Boron neutron capture therapy delays the decline in neurological function in a mouse model of metastatic spinal tumors.

Metastatic spinal tumors are increasingly prevalent due to advancements in cancer treatment, leading to prolonged survival rates. This rising prevalence highlights the need for developing more effective therapeutic approaches to address this malignancy. Boron neutron capture therapy (BNCT) offers a promising solution by delivering targeted doses to tumors while minimizing damage to normal tissue. In this study, we evaluated the efficacy and safety of BNCT as a potential therapeutic option for spine metastases in mouse models induced by A549 human lung adenocarcinoma cells. The animal models were randomly allocated into three groups: untreated (n = 10), neutron irradiation only (n = 9), and BNCT (n = 10). Each mouse was administered 4-borono-L-phenylalanine (250 mg/kg) intravenously, followed by measurement of boron concentrations 2.5 h later. Overall survival, neurological function of the hindlimb, and any adverse events were assessed post irradiation. The tumor-to-normal spinal cord and blood boron concentration ratios were 3.6 and 2.9, respectively, with no significant difference observed between the normal and compressed spinal cord tissues. The BNCT group exhibited significantly prolonged survival rates compared with the other groups (vs. untreated, p = 0.0015; vs. neutron-only, p = 0.0104, log-rank test). Furthermore, the BNCT group demonstrated preserved neurological function relative to the other groups (vs. untreated, p = 0.0004; vs. neutron-only, p = 0.0051, multivariate analysis of variance). No adverse events were observed post irradiation. These findings indicate that BNCT holds promise as a novel treatment modality for metastatic spinal tumors.

[Usefulness of Preoperative Simulation: Skull Base Approach].

Preoperative simulation images creates an accurate visualization of a surgical field. The anatomical relationship of the cranial nerves, arteries, brainstem, and related bony protrusions is important in skull base surgery. However, an operator's intention is unclear for a less experienced neurosurgeon. Three-dimensional(3D)fusion images of computed tomography and magnetic resonance imaging created using a workstation aids precise surgical planning and safety management. Since the simulation images allows to perform virtual surgery, a déjà vu effect for the surgeon can be obtained. Additionally, since 3D surgical images can be used for preoperative consideration and postoperative verification, discussion among the team members is effective from the perspective of surgical education for residents and medical students. Significance of preoperative simulation images will increase eventually.

Increasing C-reactive protein levels in a patient with glioblastoma with lymph node metastasis: a case report.

BACKGROUND: Glioblastoma usually recurs locally and extracranial metastases are rare. Most patients with extracranial metastases experience recurrence of the primary intracranial tumor. Lymph node metastases are often detected based on lymphadenopathy or symptoms caused by other metastatic sites. CASE PRESENTATION: Herein, we report a case of glioblastoma with lymph node metastasis in which the patient was asymptomatic but exhibited gradually increasing C-reactive protein levels prior to becoming febrile 9 months after the initial C-reactive protein increase. Diagnosis of lymph node metastasis that was delayed because the patient had a fever of unknown origin, no signs of infection, and the primary intracranial tumor did not recur. Chest computed tomography indicated supraclavicular, mediastinal, and hilar lymphadenopathy, and biopsy identified lymph node metastasis of glioblastoma. This is the fifth reported case of lymph node metastasis without intracranial recurrence. CONCLUSIONS: C-reactive protein levels may be a diagnostic marker for lymph node metastasis in patients with glioblastoma. Further evaluation is needed to elucidate the role of CRP in glioblastoma with lymph node metastasis.

Expression and distribution of hypoxia-inducible factor-1α and vascular endothelial growth factor in comparison between radiation necrosis and tumor tissue in metastatic brain tumor: A case report.

We report the case of a 70-year-old woman with metastatic brain tumors who underwent surgical removal of the tumor and radiation necrosis. The patient had a history of colon cancer and had undergone surgical removal of a left occipital tumor. Histopathological evaluation revealed a metastatic brain tumor. The tumor recurred six months after surgical removal, followed by whole-brain radiotherapy, and the patient underwent stereotactic radiosurgery. Six months later, the perifocal edema had increased, and the patient became symptomatic. The diagnosis was radiation necrosis and corticosteroids were initially effective. However, radiation necrosis became uncontrollable, and the patient underwent removal of necrotic tissue two years after stereotactic radiosurgery. Pathological findings predominantly showed necrotic tissue with some tumor cells. Since the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were expressed around the necrotic tissue, the main cause of the edema was determined as radiation necrosis. Differences in the expression levels and distribution of HIF-1α and VEGF were observed between treatment-naïve and recurrent tumor tissue and radiation necrosis. This difference suggests the possibility of different mechanisms for edema formation due to the tumor itself and radiation necrosis. Although distinguishing radiation necrosis from recurrent tumors using MRI remains challenging, the pathophysiological mechanism of perifocal edema might be crucial for differentiating radiation necrosis from recurrent tumors.

Boron neutron capture therapy using dodecaborated albumin conjugates with maleimide is effective in a rat glioma model.

Introduction Boron neutron capture therapy (BNCT) is a biologically targeted, cell-selective particle irradiation therapy that utilizes the nuclear capture reaction of boron and neutron. Recently, accelerator neutron generators have been used in clinical settings, and expectations for developing new boron compounds are growing. Methods and Results In this study, we focused on serum albumin, a well-known drug delivery system, and developed maleimide-functionalized closo-dodecaborate albumin conjugate (MID-AC) as a boron carrying system for BNCT. Our biodistribution experiment involved F98 glioma-bearing rat brain tumor models systemically administered with MID-AC and demonstrated accumulation and long retention of boron. Our BNCT study with MID-AC observed statistically significant prolongation of the survival rate compared to the control groups, with results comparable to BNCT study with boronophenylalanine (BPA) which is the standard use of in clinical settings. Each median survival time was as follows: untreated control group; 24.5 days, neutron-irradiated control group; 24.5 days, neutron irradiation following 2.5 h after termination of intravenous administration (i.v.) of BPA; 31.5 days, and neutron irradiation following 2.5 or 24 h after termination of i.v. of MID-AC; 33.5 or 33.0 days, respectively. The biological effectiveness factor of MID-AC for F98 rat glioma was estimated based on these survival times and found to be higher to 12. This tendency was confirmed in BNCT 24 h after MID-AC administration. Conclusion MID-AC induces an efficient boron neutron capture reaction because the albumin contained in MID-AC is retained in the tumor and has a considerable potential to become an effective delivery system for BNCT in treating high-grade gliomas.

Boron neutron capture therapy and add-on bevacizumab in patients with recurrent malignant glioma.

BACKGROUND: Although boron neutron capture therapy has shown excellent survival data, previous studies have shown an increase in radiation necrosis against recurrent malignant glioma. Herein, we proposed that bevacizumab may reduce radiation injury from boron neutron capture therapy by re-irradiation. We evaluated the efficacy and safety of a boron neutron capture therapy and add-on bevacizumab combination therapy in patients with recurrent malignant glioma. METHODS: Patients with recurrent malignant glioma were treated with reactor-based boron neutron capture therapy. Treatment with bevacizumab (10 mg/kg) was initiated 1-4 weeks after boron neutron capture therapy and was administered every 2-3 weeks until disease progression. Initially diagnosed glioblastomas were categorized as primary glioblastoma, whereas other forms of malignant glioma were categorized as non-primary glioblastoma. RESULTS: Twenty-five patients (14 with primary glioblastoma and 11 with non-primary glioblastoma) were treated with boron neutron capture therapy and add-on bevacizumab. The 1-year survival rate for primary glioblastoma and non-primary glioblastoma was 63.5% (95% confidence interval: 33.1-83.0) and 81.8% (95% confidence interval: 44.7-95.1), respectively. The median overall survival was 21.4 months (95% confidence interval: 7.0-36.7) and 73.6 months (95% confidence interval: 11.4-77.2) for primary glioblastoma and non-primary glioblastoma, respectively. The median progression-free survival was 8.3 months (95% confidence interval: 4.2-12.1) and 15.6 months (95% confidence interval: 3.1-29.8) for primary glioblastoma and non-primary glioblastoma, respectively. Neither pseudoprogression nor radiation necrosis were identified during bevacizumab treatment. Alopecia occurred in all patients. Six patients experienced adverse events ≥grade 3. CONCLUSIONS: Boron neutron capture therapy and add-on bevacizumab provided a long overall survival and a long progression-free survival in recurrent malignant glioma compared with previous studies on boron neutron capture therapy alone. The add-on bevacizumab may reduce the detrimental effects of boron neutron capture therapy, including pseudoprogression and radiation necrosis. Further studies of the combination therapy with a larger sample size and a randomized controlled design are warranted.

Folate receptor-targeted novel boron compound for boron neutron capture therapy on F98 glioma-bearing rats.

Folic acid (FA) has high affinity for the folate receptor (FR), which is limited expressed in normal human tissues, but over-expressed in several tumor cells, including glioblastoma cells. In the present work, a novel pteroyl-closo-dodecaborate conjugate (PBC) was developed, in which the pteroyl group interacts with FR, and the efficacy of boron neutron capture therapy (BNCT) using PBC was investigated. Thus, in vitro and in vivo studies were performed using F98 rat glioma cells and F98 glioma-bearing rats. For the in vivo study, boronophenylalanine (BPA) was intravenously administered, while PBC was administered by convection-enhanced delivery (CED)-a method for direct local drug infusion into the brain of rats. Furthermore, a combination of PBC administered by CED and BPA administered by intravenous (i.v.) injection was also investigated. In the biodistribution experiment, PBC administration at 6 h after CED termination showed the highest cellular boron concentrations (64.6 ± 29.6 µg B/g). Median survival time (MST) of untreated controls was 23.0 days (range 21-24 days). MST of rats administered PBC (CED) followed by neutron irradiation was 31 days (range 26-36 days), which was similar to that of rats administered i.v. BPA (30 days; range 25-37 days). Moreover, the combination group [PBC (CED) and i.v. BPA] showed the longest MST (38 days; range 28-40 days). It is concluded that a significant MST increase was noted in the survival time of the combination group of PBC (CED) and i.v. BPA compared to that in the single-boron agent groups. These findings suggest that the combination use of PBC (CED) has additional effects.

[The Efficacy of the Emergent Shunt-Clamp System for Secondary Hydrocephalus Associated with Fourth Ventricle Outlet Obstruction Syndrome:A Report of Two Cases].

Endoscopic third ventriculostomy(ETV)is the first-line treatment for fourth ventricle outlet obstruction(FVOO)-associated hydrocephalus. However, because FVOO is difficult to diagnose in the acute stage, ventriculoperitoneal shunt(VPS)is also used. Herein, we report two cases of shunted FVOO resulting in overdrainage or slit ventricle syndrome(SVS)that were treated successfully with the shunt-clamp system. In addition, we discuss the efficacy of the shunt-clamp system for FVOO-associated hydrocephalus. CASE 1:A 79-year-old man complained of severe postural headaches. One year earlier, he underwent VPS for secondary hydrocephalus associated with hemorrhagic cerebellar infarction. CT revealed that the ventricle had become slit-like. Although the shunt valve adjusted the maximum pressure, his complaint and the ventricle shape did not improve. After the on-off valve was inserted in the shunt system and clamped, his symptoms were resolved and the ventricle size was normalized. CASE 2:A 21-year-old man who complained of drowsiness, diplopia, and severe intermittent retroocular pain was admitted to our hospital. One year earlier, he underwent VPS with the shunt-clamp system for a secondary hydrocephalus after surgery for medulloblastoma. CT on admission revealed ventricle dilatation;however, the shape of the ventricle became slit-like 3 days after admission. We made a diagnosis of SVS and planned ETV. Owing to the difficulty in approaching the lateral ventricle, the shunt system was clamped 8 hours before the operation. After confirming ventricle dilatation, ETV was successfully performed. After the operation, the symptoms were resolved, and magnetic resonance imaging confirmed that the ventricle size was normalized.

Continuous Blood Glucose Monitoring May Detect Carotid Occlusion Intolerance during Carotid Artery Stenting.

BACKGROUND: The frequency of the occurrence of adverse events associated with carotid artery stenting (CAS) is usually low, but serious adverse events such as cerebral hyperperfusion syndrome (CHS) may occur. Real-time monitoring is ideal for the early detection of adverse events during the surgical procedure. This study aimed to evaluate continuous blood glucose (BG) monitoring for the detection of adverse events during CAS. METHODS: Forty patients undergoing scheduled CAS were prospectively enrolled. An artificial pancreas was used for continuous BG monitoring (once per minute), using venous blood extracted at a rate of 2 mL/hr during CAS. The primary endpoint was a correlation between BG change and adverse events. RESULTS: CAS was discontinued in 1 patient, and BG was not measured in 5 patients (12.5%) because of the inability to extract blood. Among 34 evaluable patients, no patient developed CHS, but 3 patients (9%) experienced carotid occlusion intolerance. During CAS, BG was significantly higher in patients with carotid occlusion intolerance (median: 5 mg/dL) than in patients without carotid occlusion intolerance (median: 0 mg/dL) (P = 0.0221). A cutoff BG value ≥4 mg/dL during CAS showed 50% sensitivity and 100% specificity for the detection of carotid occlusion intolerance. There was no significant correlation between BG change and other adverse events. CONCLUSIONS: BG elevation may help detect carotid occlusion intolerance although it is still unknown whether BG monitoring can detect CHS. Further studies should validate that a cutoff BG elevation value of ≥4 mg/dL during CAS indicates carotid occlusion intolerance.

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma.

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1R132H, were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1R132H-positive and 1 control IDH1R132H-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients' tumors were IDH1R132H-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1R132H-negative GBM variants, an IDH1R132H-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1R132H-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.

Transthyretin Concentrations in Acute Stroke Patients Predict Convalescent Rehabilitation.

OBJECTIVE: For stroke patients, intensive nutritional management is an important and effective component of inpatient rehabilitation. Accordingly, acute care hospitals must detect and prevent malnutrition at an early stage. Blood transthyretin levels are widely used as a nutritional monitoring index in critically ill patients. Here, we had analyzed the relationship between the transthyretin levels during the acute phase and Functional Independence Measure in stroke patients undergoing convalescent rehabilitation. METHODS: We investigated 117 patients who were admitted to our hospital with acute ischemic or hemorrhagic stroke from February 2013 to October 2015 and subsequently transferred to convalescent hospitals after receiving acute treatment. Transthyretin concentrations were evaluated at 3 time points as follows: at admission, and 5 and 10 days after admission. After categorizing patients into 3 groups according to the minimum transthyretin level, we analyzed the association between transthyretin and Functional Independence Measure. RESULTS: In our patients, transthyretin levels decreased during the first 5 days after admission and recovered slightly during the subsequent 5 days. Notably, Functional Independence Measure efficiency was significantly associated with the decrease in transthyretin levels during the 5 days after admission. Patients with lower transthyretin levels had poorer Functional Independence Measure outcomes and tended not to be discharged to their own homes. DISCUSSION: A minimal transthyretin concentration (<10 mg/dL) is predictive of a poor outcome in stroke patients undergoing convalescent rehabilitation. In particular, an early decrease in transthyretin levels suggests restricted rehabilitation efficiency. Accordingly, transthyretin levels should be monitored in acute stroke patients to indicate mid-term rehabilitation prospects.

Successful recanalization for internal carotid artery occlusion with persistent primitive trigeminal artery manifesting only as ischemia of the posterior circulation.

BACKGROUND: Internal carotid artery (ICA) occlusion mainly manifests as ischemia of the anterior circulation. There are very few reports of ICA occlusion manifesting as only ischemia of the posterior circulation related to a fetal type posterior communicating artery or other arteries. CASE PRESENTATION: The authors experienced a case of ICA occlusion with persistent primitive trigeminal artery (PPTA) manifesting only as ischemia of the posterior circulation. In this case, the initial NIHSS score was high (35/42 points). Additionally, cross flow of the anterior communicating artery, ICA occlusion and basilar artery (BA) occlusion were represented on the initial head MRA. Therefore, our first impression was a presumptive diagnosis of BA occlusion. Prior head MRI/MRA performed for screening purposes, had incidentally demonstrated a right PPTA. Based on this understanding, we were able to determine the exact angioarchitectural mechanism of the ICA occlusion. Because of the presence of the PPTA, successful recanalization was accomplished expeditiously. CONCLUSION: Although the presence of PPTA is rare and ICA occlusion patients with PPTA is even more unusual, if ICA occlusion and BA occlusion appear simultaneously on MRA, the presence of PPTA should be considered.

Spinopelvic alignment and sagittal balance of asymptomatic adults with 6 lumbar vertebrae.

PURPOSE: The purpose of this study was to evaluate total spinal alignment in asymptomatic individuals with 6 lumbar vertebrae (LVs). METHODS: The present study comprised 167 Japanese adult volunteers with no spinal symptoms. In all individuals, standing radiographs of the entire spine were taken to measure the pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), C7 sagittal vertical axis (C7SVA), T1 slope, thoracic kyphosis (TK), C2-C7 sagittal vertical axis (C2-C7 SVA), and C2-C7 lordosis (C2-C7L). We used these parameters to compare individuals with 5LVs to those with 6LVs. We performed additional investigations regarding the relationship between L6 morphological characteristics and parameters. RESULTS: Out of 167 individuals, 6LVs were present in 29 (17.4 %). PI was significantly greater in individuals with 6LVs (64.8° ± 9.54°) than in those with 5LVs (51.3° ± 10.1°, P < 0.0001). Individuals with 6LVs also had significantly larger SS, PT, and C7SVA values (SS: P = 0.0125, PT: P < 0.0001, C7SVA: P = 0.0172). LL tended to be nonsignificantly greater in individuals with 6LVs (P = 0.1588). All of these changes were more noticeable in individuals in whom the L6 vertebra was classified as type II and III according to the Castellvi classification. Meanwhile, the presence of 6LVs has little influence on the alignment of the superior lumber vertebrae. CONCLUSIONS: Asymptomatic individuals with 6LVs presented with different spinopelvic alignment compared to those with 5LVs. We need to establish a treatment strategy for symptomatic 6LV cases.

Postoperative change in sagittal balance after Kyphoplasty for the treatment of osteoporotic vertebral compression fracture.

PURPOSE: The influence of vertebral cement augmentation on spinal sagittal balance is unknown. The present study aimed to analyze the changes in total spinal alignment after Kyphoplasty in VCF patients. METHODS: The study involved 21 VCF patients who underwent Kyphoplasty. In all patients, lateral radiographs of the entire spine were taken preoperatively and 1 month after surgery, to measure the pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), sagittal vertical axis (SVA), and spinosacral angle (SSA). These parameters were compared between VCF patients and 30 healthy volunteers. In VCF patients, the parameters were compared before and after Kyphoplasty. RESULTS: In VCF patients, preoperative SVA was 7.00 ± 3.9 cm, showing a significant shift to anterior sagittal balance as compared to the healthy group (1.45 ± 2.7 cm) (P < 0.0001). Preoperative SS was smaller and PT was larger in VCF group than in the healthy group (P < 0.05). After Kyphoplasty, SVA decreased to 5.02 ± 2.91 (P = 0.0007) and LL and SSA increased (LL P = 0.028; SSA P = 0.0031). Postoperative decrease of SVA was correlated with the kyphotic change of treated vertebra (r = 0.792, P < 0.01). VAS score decreased from 7.98 ± 1.8 before Kyphoplasty to 2.38 ± 2.3 postoperatively (P < 0.0001). CONCLUSIONS: Total spinal alignment is shifted to anterior sagittal balance in VCF patients. Kyphoplasty plays a role not only in reducing pain associated with fractures but also in improving sagittal imbalance in the treatment of painful vertebral compression fracture.

Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

Comparison of outcomes with/without preoperative embolization for meningiomas with diluted N-butyl-2-cyanoacrylate.

BACKGROUND: Preoperative embolization for meningiomas is controversial regarding its effectiveness in reducing intraoperative blood loss and operative time. In contrast, some reports have documented improved surgical outcomes in large meningiomas. In this study, we retrospectively compared the outcomes of craniotomy for meningiomas with/without preoperative embolization with diluted N-butyl-2-cyanoacrylate (NBCA) primarily in a single institution. METHODS: Data (World Health Organization grade, Simpson grade, maximum tumor diameter, intraoperative bleeding, operative time, history of hypertension, and time from embolization to craniotomy) of patients with initial intracranial meningiomas were compared with or without preoperative embolization from January 2015 to April 2022. RESULTS: The embolization group consisted of 56 patients and the nonembolization group included 76 patients. Diluted NBCA (13% concentration for all patients) was used in 51 of 56 patients (91.1%) who underwent transarterial embolization. Permanent neurological complications occurred in 2 (3.6%) patients. Intraoperative bleeding was significantly lower in the embolization group for a maximum tumor diameter ≥40 mm (155 vs. 305 ml, respectively, p < 0.01). In the nonembolization group, for a maximum tumor diameter ≥30 mm, patients with hypertension had more intraoperative bleeding than non-hypertensive ones. CONCLUSIONS: Despite its limitations, the present results showed that, under certain conditions, preoperative embolization for intracranial meningiomas caused less intraoperative bleeding. The safety of treatment was comparable with that reported in the Japan Registry of NeuroEndovascular Therapy 3 (JR-NET3) with a complication rate of 3.7% for preoperative embolization of meningiomas, despite the treatment focused on the liquid embolization material.

Lot-to-lot variation in the microbiota during the brewing process of kimoto-type Japanese rice wine.

Kimoto-type Japanese rice wine (sake) has a wide variety of flavors, as the predominant microbes, including lactic acid bacteria (LAB) and nitrate-reducing bacteria, that spontaneously proliferate in the fermentation starter vary depending on the brewery. In this study, we traced the microbiota in four lots of starters manufactured in a newly established brewery and evaluated the lot-to-lot variation and characteristics of the microbiota in the brewery. The results of a 16S ribosomal RNA amplicon analysis showed that the starters brewed in the second brewing year had a more diverse microbiota than those in the first brewing year. Among the LAB predominated at the middle production stage, lactococci, including Leuconostoc spp., were detected in all the lots, while lactobacilli predominated for the first time in the second year. These results suggest that repeated brewing increased microbial diversity and altered the microbial transition pattern in the kimoto-style fermentation starters. Phylogenetic analyses for the LAB isolates from each starter identified Leuconostoc suionicum, Leuconostoc citreum, and Leuconostoc mesenteroides as predominant lactococci as well as a unique lactobacillus in place of Latilactobacillus sakei. We also found that a rice koji-derived Staphylococcus gallinarum with nitrate-reducing activity was generally predominant during the early production stage, suggesting that there was a case in which staphylococci played a role in nitrite production in the starters. These findings are expected to contribute to the understanding of the diversity of microbiota in kimoto-type sake brewing and enable control of the microbiota for consistent sake quality.

Surgical Outcomes and Medical Costs Associated with Spinal Cord Tumors: Comparison of Extramedullary and Intramedullary Tumors.

OBJECTIVE: This study aimed to clarify the differences in the perioperative data of patients with extramedullary and intramedullary tumors and estimate the impact of surgery on medical costs. METHODS: This single-center retrospective study included consecutive patients who underwent spinal tumor resection between September 2020 and December 2022. The perioperative medical information and medical costs for individual patients were obtained from their medical records. RESULTS: Thirty-two patients with extramedullary spinal cord tumors and 18 with intramedullary spinal cord tumors were included in the study. The 2 groups had no difference in surgery-related or major systemic complications. However, the operation time and the length of hospital stay were significantly longer and activities of daily living at discharge tended to worsen in the intramedullary tumor group compared to those in the extramedullary tumor group. As a result, the discharge outcome was significantly different between the 2 groups. The total medical costs for intramedullary tumors were approximately 1.43 times higher than those for extramedullary tumors. Further, a better functional outcome at discharge can save medical costs, regardless of extramedullary or intramedullary tumors. CONCLUSIONS: Surgery for intramedullary tumors can be performed with similar perioperative risks as for extramedullary tumors. However, intramedullary tumors are associated with concerns, such as prolonged hospitalization and worsening of activities of daily living at discharge, which ultimately result in higher medical costs.

Postoperative Airway Management after Anterior Cervical Spine Surgery: Retrospective Neurosurgical Multicenter Study.

Airway complications that occur after anterior cervical spine surgery pose a life-threatening risk, which encompasses complications including prolonged intubation, unplanned reintubation, and/or necessity of tracheostomy. The present study aimed to identify the surgical risks associated with postoperative airway complications in neurosurgical training institutes. A retrospective, multicenter, observational review of data from 365 patients, who underwent anterior cervical spine surgery between 2018 and 2022, at three such institutes was carried out. Postoperative airway complication was defined as either the need for prolonged intubation on the day of surgery or the need for unplanned reintubation. The perioperative medical information was obtained from their medical records. The average age of the cohort was over 60 years, with males comprising approximately 70%. Almost all surgeries predominantly involved anterior cervical discectomy and fusion or anterior cervical corpectomy and fusion, with most surgeries occurring at the level of C5/6. In total, 363 of 365 patients (99.5%) were extubated immediately after surgery, and the remaining two patients were kept under intubation because of the risk of airway complications. Of the 363 patients who underwent extubation immediately after surgery, two (0.55%) required reintubation because of postoperative airway complications. Patients who experienced airway complications were notably older and exhibited a significantly lower body mass index. The results of this study suggested that older and frailer individuals are at an elevated risk for postoperative airway complications, with immediate postoperative extubation generally being safe but requiring careful judgment in specific cases.