Background: Cancer cell line-derived feeder cells enhance natural killer (NK) cell expansion; however, concerns regarding viable residual feeder cells in the final product limit their use. Evidence supporting the safety of NK-sensitive K562-based feeders, even when irradiated, is scarce. We optimized an NK cell expansion protocol using genetically engineered K562-mbIL-18/-21 (GE-K562) feeder cells and clinical-grade media and confirmed the absence of residual feeder cells. Methods: NK cell expansion efficiency was compared between feeder-free and feederbased systems using CTS NK-Xpander Medium. To achieve optimal NK expansion, various peripheral blood mononuclear cell (PBMC)-to-feeder ratios and re-stimulation frequencies were tested over 21 days. Flow cytometry and BCR::ABL1 quantitative reverse transcription PCR (RT-qPCR) were used to confirm the absence of feeder cells in the final NK cell product. Results: Feeder-based systems showed superior NK cell fold expansion compared with that of feeder-free systems. Among feeder-based conditions, NK cells expanded 5,224-fold at a 2:1 PBMC-to-feeder ratio after 3 weeks, relative to 1,450-fold at a 6:1 ratio (P < 0.05).Re-stimulation on days 7 and 14 further increased expansion up to 261,457-fold. Irradiated feeder cells showed no proliferation and were eliminated within 3–6 days. On day 21, flow cytometry and BCR::ABL1 RT-qPCR results confirmed the absence of residual feeder cells. Conclusions Our optimized NK cell expansion protocol using irradiated GE-K562 feeder cells and clinical-grade media offers a safe and scalable approach to generating large numbers of NK cells, supporting its potential use in clinical immunotherapy applications.

Objective: Cognitive impairment is common in patients with Parkinson’s disease (PD), and few pharmacological options are available for treating this condition. We evaluated the effects of a digital cognitive training program (SUPERBRAIN), which was previously shown to be effective in populations at risk of Alzheimer’s disease, on cognitive function in individuals with PD. Methods: Twenty-three individuals with PD and mild cognitive impairment (PD-MCI) from four clinics were randomized to the intervention (n=16) or control (n=7) groups. The intervention group completed a 12-week, home-based, tablet-based cognitive training program (25–30 min/day, 7 days/week). Cognitive outcomes were assessed using the Seoul Neuropsychological Screening Battery pre- and post-intervention. Results: The adherence rate was 79.36%. The intervention group showed significant improvements in the Seoul Verbal Learning Test (SVLT) delayed recall and the Controlled Oral Word Association Test, while no changes were observed in the control group. Analysis of covariance confirmed greater SVLT improvement in the intervention group (F statistic=7.15, p=0.015, partial η2=0.28). Conclusion SUPERBRAIN is feasible and can improve cognitive function in individuals with PD-MCI.

The survival rate of children admitted in the neonatal intensive care unit (NICU) after birth is on the increase; hence, proper evaluation and care of their neurodevelopment has become an important issue. Neurodevelopmental assessments of individual domains regarding motor, language, cognition, and sensory perception are crucial in planning prompt interventions for neonates requiring immediate support and rehabilitation treatment. These assessments are essential for identifying areas of weakness and designing targeted interventions to improve future functional outcomes and the quality of lives for both the infants and their families. However, initial stratification of risk to select those who are in danger of neurodevelopmental disorders is also important in terms of cost-effectiveness. Efficient and robust functional evaluations to recognize early signs of developmental disorders will help NICU graduates receive interventions and enhance functional capabilities if needed. Several age-dependent, domain-specific neurodevelopmental assessment tools are available; therefore, this review summarizes the characteristics of these tools and aims to develop multidimensional, standardized, and regular follow-up plans for NICU graduates in Korea.

Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. Methods: A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. Results: Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. Conclusion: Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.

Radiation-induced cavernous hemangiomas (RICHs) have been increasingly reported as a late complication after conventional radiotherapy. RICH after stereotactic radiosurgery (SRS) is extremely rare and the few cases have been reported to demonstrate their properties. A 72-year-old female patient presented with progressive neurologic deficits. She underwent tumor surgery for meningioma 13 years ago and two times of SRS for treating a residual tumor. Newly-developed mass was 4.3 cm-sized heterogeneously enhancing mass with severe cerebral edema. She underwent surgical resection and the histologic examinations revealed organized hematoma. Finally, it was diagnosed as a RICH following SRS based on radiological and histological findings and a history of multiple radiosurgeries. Clinical, radiological, and histological features of a RICH following SRS were discussed in this report.

Background: We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines. Methods: This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe. Results: Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy. Conclusion According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.

BACKGROUND: The use of mouse bone marrow mesenchymal stem cells (mBMSCs) represents a promising strategy for performing preclinical studies in the field of cell-based regenerative medicine; however, mBMSCs obtained via conventional isolation methods have two drawbacks, i.e., (i) they are heterogeneous due to frequent macrophage contamination, and (ii) they require long-term culturing for expansion. METHODS: In the present study, we report a novel strategy to generate highly pure mBMSCs using liposomal clodronate.This approach is based on the properties of the two cell populations, i.e., BMSCs (to adhere to the plasticware in culture dishes) and macrophages (to phagocytose liposomes). RESULTS: Liposomal clodronate added during the first passage of whole bone marrow culture was selectively engulfed by macrophages in the heterogeneous cell population, resulting in their effective elimination without affecting the MSCs.This method allowed the generation of numerous high-purity Sca-1 ＋ CD44 ＋ F4/80 - mBMSCs ([ 95%) with just one passaging. Comparative studies with mBMSCs obtained using conventional methods revealed that the mBMSCs obtained in the present study had remarkably improved experimental utilities, as demonstrated by in vitro multilineage differentiation and in vivo ectopic bone formation assays. CONCLUSION Our newly developed method, which enables the isolation of mBMSCs using simple and convenient protocol, will aid preclinical studies based on the use of MSCs.

Symptomatic Rathke’s cleft cysts (RCCs) can be treated by surgical procedures, usually through an endonasal transsphenoidal corridor using either a microscope or an endoscope. We report a large suprasellar extended RCC causing obstructive hydrocephalus, which was efficiently managed by a novel surgical route named “reverse” trans-sellar approach using transventricular neuroendoscopy. A 48-yearold woman complained of persistent headache and a tendency to fall that had begun 6 months previously. The images obtained from MRI scan showed intra- and supra-sellar cystic masses occupying the third ventricle with obstruction of the foramina of Monro and the aqueduct of Sylvius. The cystic wall showed a slight enhancement, and the cystic contents showed iso-signal intensity on T1-and T2-weighted images. Instead of trans-nasal trans-sellar surgery, we decided to operate using a conventional transventricular endoscope. A thin cystic capsule, which blocked the foramina of Monro and the aqueduct of Sylvius, was fenestrated and removed and a third ventriculostomy was performed. The defect in the infundibulum between sellar and suprasellar cysts was widened and used as a corridor to drain cystic contents (reverse trans-sellar route). The final pathological finding revealed an RCC with focal metaplasia. We efficiently managed a large RCC by transventricular neuroendoscopic surgery with cyst fenestration and third ventriculostomy and simultaneously drained the sellar contents using a novel surgical route. Reverse trans-sellar neuroendoscopic surgery is a relevant treatment option for selective patients with large suprasellar extensions of RCCs.

Background: Anterior choroidal artery (AchA) aneurysms are usually small in diameter because of the size of the involved artery and are often wide-necked. Coil embolization of AchA aneurysm is thus challenging because of serious risks, such as thromboembolic occlusion of artery and perforation of aneurysm dome. Therefore, aneurysmal neck clipping remains widely performed despite a recent increase in the use of coil embolization for aneurysm treatment. We report the treatment results of AchA aneurysms mostly (92.3%) treated with coil embolization at our institute. Methods: The database and medical records of patients who underwent coil embolization for AchA aneurysms were retrospectively analyzed. The clinical and imaging results and procedure-related complications were investigated after coil embolization performed between January 2006 and March 2022 at our institute. Results: In total, 96 AchA aneurysms comprising 65 unruptured and 31 ruptured aneurysms, including only 1 ruptured aneurysm (1.0%) re-embolized at postoperative day 192 because of coil compaction, were evaluated. After the initial coil embolization, complete occlusion was attained in 41, residual neck in 45, and residual aneurysm in 10 patients. Follow-up radiological studies after 6–174 months were performed for 80 aneurysms. Complete occlusion was noted in 57 patients, residual neck in 22, and residual aneurysm in 1. The dysarthria experienced by one (1.0%) patient was the only symptomatic procedure-related complication. After coil embolization, neither delayed new rupture nor re-rupture was observed. Conclusions The results of this study demonstrate that coil embolization is a safe and effective treatment option for patients with AchA aneurysms.

Syncope is a common symptom in clinical practice. Rotational vertebral artery occlusion syndrome, also referred to as Bow Hunter’s syndrome (BHS), is a rare condition associated with syncope and is caused by mechanical occlusion or stenosis secondary to mechanical compression of the vertebral artery during head rotation. BHS is associated with a multifactorial etiology; however, in most cases, this condition is attributed to degenerative changes. A 53-year-old man visited our hospital for the evaluation of fainting and dizziness episodes that occurred when he turned his head. Evaluation as an outpatient in the Department of Neurology showed a positive result on the Frenzel goggle test. Transfemoral cerebral angiography performed at the Department of Neurosurgery revealed stenosis of the proximal right vertebral artery. Complete occlusion of the vertebral artery was observed, and the head was turned to the right. Decompression and fusion were performed, and the contributory lesion was completely removed. Postoperative imaging confirmed complete removal of the spur and sufficient vertebral artery decompression; the patient’s symptoms resolved postoperatively.