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Purpose@#To evaluate the long-term results of Boston type-I keratoprosthesis implantation in Korea. @*Methods@#Medical records of six patients (six eyes) who underwent Boston type-I keratoprosthesis implantation between August 2018 and November 2019 were retrospectively reviewed for more than 36 months. @*Results@#The mean follow-up period was 44.3 ± 7.0 months. Best corrected visual acuity (BCVA) improved significantly for all six eyes, from 2.33 ± 0.51 logarithm of the minimum angle of resolution (logMAR) to 0.67 ± 0.59 logMAR. The vision recovered immediately after the surgery in all patients. Retroprosthetic membrane developed in three of the patients, but the visual acuity remained unchanged. Anatomical success was achieved in all six eyes after Boston type-I keratoprosthesis implantation. @*Conclusions@#The long-term analysis of Boston type-I keratoprosthesis implantation showed a faster recovery and improved visual acuity compared with conventional penetrating keratoplasty. Without the use of systemic immunosuppressants, all six eyes showed long-term survival of the Boston keratoprosthesis. Boston type-I keratoprosthesis implantation may be used in patients with recurrent graft failure after keratoplasty. This was the first study investigating the long-term results of Boston keratoprosthesis implantation in Korean patients.
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Purpose@#To report an iris metastasis associated with non-small-cell lung cancer (NLC) confirmed via repeat aqueous humor cytology.Case summary: A 53-year-old female presented to our ophthalmology outpatient department with complaints of vision impairment and pain in the left eye 1 month in duration. In ophthalmologic examinations, the best-corrected visual acuities were 20/20 oculus dexter (OD) and 20/32 oculus sinister (OS). The intraocular pressures measured using standard Goldmann applanation tonometery were 12 mmHg OD and 42 mmHg OS. Slit-lamp examination revealed multiple iris nodules in the left eye. Thirteen months prior, the patient had been diagnosed with NLC and was on chemotherapy. Despite the maximal tolerated medical therapy, the intraocular pressure was not controlled. As an iris metastasis was suspected, anterior chamber paracentesis was performed for aqueous humor sampling. Cytological analysis did not reveal malignant cells. One week later, aqueous humor sampling was repeated. Malignant cells were histopathologically confirmed. Given the ocular metastasis, the oncologists changed the chemotherapy regimen. @*Conclusions@#When an NLC patient exhibits iris nodules, repeat aqueous humor cytology can confirm an iris metastasis.
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Background/Aims@#Although the incidence and mortality of tuberculosis are decreasing in South Korea, the number of applications for financial assistance with the cost of tuberculosis treatment made by individuals from vulnerable groups was 3.8 times higher in 2019 compared to 2017 (Tuberculosis Relief Belt Project, 2019). @*Methods@#We analyzed the data of patients who received financial aid for tuberculosis treatment (in the period 2014-2018) from the Tuberculosis Relief Belt Project, which was designed to assist vulnerable groups. This study analyzed 137 subjects, and the independent variables included patient factors (age, gender, nationality, tuberculosis type, number of comorbidities, and place of residence) and treatment type (outpatient or inpatient). The dependent variable was the treatment outcome. @*Results@#The likelihood of treatment success was significantly lower for patients with one (odds ratio [OR] 0.202), two (OR 0.147), or three or more (OR 0.070) comorbidities compared to those with no comorbidities. This was also the case for patients living alone (OR 0.097), and for those classified as homeless (OR 0.053). Korean patients (OR 8.512) had a significantly higher probability of a successful treatment outcome than foreigners. @*Conclusions@#Appropriate community-based management of individuals with tuberculosis from vulnerable groups, including foreigners, people with comorbidities, people living alone, and people with an unstable residential situation or homeless status, is important.
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BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.
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Purpose@#This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. @*Materials and Methods@#We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. @*Results@#Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). @*Conclusion@#Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.
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BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.
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Objectives@#We investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on tuberculosis (TB) management in the Republic of Korea (ROK). @*Methods@#This retrospective cross-sectional study used nationwide ROK TB notification data (98,346 cases) from 2017 to 2020. The median time from the onset of TB symptoms to treatment initiation and the compliance rates with the required timing for notification and individual case investigations were measured and compared across periods and regions affected by the COVID-19 epidemic. @*Results@#TB diagnosis during the COVID-19 pandemic was delayed. The median time to TB treatment initiation (25 days) in 2020 increased by 3 days compared to that of the previous 3 years (22 days) (p<0.0001). In the outbreak in Seoul, Incheon, and Gyeonggi province during August, the time to TB diagnosis was 4 days longer than in the previous 3 years (p=0.0303). In the outbreak in Daegu and Gyeongbuk province from February to March 2020, the compliance rate with the required timing for individual case investigations was 2.2%p points lower than in other areas in 2020 (p=0.0148). For public health centers, the rate was 13%p lower than in other areas (80.3% vs. 93.3%, p=0.0003). @*Conclusion@#TB diagnoses during the COVID-19 pandemic in the ROK were delayed nationwide, especially for patients notified by public-private mix TB control hospitals. TB individual case investigations were delayed in regional COVID-19 outbreak areas (Daegu and Gyeongbuk province), especially in public health centers. Developing strategies to address this issue will be helpful for sustainable TB management during future outbreaks.
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Objectives@#：Based on the fact that cognitive functions decline known as comorbid symptoms of depression can precede depression, this study seeks to observe the effects of depressive symptoms and anxiety symptoms on cognitive function in healthy subjects. @*Methods@#：To recruit 50 general populations to evaluate cognitive and clinical symptoms and to find out the effects of clinical symptoms on cognitive functions, Pearson correlation and multivariate regression were conducted. Correlation analysis of subdomain cognitive function was conducted for reliability analysis. @*Results@#：Trail making test-B that evaluates the execution function correlates with depressive symptoms (r=0.300, p=0.03) and age (r=0.323, p=0.02). Depressive symptoms (β=0.304, p=0.03) and age (β=0.335, p=0.01) were significantly related to Trail making test -B (Adjusted R2 =0.148). Subjective cognitive tests correlates with anxiety symptoms (r=0.434, p=0.002). In the correlation between cognitive functional items, Subjective cognitive tests was found to be correlated with other test except Spotter. @*Conclusions@#：In this study, depressive symptoms contribute independently to executive functions in addition to demographic characteristics such as age and duration of education. Given that cognitive decline is a common long-term clinical outcome in depression, we expect active early intervention and evaluation of cognitive function to be helpful.
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The explosive growth of next-generation sequencing data has resulted in ultra-large-scale datasets and ensuing computational problems. In Korea, the amount of genomic data has been increasing rapidly in the recent years. Leveraging these big data requires researchers to use large-scale computational resources and analysis pipelines. A promising solution for addressing this computational challenge is cloud computing, where CPUs, memory, storage, and programs are accessible in the form of virtual machines. Here, we present a cloud computing-based system, Bio-Express, that provides user-friendly, cost-effective analysis of massive genomic datasets. Bio-Express is loaded with predefined multi-omics data analysis pipelines, which are divided into genome, transcriptome, epigenome, and metagenome pipelines. Users can employ predefined pipelines or create a new pipeline for analyzing their own omics data. We also developed several web-based services for facilitating downstream analysis of genome data. Bio-Express web service is freely available at https://www.bioexpress.re.kr/.
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The explosive growth of next-generation sequencing data has resulted in ultra-large-scale datasets and ensuing computational problems. In Korea, the amount of genomic data has been increasing rapidly in the recent years. Leveraging these big data requires researchers to use large-scale computational resources and analysis pipelines. A promising solution for addressing this computational challenge is cloud computing, where CPUs, memory, storage, and programs are accessible in the form of virtual machines. Here, we present a cloud computing-based system, Bio-Express, that provides user-friendly, cost-effective analysis of massive genomic datasets. Bio-Express is loaded with predefined multi-omics data analysis pipelines, which are divided into genome, transcriptome, epigenome, and metagenome pipelines. Users can employ predefined pipelines or create a new pipeline for analyzing their own omics data. We also developed several web-based services for facilitating downstream analysis of genome data. Bio-Express web service is freely available at https://www.bioexpress.re.kr/.
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In this paper, the ACKNOWLEDGMENT was given incorrectly.
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BACKGROUND: Human epidermal gammadelta T cells are known to play crucial roles in the defense and homeostasis of the skin. However, their precise mechanism of action in skin inflammation remains less clear. OBJECTIVE: In this study, we analyzed the cytokine expression profile of human epidermal gammadelta T cells and compared it to that of peripheral blood gammadelta T cells to investigate the specific activity of epidermal gammadelta T cells in modulating skin inflammation. METHODS: We isolated gammadelta T cells from epidermal tissue or peripheral blood obtained from healthy volunteers. Isolated gammadelta T cells were stimulated using immobilized anti-CD3 antibody and interleukin-2 plus phytohaemagglutinin, and were then analyzed using a cytokine array kit. RESULTS: Both epidermal and peripheral blood gammadelta T cells produced comparable levels of granulocyte-macrophage colony-stimulating factor, I-309, interferon-gamma, macrophage migration inhibitory factor, macrophage inflammatory protein-1alpha, and chemokine (C-C) ligand 5. The epidermal gammadelta T cells produced significantly higher levels of interleukin-4, -8, -13, and macrophage inflammatory protein-1beta than the peripheral blood gammadelta T cells did. Notably, the epidermal gammadelta T cells produced several hundred-fold higher levels of interleukin-13 than interleukin-4. CONCLUSION: These results suggest that the epidermal gammadelta T cells have a stronger potential to participate in the Th2-type response than the peripheral blood gammadelta T cells do. Furthermore, epidermal gammadelta T cells might play an important role in the pathogenesis of Th2-dominant skin diseases because of their active production of interleukin-13.
Subject(s)
Humans , Epidermis , Granulocyte-Macrophage Colony-Stimulating Factor , Healthy Volunteers , Homeostasis , Inflammation , Interferon-gamma , Interleukin-13 , Interleukin-2 , Interleukin-4 , Macrophages , Skin , Skin Diseases , T-LymphocytesABSTRACT
The management of children with intersex or micropenis is an ongoing challenge to clinicians. Topics including the recent surgical developments and controversies of management are reviewed. In feminizing genitoplasty, clitoroplasty is done as early as the first few months of life, however there are controversy in vaginal reconstruction for high vaginal confluence. In the patients with complete androgen insensitivity the testes are left intact until after puberty, so that hormone replacement therapy may be delayed. The sex assignment and surgical management of patients with intersex is very complex and should be made by the intersex team and family. Micropenis should be diagnosed by measuring stretched penile length and differentiated from buried penis which has basically normal penile size. In most boys with small penis, the size of penis reaches the normal range through a catch-up growth after puberty. Therefore close observation is a general rule in management of small penis. However low dose androgen treatment can be applied without complication in children with micropenis, especially who have severe psychological stress.