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Abstract The extent of surgical resection is an important prognostic factor in the treatment of patients with glioblastoma. Optical coherence tomography (OCT) imaging is one of the adjunctive methods available to achieve the maximal surgical resection. In this study, the tumor margins were visualized with the OCT image obtained from a murine glioma model. A commercialized human glioblastoma cell line (U-87) was employed to develop the orthotopic murine glioma model. A swept-source OCT (SS-OCT) system of 1300 nm was used for three-dimensional imaging. Based on the OCT intensity signal, which was obtained via accumulation of each A-scan data, an en-face optical attenuation coefficient (OAC) map was drawn. Due to the limited working distance of the focused beam, OAC values decrease with depth, and using the OAC difference in the superficial area was chosen to outline the tumor boundary, presenting a challenge in analyzing the tumor margin along the depth direction. To overcome this and enable three-dimensional tumor margin detection, we converted the en-face OAC map into an en-face difference map with x- and y-directions and computed the normalized absolute difference (NAD) at each depth to construct a volumetric NAD map, which was compared with the corresponding H&E-stained image. The proposed method successfully revealed the tumor margin along the peripheral boundaries as well as the margin depth. We believe this method can serve as a useful adjunct in glioma surgery, with further studies necessary for real-world practical applications.

Abstract Background Although meningioma is the most common primary brain tumor, treatments rely on surgery and radiotherapy, and recurrent meningiomas have no standard therapeutic options due to a lack of clinically relevant research models. Current meningioma cell lines or organoids cannot reflect biological features of patient tumors since they undergo transformation along culture and consist of only tumor cells without microenvironment. We aim to establish patient-derived meningioma organoids (MNOs) preserving diverse cell types representative of the tumor microenvironment. Methods The biological features of MNOs were evaluated using WST, LDH, and collagen-based 3D invasion assays. Cellular identities in MNOs were confirmed by immunohistochemistry (IHC). Genetic alteration profiles of MNOs and their corresponding parental tumors were obtained by whole-exome sequencing. Results MNOs were established from four patients with meningioma (two grade 1 and two grade 2) at a 100% succession rate. Exclusion of enzymatic dissociation-reaggregation steps endowed MNOs with original histology and tumor microenvironment. In addition, we used a liquid media culture system instead of embedding samples into Matrigel, resulting in an easy-to-handle, cost-efficient, and time-saving system. MNOs maintained their functionality and morphology after long-term culture (> 9 wk) and repeated cryopreserving-recovery cycles. The similarities between MNOs and their corresponding parental tumors were confirmed by both IHC and whole-exome sequencing. As a representative application, we utilized MNOs in drug screening, and mifepristone, an antagonist of progesterone receptor, showed prominent antitumor efficacy with respect to viability, invasiveness, and protein expression. Conclusion Taken together, our MNO model overcame limitations of previous meningioma models and showed superior resemblance to parental tumors. Thus, our model could facilitate translational research identifying and selecting drugs for meningioma in the era of precision medicine.

Abstract Background Chronic subdural hematoma (CSDH) is a common clinical situation in neurosurgical practice, but the optimal treatment option is controversial. This study aimed to evaluate the effect of cholesterol-lowering medications on and how they affected the prognoses of CSDH patients. Methods In this multi-institutional observational study performed in Korea, data from recently treated CSDH patients were gathered from 5 hospitals. A total of 462 patients were collected from March 2010 to June 2021. Patient clinical characteristics, history of underlying diseases and their treatments, radiologic features, and surgical outcomes were analyzed. Results Seventy-five patients experienced recurrences, and 62 had reoperations after the initial burr hole surgery. Among these, 15 patients with recurrences and 12 with reoperations were taking cholesterol-lowering medications. However, the use of medications did not significantly affect recurrence or reoperation rates (P = 0.350, P = 0.336, respectively). When analyzed by type of medication, no clinically relevant differences in total cholesterol (TC), triglyceride (TG), or low-density lipoprotein cholesterol (LDL-C) levels were identified. The combination of a statin drug and ezetimibe significantly elevated high-density lipoprotein cholesterol (HDL-C) levels (P = 0.004). TC, LDL-C, and TG levels did not significantly affect patient prognoses. However, HDL-C levels and recurrence (odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.94–0.99; p = 0.010) were negatively correlated. An HDL-C level of 42.50 mg/dL was identified as the threshold for recurrence and reoperation. Conclusions In this study, using cholesterol-lowering medications did not significantly impact the prognosis of patients who underwent surgical management for a chronic subdural hematoma. However, the findings showed that the higher the HDL-C level, the lower the probability of recurrence and reoperation.

Background The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM). Methods A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary’s Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results. Results Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively. Conclusions We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor’s molecular pathology.

Abstract Purpose Addressing lymphopenia in cancer patients has been suggested as a novel immunotherapeutic strategy. As interleukin‐7 (IL‐7) is necessary for proliferation of lymphocytes and to increase total lymphocyte count (TLC), IL‐7 therapy has been attempted in various cancers. Here, we describe the clinical results of treatment of recurrent glioblastoma (GBM) with a long‐acting engineered version of recombinant human IL‐7 (rhIL‐7‐hyFc). Methods This prospective case series based on compassionate use was approved by the Ministry of Food and Drug Safety in South Korea. Primary outcomes were safety profile and TLC. Secondary outcomes were overall survival (OS) and progression‐free survival (PFS). Results Among the 18 patients enrolled, 10 received rhIL‐7‐hyFc with temozolomide, 5 received rhIL‐7‐hyFc with bevacizumab, 1 received rhIL‐7‐hyFc with PCV chemotherapy, and 2 received rhIL‐7‐hyFc alone. Mean TLC of the enrolled patients after the first rhIL‐7‐hyFc treatment increased significantly from 1131 cells/mm3 (330–2989) at baseline to 4356 cells/mm3 (661–22,661). Higher TLCs were maintained while rhIL‐7‐hyFc was repeatedly administered. Median OS and PFS were 378 days (107–864 days) and 231 days (55–726 days), respectively. Conclusion Our study reports that IL‐7 immunotherapy can restore and maintain TLC during treatment with various salvage chemotherapies in recurrent GBM patients without serious toxicity.

MoO3 thick film was manufactured by using a thermal spray process (Atmospheric Plasma Spray, or APS) and its microstructure, phase composition and properties of the coating layer were investigated. Initial powder feedstock was composed of an orthorhombic α-MoO3 phase, and the average powder particle size was 6.7 μm. As a result of the APS coating process, a MoO3 coating layer with a thickness of about 90 μm was obtained. Phase transformation occurred during the process, and the coating layer consisted of not only α-MoO3 but also β-MoO3, MoO2. Phase transformation could be due to the rapid cooling that occurred during the process. The properties of the coating layer were evaluated using a nano indentation test. Hardness and reduced modulus were obtained as 0.47 GPa and 1.4 GPa, respectively. Based on the above results, the possibility of manufacturing a MoO3 thick coating layer using thermal spray is presented.

IntroductionThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been fueled by new variants emerging from circulating strains. Here, we report results from a genomic surveillance study of SARS-CoV-2 on Jeju Island, Republic of Korea, from February 2021 to September 2022.MethodsA total of 3,585 SARS-CoV-2 positive samples were analyzed by Sanger sequencing of the gene encoding the spike protein before performing phylogenetic analyses.ResultsWe found that the Alpha variant (B.1.1.7) was dominant in May 2021 before being replaced by the Delta variant (B.1.617.2) in July 2021, which was dominant until December 2021 before being replaced by the Omicron variant. Mutations in the spike protein, including N440K and G446S, have been proposed to contribute to immune evasion, accelerating the spread of Omicron variants.DiscussionOur results from Juju Island, Republic of Korea, are consistent with and contribute to global surveillance efforts crucial for identifying new variants of concern of SARS-CoV-2 and for monitoring the transmission dynamics and characteristics of known strains.

ObjectivesWe compared the lengths of a nasoseptal flap (NSF) and skull base according to race, age, and sex.MethodsWe performed paranasal sinus computed tomography in 19,961 adult patients between 2003 and 2022. The race of the patients was East Asian (n = 71), Caucasian (n = 71), or Middle Eastern (n = 71). The expected lengths of the NSF and anterior skull base defect were measured and analyzed according to race, age, and sex.ResultsCompared with Caucasians and Middle Easterners, East Asians had a shorter NSF length (p < 0.001) and lower ratio of the expected NSF length to the expected defect length (p < 0.001). There was no difference in the values among age groups. The expected NSF length was longer, and the ratio of the expected NSF length to the expected defect length was higher, in males than females (p < 0.001 for both).ConclusionsEast Asians and females had a shorter NSF length and lower ratio of expected NSF to surgical defect lengths after anterior skull base reconstruction compared with the other races and with males, respectively. Anatomical differences should be considered when long NSF lengths are required, such as for anterior skull base reconstruction.

The number of coronavirus disease (COVID-19)-positive cases has increased in Jeju Island, Republic of Korea. Identification and monitoring of new mutations in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are extremely important to fighting the global pandemic. We report a breakout of the B.1.620 lineage, harboring the E484 mutation in the virus spike protein in a general hospital on Jeju Island. A cluster of cases was detected between August 4 and September 10, 2021, involving 20 patients positive for COVID-19 of 286 individuals exposed to the virus, comprising hospital patients, staff, and caregivers. We analyzed the epidemiological characteristics and spike proteins mutation sites using Sanger sequencing and phylogenetic analysis on these 20 patients. By analyzing genomic variance, it was confirmed that 12 of the confirmed patients harbored the SARS-CoV-2 B.1.620 lineage. The breakthrough rate of infection was 2% in fully vaccinated individuals among these patients. Next clade analysis revealed that these SARS-CoV-2 genomes belong to clade 20A. This is the first reported case of SARS-CoV-2 sub-lineage B.1.620, although the B.1.617.2 lineage has prevailed in August and September in Jeju, which has a geographical advantage of being an island. We reaffirm that monitoring the spread of SARS-CoV-2 variants with characteristic features is indispensable for controlling COVID-19 outbreaks.

Endoscopic sinus and skull base surgeries are minimally invasive surgical techniques that reduce postoperative symptoms and complications and enhance patients’ quality of life. However, to ensure excellent surgical outcomes after such interventions, intimate familiarity with important landmarks and high-level endoscope manipulation skills are essential. Cadaver training is one possible option, but cadavers are expensive, scarce, and nonreusable and cadaver work requires specialized equipment and staff. In addition, it is difficult to mimic specific diseases using cadavers. Virtual reality simulators can create a computerized environment in which the patient’s anatomy is reproduced and interaction with endoscopic handling and realistic haptic feedback is possible. Moreover, they can be used to present scenarios that improve trainees’ skills and confidence. Therefore, virtual simulator training can be implemented at all levels of surgical education. This review introduces the current literature on virtual reality training for endoscopic sinus and skull base surgeons, and discusses the direction of future developments.

Introduction: The impact of obesity on survival outcomes in patients with glioblastoma (GBM) has not been well reported and the results for patients are currently unclear. We investigated the effect of obesity on survival outcomes in patients with newly diagnosed GBM. Methods: Using electronic medical records, all GBM patients that visited the Seoul St. Mary’s Hospital between 2008 and 2018 were reviewed. A total of 177 patients met our eligibility criteria. The cut-off point for BMI was 23.0 kg/m 2 based on previous studies which focused on Asian populations. Results: A total of 177 patients met our eligibility criteria. The overall median BMI of patients was 24.5 kg/m 2 (range 15.82-39.26). About 62 patients who had a BMI less than the cut-off value were assigned to the “lower BMI” group, while 115 patients who had a BMI greater than the cut-off value were assigned to the “higher BMI” group. In Kaplan-Meier survival analysis, the median OS of the higher BMI group was longer than that of the lower BMI group (21.3 months vs 15.3 months, P = .002). In multivariate Cox regression analysis for OS, lower BMI was associated with inferior OS (HR 1.48 CI 1.06-2.08, P = .002). Conclusion: Our findings suggest that elevated BMI may be associated with better survival in patients with newly diagnosed GBM. Additional larger prospective studies could help validate our findings to confirm the effect of body composition and survival outcomes in GBM patients.

ObjectivesWe describe the strategy used to repair intraoperative leaks of various grades and define factors for preventing postoperative cerebrospinal fluid leakage (CSF) after surgery via the endoscopic endonasal transsphenoidal approach (EETA).Study designRetrospective chart review at a tertiary referral center.MethodsPatients who underwent surgery via EETA from January 2009 to May 2020 were retrospectively reviewed. Intraoperative CSF leakage was graded 0-3 in terms of the dural defect size; various repairs were used depending on the grade.ResultsA total of 777 patients underwent 869 operations via EETA; 609 (70.1%) experienced no intraoperative CSF leakage (grade 0) but 260 (29.9%) did. Leakage was of grade 1 in 135 cases (15.5%), grade 2 in 83 (9.6%), and grade 3 in 42 (4.8%). In 260 patients with intraoperative CSF leakage, a buttress was wedged into the sellar defect site in 178 cases (68.5%) and a pedicled flap was placed in 105 cases (40.4%). Autologous fat (108 cases, 41.5%) and a synthetic dural substitute (91 cases, 35%) were used to fill the dead space of the sellar resection cavity. Postoperative CSF leakage developed in 21 patients: 6 of grade 1, 7 of grade 2, and 8 of grade 3. Buttress placement significantly decreased postoperative leakage in grade 1 patients (p = 0.041). In patients of perioperative leakage grades 2 and 3, postoperative CSF leakage was significantly reduced only when both fat and a buttress were applied (p = 0.042 and p = 0.043, respectively).ConclusionA buttress prevented postoperative CSF leakage in grade 1 patients; both fat and buttress were required by patients with intraoperative leakage of grades 2 and 3.

Purpose Immune responses for cancer cells can be altered according to genetic variation of human leukocyte antigen (HLA). Association of HLA polymorphism with risk of various cancer types is well known. However, the association between HLA and glioblastoma (GBM) remains uncertain. We sought to evaluate the association of HLA polymorphism with risk of GBM development in Koreans. Materials and methods A case-control study was performed to identify the odds ratios (OR) of HLA class I and II genes for GBM. The control group consisted of 142 healthy Korean volunteers, and the GBM group was 80 patients with newly diagnosed GBM at our institution. HLA class I (-A, -B, and–C) and class II (-DR, -DQ, and–DP) genotyping was performed by high-resolution polymerase chain reaction (PCR)-sequence-based typing (PCR-SBT) methods. Results There were significantly decreased frequencies of HLA-A*26:02 (OR 0.22 CI 0.05–0.98), HLA-C*08:01 (OR 0.29 CI 0.10–0.87), and HLA-DRB1*08:03 (OR 0.32 CI 0.11–0.98), while there was significantly increased frequency of HLA-C*04:01 (OR 2.29 CI 1.05–4.97). In analysis of haplotypes, the frequency of DRB1*14:05-DQB1*05:03 was significantly decreased (OR 0.22 CI 0.05–0.98). Conclusion This study suggests that genetic variations of HLA may affect GBM development in Koreans. Further investigations with larger sample sizes are needed to delineate any potential role of the HLA polymorphisms in the pathogenesis of GBM development.

ObjectivesThe objective of this study was to investigate the relationship between the level of Electronic Medical Record (EMR) system adoption and healthcare information technology (IT) infrastructure.MethodsBoth survey and various healthcare administrative datasets in Korea were used. The survey was conducted during the period from June 13 to September 25, 2017. The chief information officers of hospitals were respondents. Among them, 257 general hospitals and 273 small hospitals were analyzed. A logistic regression analysis was conducted using the SAS program.ResultsThe odds of having full EMR systems in general hospitals statistically significantly increased as the number of IT department staff members increased (odds ratio [OR] = 1.058, confidence interval [CI], 1.003–1.115; p = 0.038). The odds of having full EMR systems was significantly higher for small hospitals that had an IT department than those of small hospitals with no IT department (OR = 1.325; CI, 1.150–1.525; p < 0.001). Full EMR system adoption had a positive relationship with IT infrastructure in both general hospitals and small hospitals, which was statistically significant in small hospitals. The odds of having full EMR systems for small hospitals increased as IT infrastructure increased after controlling the covariates (OR = 1.527; CI, 1.317–4.135; p = 0.004).ConclusionsThis study verified that full EMR adoption was closely associated with IT infrastructure, such as organizational structure, human resources, and various IT subsystems. This finding suggests that political support related to these areas is indeed necessary for the fast dispersion of EMR systems into the healthcare industry.

A 15 year old male who had been involved in a motor vehicle accident underwent a craniotomy for an acute EDH and a subsequent splenectomy for the splenic rupture, which was complicated by ischemia and a series of severe infection. Splenectomy was performed for concern of therapy refractory thrombocytopenia. We suggest that a thorough consideration on possible and potential complications along with a detailed description of his clinical courses and a review of the literature. Keywords: Combined surgery, Complications of splenectomy, Thrombosis, TBI induced ischemia

The purpose of our study was to compare two acquired muscle atrophies and the use of myostatin inhibition for their treatment. Myostatin naturally inhibits skeletal muscle growth by binding to ActRIIB, a receptor on the cell surface of myofibers. Because blocking myostatin in an adult wild-type mouse induces profound muscle hypertrophy, we applied a soluble ActRIIB receptor to models of disuse (limb immobilization) and denervation (sciatic nerve resection) atrophy. We found that treatment of immobilized mice with ActRIIB prevented the loss of muscle mass observed in placebo-treated mice. Our results suggest that this protection from disuse atrophy is regulated by serum and glucocorticoid-induced kinase (SGK) rather than by Akt. Denervation atrophy, however, was not protected by ActRIIB treatment, yet resulted in an upregulation of the pro-growth factors Akt, SGK and components of the mTOR pathway. We then treated the denervated mice with the mTOR inhibitor rapamycin and found that, despite a reduction in mTOR activation, there is no alteration of the atrophy phenotype. Additionally, rapamycin prevented the denervation-induced upregulation of the mTORC2 substrates Akt and SGK. Thus, our studies show that denervation atrophy is not only independent from Akt, SGK and mTOR activation but also has a different underlying pathophysiological mechanism than disuse atrophy.

To describe the clinical features of invagination of the sphenoid sinus mucosa (ISM) and compare them with other similar cases using a visual analog scale (VAS) to assess the various nasal symptoms and to discuss its clinical significance and means of prevention.Retrospective chart review at a tertiary referral center.Between 2010 and 2015, 8 patients who had undergone EETSA surgery displayed postoperative ISM. The comparison group consisted of 147 patients who underwent the same surgical procedures and were diagnosed with the same diseases. Pre- or postoperative paranasal sinus computed tomography (PNS CT) and VAS were performed and subsequently analyzed.The clinical features of ISM of the sphenoid sinus showed sellar floor invagination and regenerated inverted ingrowing sphenoid mucosa on endoscopic imaging. PNS CT also showed a bony defect and invaginated air densities at the sellar turcica. Pre- and postoperative VAS scores revealed that the ISM group had much less of an improvement in headaches after surgery than that of the comparison group (p = 0.049).ISM may occur because of a change in pressure, sphenoid mucosal status, or arachnoid membrane status. Moreover, ISM is related to improvements in headaches. Therefore, EETSA patients should avoid activities that cause rapid pressure changes during the healing process. In addition, sellar reconstruction that is resistant to physical pressure changes should be mandated despite the absence of an intraoperative CSF leak.

Fragile X syndrome is a developmental disorder that affects sensory systems. A null mutation of the Fragile X Mental Retardation protein 1 (Fmr1) gene in mice has varied effects on developmental plasticity in different sensory systems, including normal barrel cortical plasticity, altered ocular dominance plasticity and grossly impaired auditory frequency map plasticity. The mutation also has different effects on long-term synaptic plasticity in somatosensory and visual cortical neurons, providing insights on how it may differentially affect the sensory systems. Here we present evidence that long-term potentiation (LTP) is impaired in the developing auditory cortex of the Fmr1 knockout (KO) mice. This impairment of synaptic plasticity is consistent with impaired frequency map plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role of LTP in sensory map plasticity during early sensory development.

Benefits of exercise on nerve regeneration and functional recovery have been reported in both central and peripheral nervous system disease models. However, underlying molecular mechanisms of enhanced regeneration and improved functional outcomes are less understood. We used a peripheral nerve regeneration model that has a good correlation between functional outcomes and number of motor axons that regenerate to evaluate the impact of treadmill exercise. In this model, the median nerve was transected and repaired while the ulnar nerve was transected and prevented from regeneration. Daily treadmill exercise resulted in faster recovery of the forelimb grip function as evaluated by grip power and inverted holding test. Daily exercise also resulted in better regeneration as evaluated by recovery of compound motor action potentials, higher number of axons in the median nerve and larger myofiber size in target muscles. Furthermore, these observations correlated with higher levels of neurotrophic factors, glial derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), in serum, nerve and muscle suggesting that increase in muscle derived neurotrophic factors may be responsible for improved regeneration.

The rheological behaviour of dense suspensions of ideally conductive particles in the presence of both electric field and shear flow is studied using large-scale numerical simulations. Under the action of an electric field, these particles are known to undergo dipolophoresis (DIP), which is the combination of two nonlinear electrokinetic phenomena: induced-charge electrophoresis (ICEP) and dielectrophoresis (DEP). For ideally conductive particles, ICEP is predominant over DEP, resulting in transient pairing dynamics. The shear viscosity and first and second normal stress differences N1 and N2 of such suspensions are examined over a range of volume fractions 15% ≤ φ ≤ 50% as a function of Mason number Mn, which measures the relative importance of viscous shear stress over electrokinetic-driven stress. For Mn < 1 or low shear rates, the DIP is shown to dominate the dynamics, resulting in a relatively low-viscosity state. The positive N1 and negative N2 are observed at φ < 30 %, which is similar to Brownian suspensions, while their signs are reversed at φ ≥ 30 %. For Mn ≥ 1, the shear thickening starts to arise at φ ≥ 30 %, and an almost five-fold increase in viscosity occurs at φ = 50 %. Both N1 and N2 are negative for Mn » 1 at all volume fractions considered. We illuminate the transition in rheological behaviours from DIP to shear dominance around Mn = 1 in connection to suspension microstructure and dynamics. Lastly, our findings reveal the potential use of nonlinear electrokinetics as a means of active rheology control for such suspensions. [ABSTRACT FROM AUTHOR]