2024 KSoLA consensus on secondary dyslipidemia.

Elevated blood cholesterol and triglyceride levels induced by secondary causes are frequently observed. The identification and appropriate handling of these causes are essential for secondary dyslipidemia treatment. Major secondary causes of hypercholesterolemia and hypertriglyceridemia include an unhealthy diet, diseases and metabolic conditions affecting lipid levels, and therapeutic side effects. It is imperative to correct secondary causes prior to initiating conventional lipid-lowering therapy. Guideline-based lipid therapy can then be administered based on the subsequent lipid levels.

Risk of hepatic events associated with use of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists, and thiazolidinediones among patients with metabolic dysfunction-associated steatotic liver disease.

OBJECTIVE: To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DESIGN: This population-based cohort study was conducted using a nationwide healthcare claims database (2014-2022) of Korea. We included individuals with MASLD (aged ≥40 years) who initiated SGLT-2i or comparator drugs (GLP-1RA or TZD). Primary outcome was a composite of hepatic decompensation events, including ascites, oesophageal varices with bleeding, hepatic failure or liver transplant. Liver-cause death and all-cause death were also assessed as secondary outcomes. Cox proportional hazards models were used to estimated HRs with 95% CIs. RESULTS: After 1:1 propensity score matching, we included 22 550 patients who initiated SGLT-2i and GLP-1RA (median age=57 years, 60% male), and 191 628 patients who initiated SGLT-2i and TZD (median age=57 years, 72% male). Compared with GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR 0.93, 95% CI 0.76 to 1.14). Compared with TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (HR 0.77, 95% CI 0.72 to 0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: HR 0.87 (95% CI 0.80-0.94); female: HR 0.62 (95% CI 0.55-0.69)). CONCLUSIONS: In this nationwide cohort study, SGLT-2i was associated with a lower risk of hepatic decompensation events in patients with MASLD compared with TZD, while demonstrating similar effectiveness to GLP-1RA.

Financial Benefits of Renal Dose-Adjusted Dipeptidyl Peptidase-4 Inhibitors for Patients with Type 2 Diabetes and Chronic Kidney Disease.

BACKGRUOUND: Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes. METHODS: This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models. RESULTS: In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity. CONCLUSION: Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.

Pneumovesical vesicovaginal fistula repair: Lessons learned from an initial series of 25 patients.

OBJECTIVES: This study aims to share the experiences and outcomes of laparoscopic pneumovesical repair for vesicovaginal fistulas (VVF). MATERIALS AND METHODS: A retrospective review of medical records from a single institution over 10 years was conducted. The focus was on patients who underwent VVF repair using a pneumovesical approach with three 5 mm laparoscopic ports. The study evaluated perioperative parameters, postoperative outcomes, and complication rates to assess the efficacy and safety of this surgical method. Cumulative sum (CUSUM) analysis was used to determine the learning curve based on operative time. RESULTS: Of the 26 patients with VVF, 23 (88.5%) had successful fistula closure after the first surgery. One patient required open surgery conversion due to challenges in maintaining pneumovesicum, and two experienced recurrences, although successful repairs were achieved in subsequent surgeries. The average patient age was 47.4 years, with a mean operative time of 99.9 min. The postoperative hospital stay averaged 9.1 days, and catheterization lasted about 11 days. The CUSUM chart indicated a learning curve, with fluctuations until the 19th case, followed by a consistent upward pattern. CONCLUSION: Laparoscopic pneumovesical VVF repair is an effective and safe technique, especially suitable for fistulas near the ureteral orifice or deep in the vaginal cavity. The method demonstrates favorable outcomes with minimal complications and allows for easy reoperation if necessary.

Deep learning image reconstruction of diffusion-weighted imaging in evaluation of prostate cancer focusing on its clinical implications.

Background: Image-based assessment of prostate cancer (PCa) is increasingly emphasized in the diagnostic workflow for selecting biopsy targets and possibly predicting clinically significant prostate cancer (csPCa). Assessment is based on Prostate Imaging-Reporting and Data System (PI-RADS) which is largely dependent on T2-weighted image (T2WI) and diffusion weighted image (DWI). This study aims to determine whether deep learning reconstruction (DLR) can improve the image quality of DWI and affect the assessment of PI-RADS ≥4 in patients with PCa. Methods: In this retrospective study, 3.0T post-biopsy prostate magnetic resonance imaging (MRI) of 70 patients with PCa in Korea University Ansan Hospital from November 2021 to July 2022 was reconstructed with and without using DLR. Four DWI image sets were made: (I) conventional DWI (CDWI): DWI with acceleration factor 2 and conventional parallel imaging reconstruction, (II) DL1: DWI with acceleration factor 2 using DLR, (III) DL2: DWI with acceleration factor 3 using DLR, and (IV) DL3: DWI with acceleration factor 3 and half average b-value using DLR. Apparent diffusion coefficient (ADC) value, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured by one reviewer, while two reviewers independently assessed overall image quality, noise, and lesion conspicuity using a four-point visual scoring system from each DWI image set. Two reviewers also performed PI-RADSv2.1 scoring on lesions suspected of malignancy. Results: A total of 70 patients (mean age, 70.8±9.7 years) were analyzed. The image acquisition time was 4:46 min for CDWI and DL1, 3:40 min for DL2, and 2:00 min for DL3. DL1 and DL2 images resulted in better lesion conspicuity compared to CDWI images assessed by both readers (P<0.05). DLR resulted in a significant increase in SNR, from 38.4±14.7 in CDWI to 56.9±21.0 in DL1. CNR increased from 25.1±11.5 in CDWI to 43.1±17.8 in DL1 (P<0.001). PI-RADS v2.1 scoring for PCa lesions was more agreeable with the DL1 reconstruction method than with CDWI (κ value CDWI, DL1; 0.40, 0.61, respectively). A statistically significant number of lesions were upgraded from PI-RADS <4 in CDWI image to PI-RADS ≥4 in DL1 images for both readers (P<0.05). Most of the PI-RADS upgraded lesions were from higher than unfavorable intermediate-risk groups according to the 2023 National Comprehensive Cancer Network guidelines with statistically significant difference of marginal probability in DL1 and DL2 for both readers (P<0.05). Conclusions: DLR in DWI for PCa can provide options for improving image quality with a significant impact on PI-RADS evaluation or about a 23% reduction in acquisition time without compromising image quality.

Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial.

AIMS/HYPOTHESIS: This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP). METHODS: This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19-69 years with type 1 diabetes who had HbA1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates. RESULTS: A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: -0.7 mmol/mol [95% CI -2.0, 0.8 mmol/mol] (-0.1% [95% CI -0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group. CONCLUSIONS/INTERPRETATION: The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0008398 FUNDING: The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056).

Cumulative sum analysis of the learning curve for retrograde intrarenal stone surgery in newbie surgeons.

INTRODUCTION: This study investigated the learning curve of retrograde intrarenal surgery (RIRS) in patients with medium-sized stones using cumulative sum analysis (CUSUM) to evaluate the competence and proficiency of three new surgeons during their first RIRS procedures. MATERIALS AND METHODS: We conducted a retrospective review of 227 patients from 2019 to 2022 at a single institution. The patients were divided into four groups based on the operating surgeon: tutor surgeon (85 patients), newbie surgeon A (21 patients), newbie surgeon B (85 patients), and newbie surgeon C (36 patients). Patients had one or multiple stones with the largest stone diameter fell within the range of 10-30 mm. Fragmentation efficacy was calculated as "removed stone volume (mm3) divided by operative time (minutes)." CUSUM analysis monitored changes in fragmentation efficacy and validated surgical outcomes. RESULTS: No statistically significant differences were observed in the total stone volume, maximum stone size, or total operation time between the three newbie surgeons and the tutor surgeon. The mean fragmentation efficacy value was comparable among the newbie surgeons, but significantly different from that of the tutor surgeon. The minimum acceptable fragmentation efficacy level was set at 25.12 mL/min, based on the tutor's average value. The CUSUM curves for the three surgeons initially remained relatively flat until Cases 12-15, after which they increased and eventually plateaued. Stone-free rates and postoperative complications did not differ significantly among the surgeons. CONCLUSION: Learning curve analysis for the three newbie surgeons indicated that approximately 12-15 cases were required to reach a plateau.

Enhancing Diabetes Care through a Mobile Application: A Randomized Clinical Trial on Integrating Physical and Mental Health among Disadvantaged Individuals.

BACKGRUOUND: This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership. METHODS: The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16. RESULTS: Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups. CONCLUSION: This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

Is There a Difference in the Incidence of Depression between Radiation and Surgical Treatments in Patients with Prostate Cancer?

PURPOSE: Patients with cancer have a high risk of depression. However, a few studies have assessed differences in the incidence of depression among patients with prostate cancer (PC) based on whether they received radiotherapy (RTx) or surgical treatment. MATERIALS AND METHODS: We analyzed data from the National Health Insurance Sharing Service database regarding the entire Korean adult population with PC (n=210,924) between 2007 and 2017. The adjusted hazard ratios (HRs) of depression associated with treatment were estimated using propensity score-matched Cox proportional hazards models and Kaplan-Meier survival analyses. RESULTS: Our final cohort comprised 9,456 patients with PC; of which, 8,050 men underwent surgery. During a mean follow-up duration of 7.1 years, 503 (5.3%) patients were newly diagnosed with depression. A significant difference in the incidence of depression was noted between the RTx and surgery groups (RTx vs. surgery: 5.55% vs. 5.28%; p=0.011) in the unmatched cohort. In the matched cohort, older age (≥70 years, HR: 1.596, p<0.001) and poor Charlson comorbidity index scores (HR: 1.232, p=0.039) were correlated with the risk of depression. In addition, the adjusted HR for depression in the surgery group was 0.843 (p=0.221) compared with that in the RTx group. Kaplan-Meier analyses revealed that no significant difference in the cumulative probability of persistent depression was detected between the RTx and surgery groups in matched cohort (p=0.3386). CONCLUSIONS: In this nationwide population-based study, no significant differences in the risk of depression were observed between the surgical and RTx groups.

Risk of thyroid cancer associated with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: A population-based cohort study.

AIMS: To determine the potential association between the use of either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 (DPP-4) inhibitors, and the risk of thyroid cancer in individuals with type 2 diabetes. MATERIALS AND METHODS: This population-based cohort study used claims data from the Korean National Health Insurance Database, 2014-2020. Two distinct cohorts were established to compare each incretin-based drug with sodium-glucose cotransporter-2 (SGLT2) inhibitors, chosen as active comparators because of their previous non-association with thyroid cancer, and their common usage as add-on therapy to metformin along with GLP-1RAs and DPP-4 inhibitors. The first cohort included 21 722 new users of GLP-1RAs and 326 993 new users of SGLT2 inhibitors, whereas the second cohort included 904 300 DPP-4 inhibitor new users and 112 017 SGLT2 inhibitor new users. The outcome was the time to incident thyroid cancer. Weighted Cox proportional models were used to estimate hazard ratios of thyroid cancer incidence associated with incretin-based drugs of interest. RESULTS: The use of GLP-1RAs was not associated with an increased risk of thyroid cancer (weighted hazard ratio 0.98, 95% confidence interval 0.62-1.53) compared with that of SGLT2 inhibitors. Using DPP-4 inhibitors was also not associated with an increased risk of thyroid cancer (0.95, 0.79-1.14) compared with that of SGLT2 inhibitors. No significant effect modifications were observed across subgroup analyses. Sensitivity analyses, including alternative outcome definition analysis of medullary thyroid cancer, were consistent with the primary analysis results. CONCLUSIONS: GLP-1RAs and DPP-4 inhibitors were not associated with an increased risk of thyroid cancer in individuals with type 2 diabetes.

Dyslipidemia Fact Sheet in South Korea, 2022.

Objective: This study aimed to investigate the prevalence and status of dyslipidemia management among South Korean adults, as performed by the Korean Society of Lipid and Atherosclerosis under the name Dyslipidemia Fact Sheet 2022. Methods: We analyzed the lipid profiles, age-standardized and crude prevalence, management status of hypercholesterolemia and dyslipidemia, and health behaviors among Korean adults aged ≥20 years, using the Korea National Health and Nutrition Examination Survey data between 2007 and 2020. Results: In South Korea, the crude prevalence of hypercholesterolemia (total cholesterol ≥240 mg/dL or use of a lipid-lowering drug) in 2020 was 24%, and the age-standardized prevalence of hypercholesterolemia more than doubled from 2007 to 2020. The crude treatment rate was 55.2%, and the control rate was 47.7%. The crude prevalence of dyslipidemia (more than one out of three conditions [low-density lipoprotein-cholesterol ≥160 or the use of a lipid-lowering drug, triglycerides ≥200, or high-density lipoprotein-cholesterol (men and women) <40 mg/dL]) was 40.2% between 2016 and 2020. However, it increased to 48.2% when the definition of hypo-high-density lipoprotein-cholesterolemia in women changed from <40 to <50 mg/dL. Conclusion: Although the prevalence of hypercholesterolemia and dyslipidemia has steadily increased in South Korea, the treatment rate remains low. Therefore, continuous efforts are needed to manage dyslipidemia through cooperation between the national healthcare system, patients, and healthcare providers.

Public Awareness of Dyslipidemia Among the Korean Population: A Survey Study.

Objective: We aimed to assess the level of public awareness regarding dyslipidemia and its management among the Korean population. Methods: We conducted a web- or mobile-based survey study targeting the general population, using various recruitment methods, between July 25, 2022 and August 26, 2022. The questionnaire consisted of 12 questions designed to collect demographic information and evaluate participants' awareness and knowledge about dyslipidemia. Results: In total, 2,882 participants who completed the survey were included in the analysis. Among the participants, a substantial majority (89.1%) were familiar with the concepts of "good cholesterol" and "bad cholesterol," while a comparatively lower percentage (just 46.7%) were acquainted with the term "dyslipidemia." Noticeable variations in understanding were observed when examining specific aspects of dyslipidemia management, including diet, exercise, and pharmacotherapy. Conclusion: The results of this survey underscore the significance of enhancing public awareness about dyslipidemia within the context of health literacy, demonstrating the necessity for a more comprehensive approach that includes education and policymaking to effectively manage dyslipidemia.

Structure-Based Design and Synthesis of Potent and Selective KRAS G12D Inhibitors.

KRAS G12D mutation has been found in approximately 45% of pancreatic ductal adenocarcinoma (PDAC) cases, making it an attractive therapeutic target. Through structure-based drug design, a series of potent and selective KRAS G12D inhibitors were designed. The lead compound, ERAS-5024, inhibited ERK1/2 phosphorylation and cell proliferation in three-dimensional Cell-Titer Glo assays in AsPC-1 PDAC cells with single-digit nanomolar potency and caused tumor regression in the in vivo efficacy studies. We describe here the details of the design and synthesis program that led to the discovery of ERAS-5024.

Diabetes Mellitus in the Elderly Adults in Korea: Based on Data from the Korea National Health and Nutrition Examination Survey 2019 to 2020.

BACKGRUOUND: We evaluated the prevalence and management of diabetes mellitus (DM) in elderly Korean patients based on data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 3,068 adults aged 65 years and older (19.8% of total population) were analyzed using KNHANES from 2019 to 2020. Prevalence, awareness, treatment, and control rates, and comorbidities were analyzed. Lifestyle behaviors and energy intake were also measured. RESULTS: The prevalence of DM and prediabetes was 29.6% and 50.5%, respectively. The awareness, treatment and control rates were 76.4%, 73.3%, and 28.3%, respectively. The control rate was 77.0% if A1C <7.5% criteria was used. The mean A1C value of individuals with known DM was 7.1%, and 14.5% of the known DM patients had A1C ≥8.0%. Abdominal obesity, hypertension, and hypercholesterolemia were combined with DM in 63.9%, 71.7%, and 70.7%, respectively, and the rate of integrated management was 36.0% (A1C <7.5% criteria). A total of 40.1% of those with DM walked regularly. The percentage of energy intake from carbohydrates was higher in those with DM than in those without DM (P=0.044), while those of fat (P=0.003) and protein (P=0.025) were lower in those with DM than in those without DM in women. CONCLUSION: In 2019 to 2020, three of 10 adults aged 65 years and older in Korea had DM, and approximately 70% of them had comorbidities. A strategy for more individualized comprehensive care for the elderly patients with DM is urgently needed.

Dyslipidemia Fact Sheet in South Korea, 2022.

BACKGRUOUND: This study aimed to investigate the prevalence and status of dyslipidemia management among South Korean adults, as performed by the Korean Society of Lipid and Atherosclerosis under the name Dyslipidemia Fact Sheet 2022. METHODS: We analyzed the lipid profiles, age-standardized and crude prevalence, management status of hypercholesterolemia and dyslipidemia, and health behaviors among Korean adults aged ≥20 years, using the Korea National Health and Nutrition Examination Survey data between 2007 and 2020. RESULTS: In South Korea, the crude prevalence of hypercholesterolemia (total cholesterol ≥240 mg/dL or use of a lipid-lowering drug) in 2020 was 24%, and the age-standardized prevalence of hypercholesterolemia more than doubled from 2007 to 2020. The crude treatment rate was 55.2%, and the control rate was 47.7%. The crude prevalence of dyslipidemia-more than one out of three conditions (low-density lipoprotein cholesterol ≥160 or the use of a lipid-lowering drug, triglycerides ≥200, or high-density lipoprotein cholesterol [HDL-C] [men and women] <40 mg/dL)-was 40.2% between 2016 and 2020. However, it increased to 48.2% when the definition of hypo-HDL-cholesterolemia in women changed from <40 to <50 mg/dL. CONCLUSION: Although the prevalence of hypercholesterolemia and dyslipidemia has steadily increased in South Korea, the treatment rate remains low. Therefore, continuous efforts are needed to manage dyslipidemia through cooperation between the national healthcare system, patients, and healthcare providers.