Publications by authors named "Myung Ji Kim"

14 Publications

  • Page 1 of 1

Predictive Factors of Surgical Site Infection Following Cranioplasty: A Study Including 3D Printed Implants.

Front Neurol 2021 2;12:745575. Epub 2021 Nov 2.

Department of Neurosurgery, Korea University Medical Center, Korea University College of Medicine, Ansan Hospital, Ansan-si, South Korea.

In patients who have undergone decompressive craniectomy (DC), subsequent cranioplasty is required to reconstruct cranial defects. Surgical site infection (SSI) following cranioplasty is a devastating complication that can lead to cranioplasty failure. The aim of the present study, therefore, was to identify predictive factors for SSI following cranioplasty by reviewing procedures performed over a 10-year period. A retrospective analysis was performed for all patients who underwent cranioplasty following DC between 2010 and 2020 at a single institution. The patients were divided into two groups, non-SSI and SSI, in order to identify clinical variables that are significantly correlated with SSI following cranioplasty. Cox proportional hazards regression analyses were then performed to identify predictive factors associated with SSI following cranioplasty. A total of 172 patients who underwent cranioplasty, including 48 who received customized three-dimensional (3D) printed implants, were enrolled in the present study. SSI occurred in 17 patients (9.9%). Statistically significant differences were detected between the non-SSI and SSI groups with respect to presence of fluid collections on CT scans before and after cranioplasty. Presence of fluid collections on computed tomography (CT) scan before ( = 0.0114) and after cranioplasty ( < 0.0000) showed significant association with event-free survival rate for SSI. In a univariate analysis, significant predictors for SSI were fluid collection before ( = 0.0172) and after ( < 0.0001) cranioplasty. In a multivariate analysis, only the presence of fluid collection after cranioplasty was significantly associated with the occurrence of SSI ( < 0.0001). The present study investigated predictive factors that may help identify patients at risk of SSI following cranioplasty and provide guidelines associated with the procedure. Based on the results of the present study, only the presence of fluid collection on CT scan after cranioplasty was significantly associated with the occurrence of SSI. Further investigation with long-term follow-up and large-scale prospective studies are needed to confirm our conclusions.
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http://dx.doi.org/10.3389/fneur.2021.745575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592932PMC
November 2021

Aberrant Transcript Usage Is Associated with Homologous Recombination Deficiency and Predicts Therapeutic Response.

Cancer Res 2022 Jan 28;82(1):142-154. Epub 2021 Oct 28.

Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea.

BRCA1/2 mutations account for only a small fraction of homologous recombination (HR) deficiency (HRD) cases. Recently developed genomic HRD (gHRD) tests suffer confounding factors that cause low precision in predicting samples that will respond to PARP inhibitors and DNA damaging agents. Here we present molecular and clinical evidence of transcriptional HRD (tHRD) that is based on aberrant transcript usage (aTU) of minor isoforms. Specifically, increased TU of nonfunctional isoforms of DNA repair genes was prevalent in breast and ovarian cancer with gHRD. Functional assays validated the association of aTU with impaired HR activity. Machine learning-based tHRD detection by the transcript usage (TU) pattern of key genes was superior to directly screening for gHRD or BRCA1/2 mutations in accurately predicting responses of cell lines and patients with cancer to PARP inhibitors and genotoxic drugs. This approach demonstrated the capability of tHRD status to reflect functional HR status, including in a cohort of olaparib-treated ovarian cancer with acquired platinum resistance. Diagnostic tests based on tHRD are expected to broaden the clinical utility of PARP inhibitors. SIGNIFICANCE: A novel but widespread transcriptional mechanism by which homologous recombination deficiency arises independently of BRCA1/2 mutations can be utilized as a companion diagnostic for PARP inhibitors.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-2023DOI Listing
January 2022

siRNA Nanoparticle Targeting PD-L1 Activates Tumor Immunity and Abrogates Pancreatic Cancer Growth in Humanized Preclinical Model.

Cells 2021 10 13;10(10). Epub 2021 Oct 13.

Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea.

Pancreatic cancer is characterized by late detection, frequent drug resistance, and a highly metastatic nature, leading to poor prognosis. Antibody-based immunotherapy showed limited success for pancreatic cancer, partly owing to the low delivery rate of the drug into the tumor. Herein, we describe a poly(lactic-co-glycolic acid;PLGA)-based siRNA nanoparticle targeting PD-L1 ([email protected]). The [email protected] exhibited efficient knockdown of PD-L1 in cancer cells, without affecting the cell viability up to 6 mg/mL. Further, 99.2% of PDAC cells uptake the nanoparticle and successfully blocked the IFN-gamma-mediated PD-L1 induction. Consistently, the [email protected] sensitized cancer cells to antigen-specific immune cells, as exemplified by Ovalbumin-targeting T cells. To evaluate its efficacy in vivo, we adopted a pancreatic PDX model in humanized mice, generated by grafting CD34 hematopoeitic stem cells onto NSG mice. The [email protected] significantly suppressed pancreatic tumor growth in this model with upregulated IFN-gamma positive CD8 T cells, leading to more apoptotic tumor cells. Multiplex immunofluorescence analysis exhibited comparable immune cell compositions in control and [email protected] tumors. However, we found higher Granzyme B expression in the [email protected] tumors, suggesting higher activity of NK or cytotoxic T cells. Based on these results, we propose the application of [email protected] as an immunotherapeutic agent for pancreatic cancer.
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http://dx.doi.org/10.3390/cells10102734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534711PMC
October 2021

Metagenomic analysis of gut microbiome reveals a dynamic change in Alistipes onderdonkii in the preclinical model of pancreatic cancer, suppressing its proliferation.

Appl Microbiol Biotechnol 2021 Nov 14;105(21-22):8343-8358. Epub 2021 Oct 14.

Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea.

Pancreatic cancer is a lethal cancer with aggressive and invasive characteristics. By the time it is diagnosed, patients already have tumors extended to other organs and show extremely low survival rates. The gut microbiome is known to be associated with many diseases and its imbalance affects the pathogenesis of pancreatic cancer. In this study, we established an orthotopic, patient-derived xenograft model to identify how the gut microbiome is linked to pancreatic ductal adenocarcinoma (PDAC). Using the 16S rDNA metagenomic sequencing, we revealed that the levels of Alistipes onderdonkii and Roseburia hominis decreased in the gut microbiome of the PDAC model. To explore the crosstalk between the two bacteria and PDAC cells, we collected the supernatant of the bacteria or cancer cell culture medium and treated it in a cross manner. While the cancer cell medium did not affect bacterial growth, we observed that the A. onderdonkii medium suppressed the growth of the pancreatic primary cancer cells. Using the bromodeoxyuridine/7-amino-actinomycin D (BrdU/7-AAD) staining assay, we confirmed that the A. onderdonkii medium inhibited the proliferation of the pancreatic primary cancer cells. Furthermore, RNA-seq analysis revealed that the A. onderdonkii medium induced unique transcriptomic alterations in the PDAC cells, compared to the normal pancreatic cells. Altogether, our data suggest that the reduction in the A. onderdonkii in the gut microbiome provides a proliferation advantage to the pancreatic cancer cells. KEY POINTS: • Metagenome analysis of pancreatic cancer model reveals A. onderdonkii downregulation. • A. onderdonkii culture supernatant suppressed the proliferation of pancreatic cancer cells. • RNA seq data reveals typical gene expression changes induced by A. onderdonkii.
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http://dx.doi.org/10.1007/s00253-021-11617-zDOI Listing
November 2021

Stimulation-Induced Side Effects of Deep Brain Stimulation in the Ventralis Intermedius and Posterior Subthalamic Area for Essential Tremor.

Front Neurol 2021 9;12:678592. Epub 2021 Jun 9.

Department of Neurosurgery, Brain Research Institute, Yonsei University College of Medicine, Seoul, South Korea.

Deep brain stimulation (DBS) targeting the ventralis intermedius (VIM) nucleus of the thalamus and the posterior subthalamic area (PSA) has been shown to be an effective treatment for essential tremor (ET). The aim of this study was to compare the stimulation-induced side effects of DBS targeting the VIM and PSA using a single electrode. Patients with medication-refractory ET who underwent DBS electrode implantation between July 2011 and October 2020 using a surgical technique that simultaneously targets the VIM and PSA with a single electrode were enrolled in this study. A total of 93 patients with ET who had 115 implanted DBS electrodes (71 unilateral and 22 bilateral) were enrolled. The Clinical Rating Scale for Tremor (CRST) subscores improved from 20.0 preoperatively to 4.3 (78.5% reduction) at 6 months, 6.3 (68.5% reduction) at 1 year, and 6.5 (67.5% reduction) at 2 years postoperation. The best clinical effect was achieved in the PSA at significantly lower stimulation amplitudes. Gait disturbance and clumsiness in the leg was found in 13 patients (14.0%) upon stimulation of the PSA and in significantly few patients upon stimulation of the VIM ( = 0.0002). Fourteen patients (15.1%) experienced dysarthria when the VIM was stimulated; this number was significantly more than that with PSA stimulation ( = 0.0233). Transient paresthesia occurred in 13 patients (14.0%) after PSA stimulation and in six patients (6.5%) after VIM stimulation. Gait disturbance and dysarthria were significantly more prevalent in patients undergoing bilateral DBS than in those undergoing unilateral DBS ( = 0.00112 and = 0.0011, respectively). Paresthesia resolved either after reducing the amplitude or switching to bipolar stimulation. However, to control gait disturbance and dysarthria, some loss of optimal tremor control was necessary at that particular electrode contact. In the present study, the most common stimulation-induced side effect associated with VIM DBS was dysarthria, while that associated with PSA DBS was gait disturbance. Significantly, more side effects were associated with bilateral DBS than with unilateral DBS. Therefore, changing active DBS contacts to simultaneous targeting of the VIM and PSA may be especially helpful for ameliorating stimulation-induced side effects.
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http://dx.doi.org/10.3389/fneur.2021.678592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220085PMC
June 2021

Predictive Factors of Radiation-Induced Changes Following Single-Session Gamma Knife Radiosurgery for Arteriovenous Malformations.

J Clin Med 2021 May 19;10(10). Epub 2021 May 19.

Department of Neurosurgery, Brain Research Institute, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodamungu, Seoul 03722, Korea.

We evaluated for possible predictors of radiation-induced changes (RICs) after gamma knife radiosurgery (GKRS) for arteriovenous malformations (AVMs). We identified the nidal component within AVMs to analyze the correlation between the volume of brain parenchyma within the 50% isodose line (IDL) and RICs. We retrospectively reviewed patients with AVMs who underwent a single-session of GKRS at our institution between 2007 and 2017 with at least a 2-year minimum follow-up. Follow-up magnetic resonance images were evaluated for newly developed T2 signal changes and the proportions of nidus and intervening parenchyma were quantified. A total of 180 AVM patients (98 males and 82 females) with a median age of 34 years were included in the present study. The overall obliteration rate was 67.8%. The median target volume was 3.65 cc. The median nidus and parenchyma volumes within the 50% IDL were 1.54 cc and 2.41 cc, respectively. RICs were identified in 79 of the 180 patients (43.9%). AVMs associated with previous hemorrhages showed a significant inverse correlation with RICs. In a multivariate analysis, RICs were associated with a higher proportion of brain parenchyma within the 50% IDL (hazard ratio (HR) 169.033; < 0.001) and inversely correlated with the proportion of nidus volume within the 50% IDL (HR 0.006; < 0.001). Our study identified that a greater proportion of brain tissue between the nidus within the 50% IDL was significantly correlated with RICs. Nidus angioarchitectural complexity and the absence of a prior hemorrhage were also associated with RICs. The identification of possible predictors of RICs could facilitate radiosurgical planning and treatment decisions as well as the planning of appropriate follow-up after GKRS; this could minimize the risk of RICs, which would be particularly beneficial for the treatment of incidentally found asymptomatic AVMs.
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http://dx.doi.org/10.3390/jcm10102186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158695PMC
May 2021

Technical and operative factors affecting magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: experience from 250 treatments.

J Neurosurg 2021 May 21:1-9. Epub 2021 May 21.

1Department of Neurosurgery, Brain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; and.

Objective: Magnetic resonance imaging-guided focused ultrasound (MRgFUS) provides real-time monitoring of patients to assess tremor control and document any adverse effects. MRgFUS of the ventral intermediate nucleus (VIM) of the thalamus has become an effective treatment option for medically intractable essential tremor (ET). The aim of this study was to analyze the correlations of clinical and technical parameters with 12-month outcomes after unilateral MRgFUS thalamotomy for ET to help guide future clinical treatments.

Methods: From October 2013 to January 2019, data on unilateral MRgFUS thalamotomy from the original pivotal study and continued-access studies from three different geographic regions were collected. Authors of the present study retrospectively reviewed those data and evaluated the efficacy of the procedure on the basis of improvement in the Clinical Rating Scale for Tremor (CRST) subscore at 1 year posttreatment. Safety was based on the rates of moderate and severe thalamotomy-related adverse events. Treatment outcomes in relation to various patient- and sonication-related parameters were analyzed in a large cohort of patients with ET.

Results: In total, 250 patients were included in the present analysis. Improvement was sustained throughout the 12-month follow-up period, and 184 (73.6%) of 250 patients had minimal or no disability due to tremor (CRST subscore < 10) at the 12-month follow-up. Younger age and higher focal temperature (Tmax) correlated with tremor improvement in the multivariate analysis (OR 0.948, p = 0.013; OR 1.188, p = 0.025; respectively). However, no single statistically significant factor correlated with Tmax in the multivariate analysis. The cutoff value of Tmax in predicting a CRST subscore < 10 was 55.8°C. Skull density ratio (SDR) was positively correlated with heating efficiency (β = 0.005, p < 0.001), but no significant relationship with tremor improvement was observed. In the low-temperature group, 1-3 repetitions to the right target with 52°C ≤ Tmax ≤ 54°C was sufficient to generate sustained tremor suppression within the investigated follow-up period. The high-temperature group had a higher rate of balance disturbances than the low-temperature group (p = 0.04).

Conclusions: The authors analyzed the data of 250 patients with the aim of improving practices for patient screening and determining treatment endpoints. These results may improve the safety, efficacy, and efficiency of MRgFUS thalamotomy for ET.
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http://dx.doi.org/10.3171/2020.11.JNS202580DOI Listing
May 2021

The Establishment of a Fast and Safe Orthotopic Colon Cancer Model Using a Tissue Adhesive Technique.

Cancer Res Treat 2021 Jul 15;53(3):733-743. Epub 2020 Dec 15.

Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method.

Materials And Methods: RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 μL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis.

Results: We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels.

Conclusion: We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.
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http://dx.doi.org/10.4143/crt.2020.494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291175PMC
July 2021

Functional Neural Changes after Low-Frequency Bilateral Globus Pallidus Internus Deep Brain Stimulation for Post-Hypoxic Cortical Myoclonus: Voxel-Based Subtraction Analysis of Serial Positron Emission.

Brain Sci 2020 Oct 13;10(10). Epub 2020 Oct 13.

Department of Neurosurgery, Brain Research Institute, College of Medicine, Yonsei University, Seoul 03722, Korea.

Post-hypoxic myoclonus (PHM) and Lance-Adams syndrome (LAS) are rare conditions following cardiopulmonary resuscitation. The aim of this study was to identify functional activity in the cerebral cortex after a hypoxic event and to investigate alterations that could be modulated by deep brain stimulation (DBS). A voxel-based subtraction analysis of serial positron emission tomography (PET) scans was performed in a 34-year-old woman with chronic medically refractory PHM that improved with bilateral globus pallidus internus (Gpi) DBS implanted three years after the hypoxic event. The patient required low-frequency stimulation to show myoclonus improvement. Using voxel-based statistical parametric mapping, we identified a decrease in glucose metabolism in the prefrontal lobe including the dorsolateral, orbito-, and inferior prefrontal cortex, which was suspected to be the origin of the myoclonus from postoperative PET/magnetic resonance imaging (MRI) after DBS. Based on the present study results, voxel-based subtraction of PET appears to be a useful approach for monitoring patients with PHM treated with DBS. Further investigation and continuous follow-up on the use of PET analysis and DBS treatment for patients with PHM are necessary to help understanding the pathophysiology of PHM, or LAS.
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http://dx.doi.org/10.3390/brainsci10100730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650619PMC
October 2020

One-Year Outcome of Multiple Blood-Brain Barrier Disruptions With Temozolomide for the Treatment of Glioblastoma.

Front Oncol 2020 10;10:1663. Epub 2020 Sep 10.

Department of Neurosurgery, Brain Research Institute, Yonsei University College of Medicine, Seoul, South Korea.

To overcome the blood-brain barrier (BBB) which interferes with the effect of chemotherapeutic agents, we performed multiple disruptions of BBB (BBBD) with magnetic resonance-guided focused ultrasound on patients with glioblastoma (GBM) during standard adjuvant temozolomide (TMZ) chemotherapy [clinical trial registration no.NCT03712293 (clinicaltrials.gov)]. We report a 1-year follow-up result of BBBD with TMZ for GBM. From September 2018 to January 2019, six patients were enrolled (four men and two women, median age: 53 years, range: 50-67 years). Of the six patients, five underwent a total of six cycles of BBBD during standard TMZ adjuvant therapy. One patient underwent three cycles of BBBD but continued with TMZ chemotherapy. The 1-year follow-up results of these six patients were reviewed. The mean follow-up duration was 15.17 ± 1.72 months. Two patients showed a recurrence of tumor at 11 and 16 months, respectively. One underwent surgery, and the other patient was restarted with TMZ chemotherapy due to the tumor location with a highly possibility of surgical complications. The survival rate up to 1 year was 100%, and the other four patients are on observation without recurrence. None of the six patients had immediate or delayed BBBD-related complications. Multiple BBBDs can be regarded as a safe procedure without long-term complications, and it seems to have some survival benefits. However, since TMZ partially crosses the BBB, a further extended study with large numbers would be needed to evaluate the benefits of BBBD resulting in an increase of TMZ concentration. This study opened a new therapeutic strategy for GBM by combining BBBD with a larger molecular agent.
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http://dx.doi.org/10.3389/fonc.2020.01663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511634PMC
September 2020

Gamma Knife Radiosurgery Followed by Flow-Reductive Embolization for Ruptured Arteriovenous Malformation.

J Clin Med 2020 May 2;9(5). Epub 2020 May 2.

Departmenf of Neurosurgery, Yonsei University College of Medicine, Seoul 03722, Korea.

Background: Aggressive treatment to achieve complete obliteration of brain arteriovenous malformation (AVM) is necessary in patients with a recent history of hemorrhage. The major drawback of Gamma knife radiosurgery (GKRS) alone for AVM is risk of bleeding during the latent period until the AVM occludes. At our center, patients who present with ruptured AVMs are frequently offered GKRS followed by embolization. The goal of this study was to compare outcomes of embolization for patients who have previously undergone GKRS for ruptured AVMs.

Methods: A database including 150 GKRS for ruptured AVMs between November 2008 and October 2017 was reviewed. The embolized group was selected by including AVMs with post-GKRS embolization. The non-embolized group was defined as AVMs treated by GKRS alone. Outcomes including obliteration rate, incidence of repeat hemorrhage, and delayed cyst formation were compared between two groups. The predictive factors related to AVM obliteration and complications were analyzed.

Results: The study consisted of 81 patients in the non-embolized group and 17 patients in the embolized group. Statistically significant differences were detected between the two groups with respect to age, Pollock-Flickinger score, Spetzler-Martin (SM) grade, eloquence of adjacent brain, and presence of aneurysms. The embolized group included more AVMs with larger median nidus volume. The predictive factors for the obliteration of ruptured AVMs were nidus volume, SM grade, Virginia Radiosurgery AVM Scale (VRAS), and Pollock-Flickinger score and for the subsequent hemorrhage were marginal dose, nidus volume, SM grade, VRAS, and Pollock-Flickinger score. The obliteration rates and complication rates after GKRS between groups were not significantly different. However, this study demonstrated statistically significant difference in the cumulative incidence of obliteration in AVMs with SM grade III and IV ( = 0.037).

Conclusion: Although the current study demonstrated similar results in patients who underwent GKRS with and without embolization, the embolized group included more AVMs with larger nidus volume, higher SM grade, Pollock-Flickinger score, and aneurysm, which have a lower chance of obliteration and a higher probability of repeat hemorrhage. GKRS followed by embolization appears to be a beneficial approach for the treatment of ruptured AVMs that are at risk for obliteration failure and repeat hemorrhage during the latency period after single-session GKRS alone. Further studies involving a larger number of cases and continuous follow-up are necessary to confirm our conclusions.
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http://dx.doi.org/10.3390/jcm9051318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290943PMC
May 2020

Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy.

J Neurosurg 2020 Jan 3:1-9. Epub 2020 Jan 3.

1Brain Research Institute, Department of Neurosurgery and.

Objective: Glioblastoma (GBM) remains fatal due to the blood-brain barrier (BBB), which interferes with the delivery of chemotherapeutic agents. The purpose of this study was to evaluate the safety and feasibility of repeated disruption of the BBB (BBBD) with MR-guided focused ultrasound (MRgFUS) in patients with GBM during standard adjuvant temozolomide (TMZ) chemotherapy.

Methods: This study was a prospective, single-center, single-arm study. BBBD with MRgFUS was performed adjacent to the tumor resection margin on the 1st or 2nd day of the adjuvant TMZ chemotherapy at the same targets for 6 cycles. T2*-weighted/gradient echo (GRE) MRI was performed immediately after every sonication trial, and comprehensive MRI was performed at the completion of all sonication sessions. Radiological, laboratory, and clinical evaluations were performed 2 days before each planned BBBD.

Results: From September 2018, 6 patients underwent 145 BBBD trials at various locations in the brain. The authors observed gadolinium-enhancing spots at the site of BBBD on T1-weighted MRI in 131 trials (90.3%) and 93 trials (64.1%) showed similar spots on T2*-weighted/GRE MRI. When the 2 sequences were combined, BBBD was observed in 134 targets (92.4%). The spots disappeared on follow-up MRI. There were no imaging changes related to BBBD and no clinical adverse effects during the 6 cycles.

Conclusions: This study is the first in which repetitive MRgFUS was performed at the same targets with a standard chemotherapy protocol for malignant brain tumor. BBBD with MRgFUS was performed accurately, repeatedly, and safely. Although a longer follow-up period is needed, this study allows for the possibility of other therapeutic agents that previously could not be used due to the BBB.Clinical trial registration no.: NCT03712293 (clinicaltrials.gov).
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http://dx.doi.org/10.3171/2019.10.JNS192206DOI Listing
January 2020

Auranofin Inhibits RANKL-Induced Osteoclastogenesis by Suppressing Inhibitors of B Kinase and Inflammasome-Mediated Interleukin-1 Secretion.

Oxid Med Cell Longev 2019 22;2019:3503912. Epub 2019 Apr 22.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.

Osteoporosis is a degenerative metabolic disease caused by an imbalance between osteogenesis and osteoclastogenesis. Increased levels of proinflammatory cytokines combined with decreased estrogen levels, which are commonly seen in postmenopausal women, can lead to overactivation of osteoclasts. Therefore, targeting osteoclast maturation may represent a novel strategy for both treating and preventing osteoporosis. Auranofin is a gold-based compound first approved in 1985 for the treatment of rheumatic diseases. Here, we examined whether auranofin suppresses osteoclast differentiation and . Auranofin was shown to suppress receptor activator of NF-B ligand- (RANKL-) induced osteoclastogenesis in mouse bone marrow macrophages (BMMs) and Raw264.7 macrophages. Cotreatment of macrophages with auranofin blocked the RANKL-induced inhibitors of B kinase (IKK) phosphorylation, resulting in inhibition of nuclear translocation of p65. The pan-caspase inhibitor nivocasan potently reduced not only inflammasome-mediated interleukin-1 (IL-1) secretion but also osteoclast differentiation in BMMs. Auranofin suppressed inflammasome activation, as evidenced by decreased production of cleaved IL-1 in both bone marrow-derived macrophages (BMDMs) and J774.A1 cells. Loss of both bone mass in ovariectomized mice was significantly recovered by oral administration of auranofin. Taken together, these data strongly support the use of auranofin for the prevention of osteoclast-related osteoporosis.
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http://dx.doi.org/10.1155/2019/3503912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561666PMC
February 2020

Evaluation of risk factors of vaginal cuff dehiscence after hysterectomy.

Obstet Gynecol Sci 2014 Mar 15;57(2):136-43. Epub 2014 Mar 15.

Department of Obstetrics and Gynecology, Korea University Anam Hospital, Seoul, Korea.

Objective: The purpose of this study was to evaluate risk factors of vaginal cuff dehiscence or evisceration according to the type of operation.

Methods: Medical records of 604 women who underwent hysterectomies at Korea University Anam Hospital between June 2007 and June 2011 were reviewed. They were allocated to six groups. The six types of hysterectomies included robotic hysterectomy (n = 7), robotic radical hysterectomy and node dissection (RRHND, n = 9), total laparoscopic hysterectomy (TLH, n = 274), laparoscopy assisted vaginal hysterectomy (LAVH, n = 238), laparoscopic radical hysterectomy and node dissection (n = 11), and abdominal radical hysterectomy (ARH, n = 63). The characteristics and outcomes of each groups were compared.

Results: There was no difference in the characteristics of patients between 6 groups. In total of 604 hysterectomies, 3 evisceration (0.49%) and 21 dehiscences (3.47%) occurred. Evisceration were found in RRHND (1/9, 11.1%), TLH (1/276, 0.36%), and ARH (1/63, 1.56%). Dehiscences occurred in TLH (15/274, 5.42%), LAVH (4/238, 1.68%), and ARH (2/63, 3.17%). In 169 cases of TLH with intra-corporeal continuous suture, 1 evisceration and 4 dehiscences occurred, whereas 11 dehiscences occurred in 105 TLH cases with vaginal continuous locking suture (2.96% vs. 10.47%, P = 0.02).

Conclusion: The incidence of vaginal cuff dehiscenceand eviscerationwas significantly higher in TLH than LAVH. The intra-corporeal cuff suture was superior to the vaginal suture to prevent the vaginal cuff complications in TLH.
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http://dx.doi.org/10.5468/ogs.2014.57.2.136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965697PMC
March 2014
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