervention more than those with TOLF (83.3% vs. 9.1%; 50.0% vs. 0.0%). Although neurological deterioration just after the intervention was more common in patients with TOPLL (41.7% vs. 4.6%), no difference was observed in thoracic Japanese Orthopaedic Association score and recovery rate in the chronic phase between TOPLL and TOLF. The TOPLL group had a younger onset, female dominance, and a greater degree of obesity when compared with the TOLF group. The surgery for TOPLL is challenging, considering that it requires long-range decompression and fusion, subsequent operations, careful management, and long-term follow-up, when compared to TOLF, which necessitates only simple decompression.

Postoperative Measurement of the Retropharyngeal Space Predicts the Risk of Dysphagia After Anterior Cervical Diskectomy and Fusion.

BACKGROUND AND OBJECTIVES: Postoperative dysphagia is a common complication of anterior cervical diskectomy and fusion (ACDF), although its pathophysiology remains poorly understood. Patients with severe dysphagia may suffer from serious complications such as aspiration pneumonia, in addition to difficulty with oral intake or malnutrition; therefore, a prompt indicator for postoperative management would be helpful. We quantitatively evaluated the retropharyngeal space (RS) after ACDF and investigated its association with postoperative dysphagia. METHODS: This multicenter retrospective study analyzed the clinical data of 82 consecutive patients who underwent ACDF. The anteroposterior distance (APD) of the RS was measured at the C2 level using a lateral radiographic view on postoperative day 1. Postoperative dysphagia was subjectively assessed using the Bazaz-Yoo Dysphagia Severity Scale. We statistically evaluated the association between the APD of the RS and postoperative dysphagia. RESULTS: The mean APD of the RS in all 82 patients was 3.6 mm preoperatively and significantly increased to 8.2 mm postoperatively (P < .0001). Twenty-two patients (26.8%) had postoperative dysphagia. Multivariable analysis revealed that the postoperative APD was associated with postoperative dysphagia (odds ratio 1.27, 95% CI 1.10-1.50, P = .0007). The receiver operating characteristic curve (area under the curve 0.70, 95% CI 0.58-0.83) demonstrated that the postoperative APD of the RS cutoff value was 6.1 mm, with a sensitivity of 100% and a specificity of 35%. With this cutoff value, the positive and negative predictive values for postoperative dysphagia were 36% and 100%, respectively. CONCLUSION: Our data demonstrate that a value of 6.1 mm for the APD of the RS is an effective indicator for dysphagia after ACDF, which contributes to optimizing the patient management in the acute postoperative period.

White Cord Syndrome After Cervical Laminoplasty in an 81-Year-Old Man.

White cord syndrome (WCS) shows high intramedullary signaling in T2-weighted MRI with worsening motor nerve symptoms after cervical spinal decompression surgery. It has been reported in only 13 cases. An 81-year-old man had numbness, weakness, and impaired fine motor control in both upper limbs for the previous five years. C3, C4, C6, open-door laminoplasty, and C5 laminectomy were performed. Intraoperative transcranial motor evoked potential normalization by compound muscle action potential showed an 80% reduction in amplitude in the right abductor pollicis brevis and a 96% reduction in the right abductor hallucis. Tetraplegia occurred immediately after the operation. Magnetic resonance imaging (MRI) on the day after the operation showed intramedullary T2 high signals at the C4 and C5 levels. According to Brunnstrom's staging, the upper and lower right limbs and the lower left limb were at stage two, and the upper left limb was at stage three, six months after the operation. Thirteen cases of WCS have been reported in the literature. These were thought to be caused by reperfusion due to decompression.

Anesthetic Fade in Intraoperative Transcranial Motor Evoked Potential Monitoring Is Mainly due to Decreased Synaptic Transmission at the Neuromuscular Junction by Propofol Accumulation.

BACKGROUND: We previously reported that normalization of motor evoked potential (MEP) monitoring amplitude by compound muscle action potential (CMAP) after peripheral nerve stimulation prevented the expression of anesthetic fade (AF), suggesting that AF might be due to reduced synaptic transfer in the neuromuscular junction. METHODS: We calculated the time at which AF began for each of craniotomy and spinal cord surgery, and examined whether AF was avoided by CMAP after peripheral nerve stimulation normalization in each. Similar studies were also made with respect to the upper and lower limb muscles. RESULTS: AF was observed in surgery lasting 160 minutes for craniotomy and 260 minutes or more for spinal surgery, and 195 minutes in the upper limb muscles and 135 minutes in the lower limb muscles. In all the series, AF could be avoided by CMAP after peripheral nerve stimulation normalization. CONCLUSION: AF of MEP occurred in both craniotomy and spinal cord surgery, and it was also corrected by CMAP after peripheral nerve stimulation. AF is considered to be mainly due to a decrease in synaptic transfer of the neuromuscular junction due to the accumulation of propofol because of the avoidance by CMAP normalization. However, it may be partially due to a decrease in the excitability of pyramidal tracts and α-motor neurons, because AF occurred earlier in the lower limb muscles than in the upper limb muscles.

Atypical clinical and radiological presentations of lumbar spinal tuberculosis mimicking a spinal tumor: A case report.

INTRODUCTION: Tuberculosis (TB) is an important infectious disease worldwide. Classical spinal TB has specific radiological findings involving adjacent vertebral bodies with destruction of the intervertebral disc and involvement of paravertebral soft tissues with cold abscess formation. However, a few cases not exhibiting the radiological characteristics of TB spondylitis have been reported. We report a rare case of lumbar spinal TB with atypical clinical and radiological presentations that was difficult to differentiate from a malignant spinal tumor. PATIENT CONCERNS: A 21-year-old man, who had immigrated to Japan from the Philippines 5 years ago, without a significant medical history, presented with back pain lasting 1 month and progression of gait disturbance 2 weeks prior to presentation. DIAGNOSIS: Laboratory tests showed normal blood cell counts and normal value of C-reactive protein levels. Preoperative imaging studies indicated a possible spinal tumor. However, histopathologic findings of the epidural soft tissues at the first surgery led to the diagnosis of spinal mycobacterial infection. The diagnosis of spinal TB was confirmed by a positive culture of Mycobacterium tuberculosis obtained at the second surgery. INTERVENTIONS: Given the progressive nature of neurologic deterioration, instead of needle biopsy, we proceeded with surgical intervention 8 days after admission; simultaneous neural decompression and open biopsy. Histological findings of the excised epidural soft tissues led to the diagnosis of spinal mycobacterial infection. We performed the second surgery involving additional resection of epidural soft tissues for further dural decompression and to obtain specimens for mycobacterial culture. Immediately after the second surgery, the patient commenced combination therapy with anti-tuberculous drugs. OUTCOMES: The patient demonstrated significant recovery of motor function in the lower extremities, and was able to run at 2 months after the second surgery. The epidural granulomas completely disappeared on magnetic resonance imaging 3 months postoperatively. CONCLUSION: Atypical clinical and radiological presentations of spinal TB present a challenge for appropriate diagnosis and early treatment. Even in developed countries where there are very few spinal TB patients, clinicians should be aware that spinal TB is an important differential diagnosis, especially in elderly patients or patients coming from countries with a middle-high prevalence of TB.

Ultraearly Hematoma Evacuation (<12 Hours) Associated with Better Functional Outcome in Patients with Symptomatic Spontaneous Spinal Epidural Hematoma.

BACKGROUND: Early decompressive surgery within 24 hours improves the functional outcome of patients with traumatic spinal cord injury; however, little is known about the effect of early surgery for spontaneous spinal epidural hematoma (SSEH). In this study, we aimed to investigate the effectiveness of ultraearly hematoma evacuation (<12 hours) for SSEH. METHODS: Patients with SSEH treated with surgical hematoma evacuation at our institution between January 2000 and July 2021 were retrospectively analyzed. Neurologic function was evaluated using the American Spinal Injury Association Impairment Scale (AIS). AIS grades A-C were defined as severe, and grades D and E as mild. AIS grades D and E at the final follow-up were considered favorable outcomes. Preoperative status and postoperative treatment results were compared between patients who had hematoma evacuation within 12 hours of onset and those who underwent surgery after 12 hours. RESULTS: Twenty-five consecutive patients were included in the analysis. Preoperatively, 23 patients (92.0%) had severe AIS. Fourteen (56.0%) patients underwent early surgery. At the final follow-up, 21 patients (84.0%) achieved favorable outcomes. Patients treated with ultraearly surgery had significantly better outcomes (100% vs. 63.6%, P = 0.03). Additionally, the time from onset to surgery was significantly shorter in patients with AIS improvement by 2 or more grades than that in patients with AIS improvement of 1 or less (median 8 hours vs. 14 hours, P = 0.0001). CONCLUSIONS: Ultraearly surgery within 12 hours for SSEH was associated with better functional outcomes.

A clinical-grade HLA haplobank of human induced pluripotent stem cells matching approximately 40% of the Japanese population.

BACKGROUND: Human induced pluripotent stem cells (iPSCs) are expected to be useful for regenerative medicine for many diseases. Many researchers have focused on and enabled the generation of differentiated cells or tissue-like structures, including organoids, which help to ameliorate target diseases. To promote such cell therapies, we established a clinically applicable iPSC haplobank matching as many people as possible in Japan. METHODS: Through cooperation with several organizations, we recruited donors whose human leukocyte antigens (HLAs) involved in immunorejection were homozygous. The peripheral or umbilical cord blood collected from the donors was used for iPSC production by electroporation of episomal vectors. These iPSC lines were then subjected to testing, including genome analyses and sterility, to maximize safety. FINDINGS: We constructed a clinical-grade haplobank of 27 iPSC lines from 7 donors according to good manufacturing practice regulations. However, reasons to avoid using iPSC lines include the presence of residual episomal vectors or genetic mutations in cancer-related genes. CONCLUSIONS: This haplobank provides HLA-matched iPSC lines for approximately 40% of the Japanese population. Since the haplobank's release in 2015, these iPSC lines have been used in more than 10 clinical trials. The establishment of this haplobank is an important step toward the clinical application of iPSCs in cell therapies. FUNDING: This study was supported by a research center network for the realization of regenerative medicine of the Japan Agency for Medical Research and Development (AMED) under grant number JP20bm0104001h0108.

Metastatic renal cell carcinoma of the lumbar spine with long posterior instrumented fusion and repetitive dislodgement of the set screws of the S2 alar-iliac screw.

Background: S2 alar-iliac screws (S2AIS) are widely used to anchor the pelvis to a lumbar fusion. Here, we report a patient who experienced repetitive dislodgement of the set screws of the S2AIS following a posterior instrumented fusion. Case Description: A 68-year-old male presented with an L3 metastasis and L2-L3 subluxation attributed to renal cell cancer. Following an L2-L5 posterior decompression and T9-pelvic fusion utilizing bilateral S2AIS fixation, the set screws of the S2AIS repeatedly dislodged, requiring two additional operations. The final surgery required multiple anchors to the ilium and provided adequate fixation until the patient's expiration. Conclusion: The set screw fixing force was weaker than the fixing force of the S2AIS; multiple iliac anchors effectively salvaged this condition.

Semi-3D cultures using Laminin 221 as a coating material for human induced pluripotent stem cells.

It was previously believed that human induced pluripotent stem cells (hiPSCs) did not show adhesion to the coating material Laminin 221, which is known to have specific affinity for cardiomyocytes. In this study, we report that human mononuclear cell-derived hiPSCs, established with Sendai virus vector, form peninsular-like colonies rather than embryonic stem cell-like colonies; these peninsular-like colonies can be passaged more than 10 times after establishment. Additionally, initialization-deficient cells with residual Sendai virus vector adhered to the coating material Laminin 511 but not to Laminin 221. Therefore, the expression of undifferentiated markers tended to be higher in hiPSCs established on Laminin 221 than on Laminin 511. On Laminin 221, hiPSCs15M66 showed a semi-floating colony morphology. The expression of various markers of cell polarity was significantly lower in hiPSCs cultured on Laminin 221 than in hiPSCs cultured on Laminin 511. Furthermore, 201B7 and 15M66 hiPSCs showed 3D cardiomyocyte differentiation on Laminin 221. Thus, the coating material Laminin 221 provides semi-floating culture conditions for the establishment, culture and induced differentiation of hiPSCs.

The optimal management of ruptured basilar artery dissecting aneurysms: a case series and scoping review.

The natural history of ruptured basilar artery dissecting aneurysms (BADAs) remains unclear compared to that of ruptured vertebral artery dissecting aneurysms (VADAs). In this study, we investigated the natural history and optimal management of ruptured BADAs. We identified 17 patients with ruptured BADA among 4586 patients with aneurysmal subarachnoid hemorrhage (SAH) treated in seven participating hospitals. A scoping literature review was undertaken to investigate prognostic factors. Six patients among the profiled patients (35.3%) died, all with poor SAH grades (World Federation of Neurological Societies Grade IV and V). Rebleeding after admission was observed in three patients (17.6%) with poor SAH grades. Aggressive treatment and conservative management were initiated in seven and ten patients, respectively. Patients with good SAH grades had significantly higher favorable treatment outcomes than those with poor grades (83.3% vs. 9.1%, P = 0.005). Moreover, based on a scoping review of 158 cases with ruptured BADA, including the patients from our series, approximately 90% of patients with good SAH grades had favorable outcomes. A good SAH grade and no rebleeding after admission were favorable prognostic factors (P < 0.0001 and P = 0.002, respectively). The rebleeding rates were 20.2%, 13.3%, and 6.3% for dilated, pearl and string, and stenotic lesions, respectively. We concluded that the natural history of isolated ruptured BADAs may be better than that of VADAs. Although definitive treatment, if possible, is undoubtedly important, conservative management with careful radiological follow-up for morphological changes might be a viable option for patients in good clinical condition and with non-dilated lesions.

Quantitative Evaluation of Proliferative Potential Using Flow Cytometry Reveals Intratumoral Heterogeneity and Its Relevance to Tumor Characteristics in Vestibular Schwannomas.

This study sought to explore the existence and clinical significance of intratumoral heterogeneity of proliferative potential in vestibular schwannoma (VS). Rapid intraoperative flow cytometry was utilized with raw samples to measure the proliferative ability of VS. The proliferation index (PI) was defined as the ratio of the number of cells with greater than normal DNA content to the total number of cells. A total of 66 specimens (26 from the intrameatal portion and 40 from the cisternal portion) were obtained from 34 patients with VS. There was a moderate correlation between the PI and MIB-1 labelling index values (R = 0.57, p < 0.0001). In contrast, the patterns of heterogeneity, represented by the proportion of intrameatal PI to cisternal PI, were associated with tumor size (p = 0.03). In addition, preoperative hearing tended to be poor in cases where the intrameatal PI was higher than the cisternal PI (p = 0.06). Our data demonstrated the presence of intratumoral heterogeneity of proliferative potential in VS and its relationship with tumor characteristics. The results of this study may advocate the resection of the intrameatal portion of large VSs treated with planned subtotal resection, especially in cases of poor preoperative hearing function.

Best Motor Response Predicts Favorable Outcome for "True" WFNS Grade V Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The universal application of ultra-early surgery for World Federation of Neurological Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage (aSAH) patients may lead to the increased implementation of unnecessary treatment. Therefore, this study aimed to refine the patient selection process for timely definitive treatment. METHODS: From January 2011 to March 2020, a total of 517 aSAH patients were treated at our institution. Among these, 177 aSAH patients with WFNS grade V on admission were identified from our database. Patients with improved grades in response to the initial supportive treatment, with clinical or radiological signs of herniation, and with irreversible signs of brain damage such as bilaterally dilated pupils and global ischemia on follow-up CT scan were excluded. The outcome of definitive treatment for 54 patients without herniation who remained with WFNS grade V after the initial supportive treatment were analyzed to seek any factor for a favorable outcome (modified Rankin scale 0-2). RESULTS: Among 54 patients, 19 (35.2%) had a favorable outcome after a definitive treatment. Multivariate logistic regression analysis showed that the best motor response (BMR) 4 on Glasgow Coma Scale was significantly associated with favorable outcomes (odds ratio, 3.76; 95% confidence interval, 1.09-13.0, p = 0.03). The positive predictive value of BMR 4 was 48.3%. CONCLUSIONS: Albeit being simple, BMR 4 may facilitate the prompt aggressive treatment for patients with WFNS grade V including those with "true" grade V who do not have any clinical and radiological signs of herniation.

Risk factors of meralgia paresthetica after prone position surgery: Possible influence of operating position, laminectomy level, and preoperative thoracic kyphosis.

Obesity and a prolonged surgical duration are reported risk factors for meralgia paresthetica (MP) after prone position surgery; however, this fails to explain why MP seldom occurs after prone position craniotomy. We reviewed the incidence of MP after spinal surgery and craniotomy in the prone position and investigated whether unidentified factors are involved in the mechanism of postoperative MP. Between January 2014 and March 2020, we performed 556 prone position surgeries. We excluded patients aged ≤16 years and those who were comatose or who required redo-surgery, and reviewed 446 eligible patients (124 who underwent craniotomies and 322 who underwent posterior spinal surgeries). Postoperative MP occurred in 46 (10.3%) patients with a higher incidence after spinal surgery than after craniotomy (13.7% vs. 1.6%, p < 0.001). Among the 322 patients who received posterior spinal surgery, thoracic and lumbar laminectomies were associated with a higher incidence of MP than cervical laminectomy. Analyses limited to those patients who received thoracic and lumbar laminectomies revealed that the preoperative thoracic kyphosis (TK) angle was significantly greater in patients with MP than in those without MP (average TK angle, 38.9° vs. 23.1°; p < 0.001), and that the preoperative lumbar lordosis angle did not significantly differ between the two groups. Apart from the known predisposing factors, we found that thoracolumbar-sacral laminectomy in patients with a greater TK angle is also a risk factor for MP after prone position surgery.

A Prospective Randomized Study on the Preventive Effect of Japanese Herbal Kampo Medicine Goreisan for Recurrence of Chronic Subdural Hematoma.

Although the recurrence of chronic subdural hematoma (CSDH) after surgical treatment significantly affects the patients' quality of life, the recurrence rate has not improved in decades. Goreisan, a Japanese herbal Kampo medicine, promotes the hydragogue effect and has been empirically used in the treatment of CSDH in Japan. We conducted a prospective randomized study to investigate whether Goreisan treatment decreases the recurrence rate of CSDH. Between March 2013 and December 2018, a total of 224 patients who underwent initial burr hole surgery for CSDH were randomly assigned to receive Goreisan for 3 months (Group G) or no medication (Group N). The primary endpoint was symptomatic recurrence within 3 months postoperatively, and the secondary endpoint was complications, including the adverse effects of Goreisan. Of 224 randomized patients, 208 were included in the final analysis (104 in Group G and 104 in Group N). The overall recurrence rate was 9.1% (19/208). The recurrence rate of Group G was lower than that of Group N (5.8% vs 12.5%, P = 0.09), but the difference was not statistically significant. However, a significant preventive effect of Goreisan was found in 145 patients with high-risk computed tomography (CT) features, namely, homogeneous and separated types (5.6% vs 17.6%, P = 0.04). Although the present study did not prove the beneficial effect of Goreisan treatment, it suggested the importance of selecting patients with an increased risk of recurrence. A subset of patients whose hematoma showed homogeneous and separated patterns on CT image might benefit from Goreisan treatment.

Carotid endarterectomy restores decreased vision due to chronic ocular ischemia.

BACKGROUND: The therapeutic effect of carotid endarterectomy (CEA) on visual disturbance caused by chronic ocular ischemia due to carotid artery stenosis has not been validated. This prospective observational study aims to investigate whether CEA is associated with an increase in ocular blood flow (OBF) and postoperative visual improvement. METHODS: In total, 41 patients with carotid artery stenosis treated by CEA between March 2015 and September 2018 were enrolled in this study. OBF was evaluated by laser speckle flowgraphy, which can measure the mean blur ratio (MBR) which is well correlated to the absolute retinal blood flow. Visual acuity was assessed before and after CEA by subjective improvement and objective visual assessment using CSV-1000, an instrument used to test contrast sensitivity. RESULTS: OBF increased after CEA on the operated side (mean MBR 33.5 vs 38.2, p < 0.001) but not on the non-operated side (mean MBR 37.8 vs 37.5, p = 0.50). After CEA, 23 patients (56.1%) reported subjective visual improvement on the operated side. The mean CSV-1000 score among the patients with increased OBF after CEA (5.44 vs 5.88, p = 0.04) but not among those without increased OBF (5.48 vs 5.95, p = 0.09). The mean CSV-1000 scores increased significantly after CEA in 18 patients with decreased vision and decreased OBF (4.51 vs 5.37, p < 0.001), but not in the 23 patients without those (6.19 vs 6.31, p = 0.6). CONCLUSION: CEA may successfully reverse visual dysfunction caused by chronic ocular ischemia due to carotid artery stenosis by increasing OBF.

3-dimensional computer graphics model elucidating involvement of intraparenchymal venous malformation in trigeminal nucleus of brachium pontis with intractable trigeminal neuralgia.

Venous malformation (VM) in the posterior cranial fossa occasionally cause trigeminal neuralgia (TN), which were treated with microvascular decompression of its drainer, whereas it was effective only in the limited cases, and its pathological mechanism causing TN is controversial. A 72-year-old man had a 20-year history of typical but severe TN in his left face. Without radiographic evidence of vascular compression on the root entry zone (REZ) of the trigeminal nerve, he underwent stereotactic radiosurgery in previous hospital, resulting in only temporary improvement. On T1-wighted magnetic resonance image with enhancement, the left trigeminal nerve was focally enhanced, which was typical finding after high dose irradiation for TN. Simultaneously, it disclosed small "caput medusa" within the pontine tegmentum, indicated existence of VM in brachium pontis. A 3-dimensional computer graphics model created by fusion of magnetic resonance angiography, diffusion tensor tractography, and fast imaging employing steady-state acquisition elucidated VM was located in the trigeminal nucleus of brachium pontis, which will be very useful for understanding the anatomic correlation of VM and pontine trigeminal nucleus. Since there was no vascular compression at the REZ of the trigeminal nerve, microvascular decompression was not indicated. With minimum dose of gabapentine and carbamazepin, his facial pain completely disappeared and controlled for more than 5 years.

Non-clinical efficacy, safety and stable clinical cell processing of induced pluripotent stem cell-derived anti-glypican-3 chimeric antigen receptor-expressing natural killer/innate lymphoid cells.

The use of allogeneic, pluripotent stem-cell-derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator-initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cell (iPSC)-derived anti-glypican-3 (GPC3) chimeric antigen receptor (CAR)-expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder-free production of CAR-expressing NK/ILC cells from CAR-transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8-3.6 × 106 iPSC within 7 weeks was 1.8-4.0 × 109 . These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN-γ) production against GPC3-expressing tumor cells. When the CAR-NK/ILC cells were injected into a GPC3-positive, ovarian-tumor-bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non-clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR-NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell-based immune cell cancer therapies.

Intraoperative quantification of meningioma cell proliferation potential using rapid flow cytometry reveals intratumoral heterogeneity.

BACKGROUND: Standard sampling methods to evaluate the proliferative ability of meningioma have not been established. METHODS: This prospective study was conducted to evaluate the effectiveness of intraoperative rapid flow cytometry (iFC) using raw samples for the quantitative assessment of proliferative ability in meningioma cells and to investigate intratumoral heterogeneity. Proliferation index (PI) was defined as the ratio of aneuploid cells with an abnormal number of chromosomes to the total cells. RESULTS: From 50 patients, 118 specimens were analyzed. There was a statistically significant correlation between the postoperative MIB-1 labeling index (LI) and PI (R = 0.59, P < 0.0001). A higher PI was correlated with a higher annual growth rate (AGR, cm3 /y) (R = 0.50, P = 0.0002, 26 patients). AGR showed a correlation with the intratumoral distribution of PI. PI was the highest at the center or the peripheral section of the tumor in tumors with high AGR, whereas it was highest at the dural attachment in tumors with low AGR (P = 0.039, n = 20). Pial feeders were more frequently observed when PI was high in the center or in the peripheral section (P = 0.006, n = 37). CONCLUSIONS: Rapid iFC may thus become a substitute for MIB-1 LI. Intratumoral heterogeneity of cellular proliferative potential exists in meningiomas and is related to tumor biological characteristics such as AGR and development of pial feeders. This observation underscores the importance of standardization in the sampling method to accurately estimate the risk of meningioma recurrence.