Publications by authors named "Mi Kyung Kim"

519 Publications

Synaptotagmin 5 Controls SYP132-VAMP721/722 Interaction for Arabidopsis Immunity to pv DC3000.

Mol Cells 2021 Sep 10. Epub 2021 Sep 10.

Department of Biological Sciences, Konkuk University, Seoul 05029, Korea.

Vesicle-associated membrane proteins 721 and 722 (VAMP721/722) are secretory vesicle-localized arginine-conserved soluble -ethylmaleimide-sensitive factor attachment protein receptors (R-SNAREs) to drive exocytosis in plants. They are involved in diverse physiological processes in plants by interacting with distinct plasma membrane (PM) syntaxins. Here, we show that synaptotagmin 5 (SYT5) is involved in plant defense against () DC3000 by regulating SYP132-VAMP721/722 interactions. Calcium-dependent stimulation of SYP132-VAMP722 interaction by SYT5 and reduced SYP132-VAMP721/722 interaction in plants suggest that SYT5 regulates the interaction between SYP132 and VAMP721/722. We interestingly found that disease resistance to DC3000 bacterium but not to fungus is compromised in plants. Since SYP132 plays an immune function to bacteria, elevated growth of surface-inoculated DC3000 in VAMP721/722-deficient plants suggests that SYT5 contributes to plant immunity to DC3000 by promoting the SYP132-VAMP721/722 immune secretory pathway.
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http://dx.doi.org/10.14348/molcells.2021.0100DOI Listing
September 2021

Associations between relative grip strength and type 2 diabetes mellitus: The Yangpyeong cohort of the Korean genome and epidemiology study.

PLoS One 2021 26;16(8):e0256550. Epub 2021 Aug 26.

Department of Physical Education, College of Education, Seoul National University, Seoul, Republic of Korea.

Objective: To investigate the association between relative grip strength and the prevalence of type 2 diabetes mellitus (T2DM) independently and in combination with body mass index (BMI) in Korean adults.

Methods: The cross-sectional study includes 2,811 men and women (age 40 to 92 years old) with no history of heart disease, stroke, or cancer. Relative grip strength was measured by a handheld dynamometer and calculated by dividing absolute grip strength by body weight. Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of T2DM by sex-specific quintiles of relative grip strength. In a joint analysis, participants were classified into 4 groups: "weak (lowest 20% quintile one) and normal weight (BMI <25.0 kg/m2)", "weak and overweight/obese (BMI ≥25.0 kg/m2)", "strong (upper 80% four quintiles) and normal weight" or "strong and overweight/obese".

Results: Among the 2,811 participants, 371 were identified as having T2DM. Compared with the lowest quintile of relative grip strength (weakest), the ORs (95% CIs) of T2DM were 0.73 (0.53-1.02), 0.68 (0.48-0.97), 0.72 (0.50-1.03), and 0.48 (0.32-0.74) in upper quintiles two, three, four, and five, respectively, after adjusting for BMI and other potential confounders. In the joint analysis, compared with the "weak and overweight/obese" reference group, the odds of T2DM [ORs (95% CIs)] was lower in the "strong and overweight/obese" group [0.65 (0.46-0.92)] and the "strong and normal weight" group [0.49 (0.35-0.67)], after adjusting for potential confounders.

Conclusion: In this cross-sectional study, greater relative grip strength was associated with a lower prevalence of T2DM independent of BMI in Korean adults. Additional prospective studies are needed to determine whether a causal association exists between relative grip strength and T2DM prevalence considering BMI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256550PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389482PMC
August 2021

High Fibrosis-4 Index Is Related with Worse Clinical Outcome in Patients with Coronavirus Disease 2019 and Diabetes Mellitus: A Multicenter Observational Study.

Endocrinol Metab (Seoul) 2021 08 20;36(4):800-809. Epub 2021 Aug 20.

Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea.

Background: Based on recent evidence on the importance of the presence of diabetes mellitus (DM) and fibrosis-4 (FIB-4) index in coronavirus disease 2019 (COVID-19) mortality, we analyzed whether these factors could additively predict such mortality.

Methods: This multicenter observational study included 1,019 adult inpatients admitted to university hospitals in Daegu. The demographic and laboratory findings, mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM and/or a high FIB-4 index. The mortality risk and corresponding hazard ratio (HR) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.

Results: The patients with DM (n=217) exhibited significantly higher FIB-4 index and mortality compared to those without DM. Although DM (HR, 2.66; 95% confidence interval [CI], 1.63 to 4.33) and a high FIB-4 index (HR, 4.20; 95% CI, 2.21 to 7.99) were separately identified as risk factors for COVID-19 mortality, the patients with both DM and high FIB-4 index had a significantly higher mortality (HR, 9.54; 95% CI, 4.11 to 22.15). Higher FIB-4 indices were associated with higher mortality regardless of DM. A high FIB-4 index with DM was more significantly associated with a severe clinical course with mortality (odds ratio, 11.24; 95% CI, 5.90 to 21.41) than a low FIB-4 index without DM, followed by a high FIB-4 index alone and DM alone. The duration of quarantine and hospital stay also tended to be longer in those with both DM and high FIB-4 index.

Conclusion: Both DM and high FIB-4 index are independent and additive risk factors for COVID-19 mortality.
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http://dx.doi.org/10.3803/EnM.2021.1040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419603PMC
August 2021

COVID-19 Vaccination for Endocrine Patients: A Position Statement from the Korean Endocrine Society.

Endocrinol Metab (Seoul) 2021 08 17;36(4):757-765. Epub 2021 Aug 17.

Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.

Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients' health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.
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http://dx.doi.org/10.3803/EnM.2021.404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419616PMC
August 2021

Cardiovascular Risk Is Elevated in Lean Subjects with Nonalcoholic Fatty Liver Disease.

Gut Liver 2021 Jul 12. Epub 2021 Jul 12.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background/aims: Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear.

Methods: Data from the 2008 to 2011 Korea National Health and Nutrition Examination Surveys database were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥-0.640. ASCVD risk was evaluated using the American College of Cardiology/ American Heart Association guidelines.

Results: The frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p<0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio, 2.60 vs 1.93; p=0.023).

Conclusions: Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high risk for ASCVD than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.
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http://dx.doi.org/10.5009/gnl210084DOI Listing
July 2021

Fasting Ketonuria and the Risk of Incident Nonalcoholic Fatty Liver Disease With and Without Liver Fibrosis in Nondiabetic Adults.

Am J Gastroenterol 2021 Jun 11. Epub 2021 Jun 11.

Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Introduction: Dietary carbohydrate restriction or ketogenic diets are known to be beneficial in preventing liver fat accumulation. However, the effect of ketonemia on the risk of nonalcoholic fatty liver disease (NAFLD) in nondiabetic population is largely unknown. We investigated the association between fasting ketonuria and the risk of incident NAFLD in healthy adults.

Methods: A cohort of 153,076 nondiabetic Koreans with no hepatic steatosis and low probability of fibrosis at baseline was followed for a median of 4.1 years. The outcome was incident hepatic steatosis with or without liver fibrosis, and it was assessed by liver ultrasound and noninvasive fibrosis indices, including fibrosis-4 and the NAFLD fibrosis score (NFS). Parametric proportional hazard models were used to estimate hazard ratios (HRs) for outcome according to ketonuria status.

Results: Within 677,702.1 person-years of follow-up, 31,079 subjects developed hepatic steatosis. Compared with no ketonuria (reference), fasting ketonuria was significantly associated with a decreased risk of incident hepatic steatosis, with multivariable-adjusted HRs (95% confidence interval) of 0.81 (0.78-0.84). The corresponding HRs for incident hepatic steatosis with intermediate-to-high NFS were 0.79 (0.69-0.90). Similar associations were observed replacing NFS with fibrosis-4. In addition, the presence of persistent ketonuria at both baseline and subsequent visit was associated with the greatest decrease in the adjusted HR for incident NAFLD.

Discussion: Ketonuria was associated with a reduced risk of developing incident hepatic steatosis with and without intermediate-to-high probability of advanced fibrosis in a large cohort of nondiabetic healthy individuals. The role of hyperketonemia in the prevention of NAFLD requires further exploration.
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http://dx.doi.org/10.14309/ajg.0000000000001344DOI Listing
June 2021

A novel germline mutation in hMLH1 in three Korean women with endometrial cancer in a family of Lynch syndrome: case report and literature review.

Hered Cancer Clin Pract 2021 Jun 3;19(1):28. Epub 2021 Jun 3.

Department of Obstetrics and Gynecology, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul, 06973, South Korea.

Background: Endometrial cancer is often the sentinel cancer in women with Lynch syndrome, among which endometrioid endometrial cancer is the most common. We found a Korean case of uterine carcinosarcoma associated with Lynch syndrome. And we reviewed 27 Korean women with endometrial cancer associated with Lynch syndrome already released in case report so far.

Case Presentation: The proband, a 45-year-old Korean woman received treatment for endometrioid adenocarcinoma. Her older sister and niece were treated for endometrioid adenocarcinoma and carcinosarcoma, respectively. Family history met the Amsterdam II criteria and immunohistochemical analysis revealed a loss of MLH1 and PMS2. They all harbored a previously unreported germline likely pathogenic variant in c.1367delC in MLH1. They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. All three women were healthy without evidence of relapse for over 4 years.

Conclusion: This report indicates a novel germline c.1367delC variant in MLH1, and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant in MLH1 was suggested as a founder mutation in Lynch syndrome in Korean women.
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http://dx.doi.org/10.1186/s13053-021-00185-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176696PMC
June 2021

Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?

Cancers (Basel) 2021 May 14;13(10). Epub 2021 May 14.

Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.

In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (-2df = 1.2 × 10). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (-2df = 1.1 × 10). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
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http://dx.doi.org/10.3390/cancers13102370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156547PMC
May 2021

Correlated Magnetic Weyl Semimetal State in Strained Pr Ir O.

Adv Mater 2021 Jun 14;33(25):e2008528. Epub 2021 May 14.

Center for Correlated Electron Systems, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea.

Correlated topological phases (CTPs) with interplay between topology and electronic correlations have attracted tremendous interest in condensed matter physics. Therein, correlated Weyl semimetals (WSMs) are rare in nature and, thus, have so far been less investigated experimentally. In particular, the experimental realization of the interacting WSM state with logarithmic Fermi velocity renormalization has not been achieved yet. Here, experimental evidence of a correlated magnetic WSM state with logarithmic renormalization in strained pyrochlore iridate Pr Ir O (PIO) which is a paramagnetic Luttinger semimetal in bulk, is reported. Benefitting from epitaxial strain, "bulk-absent" all-in-all-out antiferromagnetic ordering can be stabilized in PIO film, which breaks time-reversal symmetry and leads to a magnetic WSM state. With further analysis of the experimental data and renormalization group calculations, an interacting Weyl liquid state with logarithmically renormalized Fermi velocity, similar to that in graphene, is found, dressed by long-range Coulomb interactions. This work highlights the interplay of strain, magnetism, and topology with electronic correlations, and paves the way for strain-engineering of CTPs in pyrochlore iridates.
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http://dx.doi.org/10.1002/adma.202008528DOI Listing
June 2021

Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force.

Endocrinol Metab (Seoul) 2021 Apr 6;36(2):322-338. Epub 2021 Apr 6.

Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.
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http://dx.doi.org/10.3803/EnM.2020.908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090459PMC
April 2021

Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus (Diabetes Metab J 2021;45:109-14).

Diabetes Metab J 2021 03 25;45(2):279-280. Epub 2021 Mar 25.

Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.

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http://dx.doi.org/10.4093/dmj.2020.0300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024161PMC
March 2021

Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions.

J Nutr 2021 05;151(5):1231-1240

School of Public Health, Physiotherapy & Sports Science, University College Dublin, Dublin, Ireland.

Background: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies.

Objective: To examine the prospective associations of total and types of legume intake with the risk of incident T2D.

Methods: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity.

Results: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy.

Conclusions: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.
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http://dx.doi.org/10.1093/jn/nxaa447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112771PMC
May 2021

Dietary Patterns and Frailty in Older Korean Adults: Results from the Korean Frailty and Aging Cohort Study.

Nutrients 2021 Feb 12;13(2). Epub 2021 Feb 12.

Department of Preventive Medicine and Public Health, Ajou University School of Medicine, 164 World cup-ro, Youngtong-gu, Suwon 16499, Korea.

There are few studies on dietary patterns and frailty in Asians, and the results are controversial. Therefore, this study examined the association between dietary patterns and frailty in older Korean adults using the Korean Frailty and Aging Cohort Study (KFACS). The sample consisted of 511 subjects, aged 70-84 years, community-dwelling older people from the KFACS. Dietary data were obtained from the baseline study (2016-2017) using two nonconsecutive 24-h dietary recalls, and dietary patterns were extracted using reduced rank regression. Frailty was measured by a modified version of the Fried Frailty Phenotype (FFP) in both the baseline (2016) and the first follow-up study (2018). A logistic regression analysis was used to examine the association between dietary patterns and frailty status in 2018. The "meat, fish, and vegetables" pattern was inversely associated with pre-frailty (OR = 0.41, 95% CI = 0.21-0.81, for trend = 0.009) and exhaustion (OR = 0.41, 95% CI = 0.20-0.85, for trend = 0.020). The "milk" pattern was not significantly associated with frailty status or the FFP components. In conclusion, a dietary pattern with a high consumption of meat, fish, and vegetables was associated with a lower likelihood of pre-frailty.
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http://dx.doi.org/10.3390/nu13020601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918700PMC
February 2021

Identification of genetic loci affecting body mass index through interaction with multiple environmental factors using structured linear mixed model.

Sci Rep 2021 Mar 2;11(1):5001. Epub 2021 Mar 2.

Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea.

Multiple environmental factors could interact with a single genetic factor to affect disease phenotypes. We used Struct-LMM to identify genetic variants that interacted with environmental factors related to body mass index (BMI) using data from the Korea Association Resource. The following factors were investigated: alcohol consumption, education, physical activity metabolic equivalent of task (PAMET), income, total calorie intake, protein intake, carbohydrate intake, and smoking status. Initial analysis identified 7 potential single nucleotide polymorphisms (SNPs) that interacted with the environmental factors (P value < 5.00 × 10). Of the 8 environmental factors, PAMET score was excluded for further analysis since it had an average Bayes Factor (BF) value < 1 (BF = 0.88). Interaction analysis using 7 environmental factors identified 11 SNPs (P value < 5.00 × 10). Of these, rs2391331 had the most significant interaction (P value = 7.27 × 10) and was located within the intron of EFNB2 (Chr 13). In addition, the gene-based genome-wide association study verified EFNB2 gene significantly interacting with 7 environmental factors (P value = 5.03 × 10). BF analysis indicated that most environmental factors, except carbohydrate intake, contributed to the interaction of rs2391331 on BMI. Although the replication of the results in other cohorts is warranted, these findings proved the usefulness of Struct-LMM to identify the gene-environment interaction affecting disease.
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http://dx.doi.org/10.1038/s41598-021-83684-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925554PMC
March 2021

Independent and interactive associations of season, dietary vitamin D, and vitamin D-related genetic variants with serum 25(OH)D in Korean adults aged 40 years or older.

Endocr J 2021 Jun 26;68(6):701-711. Epub 2021 Feb 26.

Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea.

Only limited information is available on the inter-relationships between genetic and non-genetic factors such as diet and sunlight exposure with serum 25-hydroxyvitamin D [25(OH)D] concentration. This cross-sectional study aimed to examine the independent and interactive associations of season, dietary vitamin D intake, and SNPs of 11 vitamin D-related candidate genes with serum 25(OH)D concentration among 2,721 adults aged ≥40 years at baseline from the Yangpyeong cohort, a part of the Korean Genome Epidemiology Study (KoGES). The interactions between season or dietary vitamin D and 556 SNPs were evaluated using 2-degree of freedom joint tests. Season was strongly (p = 1.00 × 10) and dietary vitamin D intake was slightly but significantly associated with serum 25(OH)D concentration (p = 0.0119). Among five SNPs (rs11723621-GC, rs7041-GC, rs10500804-CYP2R1, rs7129781-CYP2R1, and rs2852853-DHCR7) identified in the screening steps, only one, rs10500804-CYP2R1, significantly interacted with season (p = 8.01 × 10). The inverse association between number of minor alleles of rs10500804-CYP2R1 and concentration of 25(OH)D was significant only in summer/fall. Conversely, dietary vitamin D intake was positively associated only in winter/spring. In conclusion, season, dietary vitamin D intake, and four SNPs in GC, CYP2R1, and DHCR7 are independently and rs10500804-CYP2R1 is interactively associated with serum 25(OH)D concentration. Serum 25(OH)D is influenced by genotype of rs10500804-CYP2R1 in summer/fall when sunlight exposure is high, while dietary vitamin D intake is an important determinant of serum 25(OH)D during the seasons with low cutaneous vitamin D synthesis.
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http://dx.doi.org/10.1507/endocrj.EJ20-0519DOI Listing
June 2021

Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.

Diabetes Metab J 2021 Feb 2. Epub 2021 Feb 2.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.

Background: This study aimed to investigate the association between hepatic steatosis burden and albuminuria in Korean patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).

Methods: We recruited 100 patients with both T2DM and NAFLD, but without chronic kidney disease. Albuminuria was defined as a spot urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. Transient elastography was performed, and the steatosis burden was quantified by controlled attenuation parameter (CAP) with significant steatosis defined as CAP >302 dB/m.

Results: The prevalence of significant steatosis and albuminuria was 56.0% and 21.0%, respectively. Subjects with significant steatosis were significantly younger and had a significantly shorter duration of T2DM, greater waist circumference, and higher body mass index, total cholesterol, triglyceride, and low density lipoprotein cholesterol levels, than subjects without severe NAFLD (all P<0.05). Albuminuria was higher in patients with significant steatosis than in patients without significant steatosis (32.1% vs. 6.8%, P=0.002). Urinary ACR showed a correlation with CAP (r=0.331, P=0.001), and multiple linear regression analysis revealed a significant association between a high degree of albuminuria and high CAP value (r=0.321, P=0.001). Additionally, multivariate logistic regression analysis demonstrated the independent association between urinary ACR and significant steatosis after adjustment for confounding factors including age, body mass index, duration of T2DM, low density lipoprotein level, and renin-angiotensin system blocker use (odds ratio, 1.88; 95% confidence interval, 1.31 to 2.71; P=0.001).

Conclusion: T2DM patients with NAFLD had a higher prevalence of albuminuria, which correlated with their steatosis burden.
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http://dx.doi.org/10.4093/dmj.2020.0118DOI Listing
February 2021

Excess mortality persists in patients with rheumatoid arthritis.

Int J Rheum Dis 2021 Mar 19;24(3):364-372. Epub 2021 Jan 19.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.

Objectives: To investigate the causes and risk of death in a large cohort of Korean patients with rheumatoid arthritis (RA).

Methods: Patients in the Hanyang BAE (Bae registry of Autoimmune diseases for Epidemiology) RA cohort who fulfilled the American College of Rheumatology criteria were analyzed. A total of 2355 patients were enrolled from October 2001 to December 2015. Mortality data were derived by linking with data from the Korean National Statistical Office. Standardized mortality ratio was estimated by dividing observed deaths by expected number of deaths in the general population.

Results: Over the observation period, 225 deaths were reported. Total age- and sex-adjusted standardized mortality ratio was 1.65 (95% confidence interval 1.44-1.87). The most common cause of death was malignancy (40 cases; 17.8%), followed by respiratory disease (38 cases; 16.9%) and cardiovascular disease (32 cases; 14.2%). Mortality rate and causes of death differed according to year and age of RA onset. Compared with survivors, individuals who died were more likely to be male, smokers, diagnosed with RA at an older age, and to have long disease duration, higher erythrocyte sedimentation rate and C-reactive protein, higher rheumatoid factor positivity rate, more severe radiographic damage, and more comorbidities.

Conclusion: The mortality rate of patients with RA remains higher than that of the general population. Therefore, to improve the survival of patients with RA, attention should be paid to the management of comorbidities as well as to the RA itself.
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http://dx.doi.org/10.1111/1756-185X.14058DOI Listing
March 2021

The longitudinal associations between trajectory of and quantity of alcohol consumption and subsequent changes in blood pressure levels among non-hypertensive adults.

Br J Nutr 2021 Jan 14:1-9. Epub 2021 Jan 14.

Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.

Given the dynamic characteristic of an individual's drinking behaviours, comprehensive consideration of alcohol consumption variation using repeated measures may improve insight into the nature of its association with blood pressure (BP) change. We examined the association between longitudinal alcohol consumption (trajectory and quantity) and changes in BP and pulse pressure (PP) among Korean aged ≥ 40 years living in rural areas. Totally, 1682 hypertension-free participants who completed all three health examinations (median, 5·3 years) were included. All three visits were used to determine the cumulative trajectory of and quantity of alcohol consumption and the latest two visits and the last visit were used for the recent trajectory and the most recent quantity of alcohol consumption, respectively. Changes in BP and PP from the baseline to the third visit were used as outcome. In men, ≥30 ml/d cumulative average alcohol consumption was associated with the greatest increase in systolic BP (SBP) in both baseline outcome-unadjusted (2·9 mmHg, P = 0·032) and -adjusted models (3·6 mmHg, P = 0·001), and the given association for the most recent alcohol consumption was observed in the baseline outcome-adjusted model (3·9 mmHg, P = 0·003). For PP, similar associations were observed only in the baseline outcome-adjusted model. No meaningful associations in diastolic BP in men and any BP or PP in women existed. The quantity of alcohol consumption rather than the trajectory may be significantly related to raised SBP, and a possible short-term influence of the most recent alcohol consumption may exist when baseline SBP is adjusted in men.
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http://dx.doi.org/10.1017/S0007114521000088DOI Listing
January 2021

Analysis of the Interaction between Polygenic Risk Score and Calorie Intake in Obesity in the Korean Population.

Lifestyle Genom 2021 10;14(1):20-29. Epub 2020 Dec 10.

Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea,

Introduction: Obesity results from an imbalance in the intake and expenditure of calories that leads to lifestyle-related diseases. Although genome-wide association studies (GWAS) have revealed many obesity-related genetic factors, the interactions of these factors and calorie intake remain unknown. This study aimed to investigate interactions between calorie intake and the polygenic risk score (PRS) of BMI.

Methods: Three cohorts, i.e., from the Korea Association REsource (KARE; n = 8,736), CArdioVAscular Disease Association Study (CAVAS; n = 9,334), and Health EXAminee (HEXA; n = 28,445), were used for this study. BMI-related genetic loci were selected from previous GWAS. Two scores, PRS, and association (a)PRS, were used; the former was determined from 193 single-nucleotide polymorphisms (SNPs) from 5 GWAS datasets, and the latter from 62 SNPs (potentially associated) from 3 Korean cohorts (meta-analysis, p < 0.01).

Results: PRS and aPRS were significantly associated with BMI in all 3 cohorts but did not exhibit a significant interaction with total calorie intake. Similar results were obtained for obesity. PRS and aPRS were significantly associated with obesity but did not show a significant interaction with total calorie intake. We further analyzed the interaction with protein, fat, and carbohydrate intake. The results were similar to those for total calorie intake, with PRS and aPRS found to not be associated with the interaction of any of the 3 nutrition components for either BMI or obesity.

Discussion: The interaction of BMI PRS with calorie intake was investigated in 3 independent Korean cohorts (total n = 35,094) and no interactions were found between PRS and calorie intake for obesity.
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http://dx.doi.org/10.1159/000511333DOI Listing
December 2020

Meta-analysis of randomized controlled trials on calcium supplements and dairy products for changes in body weight and obesity indices.

Int J Food Sci Nutr 2021 Aug 8;72(5):615-631. Epub 2020 Dec 8.

Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, Korea.

This meta-analysis was performed to investigate whether calcium supplements and dairy products change obesity indices including fat mass. Original articles published in English between July 2009 and August 2019 were identified. Ten and 14 randomised controlled trials (RCTs) with ≥ 12 weeks interventions of calcium supplements and dairy products among overweight or obese adults aged ≥18 were critically reviewed. Mean difference (MD) or standardised mean difference (SMD) with 95% confidence interval (CI) were obtained using a random effect meta-analysis. Dairy products significantly changed fat mass (SMD, 95% CI; -0.40 [-0.77, -0.02]) and BMI (MD, 95% CI: -0.46 kg/m2 [-0.67, -0.26]), and calcium supplements also showed changes in fat mass (SMD, 95% CI; -0.15[-0.28, -0.02]). However, in the analysis of RCTs with low risk of bias scores, the significant changes remained only in the dairy-products intervention. Our findings suggest that dairy products without distinction of fat percentage may help reduce fat mass and BMI, but calcium supplements may not.
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http://dx.doi.org/10.1080/09637486.2020.1856794DOI Listing
August 2021

Associations of Dietary Glycemic Index, Glycemic Load and Carbohydrate with the Risk of Cervical Intraepithelial Neoplasia and Cervical Cancer: A Case-Control Study.

Nutrients 2020 Dec 4;12(12). Epub 2020 Dec 4.

Division of Cancer Epidemiology and Prevention, National Cancer Center, Ilsandong-gu, Goyang-si 10408, Korea.

Background: The association of dietary glycemic index (GI) and glycemic load (GL) with the risk of cervical cancer has never been investigated. Thus, we aimed to find evidence of any association of GI and GL with the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer.

Methods: In this hospital-based case-control study, we included 1340 women (670 controls and 262, 187 and 221 patients with CIN1, CIN2/3, and cervical cancer, respectively) from the Korean human papillomavirus cohort study. Completed demographic questionnaires and semi-quantitative food-frequency questionnaires were collected. The association of dietary GI and GL with CIN and cervical cancer was estimated using a logistic regression model.

Results: The multivariate odds ratios (OR) of the highest compared with the lowest quintile of GL for CIN1 were 2.8 (95% confidence interval (CI) = 1.33-5.88). Dietary GI and GL were not associated with CIN2/3 and cervical cancer. Stratified analyses by body mass index (BMI) indicated a positive association between GI and GL and CIN 1 risk among women with a BMI (in kg/m) <23 (OR = 2.94; 95% CI = 1.32-6.53; for trend = 0.031 for GI and OR = 3.15; 95% CI = 1.53-6.52; for trend = 0.013 for GL), but not among those with a BMI of ≥23. A stratification analysis by menopausal status showed that the highest quintile of GI and GL was significantly associated with the risk of CIN1 (OR = 2.91; 95% CI = 1.43-5.96; for trend = 0.005) (OR = 2.96; 95% CI = 1.53-5.69; for trend = 0.023) among premenopausal women. Also, in HPV positive women, dietary GL showed significant CIN1 risk (OR = 2.61; 95% CI = 1.09-6.24; for trend = 0.087).

Conclusion: Our case-control study supports the hypothesized associations of dietary GI and GL with increased risk of CIN1. Thus, the consumption of low GI and GL foods plays a significant role in the prevention of cervical carcinogenesis.
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http://dx.doi.org/10.3390/nu12123742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761966PMC
December 2020

Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus.

Diabetes Metab J 2021 01 4;45(1):109-114. Epub 2020 Dec 4.

Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.

This study investigated the impact of social distancing due to coronavirus disease 2019 (COVID-19) on glycemic control in people with type 2 diabetes mellitus (T2DM). We retrospectively analyzed the change in glycosylated hemoglobin level (ΔHbA1c) in people with T2DM who undertook social distancing because of COVID-19. We compared the ΔHbA1c between COVID-19 and non-COVID-19 cohorts that were enrolled at the same time of year. The ΔHbA1c of the COVID-19 cohort was significantly higher than that of two non-COVID-19 cohorts. Subgroup analysis according to age and baseline HbA1c level showed that social distancing significantly increased the mean HbA1c level of participants of <50 years. The ΔHbA1c of participants of <50 years and with HbA1c <7.0% in the COVID-19 cohort showed larger changes than other subgroups. In adjusted model, adjusted ΔHbA1c levels in the COVID-19 cohort remained significantly higher than those in the two other cohorts. Social distancing negatively impacts blood glucose control in people with T2DM, especially those who are younger and have good blood glucose control.
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http://dx.doi.org/10.4093/dmj.2020.0226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850869PMC
January 2021

Comparable Plasma Lipid Changes in Patients with High-Grade Cervical Intraepithelial Neoplasia and Patients with Cervical Cancer.

J Proteome Res 2021 01 26;20(1):740-750. Epub 2020 Nov 26.

Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, 150 Bugahyeon-ro, Seodaemun-gu, Seoul 03759, Korea.

Cervical cancer is the fourth most prevalent cancer among women worldwide and usually develops from cervical intraepithelial neoplasia (CIN). In the present study, we compared alterations in lipids associated with high-grade CIN and cervical cancer with those associated with a normal status and low-grade CIN by performing global lipid profiling on plasma (66 healthy controls and 55 patients with CIN1, 44 with CIN2/3, and 60 with cervical cancer) using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. We identified 246 lipids and found 31 lipids with similar alterations in both high-grade CIN and cervical cancer. Among these 31 lipids, four lipid classes (phosphatidylcholine, phosphatidylethanolamine, diglyceride, and free fatty acids) were identified as the major lipid classes with significant differences in the patients with CIN2/3 and cervical cancer compared to the healthy controls and the patients with CIN1. Lipid metabolites belonging to the same classes were positively correlated with each other. High-grade CIN and cervical cancer induce comparable changes in lipid levels, which are closely related to the development of cervical tumors. These results suggest that lipid profiling is a useful method for monitoring progression to cervical cancer.
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http://dx.doi.org/10.1021/acs.jproteome.0c00640DOI Listing
January 2021

YH12852, a Potent and Selective Receptor Agonist of 5-hydroxytryptamine, Increased Gastrointestinal Motility in Healthy Volunteers and Patients With Functional Constipation.

Clin Transl Sci 2021 03 30;14(2):625-634. Epub 2020 Nov 30.

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.

Gastrointestinal (GI) motility disorders are common, decreases quality of life, and imposes a substantial economic burden. YH12852 is a novel agonist of 5-hydroxytryptamine for the treatment of GI motility disorders. This phase I/IIa study assessed the tolerability, pharmacodynamic (PD) and pharmacokinetic (PK) profiles of YH12852. In the multiple dose (MD) cohort, healthy subjects and patients with functional constipation were randomized and received orally YH12852 at 0.3, 0.5, 1, 2, or 3 mg or prucalopride 2 mg or their matching placebo, once daily for 14 days after breakfast. In the multiple low-dose cohort (MLD), healthy subjects randomly received once-daily oral doses of YH12852 at 0.05 or 0.1 mg for 14 days after breakfast. Questionnaires, gastric emptying breath test for PDs, and plasma samples for PKs were collected. In the MD cohort, a total of 56 subjects (29 healthy volunteers and 27 patients with functional constipation) were randomized, of whom 48 completed the study. In the MLD cohort, a total of 16 healthy subjects were randomized, and 15 subjects completed the study. YH12852 increased the average weekly frequency of spontaneous bowel movements and loosened the stool. In addition, YH12852 increased quality of life satisfaction, and decreased severity of constipation symptom and GI symptoms. YH12852 was safe and well-tolerated up to 3 mg and showed nearly dose proportional PKs. In conclusion, YH12852 was safe and enhanced GI motility. YH12852 can be developed as an effective treatment option for GI motility disorders, including functional constipation. Further studies are warranted to confirm this possibility.
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http://dx.doi.org/10.1111/cts.12924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993265PMC
March 2021

Real-World Experience of Pembrolizumab Monotherapy in Patients with Recurrent or Persistent Cervical Cancer: A Korean Multi-Center Retrospective Study (KGOG1041).

Cancers (Basel) 2020 Oct 29;12(11). Epub 2020 Oct 29.

Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul 03722, Korea.

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28-79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2. Forty-nine (41.9%) patients were stage ≥III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1-6). During the median follow-up of 4.9 months (range, 0.2-35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3-13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG ≤1) ( = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3-10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade ≥3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.
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http://dx.doi.org/10.3390/cancers12113188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693862PMC
October 2020

Evogliptin, a dipeptidyl peptidase-4 inhibitor, attenuates pathological retinal angiogenesis by suppressing vascular endothelial growth factor-induced Arf6 activation.

Exp Mol Med 2020 10 14;52(10):1744-1753. Epub 2020 Oct 14.

Department of Global Innovative Drug, College of Pharmacy, Chung-Ang University, Seoul, 06974, Korea.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are used for the treatment of type 2 diabetes mellitus (DM). Recent studies have shown that beyond their effect in lowing glucose, DPP-4 inhibitors mitigate DM-related microvascular complications, such as diabetic retinopathy. However, the mechanism by which pathological retinal neovascularization, a major clinical manifestation of diabetic retinopathy, is inhibited is unclear. This study sought to examine the effects of evogliptin, a potent DPP-4 inhibitor, on pathological retinal neovascularization in mice and elucidate the mechanism by which evogliptin inhibits angiogenesis mediated by vascular endothelial growth factor (VEGF), a key factor in the vascular pathogenesis of proliferative diabetic retinopathy (PDR). In a murine model of PDR, an intravitreal injection of evogliptin significantly suppressed aberrant retinal neovascularization. In human endothelial cells, evogliptin reduced VEGF-induced angiogenesis. Western blot analysis showed that evogliptin inhibited the phosphorylation of signaling molecules associated with VEGF-induced cell adhesion and migration. Moreover, evogliptin substantially inhibited the VEGF-induced activation of adenosine 5'-diphosphate ribosylation factor 6 (Arf6), a small guanosine 5'-triphosphatase (GTPase) that regulates VEGF receptor 2 signal transduction. Direct activation of Arf6 using a chemical inhibitor of Arf-directed GTPase-activating protein completely abrogated the inhibitory effect of evogliptin on VEGF-induced activation of the angiogenic signaling pathway, which suggests that evogliptin suppresses VEGF-induced angiogenesis by blocking Arf6 activation. Our results provide insights into the molecular mechanism of the direct inhibitory effect of the DPP-4 inhibitor evogliptin on pathological retinal neovascularization. In addition to its glucose-lowering effect, the antiangiogenic effect of evogliptin could also render it beneficial for individuals with PDR.
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http://dx.doi.org/10.1038/s12276-020-00512-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080693PMC
October 2020

Kahweol activates the Nrf2/HO-1 pathway by decreasing Keap1 expression independently of p62 and autophagy pathways.

PLoS One 2020 12;15(10):e0240478. Epub 2020 Oct 12.

Department of Internal Medicine, School of Medicine, Institute for Medical Science, Keimyung University, Daegu, South Korea.

Kahweol is a diterpene found in coffee beans and unfiltered coffee drinks. Several studies have demonstrated that kahweol induces the nuclear factor erythroid-2 related factor 2/ hemeoxygenase-1 (Nrf2/HO-1) pathway; however, the mechanisms involved are currently unknown. Kelch-like ECH-associated protein 1 (Keap1) is a major regulator of Nrf2 expression and is degraded mostly by autophagy. The p62 protein enhances binding to Keap1 and contributes to the activation of Nrf2. Here, we examined the role of Keap1 regulation in the effect of kahweol on the Nrf2/HO-1 pathway in hepatocytes. In AML12 cells and primary mouse hepatocytes, kahweol increased the levels of Nrf2 and HO-1 protein without increasing expression of the Nrf2 mRNA. In addition, kahweol reduced Keap1 protein levels significantly without decreasing Keap1 mRNA levels. Although regulation of the Keap1-Nrf2-pathway by p62-dependent autophagy is well known, we confirmed here that the reduction of Keap1 protein levels by kahweol does not involve p62-dependent autophagy degradation or ubiquitination. In conclusion, kahweol increases the expression of Nrf2 in hepatocytes by inhibiting translation of the Keap1 mRNA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240478PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549774PMC
December 2020

Clinical analysis of young adult patients with ruptured intracranial aneurysms: a single-center study of 113 consecutive patients.

J Cerebrovasc Endovasc Neurosurg 2020 Sep 21;22(3):127-133. Epub 2020 Sep 21.

Department of Neurosurgery, Ajou School of Medicine, Ajou University Hospital, Suwon, Korea.

Objective: Intracranial aneurysm most frequently occurs in old aged patients; however, aneurysmal subarachnoid hemorrhage (SAH) has been occasionally reported in young adults. This study aimed to compare patients with intracranial aneurysms younger than 40 years with those ≥40 years and investigates the characteristics of their ruptured aneurysm.

Methods: We retrospectively collected the data of 389 patients (103 patients aged 20 to 39 years; 286 patients aged above 40 years) who were treated for ruptured cerebral aneurysms between January 2008 and December 2018 at our institution.

Results: The young adult patients were more often men and were smokers as compared to controls (63.1% vs. 39.2%, 40.5% vs. 36.0%, respectively). The young adult patients showed a tendency for lower Hunt and Hess grade, modified Fisher grade, less postoperative morbidity, and better clinical outcome. Aneurysm ruptures occurred most frequently in the anterior cerebral artery in both groups, but aneurysms ruptures in the internal carotid artery and posterior circulation was infrequent among young adult patients. The aneurysms in young adult patients were more often elongated or irregularly shaped (82.5% vs. 64.0%, respectively) and were significantly smaller (5.9 mm) than that in controls (6.8 mm).

Conclusions: Ruptured aneurysms of young adult patients have unique characteristics with regard to its preponderance in male smoker, elongated or irregular shape and relatively smaller size.
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http://dx.doi.org/10.7461/jcen.2020.22.3.127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522388PMC
September 2020

Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study.

Cardiovasc Diabetol 2020 09 22;19(1):143. Epub 2020 Sep 22.

Department of Biostatistics, Clinical Trial Center, Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.

Background: This study aimed to evaluate the benefit of brachial-ankle pulse wave velocity (baPWV) as a noninvasive marker of arterial stiffness for the prediction of all-cause and cause-specific mortality in patients with type 2 diabetes.

Methods: This multicenter prospective observational study analyzed 2308 patients with type 2 diabetes between 2008 and 2018. The patients were categorized according to the quartiles of baPWV. Cause of mortality was determined using death certificates and patient clinical records. We estimated proportional mortality rates from all causes, cardiovascular, cancer, and other causes among adults with diabetic status according to their baPWV. Cox regression models were used to estimate hazard ratios (HRs).

Results: There were 199 deaths (8.6%) in the study population during a median follow-up duration of 8.6 years. When baPWV was assessed as quartiles, a significantly higher risk of all-cause mortality (HR = 5.39, P < 0.001), cardiovascular-mortality (HR = 14.89, P < 0.001), cancer-mortality (HR = 5.42, P < 0.001), and other-cause mortality (HR = 4.12, P < 0.001) was found in quartile 4 (Q4, ≥ 1830 cm/s) than in quartiles 1-3 (Q1-3). Adding baPWV to baseline model containing conventional risk factors such as age, sex, diabetes duration, body mass index, glycated hemoglobin, systolic blood pressure, glomerular filtration rate, smoking, and insulin improved the risk prediction for all-cause (net reclassification index (NRI) = 49%, P < 0.001) and cause-specific (cardiovascular NRI = 28%, P = 0.030; cancer NRI = 55%, P < 0.001; other-cause NRI 51%, P < 0.001) mortality.

Conclusion: This long-term, large-scale, multicenter prospective observational cohort study provide evidence that increased arterial stiffness, as measured by baPWV, predicts the risk of all-cause and cause-specific mortality in type 2 diabetes, supporting the prognostic utility of baPWV. Trial registration Clinical Research Information Service (CRIS), KCT 0005010. Retrospectively Registered May 12, 2020. https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=16677.
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http://dx.doi.org/10.1186/s12933-020-01120-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510263PMC
September 2020

Impact of Time Interval between Index Event and Stenting on Periprocedural Risk in Patients with Symptomatic Carotid Stenosis.

J Korean Neurosurg Soc 2020 Sep 1;63(5):598-606. Epub 2020 Sep 1.

Department of Neurosurgery, Pyeongtaek St. Mary's Hospital, Pyeongtaek, Korea.

Objective: The purpose of this study was to evaluate the impact of time interval between index event and stenting on the periprocedural risk of stenting for symptomatic carotid stenosis and to determine the optimal timing of stenting.

Methods: This retrospective study included 491 (322 symptomatic [65.6%] and 169 asymptomatic [34.4%]) patients undergoing carotid stenting. The symptomatic patients were categorized into Day 0-3, 4-7, 8-10, 11-14, 15-21, and >21 groups according to the time interval between index event and stenting. Periprocedural (≤30 days) risk for clinical (any neurological deterioration) and radiological (new infarction on postprocedural diffusion-weighted imaging) events of stenting in each time interval versus asymptomatic stenosis was calculated with logistic regression analysis adjusted for confounders, and provided as odds ratio (OR) and 95% confidence interval (CI).

Results: Overall clinical event rate (4.3%) of stenting for symptomatic carotid stenosis was higher than that for asymptomatic stenosis (1.2%; OR, 3.979 [95% CI, 1.093-14.489]; p=0.036). Stenting in Day 0-3 (13.2%; OR, 10.997 [95% CI, 2.333-51.826]; p=0.002) and Day 4-7 (8.3%; OR, 6.775 [95% CI, 1.382-33.227]; p=0.018) was associated with high risk for clinical events. However, the clinical event rates in stenting after 7 days from index event (Day 8-10, 1.8%; Day 11-14, 2.5%; Day 15-21, 0%; Day >21, 2.9%) were not different from that in stenting for asymptomatic stenosis. Overall radiological event rate (55.6%) in symptomatic stenosis was also higher than that in asymptomatic stenosis (35.5%; OR, 2.274 [95% CI, 1.553-3.352]; p<0.001). The high risk for radiological events was maintained in all time intervals (Day 0-3 : 55.3%; OR, 2.224 [95% CI, 1.103-4.627]; p=0.026; Day 4-7 : 58.3%; OR, 2.543 [95% CI, 1.329-4.949]; p=0.005; Day 8-10 : 53.6%; OR, 2.096 [95% CI, 1.138-3.889]; p=0.018; Day 11-14 : 57.5%; OR, 2.458 [95% CI, 1.225-5.021]; p=0.012; Day 15-21 : 55.6%; OR, 2.271 [95% CI, 1.099-4.764]; p=0.028; Day >21 : 54.8%; OR, 2.203 [95% CI, 1.342-3.641]; p=0.002).

Conclusion: This study showed that as stenting was delayed, the periprocedural risk for clinical events decreased. The clinical event risk was high only in stenting within 7 days and comparable with that for asymptomatic stenosis in stenting after 7 days from index event, although the radiological event risk was not affected by stenting timing. Therefore, our results suggest that delayed stenting after 7 days from symptom onset is a safe strategy for symptomatic stenosis.
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http://dx.doi.org/10.3340/jkns.2020.0113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477147PMC
September 2020
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