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Objective The aims of our study were to identify distinct trajectories of cognitive function using the group-based trajectory model. We also investigate which demographic factors act as risk factors for cognitive decline in each group.Methods The data from the Seoul National University Hospital Healthcare System Gangnam Center, from 2005 to 2019. The number of study subjects was 637. We used a group-based model to identify cognitive function trajectories. Multinomial logistic regression was employed to define risk factors for cognitive function decline.Results The cognitive function trajectories among adults over 40 years of age were heterogeneous. We identified four trajectories: high (27.3%), medium (41.0%), low (22.7%), and rapid decline (9.1%). Older age, male, low educational level, bad dietary habits, diabetes mellitus, technical worker, and lower income increased the likelihood of a cognitive function decline.Conclusion A younger age, a higher educational level, professional worker, good dietary habits, no diabetes mellitus, and no obesity improved cognitive function. A combination of these factors can improve “cognitive reserve” and delay cognitive decline. Interventions to prevent cognitive decline are needed after identification of high-risk groups for cognitive decline.

Purpose We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients.Materials and Methods Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL.Results A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS.Conclusion The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

Purpose: We report a case of primary mucinous adenocarcinoma diagnosed in a patient presenting with a mass of the lower eyelid.Case summary: A 60-year-old man presenting with a mass on the left lower eyelid that had increased in size for 3 years was referred to our center after being diagnosed as mucinous adenocarcinoma. The mass was limited to the dermis and subcutaneous fat layer. The extent of the lesion was confirmed through frozen section examination, and tumor removal was performed. In immunohistochemistry, estrogen receptor, progesterone receptor, and cytokeratin-7 were positive, and cytokeratin-20 was negative. No metastasis was found, so it was diagnosed as primary mucinous adenocarcinoma of the eyelid. After surgery, adjuvant radiotherapy was administered to the tissues surrounding the lesion, and it did not recur during 12 months of follow-up period.Conclusions: Primary mucinous adenocarcinoma of the skin, especially of the eyelid, is rare, and it is important to differentiate it from metastatic mucinous adenocarcinoma of other organs. The authors diagnosed primary mucinous adenocarcinoma using immunohistochemistry, and we report how it was successfully treated through surgical excision and reconstruction of the eyelid.

Purpose: To evaluate clinical outcomes of brolucizumab injection in neovascular age-related macular degeneration (nAMD) that shows limited response to aflibercept therapy.Methods: Retrospective review of medical records was performed for patients diagnosed with nAMD who underwent switching to brolucizumab due to limited response to aflibercept. Visual acuity (VA) and central retinal thickness (CRT) were compared between before switching, 1 month and 3 months after the switching. The proportion of patients exhibiting subretinal fluid (SRF) and intraretinal fluid (IRF) were identified. Development of intraocular inflammation was additionally evaluated.Results: Thirteen patients were included. The mean VA and CRT was 0.38 ± 0.20 and 379.7 ± 100.9 µm before the switching, 0.34 ± 0.19 and 262.2 ± 94.3 µm at 1 month, and 0.39 ± 0.24 and 322.9 ± 92.8 µm at 3 months. There was a significant decrease in CRT at 1 month after the switching (p = 0.003). However, VA changes were not significant. The proportion of patients showing SRF and IRF was 100% and 23.1% before the switching, 30.8% and 7.7% at 1 month, and 69.2% and 30.8% at 3 months. Retinal vasculitis developed in one patient (7.7%). The inflammation was resolved after steroid treatment.Conclusions: Despite the inherent limitations posed by the small sample size, this study represents the first domestic report evaluating the outcomes of switching to brolucizumab. Brolucizumab injection was found to be a useful alternative treatment for short-term resolution of retinal edema in nAMD showing limited response to aflibercept. However, the risk of intraocular inflammation should be considered.

Purpose: To compare optical coherence tomography angiography (OCTA) findings between severe non-proliferative diabetic retinopathy (NPDR) and unexposed proliferative diabetic retinopathy (PDR), and identify predictive factors.Methods: Patients newly diagnosed with severe NPDR or unexposed PDR between January 2018 and December 2021 were reviewed retrospectively. Unexposed PDR was diagnosed using fluorescein fundus angiography, because new vessels could not be observed in the poster pole or clearly distinguished in the retinal periphery on wide fundus photography. Clinical features at the time of diagnosis, and OCTA measurements (mean vascular density, superficial capillary plexus (SCP) foveal avascular zone (FAZ) area, and mean retinal thickness), were compared between the two groups. Factors that could predict unexposed PDR were investigated using multivariate analysis with a generalized estimating equation.Results: A total of 61 severe NPDR and 23 unexposed PDR eyes were included. The unexposed PDR had significantly larger SCP-FAZ areas (p = 0.031) and lower total and parafoveal mean inner retinal thicknesses (p = 0.014 and p < 0.001, respectively). However, there were no differences in mean vascular density between the groups (p > 0.05). Multivariate analysis showed that SCP-FAZ area and parafoveal mean inner retinal thickness were significant predictors of unexposed PDR (p = 0.027 and p = 0.001, respectively).Conclusions: In severe NPDR patients, unexposed PDR may be considered a differential diagnosis when the SCP-FAZ area is large or the parafoveal mean inner retinal thickness is small.

Background: We had identified somatic mutations of the NAD(P) Dependent Steroid Dehydrogenase-Like (NSDHL) gene from breast tumors of patients with distant metastasis using whole-exome sequencing. This study aimed to investigate the function of NSDHL mutants in breast cancer. Methods: ER-positive and tamoxifen-resistant human breast cancer cell line (ZR75-1) and mouse macrophage cell line (RAW264,7) were used. GFP-tagged NSDHL mutants were generated by subcloning the mutant NDHL into a lentiviral vector yielding an in-frame fusion of 3′ to GFP. ZR75-1 cells expressing the GFP-tagged NSDHL mutants were selected by puromycin with subsequent FACS analysis. The following experiments were performed: western blot, immunofluorescence staining, qRT-PCR, CellTiter-Glo assay, cell cycle assay, transwell migration assay, wound healing assay, tumor spheroid formation assay, and total cellular cholesterol measurement. An orthotopic breast tumor mouse model by injection of ZR75.1 cells into mammary gland fat pad was used in vivo. Results: Four novel NSDHL somatic mutations were discovered in the breast tumor tissues of patients. While total cholesterol levels in NSDHL mutant-transduced cells did not significantly increase, they were notably higher in wild-type NSDHL-transduced cells than in parent ZR75-1 cells. When compared to the parent and wild-type NSDHL-transduced cells, there was a minor increase in growth rate and a large increase in migratory capacities in NSDHL mutant-transduced cells (P< 0.05). The size of tumor spheroids is significantly larger in NSDHL mutant-transduced cells than in wild-type NSDHL-transduced cells. Both EGFR expression and epithelial to mesenchymal transition (EMT) markers were higher in NSDHL mutant-transduced cells than in parent and wild-type NSDHL-transduced cells. The NSDHL mutant-transduced cells’ conditioned media promoted the migratory ability and M2 polarization of RAW264.7 cells. In an orthotopic xenograft mouse model, NSDHL mutant-transduced cells were shown to promote tumor growth better than parent and wild-type NSDHL-transduced cells, suggesting that somatic mutation of the NSDHL contributes to the malignant progression of breast cancer cells. Conclusion: The present data indicate that breast cancer cells harboring somatic mutants of the NSDHL gene seem to display more aggressive behavior by gaining biological worse phenotype both in vitro and in vivo. More investigation is required into the mechanisms behind the function and accumulation of mutant NSDHL proteins to speed the development of therapies for patients with breast cancer harboring mutant NSDHL. Citation Format: Moonjou Baek, Hoe Suk Kim, So-Hyun Yoon, Seungyeon Ryu, Sangeun Lee, Kyoungsook Park, Han-Byoel Lee, Wonshik Han. Overexpression of somatic mutation in NSDHL promotes breast cancer cell migration and tumor growth [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-13-06.

Background: Statins were suggested for repurposed drugs, having multifaceted effects which include anti-tumor activities by modulating the immune response. Here, we aimed to demonstrate the effect of statins on programmed death-ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC) cells. Methods: Thirteen human TNBC cell lines, mouse macrophage cell line (RAW 264.7), cholesterol and 27-hydroxycholesterol, and clinically approved lovastatin and simvastatin were used. Flow cytometry, Annexin V/propidium iodide assay, western blot, qRT-PCR, transwell migration assay, and immunohistochemistry were employed. A co-culture of macrophages with various breast cancer cells was performed. An orthotopic breast tumor mouse model and metastasis model by injection of GFP-tagged MDA-MB-231 cells into mammary gland fat pad and the tail vein injection were produced. In tumor model mice, lovastatin(10mg/kg) was daily injected intraperitoneally. In vivo fluorescent imaging was used to identify primary tumor development and lung metastasis. Results: Among thirteen TNBC cell lines, MDA-MB-231, HCC38, and HCC70 highly expressed endogenous/constitutive PD-L1. Statins reduced PD-L1 expression and exerted anti-proliferative and apoptotic effects in MDA-MB-231, HCC38, HCC70, and Raw264.7 in a dose- and time-dependent manner (p< 0.05). Meanwhile, statins increased the expression of PD-L1 in Hs578T and MDA-MB-468. STAT3 phosphorylation was inhibited in MDA-MB-231 and HCC70, but not in Hs578T, while AKT phosphorylation was reduced in MDA-MB-231, HCC70, Hs578T, and MDA-MB-468 when statins were treated. The migration of MDA-MB-231 and Raw264.7 in statin-treated conditioned media was decreased (p< 0.05). Cholesterol and 27-hydroxy cholesterol did not restore PD-L1 expression in statin-treated MDA-MB-231. Statins suppressed the expression of M2 markers (PD-L1, CD206, YM-1, Fizz1, arginase-1) in RAW26437 stimulated by a conditioned medium of MDA-MB-231. Lovastatin suppressed the primary tumor growth and metastasis in xenograft tumor mice. Conclusions: Our findings show that statins have an anti-tumor effect, which kills breast cancer cells and triggers macrophage reprogramming by reducing PD-L1 expression, impairing the AKT, ERK, and STAT3 signal pathways, and decreasing M2 markers. Further study is needed to investigate an in-depth molecular mechanism study by which statins regulate PD-L1 expression in TNBC and to confirm the safe and effective use of statins as adjuvant therapy in TNBC. Citation Format: Sangeun Lee, Hoe Suk Kim, So-Hyun Yoon, Seungyeon Ryu, Moonjou Baek, A Young Park, Han-Byoel Lee, Wonshik Han. Statins exhibit an anti-tumor effect by attenuating PD-L1 in breast cancer cells and macrophages and reducing breast tumor progression in xenograft mouse model [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-10.

Objectives : To identify and estimate the non-point source (NPS) pollution loads in the Yongdam watershed, and to take an appropriate NPS management plan suitable for the environmental conditions of the sub-basin of Yongdam watershed.Methods : The NPS pollutant loads of the Yongdam watershed was investigated to establish the hydrological simulation program-fortran (HSPF) model for the study area so that the characteristics of non-point runoff were simulated. Furthermore, the detailed catchment area subject to non-point pollution management was selected and the effect of reducing non-point pollution was examined based on the various simulation results.Results and Discussion : The three sub-basins, including specific component of catchments, of Yongdam watershed was selected according to the load intensity and distribution of NPS pollution. The result of analyzing the load flowing into the downstream by rainfall intensity revealed that the pollutant load accounted for 11.8~19.9% in the dry season, and for Jinan-cheon sub-basin the load was high in the range of 10~30 mm while Janggye-cheon sub-basin and downstream of Janggye-cheon junction sub-basin showed a high load in the range 30~60 mm. In addition, the load duration curve (LDC) showed the excess frequency of BOD load was high when the flow rate increased at the end of stream for each sub-basin, whereas the load excess frequency was high in T-P in the entire flow range. LDC analysis led to us that the water quality of stream was affected by point and non-point pollutants in a complex way. When the ground cover in a farm were installed by selecting 10 detailed catchments with high need for NPS pollution management, the reduction of T-P load was estimated to be reduced by 325.256~995.912 g/d in Jinan-cheon sub-basin, 1279.813~3327.513 g/d in Janggye-cheon sub-basin, and 1316.831~3555.443 g/d in downstream of Janggye-cheon junction sub-basin.Conclusion : Through various simulation experiments using the HSPF model, it was feasible to select an catchment subject to NPS pollution control in detail and evaluate the effect of reducing NPS pollution.

The interaction of upconversion nanoparticles (UCNPs) with peripheral blood mononuclear cells was investigated using single-cell mass cytometry (CyTOF).

This study was conducted to evaluate the effects of soil amendments on arsenic (As) bioavailability in As-polluted soils. We determined the subsequent changes in As toxicity toward earthworms (Eisenia fetida) and As uptake by earthworms. We also investigated whether As bioaccumulation could be used as an index to evaluate changes in quality of As-polluted soils. No significant changes in acute toxicity to earthworms were observed, and the observed increases (70-93 mg kg-1) or decreases (27-38 mg kg-1) in bioavailable As in soils at the end of test were not related to the As concentrations in earthworms. The As concentration in earthworms 14 days after exposure was significantly lower in calcium superphosphate (CSP)- and S-treated soils (101.4-112.8 mg kg-1) than in control soil (138.9 mg kg-1), probably owing to reduced earthworm growth due to lower pH in CSP- and S-treated soils (6.3-7.3) relative to control and steel slag-treated soils (7.5-8.4). Comparisons of As toxicity and the effects of soil properties on this toxicity toward various species of earthworms could facilitate the use of earthworms to produce biological indices for evaluating changes in quality of As-polluted soils following amendment treatments.

Purpose: Surgery and nonoperative management (NOM) are the treatment modalities for acute appendicitis (AA). There is little evidence to indicate which treatment method should be performed according to the patient's condition or disease severity, surgical extension, and timing after an appendectomy. This study aimed to evaluate postoperative intra-abdominal abscess (PIAA) associated with these factors.Methods: The medical records of 839 patients who underwent appendectomy after a diagnosis of AA between 2019 and 2020 at Gangneung Asan Medical Centre were reviewed retrospectively. The factors associated with PIAA were evaluated.Results: Postoperative complications occurred in 92 patients. Following appendectomy, 16 (1.9%), 83 (9.9%), and three (0.4%) patients developed PIAA, surgical site infection, and incisional hernia, respectively. The American Society of Anesthesiologists class, complicated appendicitis on preoperative abdominal computed tomography, failure of NOM, and extensive surgery above appendectomy were associated with the development of PIAA. However, a laparoscopic approach, irrigation, indwelling drain, ultrasonic dissection, and use of sterile bags were not associated with the development of PIAA.Conclusion: NOM for some patients with complicated AA is an attractive treatment modality. However, to reduce the incidence of PIAA, the application of NOM should be circumspect considering patient factors and the nature of acute appendicitis. Furthermore, appendectomy should be performed as early as possible for patients not indicated for NOM.

Owing to the recent developments in computer technology and nationally accumulated hydrology, land use, soil characteristics and flow and water quality monitoring data, high-level modelling results are required. However, as most catchments have a mixture of urban and rural areas, it is challenging to apply one effective model. This study applied a hydrological simulation program to a storm water management model for the Jeonju catchment, South Korea, which has complex land-use characteristics, to determine the hydrological cycle of the catchment, analyse the river water quality and examine the structure of discharge pollutants. The linked model includes an analysis of the sewer pipes, which are the main path of hydrology and pollution loads in urban areas, a low-impact development application, a water circulation improvement technique and an initial storm water treatment facility installation project. This linked model will be very useful for guiding future urban water quality policy.

We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder.The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts.For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state.The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.

This study was conducted to assess the association of uric acid (UA) with the homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) by gender in nondiabetic Korean adults. The study was carried out using data from the 2019 Korean National Health and Nutrition Examination Survey and included nondiabetic Korean men, premenopausal women, and postmenopausal women aged 20 years or older. First, after adjusted for the related variables (excluding obesity), the prevalence of hyperuricemia (UA ≥ 7.0 mg/dL in men or UA ≥ 6.0 mg/dL in women) was positively associated with the quartiles of HOMA-IR and HOMA-B in men, premenopausal women, and postmenopausal women. Second, when further adjusted for obesity, hyperuricemia was positively associated with the quartiles of HOMA-IR and HOMA-B in men and postmenopausal women but not in premenopausal women. Third, after adjusted for the related variables (including obesity), UA level was positively associated with the quartiles of HOMA-IR and HOMA-B in men and postmenopausal women but not in premenopausal women. hyperuricemia is positively associated with insulin resistance and beta-cell function in nondiabetic Korean men and postmenopausal women but not in premenopausal women.

PurposeFebrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Materials and methodsWe conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). ResultsSince January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p

Purpose: This study evaluated how artificial intelligence-based computer-assisted diagnosis (AICAD) for breast ultrasonography (US) influences diagnostic performance and agreement between radiologists with varying experience levels in different workflows.Methods: Images of 492 breast lesions (200 malignant and 292 benign masses) in 472 women taken from April 2017 to June 2018 were included. Six radiologists (three inexperienced [

Surgical resection is one of the most widely used modalities for the treatment of hepatocellular carcinoma (HCC). Early extrahepatic recurrence (EHR) of HCC after surgical resection is considered to be closely associated with poor prognosis. However, data regarding risk factors and survival outcomes of early EHR after surgical resection remain scarce.To investigate the clinical features and risk factors of early EHR and elucidate its association with survival outcomes.From January 2004 to December 2019, we enrolled treatment-naïve patients who were ≥ 18 years and underwent surgical resection for HCC in two tertiary academic centers. After excluding patients with tumor types other than HCC and/or ineligible data, this retrospective study finally included 779 patients. Surgical resection of HCC was performed according to the physicians' decisions and the EHR was diagnosed based on contrast-enhanced computed tomography or magnetic resonance imaging, and pathologic confirmation was performed in selected patients. Multivariate Cox regression analysis was performed to identify the variables associated with EHR.Early EHR within 2 years after surgery was diagnosed in 9.5% of patients during a median follow-up period of 4.4 years. The recurrence-free survival period was 5.2 mo, and the median time to EHR was 8.8 mo in patients with early EHR. In 52.7% of patients with early EHR, EHR occurred as the first recurrence of HCC after surgical resection. On multivariate analysis, serum albumin4.0 g/dL, serum alkaline phosphatase100 U/L, surgical margin involvement, venous and/or lymphatic involvement, satellite nodules, tumor necrosis detected by pathology, tumor size ≥ 7 cm, and macrovascular invasion were determined as risk factors associated with early EHR. After sub-categorizing the patients according to the number of risk factors, the rates of both EHR and survival showed a significant correlation with the risk of early EHR. Furthermore, multivariate analysis revealed that early EHR was associated with substantially worse survival outcomes (Hazard ratio, 6.77; 95% confidence interval, 4.81-9.52;Early EHR significantly deteriorates the survival of patients with HCC, and our identified risk factors may predict the clinical outcomes and aid in postoperative strategies for improving survival.

The effectiveness of early treatment for biochemical relapse of multiple myeloma (MM) is unclear. To clarify this issue, this retrospective study was performed to evaluate the survival outcomes of 315 patients with relapsed MM after upfront autologous stem cell transplantation (ASCT). Over a median follow-up of 66.6 months (range, 15.1-195.5 months), 48.2% of patients showed biochemical relapse, 41.3% showed clinical relapse, and 10.5% showed significant biochemical relapse. Progression-free survival (PFS) and overall survival (OS) were inferior for patients with clinical relapse compared to the other patients. Multivariate analysis showed that clinical relapse was an independent prognostic factor for OS. In patients with biochemical relapse, there was no significant difference in survival between patients treated while asymptomatic and those treated once clinical symptoms had appeared. Relapse type after upfront ASCT was a significant prognostic factor in patients with MM. In addition, no survival benefit of early treatment at biochemical relapse was observed, but a triplet regimen may be beneficial for MM patients with biochemical relapse.