1.Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun LEE ; Seung Hee YU ; Sung Rae KIM ; Kyu Jeung AHN ; Kee-Ho SONG ; In-Kyu LEE ; Ho-Sang SHON ; In Joo KIM ; Soo LIM ; Doo-Man KIM ; Choon Hee CHUNG ; Won-Young LEE ; Soon Hee LEE ; Dong Joon KIM ; Sung-Rae CHO ; Chang Hee JUNG ; Hyun Jeong JEON ; Seung-Hwan LEE ; Keun-Young PARK ; Sang Youl RHEE ; Sin Gon KIM ; Seok O PARK ; Dae Jung KIM ; Byung Joon KIM ; Sang Ah LEE ; Yong-Hyun KIM ; Kyung-Soo KIM ; Ji A SEO ; Il Seong NAM-GOONG ; Chang Won LEE ; Duk Kyu KIM ; Sang Wook KIM ; Chung Gu CHO ; Jung Han KIM ; Yeo-Joo KIM ; Jae-Myung YOO ; Kyung Wan MIN ; Moon-Kyu LEE
Diabetes & Metabolism Journal 2024;48(4):730-739
Background:
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods:
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results:
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
2.Deep Learning-Based Automatic Classification of Ischemic Stroke Subtype Using Diffusion-Weighted Images
Wi-Sun RYU ; Dawid SCHELLINGERHOUT ; Hoyoun LEE ; Keon-Joo LEE ; Chi Kyung KIM ; Beom Joon KIM ; Jong-Won CHUNG ; Jae-Sung LIM ; Joon-Tae KIM ; Dae-Hyun KIM ; Jae-Kwan CHA ; Leonard SUNWOO ; Dongmin KIM ; Sang-Il SUH ; Oh Young BANG ; Hee-Joon BAE ; Dong-Eog KIM
Journal of Stroke 2024;26(2):300-311
Background:
and Purpose Accurate classification of ischemic stroke subtype is important for effective secondary prevention of stroke. We used diffusion-weighted image (DWI) and atrial fibrillation (AF) data to train a deep learning algorithm to classify stroke subtype.
Methods:
Model development was done in 2,988 patients with ischemic stroke from three centers by using U-net for infarct segmentation and EfficientNetV2 for subtype classification. Experienced neurologists (n=5) determined subtypes for external test datasets, while establishing a consensus for clinical trial datasets. Automatically segmented infarcts were fed into the model (DWI-only algorithm). Subsequently, another model was trained, with AF included as a categorical variable (DWI+AF algorithm). These models were tested: (1) internally against the opinion of the labeling experts, (2) against fresh external DWI data, and (3) against clinical trial dataset.
Results:
In the training-and-validation datasets, the mean (±standard deviation) age was 68.0±12.5 (61.1% male). In internal testing, compared with the experts, the DWI-only and the DWI+AF algorithms respectively achieved moderate (65.3%) and near-strong (79.1%) agreement. In external testing, both algorithms again showed good agreements (59.3%–60.7% and 73.7%–74.0%, respectively). In the clinical trial dataset, compared with the expert consensus, percentage agreements and Cohen’s kappa were respectively 58.1% and 0.34 for the DWI-only vs. 72.9% and 0.57 for the DWI+AF algorithms. The corresponding values between experts were comparable (76.0% and 0.61) to the DWI+AF algorithm.
Conclusion
Our model trained on a large dataset of DWI (both with or without AF information) was able to classify ischemic stroke subtypes comparable to a consensus of stroke experts.
3.Developmental Delay and Rehabilitation in an Infant with Partial Trisomy 1q32.1 to 1q44: A Case Report
Woo Kyung KIM ; Na Mi LEE ; In Seok LIM ; Soo Ahn CHAE ; Sin Weon YUN ; Dae Yong YI ; Su Yeong KIM
Neonatal Medicine 2022;29(2):91-95
Partial trisomy 1q is a rare chromosomal disorder characterized by ventriculomegaly with craniofacial, renal, cardiac, and finger and toe anomalies. Most reported cases of partial trisomy1q have involved stillborn or premature deaths due to cardiac or liver failure. This case report describes an 18-month-old patient with partial duplication of the 1q32-44 segments and consequent developmental delays who exhibited improvement in developmental status with rehabilitation. Prenatal ultrasonography and magnetic resonance imaging of the mother revealed ventriculomegaly and atrophic changes in the left cerebral hemisphere of the fetus. The infant was born with micrognathia, microphthalmia, macrocephaly, low-set ears, polydactyly, and long feet at 37+5 weeks of gestation. A chromosomal study revealed an abnormal male karyotype of 46,XY,rec(1)dup(1)(q32.1q44)inv(1)(p36.3q32.1)pat. In this rare case of a patient with partial trisomy, we observed improvement in developmental delays following treatment using appropriate rehabilitation techniques. Further research is required to help validate the findings of this case study and establish a standardized rehabilitation technique that can be subsequently applied to such cases.
4.Characterization of Chitinolytic and Antifungal Activities in Marine-Derived Trichoderma bissettii Strains
Dawoon CHUNG ; Yong Min KWON ; Ji Yeon LIM ; Seung Sub BAE ; Grace CHOI ; Dae-Sung LEE
Mycobiology 2022;50(4):244-253
Trichoderma fungi have been intensively studied for mycoparasitism, and the latter is closely related to their cell-wall degrading enzymes including chitinase. Here, we studied marinederived Trichoderma spp., isolated from distinct sources and locations, for chitinolytic and antifungal activity. Based on morphological and phylogenetic analyses, two strains designated GJ-Sp1 and TOP-Co8 (isolated from a marine sponge and a marine alga, respectively) were identified as Trichoderma bissettii. This species has recently been identified as a closely related species to Trichoderma longibrachiatum. The extracellular crude enzymes of GJ-Sp1 and TOP-Co8 showed activities of chitobiosidase and β-N-acetylglucosaminidase (exochitinase) and chitotriosidase (endochitinase). The optimum chitinolytic activity of the crude enzymes was observed at 50°C, pH 5.0, 0–0.5% NaCl concentrations, and the activities were stable at temperatures ranging from 10 to 40 C for 2 h. Moreover, the crude enzymes showed inhibitory activity against hyphal growth of two filamentous fungi Aspergillus flavus and Aspergillus niger. To the best of our knowledge, this is the first report of the chitinolytic and antifungal activity of T. bissettii.
5.Possibility of Combined Meningitis in Under 90-Day-Old Infants With Urinary Tract Infection
Jun Ho HWANG ; Su Yeong KIM ; Na Mi LEE ; Dae Yong YI ; Sin Weon YUN ; Soo Ahn CHAE ; In Seok LIM ; Ji Young PARK
Pediatric Infection & Vaccine 2022;29(2):84-95
Purpose:
Urinary tract infections (UTIs) are the most common serious bacterial infections in young infants. Lumbar puncture (LP) has been used to diagnose coexisting meningitis in infants under 90 days of age with suspected UTI in many hospitals. However, the incidence of bacterial meningitis associated with UTIs is low. We aimed to describe the prevalence of concomitant bacterial meningitis in young infants with UTIs.
Methods:
The medical records of infants with the first episode of UTI admitted to the ChungAng University Hospital from January 2010 to December 2019 were retrospectively reviewed. Infants aged < 90 days who underwent LP with initial evaluation were included. Demographic and clinical features, laboratory findings, and imaging findings were collected and analyzed.
Results:
Eighty-six infants with UTIs were enrolled in the study. The median age was 61.5 days (interquartile range, 42.3–73.8 days) and boys (90.7%) were predominant. Escherichia coli was the most common pathogen (n=80, 93.0%) and followed by Klebsiella species (n=5, 5.8%). Fifteen (18.1%) specimens produced extended spectrum β-lactamase (ESBL). Five (5.8%) infants had positive blood culture results. Seven (8.1%) infants showed pleocytosis in the cerebrospinal fluid, but none had coexisting bacterial meningitis. Twenty-four (30.8%) infants showed renal dilatation or hydronephrosis on ultrasonography. Dimercaptosuccinic acid (DMSA) scans revealed cortical defects in 17 (21.3%) infants while voiding cystourethrography revealed vesicoureteral reflux in 6 (46.2%) infants.
Conclusion
Co-existing bacterial meningitis was not observed in young infants with UTIs. LP could not be routinely performed considering the clinical condition of <90 days old UTI patients.
6.Relationship between Stress-Coping and Personality in Patients with Bipolar and Depressive Disorders
Hyun Ju LIM ; Eunsoo MOON ; Hwagyu SUH ; Sun Kyeong YANG ; Je Min PARK ; Byung Dae LEE ; Young Min LEE ; Hee Jeong JEONG ; Soo Yeon KIM ; Kang Yoon LEE ; Young In CHUNG
Mood and Emotion 2021;19(2):35-46
Background:
Personality might be one of the important factors related to stress-coping in mood disorders. This study aimed to investigate the relationship between personality and stress-coping strategies in patients with bipolar and depressive disorders.
Methods:
A total of 195 patients diagnosed with bipolar and depressive disorders according to the criteria mentioned in Diagnostic and Statistical Manual of Mental disorders’ 5th edition were included. Pearson’s correlation and multiple regression analyses were used to analyze the relationship between personality, measured by Temperament and Character Inventory and NEO-Five Factor Inventory, and coping strategies, measured by Coping Inventory for Stressful Situations.
Results:
Self-directedness was reported to be positively associated with task-oriented coping in bipolar disorders, and harm avoidance was negatively associated with task-oriented coping in depressive disorders. Beck Depression Inventory score, neuroticism, and extroversion were found to be positively associated with emotion-oriented coping in bipolar disorders, and neuroticism was positively associated with emotion-oriented coping in depressive disorders. Extroversion was reported to be positively associated with avoidance-oriented coping in bipolar disorders, and extroversion, novelty seeking, and reward dependence were positively associated with avoidance-oriented coping in depressive disorders.
Conclusion
This study concluded that the relationship between personality and stress-coping strategies may vary based on the type of mood disorder that is diagnosed. The interaction between personality and stress-coping might be considered for the modification of coping strategies in mood disorders.
7.Multicenter retrospective analysis of patients with chronic lymphocytic leukemia in Korea
Jun Ho YI ; Gyeong-Won LEE ; Ji Hyun LEE ; Kwai Han YOO ; Chul Won JUNG ; Dae Sik KIM ; Jeong-Ok LEE ; Hyeon Seok EOM ; Ja Min BYUN ; Youngil KOH ; Sung Soo YOON ; Jin Seok KIM ; Jee Hyun KONG ; Ho-Young YHIM ; Deok-Hwan YANG ; Dok Hyun YOON ; Do Hyoung LIM ; Won-Sik LEE ; Ho-Jin SHIN
Blood Research 2021;56(4):243-251
Background:
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea.
Methods:
The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%).
Results:
The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P <0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively.
Conclusion
This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.
8.Changes in the Occurrence of Gastrointestinal Infections after COVID-19 in Korea
So Yun AHN ; Ji Young PARK ; In Seok LIM ; Soo Ahn CHAE ; Sin Weon YUN ; Na Mi LEE ; Su Yeong KIM ; Byung Sun CHOI ; Dae Yong YI
Journal of Korean Medical Science 2021;36(24):e180-
Background:
After the global epidemic of coronavirus disease 2019 (COVID-19), lifestyle changes to curb the spread of COVID-19 (e.g., wearing a mask, hand washing, and social distancing) have also affected the outbreak of other infectious diseases. However, few studies have been conducted on whether the incidence of gastrointestinal infections has changed over the past year with COVID-19. In this study, we examined how the incidence of gastrointestinal infections has changed since COVID-19 outbreak through open data.
Methods:
We summarized the data on the several viruses and bacteria that cause gastrointestinal infections from the open data of the Korea Disease Control and Prevention Agency for 3 years from March 2018 to February 2021 (from Spring 2018 to Winter 2020). Moreover, we confirmed three most common legal gastrointestinal infectious pathogens from March 2016.
Results:
From March 2020, when the COVID-19 epidemic was in full swing and social distancing and personal hygiene management were heavily emphasized, the incidence of infection from each virus was drastically decreased. The reduction rates compared to the averages of the last 2 years were as follows: total viruses 31.9%, norovirus 40.2%, group A rotavirus 31.8%, enteric adenovirus 13.4%, astrovirus 7.0%, and sapovirus 12.2%. Among bacterial pathogens, the infection rates of Campylobacter and Clostridium perfringens did not decrease but rather increased in some periods when compared to the average of the last two years. The incidence of nontyphoidal Salmonella, Staphylococcus aureus, or enteropathogenic Escherichia coli somewhat decreased but not significantly compared to the previous two years.
Conclusion
The incidence of infection from gastrointestinal viruses, which are mainly caused by the fecal-to-oral route and require direct contact among people, was significantly reduced, whereas the incidence of bacterial pathogens, which have food-mediated transmission as the main cause of infection, did not decrease significantly.
9.Changes in the Occurrence of Gastrointestinal Infections after COVID-19 in Korea
So Yun AHN ; Ji Young PARK ; In Seok LIM ; Soo Ahn CHAE ; Sin Weon YUN ; Na Mi LEE ; Su Yeong KIM ; Byung Sun CHOI ; Dae Yong YI
Journal of Korean Medical Science 2021;36(24):e180-
Background:
After the global epidemic of coronavirus disease 2019 (COVID-19), lifestyle changes to curb the spread of COVID-19 (e.g., wearing a mask, hand washing, and social distancing) have also affected the outbreak of other infectious diseases. However, few studies have been conducted on whether the incidence of gastrointestinal infections has changed over the past year with COVID-19. In this study, we examined how the incidence of gastrointestinal infections has changed since COVID-19 outbreak through open data.
Methods:
We summarized the data on the several viruses and bacteria that cause gastrointestinal infections from the open data of the Korea Disease Control and Prevention Agency for 3 years from March 2018 to February 2021 (from Spring 2018 to Winter 2020). Moreover, we confirmed three most common legal gastrointestinal infectious pathogens from March 2016.
Results:
From March 2020, when the COVID-19 epidemic was in full swing and social distancing and personal hygiene management were heavily emphasized, the incidence of infection from each virus was drastically decreased. The reduction rates compared to the averages of the last 2 years were as follows: total viruses 31.9%, norovirus 40.2%, group A rotavirus 31.8%, enteric adenovirus 13.4%, astrovirus 7.0%, and sapovirus 12.2%. Among bacterial pathogens, the infection rates of Campylobacter and Clostridium perfringens did not decrease but rather increased in some periods when compared to the average of the last two years. The incidence of nontyphoidal Salmonella, Staphylococcus aureus, or enteropathogenic Escherichia coli somewhat decreased but not significantly compared to the previous two years.
Conclusion
The incidence of infection from gastrointestinal viruses, which are mainly caused by the fecal-to-oral route and require direct contact among people, was significantly reduced, whereas the incidence of bacterial pathogens, which have food-mediated transmission as the main cause of infection, did not decrease significantly.
10.Molecular Epidemiology of Ciprofloxacin-Resistant Escherichia coli Isolated from Community-Acquired Urinary Tract Infections in Korea
Bongyoung KIM ; Mi-Ran SEO ; Jieun KIM ; Yeonjae KIM ; Seong-Heon WIE ; Moran KI ; Yong Kyun CHO ; Seungkwan LIM ; Jin Seo LEE ; Ki Tae KWON ; Hyuck LEE ; Hee Jin CHEONG ; Dae Won PARK ; Seong Yeol RYU ; Moon-Hyun CHUNG ; Hyunjoo PAI
Infection and Chemotherapy 2020;52(2):194-203
Background:
Escherichia coli is the predominant causative pathogen for community-acquired urinary tract infections (UTIs), and the increase in fluoroquinolone-resistant E. coli is of great concern in Korea. The objectives of this study were to investigate the genotypic characteristics and molecular epidemiology of ciprofloxacin-resistant (CIP-R) E. coli isolated from community-acquired UTIs in Korea.
Materials and Methods:
E. coli samples isolated from the blood or urine were collected from patients with community-acquired acute pyelonephritis aged 15 years and more who were admitted to 12 Korean hospitals from 1st April 2010 to 29th February 2012. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase and plasmidmediated quinolone resistance determinants were performed for CIP-R E. coli isolates.
Results:
A total of 569 E. coli isolates were collected, and 122 (21.4%) isolates were CIP-R isolates. The most prevalent sequence type (ST) was ST131 (28.7%, 35/122), followed by ST393 (14.7%, 18/122), ST1193 (13.1%, 16/122), ST38 (9.0%, 11/122), and ST405 (8.2%, 10/122). The antimicrobial resistance rates of ST131 to cefepime (22.9%, 8/35), ST38 to gentamicin (100%, 11/11), and ST405 to cefotaxime (66.7%, 6/9) were significantly higher than the resistance rates of all other STs combined. Notably, 40% (4/10) of ST405 clones produced extendedspectrum β-lactamases and were co-resistant to trimethoprim/sulfamethoxazole. aac(6′)-1b-cr (20%, 7/35) and CTX-M-14 (40%, 4/10) were more frequently observed in ST131 and ST405 compared with other clones, respectively.
Conclusions
Among the CIP-R uropathogenic E. coli isolates in this study, ST131, ST38, and ST405 were specifically associated with antimicrobial resistance.

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