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Introduction: Craniopharyngiomas are challenging benign tumors arising from Rathke's pouch remnants, often requiring multidisciplinary management due to their proximity to critical neurovascular structures. This meta-analysis systematically compares conventional radiation therapy (RT) and stereotactic radiosurgery (RS) in treating residual or recurrent craniopharyngiomas., Method: A comprehensive literature search identified 44 studies, including 46 reports, meeting inclusion criteria such as progression-free survival (PFS) and post-radiotherapy complications. Data extraction followed PRISMA guidelines., Results: The pooled 5-year PFS favored RT (0.843; 95% CI: 0.767-0.898) over RS (0.680; 95% CI: 0.631-0.727), as did 10-year PFS (RT: 0.813; 95% CI: 0.683-0.888; RS: 0.553; 95% CI: 0.470-0.634). RT demonstrated mitigating tumor recurrence risks. Visual and hormonal complication rates between the modalities were comparable (visual: ~4%; hormonal: ~6%)., Conclusion: RT consistently achieved superior long-term PFS compared to RS, reaffirming its role as the standard for adjuvant therapy in craniopharyngiomas. This analysis highlights the need for tailored treatment strategies balancing efficacy and safety, ultimately enhancing patient outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare that they have no conflicts of interest. Ethical declaration: This study is a meta-analysis and did not involve direct interaction with human participants or collection of identifiable personal data. Therefore, the requirement for informed consent was waived. The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki.The authors declare that there are no conflicts of interest related to this study. , (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Surgical treatments for degenerative lumbar spinal disorders involve decompression of neural structures and arthrodesis to address pain from unstable intervertebral segments. Lumbar instrumented facet fusion (IFF), a less invasive technique, has shown positive short-term outcomes, but reports on its long-term outcomes are scarce. This study aims to report its long-term biomechanical stability and clinical outcomes., Methods: This single-center retrospective observational case-series included patients who underwent single or two-level IFF for degenerative lumbar spinal disorders from January 1996 to January 2021. Patient demographics, Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) scores, and radiographic fusion were assessed using flexion-extension radiographs and CT scans. Instrument failures and fusion segment angles were measured., Results: A total of 494 patients underwent instrumented facet fusion during the studied period. Of those, 208 were followed up for more than 24 months (mean follow-up of 89.96 +/- 55.59 months). The overall fusion rate was 92.05%. Revision surgery due to adjacent segmental disease was done in 11.06% of patients. Screw loosening was observed in 6 patients, of whom 2 underwent revision surgery. Significant improvements in ODI and VAS were observed., Conclusion: Instrumented facet fusion is a safe and less invasive alternative method of lumbar spinal arthrodesis with comparable fusion rate and clinical outcome. This method show relatively low revision rate., (Copyright © 2025. Published by Elsevier Inc.)

Spinal cord injury (SCI) following high-energy trauma often leads to lasting neurologic deficits and severe socioeconomic impact. Effective neurointensive care, particularly in the early stages post-injury, is essential for optimizing outcomes. This review discusses the role of neurointensive care in managing SCI, emphasizing early assessment, stabilization, and intervention strategies based on recent evidence-based practices. SCI results from primary mechanical damage to the spinal cord, triggering secondary injuries involving vascular and cellular dysfunction. Early neurointensive care focuses on stabilizing airway, breathing, and circulation while preventing further spinal damage. Imaging and neurologic assessments, including the ASIA scale, guide the management plan. Early decompressive surgery within 24 hours is widely supported for patients with spinal instability or cord compression. Pharmacologic strategies aim to reduce secondary injury, though standardization remains limited. Prophylaxis for deep vein thrombosis and pulmonary embolism, intensive pulmonary support, and monitoring for pressure sores are critical in early-phase SCI. Early neurointensive care and surgical interventions play a pivotal role in mitigating SCI progression. Optimal care requires a multifaceted approach addressing both neurologic and systemic complications, significantly influencing recovery and long-term quality of life. Further research is needed to standardize pharmacologic treatments and optimize surgical timing., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 Korean Neurotraumatology Society.)

Spinal cord injury (SCI) remains a significant clinical challenge, with no fully effective treatment available despite advancements in various therapeutic approaches. This review examines the emerging role of induced neural stem cells (iNSCs) as promising candidates for SCI treatment, highlighting their potential for direct neural regeneration and integration with host tissue. We explore the biology of iNSCs, their mechanisms of action, and their interactions with host tissue, including modulating inflammatory responses, promoting axonal growth, and reconstructing neural circuits. Additionally, the importance of administration route, optimal timing for transplantation, and potential adverse events are discussed to address key challenges in translating these therapies to clinical applications. The review also emphasizes recent innovations, such as combining iNSC transplantation with rehabilitative training and the integration of biomaterials and growth factors to enhance therapeutic efficacy. Although preclinical studies have demonstrated positive outcomes, larger, controlled trials and standardized protocols are essential for validating the safety and effectiveness of iNSC-based therapies for SCI patients., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 Korean Neurotraumatology Society.)

Spinal cord injury (SCI) frequently results in persistent motor, sensory, or autonomic dysfunction, and the outcomes are largely determined by the location and severity of the injury. Despite significant technological progress, the intricate nature of the spinal cord anatomy and the difficulties associated with neuroregeneration make full recovery from SCI uncommon. This review explores the potential of artificial intelligence (AI), with a particular focus on machine learning, to enhance patient outcomes in SCI management. The application of AI, specifically machine learning, has revolutionized the diagnosis, treatment, prognosis, and rehabilitation of patients with SCI. By leveraging large datasets and identifying complex patterns, AI contributes to improved diagnostic accuracy, optimizes surgical procedures, and enables the personalization of therapeutic interventions. AI-driven prognostic models provide accurate predictions of recovery, facilitating improved planning and resource allocation. Additionally, AI-powered rehabilitation systems, including robotic devices and brain-computer interfaces, increase the effectiveness and accessibility of therapy. However, realizing the full potential of AI in SCI care requires ongoing research, interdisciplinary collaboration, and the development of comprehensive datasets. As AI continues to evolve, it is expected to play an increasingly vital role in enhancing the outcomes of patients with SCI., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 Korean Neurotraumatology Society.)

Tuberculous (TB) spondylitis, also known as Pott's disease, was first described by Percivall Pott in 1779. The diagnosis of TB spondylitis is often delayed because of the non-specific nature of the infection, which can lead to severe consequences. Differential diagnosis is especially critical in cancer patients undergoing chemotherapy who present with lymph node or bone metastasis. We present the case of a 76-year-old female with advanced gastric cancer, who was initially suspected of having a metastatic spinal tumor and bacterial spondylitis. The patient presented with lower limb paralysis and was diagnosed with metastatic cancer, resulting in a loss of hope for recovery. However, following the subsequent diagnosis of TB spondylitis and multiple surgical interventions, the patient achieved complete remission and significant improvement, ultimately regaining the ability to walk independently. This case highlights the importance of accurate diagnosis and timely intervention in cases where the initial presentations may mimic metastatic disease., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 Korean Neurotraumatology Society.)

Background Context: The ligamentum flavum (LF) is a crucial structure in maintaining spinal stability; however, hypertrophy of the LF is a significant contributor to lumbar spinal canal stenosis (LSCS). The mechanisms linking LF hypertrophy to the exacerbation of LSCS remain incompletely understood., Purpose: This study aimed to investigate the cellular proportions and signaling pathways observed in the hypertrophied LF., Study Design: LF tissues were obtained from 3 patients undergoing lumbar decompressive surgery. These patients had been diagnosed with LSCS prior to surgery and had an LF thickness exceeding 3.5 mm., Methods: Single-cell RNA sequencing was performed following LF tissue dissociation, and data were processed for quality control, dimensional reduction, and clustering. Differential gene expression and gene ontology analyses revealed key molecular pathways driving LF hypertrophy. Cell-cell communication analysis was analyzed to elucidate interactions among various cell types within the LF tissues., Results: Fibroblasts accounted for 75% of the total cells, followed by endothelial cells, T cells, macrophages, and B cells. Among heterogeneous types of fibroblasts, we identified that a subset of fibroblasts trans-differentiated into myofibroblasts. Two types of macrophages that exhibited phenotypic plasticity akin to M1 and M2 states were observed. We also identified novel signaling pathways involved in fibroblast and immune cell interaction in the hypertrophied LF, such as GAS and GRN, as well as known signaling pathways, such as TGF-β, PDGF, CXCL, and ANGPTL., Conclusion: Our study shows the changing cellular composition and pathogenic signaling pathways involved during the process of chronic inflammation highlighting the transdifferentiation process from fibroblasts to myofibroblasts in the hypertrophied LF., Clinical Significance: The identification of pathways such as GAS, GRN, TGF-β, ANGPTL, and CXCL, which appear to potentially contribute to LF hypertrophy, could significantly enhance our understanding of the pathogenesis of LSCS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Anterior cervical discectomy and fusion (ACDF) with anterior plating is a commonly performed procedure for cervical disc diseases. While the clinical outcomes of most reported multilevel ACDF cases are excellent, symptomatic pseudarthrosis remains a challenge, often requiring revision surgeries. This study aims to present the radiological characteristics of multilevel ACDF constructs, which can be considered during intraoperative management to prevent pseudarthrosis., Methods: This retrospective cohort study included patients who underwent multilevel (3 or 4 levels) ACDF with anterior plating between June 2010 and August 2022. Patients were regularly followed at 4 months, 12 months, and then annually postoperation. Fusion rates and characteristic radiological patterns, such as the formation of bony buttresses underneath the anterior plate, were graded and evaluated., Results: A total of 163 patients were included in the study. Overall fusion rates were 26.38%, 64.34%, and 81.58% at 4-month, 1-year, and the final follow-up, respectively. Nonunions at 4-month follow-up with tightly engaged anterior plate with bony buttress formation were more likely to fuse in the later period (Buttress grade 0 vs. 1; p=0.01, odds ratio [OR], 5.70, Buttress grade 1 vs. >2; p<0.01, OR, 12.00)., Conclusion: This study emphasizes the significance of pseudarthrosis following multilevel ACDF. Pseudarthrosis predominantly occurs in the caudal-most segment of the construct, particularly when it terminates at C7. Constructs that are not tightly engaged and lack bony buttress formation in the caudal part of multilevel ACDF are more likely to develop pseudarthrosis.

Bur cucumber ( Sicyos angulatus ), known as gasibak in Korea, is an invasive species that has spread widely since its introduction. In July 2024, populations were surveyed along riverbanks in five southeastern regions of South Korea (Andong, Daegu, Cheongsong, Chilgok, and Gunwi). Across these locations, approximately 5% of the plants displayed viral symptoms such as yellowing and mosaic. A total of 25 symptomatic and asymptomatic leaf samples were collected. To identify viral infections, RT-PCR was conducted to detect nine cucurbit viruses common in Korea (Kwak et al., 2018; Park et al., 2011): cucumber mosaic virus (CMV, Cucumovirus CMV ), cucumber green mottle mosaic virus (CGMMV, Tobamovirus viridimaculae ), cucurbit aphid-borne yellows virus (CABYV, Polerovirus CABYV ), cucurbit chlorotic yellows virus (CCYV, unclassified genus Crinivirus ), kyuri green mottle mosaic virus (KGMMV, Tobamovirus kyuri ), melon necrotic spot virus (MNSV, Gammacarmovirus melonis ), papaya ringspot virus (PRSV, Potyvirus papayanuli ), watermelon mosaic virus (WMV, P. citrulli ), and zucchini yellow mosaic virus (ZYMV, P. cucurbitaflavitesselati ). WMV and WMV+CABYV were present in 16 and 6 samples, respectively, across four regions, with no viral infections detected in Andong. All positive samples were infected with WMV, with no CABYV alone and none of the other seven viruses were detected. WMV-infected samples primarily showed mosaic symptoms with irregular discoloration and mottling, while co-infected samples displayed more pronounced yellowing or chlorosis in addition to mosaic patterns. This suggests a specific association of CABYV with the yellowing symptoms, significantly contributing to chlorosis alongside WMV. The observed co-infection aligns with prior reports of WMV and CABYV in cucurbits, emphasizing the need for monitoring both viruses due to their combined impact on symptom severity and yield losses (Rabadán and Gómez, 2023). Asymptomatic samples tested negative for viral infections. To confirm the CABYV infection, cDNA synthesis was conducted on a CABYV-positive sample, followed by PCR with newly designed coat protein gene-specific primers (5'-GTCTCGTTACCAAGAGTCCA/CGACGAACTCACCATCAGC-3'). The resulting amplicon was cloned, sequenced, and submitted to GenBank (accession no. PQ303621.1). This CABYV sequence, designated as isolate Gasibak, showed 100% identity (600/600 bp) with five isolates (KR231962.1, KR231961.1, KR231959.1, KR231949.1, and KR231944.1) previously identified from Korean melons through a BLASTn search. This marks the first report of bur cucumber as a natural host of CABYV worldwide. CABYV belongs to the genus Polerovirus in the family Solemoviridae (Sõmera et al., 2021). Although not commonly found in Korea in the past, this virus has become increasingly prevalent, particularly in oriental melon crops. Recently, Korean authorities recognized that CABYV causes yellowing symptoms in various cucurbit crops, leading to economic damage. While WMV has been reported in bur cucumber (Park et al., 2020), details remain limited. Both WMV and CABYV are known to be transmitted by aphids, raising the possibility that bur cucumber may contribute to the spread of these viruses, particularly in areas near cucurbit crops. Previous studies have shown that bur cucumber can rapidly spread along riverbanks and into agricultural areas, potentially impacting nearby ecosystems and crops (Osawa et al., 2013).

In this study, we aimed to screen potential antagonistic microorganisms against Erwinia amylovora , the causal agent of fire blight. From 127 unknown bacterial isolates tested, 2 bacterial strains (BCA3 and BCA19) were identified to show distinct antagonistic activity against E. amylovora in agar plate assay. Phylogenetic analysis of the 16s rRNA sequence identified both BCA3 and BCA19 as Pantoea ananatis . Among these BCA19 showed 13.9% stronger antagonistic activity than BCA3. Thus we further characterized antagonistic activity of BCA19. Culture filtrates ( CF ) of BCA19 significantly inhibited the swimming and swarming motility of E. amylovora . Ethyl acetate and n-butanol extracts of CF of BCA19 exhibited antibacterial activity in disk diffusion assay. Furthermore, gas chromatography-mass spectrometry analysis of ethyl acetate and n-butanol extracts of CF of BCA19 identified antibacterial compounds, including indole and hexahydropyrrolo[1,2-a]pyrazine-1,4-dione. Importantly, indole inhibited growth of E. amylovora with IC 50 value of 0.109 ± 0.02 mg/mL (~930.4 μM). Whole genome sequence analysis of BCA 19 revealed gene clusters related with siderphore, andrimid, arylpolyene and carotenoid-type terpene production. This study indicates that BCA19 can be used as a potential biological control agent against Erwinia amylovora ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Lee, Jung, Ahsan, Jung and Choi.)

Objective: To demonstrate the noninferiority of the novel hemostatic agent, Hemofence (BMI Korea Co., Ltd., thrombin cross-linked sodium hyaluronate gel matrix) compared to the established agent, Floseal Hemostatic Matrix (Baxter, thrombin-gelatin matrix) in achieving hemostasis for spinal surgeries, with secondary objectives to assess additional efficacy and safety., Methods: This clinical trial was a multicenter, randomized, subject-blinded, active-controlled, parallel-group, phase 3 study. Investigational drugs were administered to the first and second bleeding sites of each participant (or only to the first site if a second site was absent), evaluating hemostasis success rate within 10 minutes and the time to achieve hemostasis. Subsequent visits were conducted for safety assessments. For noninferiority test, a 97.5% one-sided confidence interval (CI) was used; the test group was deemed noninferior if the lower limit exceeded -10%., Results: This trial showed a 97.10% success rate in the test group and 96.05% in the control group for primary efficacy. The 95% CI (-4.90% to 7.44%) confirmed the test drug's noninferiority. Time to hemostasis showed no significant difference between groups. All adverse events, adverse drug reactions, and serious adverse events were statistically similar between groups (p=1.000, p=0.243, and p=0.966, respectively)., Conclusion: A novel hemostatic agent, Hemofence, demonstrated an efficacy and safety profile comparable to that of Floseal.

Background Context: Fusions for lumbar spine diseases are widely performed and have a growing incidence, especially in elderly population., Purpose: The goal of this study was to assess national trends of lumbar spinal fusions and examine the risk for reoperations after a lumbar fusion with a focus on 'epidemiologic transition' relating to age., Study Design/setting: The prospectively collected Korean Health Insurance Review and Assessment Service (HIRA) nationwide cohort database was retrospectively reviewed., Patient Sample: The total 278,815 patients who underwent lumbar spinal fusions for degenerative spine diseases between 2010 and 2018 were reviewed and used to assess trends in operative incidence. The 37,050 patients who underwent lumbar fusions between 1/2010 and 12/2011 were enrolled to determine 8-year reoperation rates., Outcome Measures: The overall number of lumbar spinal fusions were analyzed for the national annual trend. Demographic data, reoperation rates, and confounding clinical factors were evaluated., Methods: The overall number of lumbar spinal fusions was analyzed to determine the national annual trend of operative incidence. For the reoperation rate analysis, the primary outcome measured was the cumulative incidence of revision operations within a minimum 8-year follow-up period. Additional outcomes included comparative analyses of the reoperation rate with respect to age, sex, or other underlying comorbidities., Results: Over time, elderly patients comprised a larger portion of the cohort (2010:24.2%; 2018:37.6%), while operations in younger patients decreased over time (2010:40.3%; 2018:27.0%). In the cohort of patients with a minimum 8-year follow-up (n=37,050), rates of reoperation peaked in patients aged 60-69 years (17.6 per 1000 person-years [HR 2.20 compared to <40years]) and decreased for more elderly patients (14.3 per 1000 person-years [HR 1.80 compared to <40years]). Age was the most significant risk factor for reoperation. Osteoporosis was also a risk factor for reoperation in postmenopausal females., Conclusions: Increasing incidence of lumbar fusions in elderly patients was seen however the risk of reoperation decreased in patients aged 70 or more. Lumbar fusion for elderly patients should not be hesitated in the decision-making process because of concerns about reoperation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

raumatic brain injury (TBI) is a significant global health concern, particularly affecting young individuals, and is a leading cause of mortality and morbidity worldwide. Despite improvements in treatment infrastructure, many TBI patients choose discharge against medical advice (DAMA), often declining necessary surgical interventions. We aimed to investigate the factors that can be associated with DAMA in TBI patients that were recommended to have surgical treatment. This study was conducted at single tertiary university center (2008-2018), by retrospectively reviewing 1510 TBI patients whom visited the emergency room. We analyzed 219 TBI surgical candidates, including 50 declining surgery (refused group) and the others whom agreed and underwent decompressive surgery. Retrospective analysis covered demographic characteristics, medical history, insurance types, laboratory results, CT scan findings, and GCS scores. Statistical analyses identified factors influencing DAMA. Among surgical candidates, 169 underwent surgery, while 50 declined. Age (60.8 ± 17.5 vs. 70.5 ± 13.8 years; p < 0.001), use of anticoagulating medication (p = 0.015), and initial GCS scores (9.0 ± 4.3 vs. 5.3 ± 3.2; p < 0.001) appeared to be associated with refusal of decompressive surgery. Based on our analysis, factors influencing DAMA for decompressive surgery included age, anticoagulant use, and initial GCS scores. Contrary to general expectations and some previous studies, our analysis revealed that the patients' medical conditions had a larger impact than socioeconomic status under the Korean insurance system, which fully covers treatment for TBI. This finding provides new insights into the factors affecting DAMA and could be valuable for future administrative plans involving national insurance., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Calcium pyrophosphate deposition disease (CPPD), known as pseudogout, is characterized by the accumulation of calcium pyrophosphate crystals in musculoskeletal structures, primarily joints. While CPPD commonly affects various joints, involvement in the cervical spine leading to myelopathy is rare. Surgical intervention becomes necessary when conservative measures fail, but reports on full endoscopic surgeries are extremely rare. We present two successful cases where full endoscopic systems were used for CPPD removal in the cervical spine. The surgical technique involved a full endoscopic approach, adapting the previously reported technique for unilateral laminotomy bilateral decompression. Full-endoscopic removal of cervical CPPD inducing myelopathy were successfully removed with good clinical and radiologic outcomes. The scarcity of endoscopic cases for cervical ligamentum flavum CPPD is attributed to the condition's rarity. However, our successful cases advocate for endoscopic surgery as a potential primary treatment option for CPPD-induced cervical myelopathy, especially in elderly patients or those with previous cervical operation histories. This experience encourages the consideration of endoscopic surgery for managing cervical ligamentum flavum CPPD as a viable alternative., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The symptom of hyposalivation associated with hypofunction of the salivary glands is a common feature of diabetes. Inadequate saliva production can cause tissue damage in the mouth, making it susceptible to infections and leading to oral health diseases. Previous studies have highlighted the harmful effects of methylglyoxal (MGO) and MGO-derived advanced glycation end products (AGEs) in diabetes. In this study, we investigated the protective effects of gemigliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, against MGO-induced salivary gland dysfunction. MGO treatment of immortalized human salivary gland acinar cells induced apoptosis via reactive oxygen species (ROS)-mediated pathways, but this effect was mitigated by gemigliptin. In vivo experiments involved the simultaneous administration of MGO (17.25 mg/kg) with aminoguanidine (100 mg/kg) and gemigliptin (10 and 100 mg/kg) daily to rats for two weeks. Gemigliptin increased the saliva volume and amylase levels in MGO-injected rats. Gemigliptin reduced the DPP-4 activity in both the salivary glands and serum of MGO-injected rats. Furthermore, gemigliptin exerted anti-glycation effects by reducing the accumulation of AGEs in the saliva, salivary glands, and serum and suppressing the expression of the receptor for AGEs. These actions protected the salivary gland cells from ROS-mediated apoptosis. Overall, gemigliptin protected the salivary gland cells from ROS-mediated cell death, reduced the accumulation of amylase and mucins in the salivary glands, and enhanced the salivary function by upregulating aquaporin 5 expression, and it exerted protective effects against MGO-induced salivary gland dysfunction by enhancing the anti-glycation, antioxidant, and salivary secretion activities. Our findings suggest gemigliptin as a potential therapeutic for patients with salivary gland dysfunction caused by the complications of diabetes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Ultrafiltration (UF) would enhance coagulation profiles by concentrating coagulation elements during cardiopulmonary bypass (CPB) for cardiac surgery., Methods: We retrospectively reviewed electronic medical records of 75 patients who had undergone cardiac surgery with rotational thromboelastometry-based coagulation management in a university hospital and analyzed the UF-induced changes in the maximum clot firmness (MCF) of extrinsically activated test with tissue factor (EXTEM) during CPB in 30 patients., Results: The median volume of filtered-free water was 1,350 ml, and median hematocrit was significantly increased from 22.5% to 25.5%. As the primary measure, UF significantly increased the median MCF-EXTEM from 48.0 mm to 50.5 mm (P = 0.015, effect size r = 0.44). The area under the receiver operating characteristic curve pre-UF MCF-EXTEM for discrimination of any increase of MCF-EXTEM after applying UF was 0.89 (95% CI [0.77, 1.00], P < 0.001), and its cut-off value was 50.5 mm (specificity of 81.8% and sensitivity of 84.2% in Youden's J statistic). In the secondary analyses using the cut-off value, UF significantly increased the median MCF-EXTEM from 40.5 mm to 42.5 mm in 18 patients with pre-UF MCF-EXTEM ≤ 50.5 mm. However, it did not increase MCF-EXTEM in 12 patients with pre-UF MCF-EXTEM > 50.5 mm. There was a significant interaction between pre-UF MCF-EXTEM values and applying UF (P < 0.001 for the subgroup, P = 0.046 for UF, P = 0.003 for interaction)., Conclusions: Applying UF improved clot firmness, and the improvement was more pronounced when pre-UF MCF-EXTEM had been reduced during CPB.

Background: It is difficult to predict the expected survival after lumbar instrumented surgery for metastases owing to the difference among different cancer origins and the relatively short survival after surgery., Aims: The aim of this study is to analyze the postoperative survival period of lumbar spinal metastasis patients who underwent lumbar instrumented surgery., Methods: Data were collected from the Korean National Health Insurance Review and Assessment Service database. Patients who underwent lumbar spinal surgery with instrumentation between January 2011 and December 2015 for metastatic lumbar diseases were reviewed. The mean postoperative survival period of patients with metastatic lumbar cancer according to each primary cancer type was evaluated., Results: A total of 628 patients were enrolled and categorized according to primary cancer type. The overall median survival rate was 1.11±1.30 years. The three most prevalent primary cancer groups were lung, hepatobiliary, and colorectal cancers, presenting relatively short postoperative survival rates (0.93±1.25, 0.74±0.75 and 0.74±0.88 years, respectively). The best postoperative survival period was observed in breast cancer (2.23±1.83 years), while urinary tract cancer showed the shortest postoperative survival period (0.59±0.69 years)., Conclusion: The postoperative survival period of patients with lumbar metastatic spinal tumors according to different primary cancers after instrumented fusion was ˃1 year overall, with differences according to different primary origins. This result may provide information regarding the expected postoperative survival after instrumented surgery for lumbar spinal metastases., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

A novel null HLA-A*24 allele, HLA-A*24:608N, was identified in five Korean subjects including three from a family and two separate individuals. This study was performed to discern its immunological function in transplantation settings. Because this null variant had deletions of approximately 12 k base pairs from intron 3 to 3' end of the HLA-A gene, low resolution HLA typing and amplicon-based next generation sequencing (NGS) typing methods had failed to assign it. Hybrid capture-based NGS method confirmed that this novel variant had a large deletion. T-lymphocyte crossmatching by complement-dependent lymphocytotoxicity and flow cytometry with a serum consisting anti-HLA-A24 antibody revealed negative results, implying that an individual with this allele would not carry a functioning A24 antigen. These findings highlight the importance of identifying a null HLA allele by employing appropriate molecular method and providing expected crossmatching outcomes in a real-world transplantation setting., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oral dryness is among the most common conditions experienced by the elderly. As saliva plays a crucial role in maintaining oral health and overall quality of life, the condition is increasingly taking its toll on a rapidly growing aging population. D-galactose (D-gal) stimulates their formation, which in turn cause oxidative stress and accelerate age-related decline in physical function. In this study, we observed a reduction in salivary secretion and amylase levels in aged rats injected with D-gal, confirming salivary gland dysfunction. Treatment with gemigliptin increased DPP-4 inhibition and GLP-1 levels in the salivary glands of aging rats and reduced the expression of AGEs and receptors for advanced glycation end products (RAGE). This effect was caused by the presence of additional reactive oxygen species (ROS) in the salivary glands of the examined rats. Gemigliptin's cytoprotective effect reduced amylase and mucin accumulation and increased AQP5 expression, which are important indicators of salivary gland function. In sum, gemigliptin was shown to improve D-gal-induced decline in the salivary gland function of aged rats through its anti-glycation and antioxidant activities. Gemigliptin shows promise as a treatment strategy for patients experiencing decreased salivary function associated with their advancing age.

Objective: Since its introduction, electrocautery has served as a valuable surgical tool, enabling precise tissue cutting and effective hemostasis in spine surgery. While there have been numerous efforts to elucidate the possible hazardous effects of surgical smoke in various surgical fields, there has been very little discussion in the context of spine surgery. The objective of this study was to measure and conduct a quantitative analysis of the particulate matter (PM) of different sizes and of formaldehyde (HCHO) generated by smoke during spine surgeries., Methods: This study included a consecutive series of patients who underwent 1- or 2-level lumbar spinal fusion surgery between June and November 2021. Particle counts were measured using a particle counter, specifically focusing on six different sizes of PM (0.3, 0.5, 1, 2.5, 5, and 10 µm). Additionally, measurements were taken for HCHO in parts per million (ppm). Monopolar cautery was used in the surgical setting. Systematic measurements were conducted at specific time points during the surgical procedures to assess the levels of PM and HCHO. Furthermore, the efficacy of surgical smoke suction was evaluated by comparing the PM levels with and without adjacent placement of suction., Results: This study involved 35 patients, with measurements of both PM and HCHO taken in 27 cases. The remaining 8 cases had measurements only for PM. In this study, statistically significant quantitative changes in various PM sizes were observed when electrocautery was used during spine surgery (12.3 ± 1.7 vs 1975.7 ± 422.8, 3.4 ± 0.5 vs 250.1 ± 45.7, and 1.9 ± 0.2 vs 78.1 ± 13.3, respectively, for 2.5-, 5-, and 10-µm PM; p < 0.05). The level of HCHO was also significantly higher (0.085 ± 0.006 vs 0.131 ± 0.014 ppm, p < 0.05) with electrocautery use. Utilization of adjacent suction of surgical smoke during electrocautery demonstrated a statistically significant reduction in PM levels., Conclusions: The findings of this study highlight the potential surgical smoke-related hazards that spine surgeons may be exposed to in the operating room. Implementing simple interventions, such as utilizing nearby suction, can effectively minimize the amount of toxic surgical smoke and mitigate these risks.

The purpose of this study was to systematically review studies in the literature to assess the superiority between microsurgery and radiosurgery regarding the efficacy in improving petroclival meningioma (PCM)-related trigeminal neuralgia (TN). PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched from the inception until December 08, 2022. The overall proportion of patients with improved TN after treatment in all six included studies was 56% (95% confidence interval [CI], 35-76.9%). Higgins I 2 statistics showed significant heterogeneity (I 2  = 90%). Subgroup analysis showed that the proportion of improved TN was higher in the microsurgery group than that in the radiosurgery group (89%; 95% CI, 81-96.5% vs. 37%, 95% CI, 22-52.7%, respectively, p < 0.01). Subgroup analysis (for studies that documented the number of posttreatment Barrow Neurological Institute scores 1 and 2) revealed that the proportion of pain-free without medication after treatment was higher in the microsurgery group than that in the radiosurgery group (90.7%; 95% CI, 81-99.7% vs. 34.5%, 95% CI, 21.3-47.7.7%, respectively, p < 0.01). Based on the results of this meta-analysis, we concluded that microsurgery is superior to radiosurgery in controlling PCM-related TN., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Encephaloduroarteriosynangiosis (EDAS), an indirect anastomosis procedure, is widely accepted as a primary treatment for moyamoya disease (MMD) to improve collateral blood flow. During surgical intervention, dural fibroblasts (DuF) are thought to produce various proteins that create an angiogenic microenvironment. However, the biophysiological evidence supporting the angiogenic properties of this surgical technique has not been thoroughly elucidated. The purpose of these studies was to determine whether DuF releases pro-angiogenic factors and chemokines and promotes angiogenic properties in human endothelial cells (ECs) under IL-1β-mediated wound conditions, which are expected to occur during the process of neo-vascularization within the dura mater. Furthermore, a microfluidic chemotaxis platform was implemented to investigate the angiogenic activity of ECs in response to a reconstituted dura model. Transcriptome sequencing revealed that IL-1β stimulation on DuF induced a significant upregulation of various pro-angiogenic genes, including IL-6, IL-8, CCL-2, CCL-5, SMOC-1, and SCG-2 ( p  < 0.05). Moreover, compared to ECs cultured in naïve media or naïve DuF media, those exposed to IL-1β-DuF conditioned media expressed higher mRNA and protein levels of these pro-angiogenic factors ( p  < 0.001). ECs co-cultured with IL-1β-DuF also exhibited considerable migration on the microfluidic chemotaxis platform. Furthermore, the chemotactic effects on the ECs were reduced upon neutralization of IL-8 or inhibition of NF-κB signaling. Our findings demonstrate that IL-1β-DuFs release factors that activate and enhance the angiogenic properties of ECs. These results suggest a potential interaction between DuF and ECs following EDAS for MMD, and these components could be targeted for the development of therapeutic biomarkers., Competing Interests: The authors have declared no conflict of interest., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Hyperosmotic stress caused by tear hyposection is a leading cause of dry eye disease. We investigated the prevention of dry eye disease in corneal epithelial cells and in rats that were induced to develop dry eye disease via unilateral excision of their exorbital lacrimal gland using Sargassum horneri extract (AB&#95;SH) and its bioactive component fucoidan. Oral administration of AB&#95;SH (250 mg/kg and 500 mg/kg) and fucoidan (100 mg/kg) was conducted for 7 days. In order to measure tear secretion, phenol red thread tear tests were performed along with corneal irregularity measurements. The apoptotic injury in the cornea and the lacrimal gland was evaluated using TUNEL staining. AB&#95;SH and fucoidan were shown to suppress apoptosis and the expression of apoptosis-related proteins in human corneal epithelial cells under hyperosmotic conditions. Oral administration of AB&#95;SH and fucoidan attenuated tear hyposecretion and corneal irregularity in the lacrimal gland-excised rats. In addition, AB&#95;SH and fucoidan also reduced apoptosis in the cornea and lacrimal gland. This study suggests that S. horneri extract and fucoidan can effectively ameliorate dry eye disease by suppressing the apoptosis of ocular tissues.

Purpose: To report incidence of dural lacerations in lumbar endoscopic unilateral laminotomy for bilateral decompression (LE-ULBD) and to describe patient outcomes following a novel full-endoscopic bimanual durotomy repair., Methods: Retrospective review of prospectively collected database including 5.5 years of single surgeon experience with LE-ULBD. Patients with no durotomy were compared with patients who experienced intraoperative durotomy, including demographics, ASA score, prior surgery, number of levels treated, procedure time, hospital length of stay (LOS), visual analogue scale, perioperative complications, revision surgeries, use of analgesics, and Oswestry Disability Index (ODI)., Results: In total, 13/174 patients (7.5%) undergoing LE-ULBD experienced intraoperative durotomy. No significant differences in demographic, clinical or operative variables were identified between the 2 groups. Sustaining a durotomy increased LOS (p = 0.0019); no differences in perioperative complications or rate of revision surgery were identified. There was no difference in minimally clinically important difference for ODI between groups (65.6% for no durotomy versus 55.6% for durotomy, p = 0.54)., Conclusion: In this cohort, sustaining a durotomy increased LOS but, with accompanying intraoperative repair, did not significantly affect rate of complications, revision surgery or functional outcomes. Our method of bimanual endoscopic dural repair provides an effective approach for repair of dural lacerations in interlaminar ULBD cases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Avulsion fracture of the occipital condyle are rare lesion at craniovertebral junction. It is often related to high-energy traumatic injuries and show diverse clinical presentations. Neurologic deficit and instabilities may justify surgical treatment. However, the integrity of neurovascular structures is undervalued in the current literatures. In this case report, we described a 26-year-old female patient with avulsion fracture of occipital condyle following a traffic accident. On initial presentation, her Glasgow Coma Scale was 8. She presented with fracture compound comminuted depressed, on the left side of her forehead with skull base fracture extending into clivus and occipital condyle. Her left occipital condyle showed avulsion injury with displacement deep into the skull base. On her computed tomography angiography, the displaced occipital condyle compressed on the sigmoid sinus resulting in its obstruction. While she was recovering her consciousness during her stay in the hospital, the lower cranial nerves showed dysfunctions corresponding to Collet-Sicard syndrome. Due to high risk of vascular injury, the patient was conservatively treated for the occipital condyle fracture. On the 4 months postdischarge follow-up, her cranial nerve symptoms practically recovered, and the occipital condyle showed signs of fusion without further displacement. Current literatures focus on neurologic deficit and stability for the surgical decisions. However, it is also important to evaluate the neurovascular integrity to assess the risk of its manipulation as it may result in fatal outcome. This case shows, an unstable avulsion occipital condyle fracture with neurologic deficit can be treated conservatively and show a favorable outcome., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (© 2023 The Korean Society of Traumatology.)

Among natural products with sleep-promoting activity, hops have been used since ancient times as a tranquilizer and hypnotic agent. This study investigated the sleep-promoting effects of extracts of various hop (Humulus lupulus L.) varieties in invertebrate and vertebrate models. The content of α-acids, β-acids, and xanthohumol was higher in hop 70% alcohol extracts than in hop hot water extracts. Among the alcohol extracts, Citra contained a high α-acid content (229.32 µg/mg), while Saphir showed high β-acid and xanthohumol content (66.37 and 4.23 µg/mg, respectively). In Drosophila melanogaster, Simcoe and Mosaic water extracts and Saphir and Simcoe alcohol extracts significantly increased total nighttime sleep. Total sleep time of mice with pentobarbital-induced sleep was significantly increased by Simcoe and Mosaic water extracts and Saphir and Simcoe ethanol extracts compared to the normal group. Oral administration of Simcoe water extract and Saphir alcohol extract improved sleep in the caffeine-induced insomnia model and upregulated the mRNA expression of GABA A (gamma 2 subunit) and GABA B receptors in mouse brains. Additionally, Saphir alcohol extract significantly increased the GABA content in mouse brains. Simcoe water extract and Saphir ethanol extract modulated GABAergic signaling to improve sleep-related behaviors, including sleep duration., (© 2023 Institute of Food Technologists.)

Study Design: Retrospective Cohort Study OBJECTIVE: Myelopathy following ossification of the posterior longitudinal ligament (OPLL) is one of the devastating clinical features in these patients, while we still know little about which factors are associated with development of myelopathy. We evaluated the difference of radiologic measurements between OPLL patients with or without myelopathy and searched for the clinical significance with emphasis on the impact of dynamic motion., Methods: 305 patients diagnosed of OPLL were enrolled for retrospective review. They were divided into two groups according to the coexistence of radiographic evidence of myelopathy. Demographic data as well as radiologic measures including the presence of disc degeneration (DD), anterior-posterior diameter (APD) of central canal, canal compromise (CC) ratio, global and segmental range of motion (gROM and sROM), OPLL type (morphologic classification) and K-line were collected., Results: APD (odds ratio (OR); 0.411), CC ratio (OR; 1.100) and sROM (OR; 1.371) were significantly associated with the presence of myelopathy in the multivariate analysis. While the statistically significant factors were same in OPLLs with CC larger than 50%, presence of DD (OR; 4.509) and sROM (OR; 1.295) were significantly associated with myelopathy but not the CC itself in OPLLs with CC smaller than 50%., Conclusions: We discovered that the APD, CC ratio and sROM had significant association with development of myelopathy in OPLLs. And the presence of dynamic factors had significant association with myelopathy in OPLLs with smaller CC ratios. This observation and its clinical significance on development of myelopathy might enhance our understanding of OPLL., Competing Interests: Conflict of Interests The authors have no personal, financial, or institutional conflict of interests to report., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Perioperative prophylactic antibiotic (PPA) use in spine surgery is known to reduce the rate of surgical site infections. In the past decade, several evidence-based guidelines have been published and surveillance systems to monitor the proper use of antimicrobials had been adapted by many institutes., Objective: To report the trends of PPA prescription in lumbar fusion surgeries nationwide in the Republic of Korea., Methods: This is a nationwide registry study. Using the population-based data from the Republic of Korea provided by the Korean Health Insurance Review and Assessment Service, data of all lumbar spinal fusion surgeries performed between 2010 and 2018 in adult patients (age ≥19 years) were reviewed., Results: The most frequently used antibiotics were first-generation cephalosporins, which accounted for 38.2 % of total PPA prescriptions and were prescribed in 58.96 % of lumbar fusion surgeries. A gradual increase in prescription trends was observed. The second most frequently used PPAs were second-generation cephalosporins, which showed decrease in use from 2016. The frequency of vancomycin prescriptions gradually increased over the observation period and showed an almost four-fold increase in 2018 compared to 2010. First- and second-generation cephalosporins were prescribed less frequently to patients with renal disease., Conclusion: The pattern of PPA use has changed remarkably over the observation period. Furthermore, specific differences in PPA prescriptions were observed among patients with certain co-morbidities., Competing Interests: Conflict of interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Esculetin is a coumarin-derived compound with antioxidant and anti-inflammatory properties. The current study aims to evaluate the therapeutic implications of esculetin on retinal dysfunction and uncover the underlying mechanisms. Tert -butyl hydroperoxide ( t -BHP) at a concentration of 300 μM was used to induce oxidative stress in human retinal pigment epithelial cell line (ARPE-19) cells. Esculetin at concentrations below 250 μM did not cause cytotoxicity to ARPE-19 cells. Cell viability analysis confirmed that t -BHP induced oxidative injury of ARPE-19 cells. However, ARPE-19 cells were protected from t -BHP-induced oxidative injury by esculetin in a concentration-dependent manner. As a result of the TUNEL assay to confirm apoptosis, esculetin treatment reduced the number of TUNEL-positive cells. Esculetin down-regulated the expression levels of Bax, Caspase-3, and PARP and up-regulated the expression level of Bcl2. Collectively, this study demonstrates that esculetin exerts potent antioxidant properties in ARPE-19 cells, inhibiting t -BHP-induced apoptosis under the regulation of apoptotic factors.

Purpose: We provide evidence for the reclassification of the BRCA1 :c.5017&#95;5019del variant by presenting the clinicopathological characteristics, clinical outcomes, and family history of breast or ovarian cancer in 17 patients with this variant., Methods: This study included breast or ovarian cancer patients tested for BRCA1/2 genes between January 2008 and June 2020 at 10 medical centers in Korea. We retrospectively reviewed 17 probands from 15 families who had the BRCA1 :c.5017&#95;5019del variant according to the electronic medical records., Results: We present 10 breast cancer patients and 7 ovarian cancer patients from 15 families identified as having BRCA1 :c.5017&#95;5019del and a total of 19 cases of breast cancer and 14 cases of ovarian cancer in these families. The ratio of breast-to-ovarian cancer was 1.3:1. Breast cancer patients with this variant showed a rich family history of breast or ovarian cancer, 8 patients (80.0%). The mean age at diagnosis was 45.4 years and 6 patients (60.0%) were categorized into hormone-receptor-negative breast cancer. Also, the ovarian cancer patients with this variant showed strong family histories of breast and/or ovarian cancer in 4 patients (57.1%)., Conclusion: We presented clinical evidence for the reclassification of BRCA1 :c.5017&#95;5019del as a likely pathogenic variant (LPV). Reclassification as LPV could result in the prophylactic treatment and medical surveillance of probands, family testing recommendations, and appropriate genetic counseling of their families., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2022, the Korean Surgical Society.)

Objective: Interlaminar endoscopic spine surgery has been introduced and utilized for lumbar lateral recess decompression. We modified this technique and utilized it for bilateral lateral recess stenoses without significant central stenosis. Here we present the surgical details and clinical outcome of ligamentum flavum sparing unilateral laminotomy for bilateral recess decompression (ULBRD)., Methods: Prospectively collected registry for full-endoscopic surgeries was reviewed retrospectively. One hundred eighty-two consecutive cases from a single center between September 2015 and March 2021 were reviewed and 57 of them whom underwent ULBRD were enrolled for analysis. Basic patient demographic data, perioperative details, surgeryrelated complications, and clinical outcome were reviewed. The detailed surgical technique is presented as well., Results: Among the 57 patients enrolled, 37 were males while the other 20 were females. The mean age was 58.53 ± 14.51 years, and a bimodal age distribution at the age of mid-fifties and mid-sixties or older was noted. The later age-peak was related to coexistence of degenerative scoliosis. The average operative time per lamina was 70.34 ± 20.51 minutes and mean length of stay was 0.56 ± 0.85 days. Four perioperative complications were reported (7.0%) and the overall reoperation rate at the index level within 1 year was 8.8%. The preoperative back/leg visual analogue scale scores and functional outcome scales including EuroQol-5 dimension questionnaire, Oswestry Disability Index presented significant improvement immediately after surgery and were maintained until final follow-up., Conclusion: ULBRD for bilateral lateral recess stenoses without significant central stenosis resulted in good clinical outcomes with acceptably low perioperative complications rates. Sufficient decompression was achieved with the central ligamentum flavum being preserved.

Esculetin is an antioxidant and anti-inflammatory compound derived from coumarin. Oxidative stress can cause overproduction of reactive oxygen species (ROS), which can lead to the development of chronic kidney failure. In this study, human embryonic kidney 293 (HEK293) cells were treated with tert-butyl hydroperoxide (t-BHP) to determine the antioxidant effects of esculetin. HEK293 cells were treated with t-BHP to validate changes in cell viability, ROS production, and apoptosis, and then treated with esculetin to evaluate the changes. Changes in mRNA and protein levels were analyzed using a proteome kit, PCR, and Western blotting. Esculetin improved HEK293 cell viability and reduced apoptosis caused by t-BHP-induced oxidative stress. At the mRNA and protein levels, esculetin decreased pro-apoptotic factor expression as well as increased anti-apoptotic factor expression. The antioxidant efficacy of esculetin was validated when it inhibited the apoptosis caused by t-BHP-induced oxidative stress in HEK293 cells.

Objective: We developed a novel multi-torsional mechanical stretch stress loading device for ligamentum flavum cells and evaluated its influence on the development of ligamentum flavum hypertrophy, a common cause of lumbar spinal canal stenosis., Materials and Methods: Stretch strength of the device was optimized by applying 5% and 15% MSS loads for 24, 48, and 72 h. A cytotoxicity assay of human ligamentum flavum cells was performed and the results were compared to control (0% stress). Inflammatory markers (interleukin [IL]-6, IL-8), vascular endothelial growth factor [VEGF], and extracellular matrix (ECM)-regulating cytokines (matrix metalloproteinase [MMP]-1, MMP-3 and MMP-9, and tissue inhibitor of metalloproteinase [TIMP]-1 and TIMP-2) were quantified via enzyme-linked immunosorbent assay., Results: Using our multi-torsional mechanical stretch stress loading device, 5% stress for 24 hour was optimal for ligamentum flavum cells. Under this condition, the IL-6 and IL-8 levels, VEGF level, and MMP-1, MMP-3, and TIMP-2 were significantly increased, compared to the control., Conclusion: Using the novel multi-torsional mechanical stretch stress loading device we confirmed that, mechanical stress enhances the production of inflammatory cytokines and angiogenic factors, and altered the expression of ECM-regulating enzymes, possibly triggering ligamentum flavum hypertrophy., Competing Interests: The authors have declared that no competing interests exist.

Rett syndrome (RTT) is a progressive neurodevelopmental disorder caused by variants in MECP2. Emerging evidence of ethnic specificity of genetic variations has allowed precise diagnostic approaches with tailored therapies. In this study, we reviewed the variation spectrum of MECP2 in Korean RTT(-like) patients and compared it with previous reports in multiple ethnic groups. We reevaluated variants found in Korean RTT patients according to the new Clinical Genome Resource guideline to reinterpret and reclassify variants of uncertain significance in MECP2. Among 377 cases, 56 (14.9%) showed pathogenic variants, and three novel variants, p.(Ala277Argfs*7), p.(Ala378Glyfs*8), and p.(Arg270&#95;Ser332del), were identified. Comprehensive data from Korea revealed an overall consistent variation spectrum with those from other ethnicities. Through the reevaluation of variants, nine that previously had insufficient evidence for pathogenicity were reclassified into pathogenic variants. Our study provided insight on the genetic contribution of MECP2 in RTT and a useful background for genetic counseling in the Korean population., (© 2022. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Ligamentum flavum hypertrophy (LFH) is a known contributor to lumbar spinal canal stenosis (LSCS). However, the clinical significance and quantitative role of LFH compared to other components, such as disc bulging and facet hypertrophy, have not yet been examined. We investigated the correlation between the quantitative radiological factors, clinical symptoms, and outcomes in patients with LSCS. In total, 163 patients diagnosed with single-level (L4-L5) stenosis were included. The patients were divided into 2 groups according to claudication severity: >100 m for mild (n = 92) and < 100 m for severe (n = 71). The visual analog scale (VAS) was used to quantify back and leg pain, and the Oswestry Disability Index (ODI) and Short form-36 (SF-36) physical component summary (PCS) scores, and Macnab criteria were evaluated as clinical factors 6 months after treatment. We measured the baseline canal cross-sectional area, ligamentum flavum (LF) area, disc herniation area, dural sac area, fat area, and LF thickness using MRI. A comparative analysis was performed to evaluate the association between radiologic and clinical factors. Additionally, further comparative analyses between the types of surgeries were performed. Among various radiologic factors, the baseline LF thickness (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.25-2.41) was the only major contributing factor to the severity of claudication in the multivariate logistic regression analysis. The types of surgery (decompression alone vs fusion) did not significantly differ in terms of their clinical outcomes, including back and leg VAS, ODI, SF-36 PCS, and satisfaction with the MacNab classification. LF thickness is a major factor contributing to claudication severity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sagittal spinopelvic alignment (SSPA) parameters are essential for the diagnosis of adult spinal deformities (ASDs) and their progression. Certain clinical symptoms that occur in patients with lumbar spinal stenosis (LSS) and herniated nucleus pulposus (HNP) may distort the SSPA and mimic ASD., Objective: To differentiate SSPA in symptomatic patients from asymptomatic patients within 10 minutes in the standing position., Methods: This retrospective cohort study evaluated changes in SSPA after simple lumbar decompression surgery in patients with LSS and HNP. Relative sagittal alignment (RSA), relative pelvic version, relative lumbar lordosis (RLL), Lordosis Distribution Index (LDI), and global alignment and proportion (GAP) values were calculated using the conventional Schwab classification method. First, the preoperative and postoperative SSPA parameters were compared. Second, patients were subgrouped into symptomatic within 10 minutes of standing (SP group) and other symptoms of LSS and HNP as controls. Changes in SSPA parameters after symptom relief after simple lumbar decompression surgery were compared between the two groups., Results: Overall, all SSPA parameters improved after surgery. However, after subgrouping, patients in the control group did not show significant SSPA alterations, except for LDI, whereas patients in the SP group significantly improved in terms of their RSA, RLL, LDI, and GAP values after symptom relief after surgery., Conclusion: Patients with pain on standing within 10 minutes showed significant correction in RSA, RLL, and GAP values after simple lumbar decompression. Therefore, it is important to observe such clinical symptoms to avoid misdiagnosis of ASD., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

A significant number of hereditary breast or ovarian cancers are caused by germline variants, mostly BRCA1/BRCA2 genes. Because genetic predispositions vary by ethnicity, several studies have reported founder variants of BRCA1/BRCA2 genes. Such founder variants were reported primarily based on their relevant population frequencies. We reviewed the variant data relating to BRCA1 and BRCA2 genes from January 2012 to March 2019 at Samsung Medical Center, Seoul, Korea. Among the cases with pathogenic variants (PVs) or likely pathogenic variants (LPVs), we defined recurrent variants as those found in more than five unrelated patients. Using single nucleotide polymorphisms, we analyzed patient haplotypes. There were 14 recurrent variants in the BRCA1 gene and seven variants in the BRCA2 gene. Of note, three variants in each gene were primarily detected in Korean populations. Among them, the c.5339T>C (p.Leu1780Pro) BRCA1 variant had a long block sized 74.5 kb. In BRCA2, the c.1399A>T (p.Lys467*) variant had a long block sized 35.5 kb. We suggest that BRCA1 c.5339T>C (p.Leu1780Pro) and BRCA2 c.1399A>T (p.Lys467*) are founder variants of the Korean population. These two recurrent variants were ethnicity-prevalent, primarily found in Korean populations, and the sizes of the linkage disequilibrium blocks are longer than others., Competing Interests: Declaration of Competing Interest All of the authors have no conflict of interest or potential conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Double heterozygosity (DH) for BRCA1 and BRCA2 variant is very rare with only a few cases reported, and most those in Caucasians. In this article, we present seven unrelated cases of DH for BRCA1/2 identified from a single institution in Korea, and describe the characteristics and phenotype of DH individuals compared to those with a single BRCA variant., Materials and Methods: This study included 27,678 patients diagnosed with breast cancer and surgically treated at Samsung Medical Center (SMC) between January 2008 and June 2020. In total, 4,215 high-risk breast cancer patients were tested for the BRCA1/2 genes, and electronic medical records from 456 cases with pathogenic/likely pathogenic variants (PVs/LPVs) were reviewed., Results: A younger mean age at diagnosis was associated with DH than a single variant of BRCA1/2. More triple-negative breast cancer (TNBC) and higher nuclear and histologic grade cancer occurred with DH than BRCA2 variant. All 7 cases of DH were unrelated, and their mutation combinations were different. There were no Ashkenazi founder variants detected., Conclusion: We suggest that patients with DH for BRCA1/2 variants develop breast cancer at a younger age, but the histopathologic features are similar to those of BRCA1.

Exposure to particulate matter is a causative factor of dry eye disease. We aimed to investigate the beneficial effect of eye drops containing aucubin on dry eye disease induced by urban particulate matter (UPM). Dry eye was induced in male SD rats (6 weeks old) by topical exposure to UPM thrice a day for 5 d. Eye drops containing 0.1% aucubin or 0.5% aucubin were topically administered directly into the eye after UPM exposure for an additional 5 d. Tear secretion was evaluated using a phenol red thread tear test and corneal irregularity. The oxidative damage in the lacrimal gland was evaluated using TUNEL and immunohistochemical staining. The topical administration of aucubin significantly attenuated UPM-induced tear hyposecretion (control group: 9.25 ± 0.62 mm, UPM group: 4.55 ± 0.25 mm, 0.1% aucubin: 7.12 ± 0.58 mm, and 0.5% aucubin: 7.88 ± 0.75 mm) and corneal irregularity (control group: 0.00 ± 0.00, UPM group: 3.40 ± 0.29, 0.1% aucubin: 1.80 ± 0.27, and 0.5% aucubin: 1.15 ± 0.27). In addition, aucubin also reduced the UPM-induced apoptotic injury of lacrimal gland cells induced by oxidative stress through the increased expression of HMGB1 and RAGE. These findings indicate that the topical administration of aucubin eye drops showed a beneficial effect against UPM-induced abnormal ocular changes, such as tear hyposecretion and lacrimal gland damage. Therefore, our results reveal the pharmacological activities of aucubin in dry eye disease.

Background: von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by variants of the VHL tumor suppressor gene ( VHL ). Early detection and treatment are essential to prevent morbidity and mortality. We evaluated the effectiveness of surveillance strategies and the utility of a VHL clinic with a multidisciplinary team for the first time in Korea., Methods: The VHL clinic was organized at the Samsung Medical Center in 2011 and consisted of a multidisciplinary team, including an endocrinologist, urologist, general surgeon, neurosurgeon, ophthalmologist, otolaryngologist, and radiologist. Biochemical and imaging surveillance and personalized genetic counseling were conducted at the VHL clinic and patients were referred to the necessary departments upon detection of disease manifestation. We divided the patients in three groups (I-III) based on their compliance to VHL clinic attendance., Results: Between 2011 and 2018, 50 VHL patients were identified by VHL molecular analysis and referred to the VHL clinic. Most patients regularly participated in imaging of the central nervous system (43/50, 86.0%) and of the abdomen (46/50, 92.0%). However, there were differences in compliance to determination of the catecholamine level, audiometry, and ophthalmic examination among the three groups., Conclusions: We present the results of using a multidisciplinary team approach and showed that the VHL clinic strategy is useful for the comprehensive surveillance and management of VHL disease. We hope that VHL clinics will be widely set up in hospitals to improve prognosis in patients with VHL.

Background: Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary cancer syndrome characterized by hundreds to thousands of colorectal adenomatous polyps. Without treatment, progression to colorectal cancer is inevitable. Most pathogenic mutations in the APC gene were nonsense or frameshift mutations; however, some previous studies reported large deletions or duplications., Method: We reviewed the results of APC gene analyses from January 2010 to December 2020. We analyzed the entire coding sequence of the APC gene by Sanger sequencing to detect genetic abnormalities. Moreover, multiplex ligation-dependent probe amplification (MLPA) testing was performed starting in September 2017, and a multigene panel study that includes the APC gene was begun in July 2019., Results: In the 266 collected cases, pathogenic variants/likely pathogenic variants (PV/LPVs) in the APC gene were detected in 73 patients, and variants of uncertain significance were found in 13 patients. Among those variants, 14 variants were novel. We performed MLPA for 29 patients, and 7 of them (24.1%) were positive for a large duplication/deletion. Among the 73 cases in the multigene panel study, 17 cases (23.3%) of APC gene variation were detected., Conclusion: We retrospectively analyzed the APC gene in Korean patients suspected to have FAP. Variants truncated by nonsense and frame shift mutations were common PV/LPVs. However, the detection rate in the MLPA study was higher than in previous studies of Caucasian populations. We suggest that MLPA should be performed for patients likely to have FAP but in whom no variant is detected by sequencing methods., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests., (Copyright © 2022. Published by Elsevier Inc.)

X-linked lymphoproliferative disease type 1 (XLP1), an X-linked recessive genetic disorder, is associated with primary immunodeficiency. Patients with XLP1 are susceptible to Epstein-Barr virus (EBV) infection. SH2D1A gene is known as the causative gene. We found a novel hemizygous variant of SH2D1A , c.162&#95;201+31delinsTACAAGGACATATACA, from a 5-year-old male patient who had been diagnosed with EBV infection and Hodgkin's lymphoma. In targeted next-generation sequencing (NGS), complex variants at exon 2 were not consistently identified with two software programs. They showed a soft-clipped read pattern. The variant had a 71-bp deletion and a 16-bp insertion across exon 2 as confirmed by direct sequencing. As the variant was located within the exon-intron boundary, two aberrant transcripts were shown by RNA study. Although NGS method has a limitation in detecting large deletion/duplication variants, proper bioinformatics pipeline and careful review of data might enable the detection of complex variants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kwon, Kim, Park, Kim, Park, Kim, Yoo, Jang and Kang.)

Intervertebral disc (IVD) degeneration is the main source of intractable lower back pain, and symptomatic IVD degeneration could be due to different degeneration mechanisms. In this article, we describe the molecular basis of symptomatic IVD degenerative disc diseases (DDDs), emphasizing the role of degeneration, inflammation, angiogenesis, and extracellular matrix (ECM) regulation during this process. In symptomatic DDD, pro-inflammatory mediators modulate catabolic reactions, resulting in changes in ECM homeostasis and, finally, neural/vascular ingrowth-related chronic intractable discogenic pain. In ECM homeostasis, anabolic protein-regulating genes show reduced expression and changes in ECM production, while matrix metalloproteinase gene expression increases and results in aggressive ECM degradation. The resultant loss of normal IVD viscoelasticity and a concomitant change in ECM composition are key mechanisms in DDDs. During inflammation, a macrophage-related cascade is represented by the secretion of high levels of pro-inflammatory cytokines, which induce inflammation. Aberrant angiogenesis is considered a key initiative pathologic step in symptomatic DDD. In reflection of angiogenesis, vascular endothelial growth factor expression is regulated by hypoxia-inducible factor-1 in the hypoxic conditions of IVDs. Furthermore, IVD cells undergoing degeneration potentially enhance neovascularization by secreting large amounts of angiogenic cytokines, which penetrate the IVD from the outer annulus fibrosus, extending deep into the outer part of the nucleus pulposus. Based on current knowledge, a multi-disciplinary approach is needed in all aspects of spinal research, starting from basic research to clinical applications, as this will provide information regarding treatments for DDDs and discogenic pain., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Polydatin (resveratrol-3-O-β-mono-D-glucoside) is a polyphenol that can be easily accessed from peanuts, grapes, and red wine, and is known to have antiglycation, antioxidant, and anti-inflammatory effects. Diabetes mellitus is a very common disease, and diabetic complications are very common complications. The dry mouth symptom is one of the most common oral complaints in patients with diabetes mellitus. Diabetes mellitus is thought to promote hyposalivation. In this study, we aimed to investigate the improvement effect of polydatin on diabetes-induced hyposalivation in db/db mouse model of type 2 diabetes. We examined salivary flow rate, TUNEL assay, PAS staining, and immunohistochemical staining for AGEs, RAGE, HMGB1, 8-OHdG, and AQP5 to evaluate the efficacy of polydatin in the submandibular salivary gland. Diabetic db/db mice had a decreased salivary flow rate and salivary gland weight. The salivary gland of the vehicle-treated db/db mice showed an increased apoptotic cell injury. The AGEs were highly accumulated, and its receptor, RAGE expression was also enhanced. Expressions of HMGB1, an oxidative cell damage marker, and 8-OHdG, an oxidative DNA damage marker, increased greatly. However, polydatin ameliorated this hypofunction of the salivary gland and inhibited diabetes-related salivary cell injury. Furthermore, polydatin improved mucin accumulation, which is used as a damage marker for salivary gland acinar cells, and decreased expression of water channel AQP5 was improved by polydatin. In conclusion, polydatin has a potent protective effect on diabetes-related salivary gland hypofunction through its antioxidant and anti-glycation activities, and its AQP5 upregulation. This result suggests the possibility of the use of polydatin as a therapeutic drug to improve hyposalivation caused by diabetes.

Hops contain flavonoids that have sedative and sleep-promoting activities such as α-acid, β-acid, and xanthohumol. In this study, the sleep-enhancing activity of a Saaz-Saphir hops mixture was measured. In the caffeine-induced insomnia model, the administration of a Saaz-Saphir mixture increased the sleep time compared to Saaz or Saphir administration alone, which was attributed to the increase in NREM sleep time by the δ-wave increase. Oral administration of the Saaz-Saphir mixture for 3 weeks increased the γ-amino butyric acid (GABA) content in the brain and increased the expression of the GABA A receptor. As the GABA antagonists picrotoxin and bicuculline showed a decrease in sleep activity, it was confirmed that the GABA A receptor was involved in the Saaz-Saphir mixture activity. In addition, the GABA A receptor antagonist also reduced the sleep activity induced by xanthohumol and humulone contained in the Saaz-Saphir mixture. Therefore, xanthohumol and humulone contained in the Saaz-Saphir mixture showed sleep-promoting activity mediated by the GABA A receptors. The mixture of the Saaz and Saphir hop varieties may thus help mitigate sleep disturbances compared to other hop varieties.

A declined salivary gland function is commonly observed in elderly people. Advanced glycation end products (AGEs) are believed to contribute to the pathogenesis of aging. Although physical exercise is shown to increase various organ functions in human and experimental models, it is not known whether it has a similar effect in the salivary glands. In the present study, we evaluated the AGEs burden in the salivary gland in the aging process and the protective effect of physical exercise on age-related salivary hypofunction. To accelerate the aging process, rats were peritoneally injected with D-galactose for 6 weeks. Young control rats and d-galactose-induced aging rats in the old group were not exercised. The rats in the physical exercise group ran on a treadmill (12 m/min, 60 min/day, 3 days/week for 6 weeks). The results showed that the salivary flow rate and total protein levels in the saliva of the d-galactose-induced aging rats were reduced compared to those of the young control rats. Circulating AGEs in serum and secreted AGEs in saliva increased with d-galactose-induced aging. AGEs also accumulated in the salivary glands of these aging rats. The salivary gland of aging rats showed increased reactive oxygen species (ROS) generation, loss of acinar cells, and apoptosis compared to young control mice. However, physical exercise suppressed all of these age-related salivary changes. Overall, physical exercise could provide a beneficial option for age-related salivary hypofunction.

Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP) in the lumbar spine. This phenomenon is caused by several processes, including matrix degradation in IVD tissues, which is mediated by matrix metalloproteinases (MMPs) and inflammatory responses, which can be mediated by interactions among immune cells, such as macrophages and IVD cells. In particular, interleukin (IL)-1 beta (β), which is a master regulator secreted by macrophages, mediates the inflammatory response in nucleus pulposus cells (NP) and plays a significant role in the development or progression of diseases. In this study, we developed a custom electrical stimulation (ES) platform that can apply low-constant-current stimulation (LCCS) signals to microfluidic chips. Using this platform, we examined the effects of LCCS on IL-1β-mediated inflammatory NP cells, administered at various currents (5, 10, 20, 50, and 100 μA at 200 Hz). Our results showed that the inflammatory response, induced by IL-1β in human NP cells, was successfully established. Furthermore, 5, 10, 20, and 100 μA LCCS positively modulated inflamed human NP cells' morphological phenotype and kinetic properties. LCCS could affect the treatment of degenerative diseases, revealing the applicability of the LCCS platform for basic research of electroceuticals.

Abstract: Previous comparison studies regarding 2 types of transportation, helicopter (HEMS) versus ground emergency medical services (GEMS), have shown underlying heterogeneity as these options have completely different routes and consequent times with reference to one patient. To compare the 2 types of transportation on a case-by-case basis, we analyzed the retrospectively reviewed HEMS and predicted GEMS data using an open-source navigation software.Patients transferred by military HEMS from 2016 to 2019 were retrospectively enrolled. The HEMS records on the time of notification, injury point and destination address, and time required were reviewed. The GEMS data on distance and the predicted time required were acquired using open-source social navigation systems. Comparison analyses between the two types of transportation were conducted. Furthermore, linear logistic regression analyses were performed on the distance and time of the two options.A total of 183 patients were enrolled. There was no statistical difference (P = .3021) in the distance between the 2 types of transportation, and the HEMS time was significantly shorter than that of GEMS (61.31 vs 116.92 minutes, P < .001). The simple linear curves for HEMS and GEMS were separately secured, and two graphs presented the statistical significance (P) as well as reasonable goodness-of-fit (R2). In general, the HEMS graph demonstrates a more gradual slope and narrow distribution compared to that of GEMS.Ideally, HEMS is identified as a better transportation modality because it has a shorter transportation time (56 minutes saved) and a low possibility of potential time delays (larger R2). With a strict patient selection, HEMS can rescue injured or emergent patients who are "out of the golden hour.", Competing Interests: Conflict of interest statement: The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. No financial support has been received in association with this submission., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Patients with diabetes commonly experience hyposalivation, which induces discomfort in eating, swallowing, dryness, smell, and speaking, as well as increases the incidence of periodontal disease. Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently used as antidiabetic drugs that lower glucose levels by utilizing similar mechanisms; however, additional protective functions of each gliptin have been discovered. In this study, the protective roles of gemigliptin, a DPP4 inhibitor, against salivary dysfunction under diabetic conditions were investigated. Streptozotocin-induced diabetic rats received gemigliptin 10 mg/kg or 100 mg/kg via oral gavage for 3 weeks. The weights of salivary gland tissues, saliva secretion, and antioxidant capacity in salivary glands were reduced after diabetes induction, but were significantly preserved following gemigliptin treatment. In salivary gland analysis, expression of apoptotic proteins, as well as amylase and aquaporin-5 (AQP5) protein expression, were increased following gemigliptin treatment. Furthermore, the number of TUNEL-positive cells decreased after gemigliptin treatment. Therefore, gemigliptin has protective roles against salivary dysfunction observed in diabetes, mediated via antioxidant, anti-apoptotic, and salivary secretion mechanisms. These results may help in selecting a suitable drug for patients with diabetes experiencing salivary dysfunction., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)