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Purpose@#The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. @*Methods@#We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. @*Results@#CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. @*Conclusion@#This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.
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Paroxysmal kinesigenic dyskinesia (PKD) is a diagnostic term for transient, involuntary abnormal movements triggered by sudden motions. The treatment for PKD differs from other paroxysmal dyskinesias, as it notably responds well to sodium channel blockers. We report a case of atypical PKD, coupled with paroxysmal exercise-induced dyskinesia (PED). Both PKD and PED in this patient showed a good response to oxcarbazepine. This case could be clinical evidence that paroxysmal dyskinesias could potentially be regarded as a spectrum disorder with overlapping features.
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Background@#Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). @*Objectives@#This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. @*Methods@#We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. @*Results@#When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h (p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased (p < 0.01), and the G2/M phase ratio showed a significant increase (p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. @*Conclusion@#In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs.
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Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin’s lymphoma that selectively involves the lumina of vessels, and may present as ischemic stroke. A 62-year-old man presented with progressive aphasia, dementia, seizure and stroke-like symptom. Brain magnetic resonance imaging revealed dynamic progressive fluid attenuated inversion recovery lesions and multiple punctate microbleeds in the bilateral subcortical region. A kidney biopsy revealed IVLBCL. We report a patient with IVLBCL presenting as rapidly progressive encephalopathy.
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Objectives@#Acute low-tone sensorineural hearing loss (ALHL) is thought to have a different etiology from that of idiopathic sudden sensorineural hearing loss. We hypothesized that endolymphatic hydrops (EH) in the inner ear organ contributes to ALHL, even in patients without vertigo. This study investigated the presence of EH in ALHL and compared the clinical characteristics of patients with or without EH. @*Methods@#We retrospectively reviewed 38 patients diagnosed with ALHL without vertigo from January 2017 to March 2022. EH was measured in all patients using inner ear magnetic resonance imaging (MRI). In addition, we selected patients who showed only mid- or high-frequency hearing loss and had available MRI data as a control group and compared the ALHL and control groups. @*Results@#After treatment, the pure-tone average at low frequencies significantly improved compared to the initial hearing (P<0.001). Hearing recovery was observed in 63.1% of patients; however, the recovery rate did not differ based on the treatment method. During the follow-up period, six patients (15.8%) progressed to Meniere’s disease, and 18 (47.4%) experienced recurrence. In the ALHL group, the cochlear hydrops ratio on the affected side (0.34±0.09) was significantly higher than on the contralateral side (0.29±0.12) (P=0.005), and most patients showed hydrops in the apex area of the cochlea. Compared with the control group (0.25±0.15), the ALHL group showed a significantly higher cochlear hydrops ratio (P=0.043). The correlation analysis showed a tendency for hearing thresholds at low frequencies to increase as the hydrops ratio increased, albeit without statistical significance. @*Conclusion@#The cochlear hydrops ratio, especially in the apex area on the affected side, was significantly higher in patients with ALHL, suggesting that EH in the cochlea contributes to the pathogenesis of ALHL.
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Purpose@#This study aimed to analyze the incidence and risk factors of complications following gastric cancer surgery in Korea and to compare the correlation between hospital complications based on the annual number of gastrectomies performed. @*Materials and Methods@#A retrospective analysis was conducted using data from 12,244 patients from 64 Korean institutions. Complications were classified using the Clavien-Dindo classification (CDC). Univariate and multivariate analyses were performed to identify the risk factors for severe complications. @*Results@#Postoperative complications occurred in 14% of the patients, severe complications (CDC IIIa or higher) in 4.9%, and postoperative death in 0.2%. The study found that age, stage, American Society of Anesthesiologists (ASA) score, Eastern Cooperative Oncology Group (ECOG) score, hospital stay, approach methods, and extent of gastric resection showed statistically significant differences depending on hospital volumes (P<0.05). In the univariate analysis, patient age, comorbidity, ASA score, ECOG score, approach methods, extent of gastric resection, tumor-node-metastasis (TNM) stage, and hospital volume were significant risk factors for severe complications. However, only age, sex, ASA score, ECOG score, extent of gastric resection, and TNM stage were statistically significant in the multivariate analysis (P<0.05). Hospital volume was not a significant risk factor in the multivariate analysis (P=0.152). @*Conclusions@#Hospital volume was not a significant risk factor for complications after gastric cancer surgery. The differences in the frequencies of complications based on hospital volumes may be attributed to larger hospitals treating patients with younger age, lower ASA scores, better general conditions, and earlier TNM stages.
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A resorbable barrier membrane is commonly used for the repair of perforated sinus membranes during sinus lifting surgeries. However, repairing largescale perforations poses challenges for clinicians as the protection and isolation of graft material remain uncertain. With this technique, we aimed to prevent graft material loss and subsequent sinus-related complications using intra-sinus rigid fixation of the resorbable barrier membrane in cases with a large perforation of the sinus membrane.
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Background@#This study aimed to differentiate video nystagmography (VNG) characteristics, including the video head impulse test (vHIT), in patients with idiopathic rapid eye movement behavior disorder (RBD) from healthy controls, which is considered a precursor to degenerative diseases. @*Methods@#One hundred eighty-five patients underwent overnight polysomnography (PSG) and VNG. Based on overnight PSG, 27 patients with RBD or REM sleep without atonia (RWA) and AHI<15 were categorized into the RBD group, 34 patients with RBD/RWA and AHI≥15 were grouped into the combined group. Sixty patients with AHI≥15 and no RBD/RWA were included in the obstructive sleep apnea (OSA) group, and 64 negative participants were assigned to the control group. In VNG, we measured the gain of vHIT in each canal, with the latency, amplitude, and velocity of horizontal saccades and smooth pursuit. We compared the results between groups using ANOVA, after normalization and adjustment for age and sex. @*Results@#The gain of vHIT in the left horizontal canal was decreased in the RBD group, but it was more pronounced in the OSA group. Elevated gain of the left posterior canal was seen in the RBD group, but technical errors were attributable. The RBD group displayed prolonged latency of saccade on the left side and slowed saccade on the right side, but these were statistically insignificant. @*Conclusions@#The VNG study revealed differences between the sleep disorders, potentially reflecting brainstem function in each disorder. However, these differences lacked statistical significance. We anticipate that significant results could be obtained with more controlled conditions.
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Background@#Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology. @*Methods@#We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured. @*Results@#There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336). @*Conclusions@#Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.
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Background@#Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals. @*Objectives@#This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model. @*Methods@#Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. @*Results@#TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b + CD206 + macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2 ) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells. @*Conclusions@#These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE2 pathway.
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Background@#It was to describe collaborative educational efforts under Coronavirus disease 2019 period to advocate pharmacybased immunization delivery and meet unmet needs of partnership institution using virtual learning platforms. @*Methods@# A partnership was established among three pharmacy schools from two countries. The class content included the history of pharmacy immunization, pharmacists’ roles and contribution to public health of the USA. The class also reviewed the value of pharmacists as frontline healthcare workers to foster student insights and the scope of pharmacy. The virtual class featured an interactive video simulation and small breakroom discussion besides a lecture. @*Results@#Participants indicated that public accessibility to pharmacy and six-year education system in South Korea as advantages. However, legislative restrictions, pharmacist burden, and interprofessional disagreements were expressed as barriers to introduce the pharmacist immunization. @*Conclusion@# A virtual learning platform was used to advocate for pharmacy-based immunization and fulfilled an unmet educational gap at a partnership institution.
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Objectives@#We investigated differences in high-sensitivity C-reactive protein (hs-CRP) levels by age group according to working hours, socioeconomic level, health behavior and status, and occupational class, and aimed to identify factors affecting hs-CRP levels in various age groups using data from the Korean National Health and Nutrition Examination from 2016 to 2018. @*Methods@#The study included a total of 4,786 male wage workers across the nation, aged between 19 and 65. Data from 4,674 workers were analyzed using multiple logistic regression analysis. @*Results@#Obesity, metabolic syndrome, and weekly working hours were associated with hs-CRP, a biomarker of inflammation. Participants with a body mass index (BMI) ≥25.0 kg/m2 showed significantly higher hs-CRP levels than those with a BMI 23.0 to 25.0 kg/m2 . Workers with highrisk drinking and metabolic syndrome showed significantly higher hs-CRP levels in the 50 to 65 years group. Obesity, walking 0 to 149 min/wk, and working ≥61 hours a week were associated with significantly higher hs-CRP levels in the 35 to 49 years group. The factors that significantly affected hs-CRP levels were different among age groups. @*Conclusion@#Plans to adjust working hours should be considered health behaviors, such as drinking and physical activity, and health conditions, such as metabolic syndrome and obesity, according to workers’ age.
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The Korean government initiated a plan to designate and establish Regional Trauma Centers to reduce the preventable trauma death rate to <20% so as to be on par with advanced countries by 2020. This initiative was undertaken because the reported preventable trauma death rate was close to 40% in South Korea from 1997 to 2009. This review aimed to provide an overview of these Regional Trauma Centers and discuss further development of the trauma care system to assess its performance. As of September 2021, 15 Regional Trauma Centers had been established through a metropolitan-based designation process. Each center has been equipped with Level-I facilities. These Regional Trauma Centers have had 2 positive effects; namely, an increase in the number of severely injured patients attending these centers and a decrease in the national preventable trauma death rate from 30.5% in 2015 to 19.9% in 2017. The establishment of Regional Trauma Centers can lead to improved performance, maximal efficiency, and reduction of preventable deaths in trauma patients.They can also play a key role in prehospital triage and transportation in the trauma care system.
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Robotic bariatric surgery renders it unnecessary for surgeons to manually apply torque while simplifying intracorporeal suturing. Surgeons can comfortably manipulate instruments. Also, the three-dimensional operative field is very clear. Unfortunately, robotic bariatric surgery is still not the first choice for morbidly obese patients in Korea because it currently is not covered by the National Healthcare Insurance system. In this video, we show the totally robotic Roux-en-Y gastric bypass conducted using robotic staplers, in a morbidly obese patient with diabetes mellitus and private medical insurance.
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Background@#and Purpose: We investigated the correlation between the deep distribution of white matter hyperintensity (WMH) (dWMH: WMH in deep and corticomedullary areas, with minimal periventricular WMH) and a positive agitated saline contrast echocardiography result. @*Methods@#We retrospectively recruited participants with comprehensive dementia evaluations, an agitated saline study, and brain imaging. The participants were classified into two groups according to WMH-distributions: dWMH and dpWMH (mainly periventricular WMH with or without deep WMH.) We hypothesized that dWMH is more likely associated with embolism, whereas dpWMH is associated with small-vessel diseases. We compared the clinical characteristics, WMH-distributions, and positive rate of agitated saline studies between the two groups. @*Results@#Among 90 participants, 27 and 12 met the dWMH and dpWMH criteria, respectively. The dWMH-group was younger (62.2±7.5 vs. 78.9±7.3, p<0.001) and had a lower prevalence of hypertension (29.6% vs. 75%, p=0.008), diabetes mellitus (3.7% vs.25%, p=0.043), and hyperlipidemia (33.3% vs. 83.3%, p=0.043) than the dpWMH-group. Regarding deep white matter lesions, the number of small lesions (<3 mm) was higher in the dWMH-group(10.9±9.7) than in the dpWMH-group (3.1±6.4) (p=0.008), and WMH was predominantly distributed in the border-zones and corticomedullary areas. Most importantly, the positive agitated saline study rate was higher in the dWMH-group than in the dpWMH-group (81.5% vs. 33.3%, p=0.003). @*Conclusions@#The dWMH-group with younger participants had fewer cardiovascular risk factors, showed more border-zone-distributions, and had a higher agitated saline test positivity rate than the dpWMH-group, indicating that corticomedullary or deep WMHdistribution with minimal periventricular WMH suggests embolic etiologies.
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This study aims to propose the implementation of innovative payment models in Korea in order to promote the financial sustainability of the national health insurance system by reviewing the current status of the payment system in Korea and examining other countries’ experiences with various innovative payment models. Korea primarily uses a fee-for-service payment system and additionally uses various payment systems such as case payment, per diem, and pay-for-performance. However, each payment system has its limitations. Many OECD (Organization for Economic Cooperation and Development) countries have pointed out the limitations of existing payment systems and have been attempting various innovative payment models (e.g., add-on payment, bundled payment, and population-based payment). Therefore, it is essential for Korea to consider innovative payment models, such as a mixed payment model that takes into account the strengths and weaknesses of each payment system, and to design and pilot these models.This process requires stakeholders to work together to build a social consensus on the implementation of innovative payment systems and to refine legal and systematic aspects, develop an integrated health information system, and establish dedicated organizations and committees. These efforts towards innovative payment models will contribute to developing a sustainable health insurance system that ensures the public’s health and well-being in Korea.
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Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis.Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from Ldlr−/− mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including Pnpla2 and Lpl< were markedly increased but expressions of Lpin2 and Dgat1 related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.
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Purpose@#The purpose of this study is to analyze the brain waves and develop various exercise programs to improve the physical and mental aspects of stroke patients when neurological physical therapy and sitting table tennis exercise are applied to stroke patients. @*Methods@#In this study, an experiment was conducted on 15 patients diagnosed with stroke, and training was performed after changing the ping-pong table to a sitting position to apply ping-pong exercise to stroke patients. After training was conducted for 40 minutes twice a week for 4 weeks, brain waves were measured before and after. EEG was measured using Laxtha’s DSI-24 equipment as a measurement tool, and data values were extracted through the Telescan program. @*Results@#Most of the relative beta waves showed a significant difference before and after the intervention. As for the characteristics of beta waves, this result can be seen as being highly activated during exercise or other activities. @*Conclusion@#Ping-pong exercise in a sitting position is a good intervention method for stroke patients, and it can help to use it as basic data in clinical practice by showing brain activity.
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Objectives@#The prognostic significance of CDC42 effector protein 2 (CDC42EP2) and its association with tumor-infiltrating immune cells (TIICs) have not been explored in liver hepatocellular carcinoma (LIHC). This study aims to assess the potential prognostic value of CDC42EP2 by conducting a comprehensive analysis of online databases pertaining to LIHC. @*Methods@#We evaluated the potential of CDC42EP2 as a prognostic biomarker by utilizing online databases such as TIMER, GEPIA2, KM, OSlihc, HPA, and LinkedOmics. @*Results@#In LIHC, we observed that the mRNA and protein expression of CDC42EP2 were upregulated compared to normal tissues. Upregulated CDC42EP2 expression was associated with a worse prognosis based on the clinicopathological characteristics of patients with LIHC. Furthermore, CDC42EP2 was positively associated with TIICs. In the co-expression and functional enrichment analyses of CDC42EP2, 11,416 genes showed positive associations with CDC42EP2 while 8,008 genes showed negative associations. CDC42EP2-related co-expression genes were involved in protein localization to the endoplasmic reticulum, translational initiation, and RNA catabolic processes in gene set enrichment analysis-Gene Ontology (GSEA-GO), and regulated the ribosome, spliceosome, and primary immune deficiency in the GSEA-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. In a survival map, 23 and 17 genes that exhibited positive associations with CDC42EP2 showed a significant hazard ratio (HR) for overall survival and disease-free survival, respectively. @*Conclusion@#Our findings demonstrated that CDC42EP2 is a novel prognostic biomarker and a potential tumor immune therapeutic target in patients with LIHC.
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Purpose@#To evaluate the long-term outcome and prognostic factors according to the degree of obstruction after silicone tube intubation in patients with nasolacrimal duct obstruction (NLDO). @*Methods@#From March 2016 to July 2020, the medical records of 145 eyes of 107 patients with NLDO who underwent silicone tube intubation and had been followed for more than 6 months were analyzed retrospectively. The preoperative lacrimal irrigation and degree of obstruction were classified into three groups, and the surgery outcome was also evaluated. Successful surgery was defined as a case in which the epiphora improved, the height of the tear meniscus decreased, and there was no reflux in the postoperative lacrimal irrigation. Risk factors for recurrence were analyzed using a Cox proportional hazards model and Kaplan-Meier survival analysis. @*Results@#Surgery was successful in 99 eyes (68.3%), while recurrence occurred in 46 eyes (31.7%) after silicone tube removal. The average follow-up period was 23.09 months. The recurrence rate was 30.4%, 29.3%, and 50.0% for functional, partial, and total NLDO, respectively, and did not differ significantly (p = 0.300). The risk of recurrence was higher at older age (adjusted hazard ratio [aHR] = 1.079, p < 0.001) and with a history of facial palsy (aHR = 4.031, p = 0.019), and was lower in the functional NLDO group than in the total NLDO group (aHR = 0.368, p = 0.040). In the Kaplan–Meier survival analysis, the total NLDO group differed significantly from the functional NLDO group (log-rank, p = 0.011). @*Conclusions@#Age, a history of facial palsy, and the degree of preoperative obstruction were associated with the prediction of recurrence after silicone tube intubation in patients with NLDO.