OBJECTIVES: Because effective decolonization options are not available, and treatment options are limited, carbapenem-resistant Enterobacterales (CRE) constitute increasingly threatening nosocomial pathogens. To prevent CRE-associated transmission and ensure patient safety, healthcare personnel and everyone in contact with CRE-infected patients must implement stringent infection control practices. This report describes a CRE outbreak, possibly related to a caregiver at a long-term care facility (LTCF), and presents a new surveillance model to improve the infection control of CRE in Seoul, Korea. METHODS: The Seoul Metropolitan Government surveillance system identified an outbreak of CRE in an LTCF in 2022. We obtained data on the demographic characteristics and contact histories of the inpatients, medical staff, and caregivers. To isolate the inpatients and employees exposed to CRE, we used rectal swab samples and environmental sampling during the study period (May-December 2022). RESULTS: We identified 18 cluster cases (1 caregiver and 17 inpatients) and 12 sporadic cases with CRE, and conducted a complete 197-day follow-up of all cases in the LTCF’s isolation wards. CONCLUSIONS This investigation demonstrated that our surveillance model and targeted intervention, based on the cooperation of the municipal government, public health center, and infection control advisory committee, effectively contained the epidemic at the LTCF. Measures to improve the compliance of all employees in LTCFs with infection control guidelines should also be adopted.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

BACKGROUND: Enhancement and maintenance of the stemness of mesenchymal stem cells (MSCs) is one of the most important factors contributing to the successful in vivo therapeutic application of these cells. In this regard, three-dimensional (3D) spheroid formation has been developed as reliable method for increasing the pluripotency of MSCs. Moreover, using a new protocol, we have previously shown that dental tissues of extracted wisdom teeth can be effectively cryopreserved for subsequent use as a source of autologous stem cells. The main purpose of this study is to analyze the stemness and in vitro osteogenic differentiation potential of 3D spheroid dental MSCs compared with conventional monolayer cultured MSCs. METHODS: In this study, MSC-characterized stem cells were isolated and cultured from long-term cryopreserved dental follicles (hDFSCs), and then 2D hDFSCs were cultured under 3D spheroid-forming conditions using a newly designed microchip dish. The spheroids (3D hDFSCs) thus produced were investigated and characterized with respect to stemness, MSC marker expression, apoptosis, cell cycle analysis, extracellular matrix (ECM) production, and osteogenic and adipogenic differentiation properties. RESULTS: In terms of MSC and senescence markers, spheroid cells showed no difference when compared with 2D hDFSCs; however, 3D hDFSCs were observed to have a higher proportion of cell cycle arrest and a larger number of apoptotic cells. Moreover, spheroids showed substantially increased levels of pluripotency marker (early transcription factors) and ECM protein expression. Compared with 2D hDFSCs, there was also a notable enhancement in the osteogenic induction potential of spheroids, although no differences were observed with respect to in vitro adipogenesis. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate the application of a spheroid culture system for dental follicle-derived stem cells using a microchip dish. Although further studies are needed, including in vivo transplantation, the results obtained in this study indicate that spheroid hDFSCs derived from cryopreserved dental follicle tissues could be used as a valuable source of autologous stem cells for bone tissue regeneration.
Adipogenesis ; Aging ; Apoptosis ; Bone and Bones ; Cell Cycle ; Cell Cycle Checkpoints ; Dental Sac ; Extracellular Matrix ; Humans ; In Vitro Techniques ; Mesenchymal Stromal Cells ; Methods ; Molar, Third ; Osteogenesis ; Regeneration ; Stem Cells

PURPOSE: We evaluated the clinical value of breast magnetic resonance imaging (MRI) in patients who underwent breast-conserving surgery (BCS). The degree of correlation between pathology size and MRI or ultrasonography (US) size was compared based on breast cancer subtypes. In addition, we investigated the positive margin rates. METHODS: Patients with invasive breast cancer who underwent preoperative breast MRI and US between 2011 and 2016 were included in the study. Lin's concordance correlation coefficient was used to measure the correlation between MRI or US andpathologic tumor extent. Tumor extent was defined as pathologic tumor size, including in situ carcinoma. Margin positivity was assessed based on frozen-section examination. RESULTS: A total of 516 patients with a single tumor who underwent BCS were included in the study. The correlation between pathologic size and MRI was significantly higher than that of US (r = 0.6975 vs. 0.6211, p = 0.001). The superiority of MRI over US in measuring the pathologic extent was only observed in triple-negative breast cancer (TNBC; r = 0.8089 vs. 0.6014, p < 0.001). The agreement between MRI or US and tumor extent was low for the human epidermal growth factor receptor 2 (HER2)-positive subtype (MRI: 0.5243, US: 0.4898). Moreover, the positive margin rate was higher in the HER2-positive subtype than in the others (luminal/HER2-negative: 11.6%, HER2-positive: 23.2%, TNBC: 17.8%, p = 0.019). The post hoc analysis showed that the HER2-positive subtype was more likely to show positive margins than the luminal/HER2-negative subtype (p = 0.007). CONCLUSION: Breast MRI was superior to US in the preoperative assessment of the pathologic extent of tumor size; this was most evident in TNBC. For HER2-positive tumors, imaging-pathologic discordance resulted in higher positive margin rates than that with other subtypes.
Breast Neoplasms ; Breast ; Humans ; Magnetic Resonance Imaging ; Mastectomy, Segmental ; Pathology ; Receptor, Epidermal Growth Factor ; Receptor, ErbB-2 ; Triple Negative Breast Neoplasms ; Ultrasonography

PURPOSE: There is still a clinical need to easily evaluate the metastatic status of lymph nodes during breast cancer surgery. We hypothesized that ex vivo shear-wave elastography (SWE) would predict precisely the presence of metastasis in the excised lymph nodes. METHODS: A total of 63 patients who underwent breast cancer surgery were prospectively enrolled in this study from May 2014 to April 2015. The excised axillary lymph nodes were examined using ex vivo SWE. Metastatic status was confirmed based on the final histopathological diagnosis of the permanent section. Lymph node characteristics and elasticity values measured by ex vivo SWE were assessed for possible association with nodal metastasis. RESULTS: A total of 274 lymph nodes, harvested from 63 patients, were examined using ex vivo SWE. The data obtained from 228 of these nodes from 55 patients were included in the analysis. Results showed that 187 lymph nodes (82.0%) were nonmetastatic and 41 lymph nodes (18.0%) were metastatic. There was significant difference between metastatic and nonmetastatic nodes with respect to the mean (45.4 kPa and 17.7 kPa, p<0.001) and maximum (55.3 kPa and 23.2 kPa, p<0.001) stiffness. The elasticity ratio was higher in the metastatic nodes (4.36 and 1.57, p<0.001). Metastatic nodes were significantly larger than nonmetastatic nodes (mean size, 10.5 mm and 7.5 mm, p<0.001). The size of metastatic nodes and nodal stiffness were correlated (correlation coefficient of mean stiffness, r=0.553). The area under curve of mean stiffness, maximum stiffness, and elasticity ratio were 0.794, 0.802, and 0.831, respectively. CONCLUSION: Ex vivo SWE may be a feasible method to predict axillary lymph node metastasis intraoperatively in patients undergoing breast cancer surgery.
Area Under Curve ; Axilla ; Breast Neoplasms* ; Breast* ; Diagnosis ; Elasticity ; Elasticity Imaging Techniques* ; Humans ; Lymph Nodes* ; Lymphatic Metastasis ; Methods ; Neoplasm Metastasis* ; Prospective Studies

PURPOSE: We assessed the visual and anatomical outcomes, and the safety profile of long-term intravitreal anti-vascular endothelial growth factor (VEGF) injections (aflibercept, ranibizumab, and bevacizumab) given to treat neovascular age-related macular degeneration (NAMD). METHODS: We analyzed medical records collected over 7 years of treatment-naive NAMD patients who received outpatient clinic-based intravitreal anti-VEGF injections. All were treated employing either “treat-and-extend” or “as needed” protocols at the discretion of the retinal specialist. The number of injections, adverse events associated with injection, and measures of visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP) were recorded. RESULTS: Overall, we assessed 196 eyes of 196 patients (average age 68.6 ± 9.6 years; 77 females). Patients received an average of 17.3 ± 13.5 injections over 78.0 ± 16.5 months of clinical follow-up. The initial mean VA (logMAR) was 0.75 ± 0.58 and the CFT was 349.7 ± 152.6 µm. Both parameters exhibited maximal improvements at the 6-month visit (p < 0.05). However, the clinical outcomes worsened over the 7-year clinical course; the best-corrected visual acuity (BCVA) was 0.91 ± 0.78 and the CFT was 284.5 ± 105.8 µm at 7 years. The BCVA at 7 years was significantly correlated with the initial BCVA. IOP-related events increased 11-fold and anterior chamber reactions increased 3-fold over the years, but no significant complications such as endophthalmitis were recorded. CONCLUSIONS: The use of intravitreal anti-VEGF agents was associated with initial visual improvements over 6 months but did not prevent the worsening of NAMD over 5 years. The BCVA at the initial visit was a strong predictor of the final BCVA. A more intensive injection schedule might improve long-term outcomes.
Anterior Chamber ; Appointments and Schedules ; Choroidal Neovascularization ; Endophthalmitis ; Endothelial Growth Factors ; Follow-Up Studies ; Humans ; Intraocular Pressure ; Macular Degeneration ; Medical Records ; Outpatients ; Ranibizumab ; Retinaldehyde ; Specialization ; Visual Acuity

BACKGROUND: To examine survival rates and renal function after partial nephrectomy (PN) and radical nephrectomy (RN) in patients with chronic kidney disease (CKD). METHODS: We studied 4,332 patients who underwent PN or RN for pathological T1a-T2N0M0 renal cell carcinoma from 1988 to 2014. Patients were divided into two subgroups of CKD stage I–II and stage III. Kidney function, and survival outcomes were compared between groups. RESULTS: We included 1,756 patients with CKD I–II and 276 patients with CKD III in the final pair-matched analysis. Kidney function was significantly better preserved in the PN than in the RN group among all patients. However, the beneficial effect of PN on kidney function gradually disappeared over time in CKD III patients. The 5-year overall survival (OS) rates after PN and RN differed in patients with CKD I–II disease (99.4% vs. 96.5%, respectively, P = 0.015). The 5-year OS rates after surgery were not affected by mode of nephrectomy in CKD III patients (97.8% vs. 93.5%, P = 0.103). The 5-year cancer-specific survival rates did not differ between treatment groups in all CKD stage. Cox hazard analysis showed that the operative method was a significant factor for OS in CKD I–II patients (hazard ratio [HR], 0.320; confidence interval [CI], 0.122–0.840; P = 0.021). However, PN was not beneficial in terms of OS in CKD III patients (HR, 0.395; CI, 0.086–1.172; P = 0.117). CONCLUSION: PN is associated with a higher OS rate and better kidney function in patients with preoperative CKD stage I and II, but not in those with CKD stage III.
Carcinoma, Renal Cell* ; Humans ; Kidney* ; Methods ; Nephrectomy* ; Renal Insufficiency ; Renal Insufficiency, Chronic* ; Survival Rate*

Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD⁺) metabolism. However, the functional role of NAD⁺ metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD⁺ levels affect the characteristics of glioma-driven SSEA1⁺ TICs, including clonogenic growth potential. An increase in the mitochondrial NAD⁺ levels by the overexpression of the mitochondrial enzyme nicotinamide nucleotide transhydrogenase (NNT) significantly suppressed the sphere-forming ability and induced differentiation of TICs, suggesting a loss of the characteristics of TICs. In addition, increased SIRT3 activity and reduced lactate production, which are mainly observed in healthy and young cells, appeared following NNT-overexpressed TICs. Moreover, in vivo tumorigenic potential was substantially abolished by NNT overexpression. Conversely, the short interfering RNA-mediated knockdown of NNT facilitated the maintenance of TIC characteristics, as evidenced by the increased numbers of large tumor spheres and in vivo tumorigenic potential. Our results demonstrated that targeting the maintenance of healthy mitochondria with increased mitochondrial NAD⁺ levels and SIRT3 activity could be a promising strategy for abolishing the development of TICs as a new therapeutic approach to treating aging-associated tumors.
Glioblastoma* ; Lactic Acid ; Metabolism ; Mitochondria ; NAD ; NADP Transhydrogenases ; Phenotype ; Tics ; Up-Regulation*

BACKGROUND/AIMS: The aim of this study was to identify the ability of Glasgow-Blatchford score (GBS) and pre-endoscopic Rockall score (pre-E RS) to predict the occurrence of hypotension in patients with non-variceal upper gastrointestinal bleeding who are initially normotensive at emergency department. METHODS: Retrospective observational study was conducted at Asan Medical Center emergency department (ED) in patients who presented with non-variceal upper gastrointestinal bleeding from January 1, 2011 to December 31, 2013. Study population was divided according to the development of hypotension, and demographics, comorbidities, and laboratory findings were compared. GBS and pre-E RS were estimated to predict the occurrence of hypotension. RESULTS: A total of 747 patients with non-variceal upper gastrointestinal bleeding were included during the study period, and 120 (16.1%) patients developed hypotesion within 24 hours after ED admission. The median values GBS and pre-E RS were statistically different according to the occurrence of hypotension (8.0 vs. 10.0, 2.0 vs. 3.0, respectively; p<0.001). In the receiver operating characteristic curve analysis of hypotension development, the area under the curve of GBS and pre-E RS were 66% and 64%, respectively. The sensitivity and the specificity of GBS using optimal cut-off value were 81% and 46%, respectively, while those based on the pre-E RS were 74% and 46%, respectively. CONCLUSIONS: GBS and pre-E RS were both not sufficient for predicting the occurrence of hypotension in non-variceal upper gastrointestinal bleeding. Development of other scoring systems are needed.
Adult ; Aged ; Area Under Curve ; Demography ; Emergency Service, Hospital ; Female ; Gastrointestinal Hemorrhage/complications/*diagnosis/pathology ; Humans ; Hypotension/epidemiology/*etiology ; Male ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Retrospective Studies ; Severity of Illness Index ; Upper Gastrointestinal Tract