Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Purpose: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. Methods The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuumassisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.

Background: As the prevalence of hypertension increases with age and the proportion of the older population is also on the rise, research on the characteristics of older hypertensive patients and the importance of frailty is necessary. This study aimed to identify clinical characteristics of older hypertension in Korea and to investigate these characteristics based on frailty status. Methods: The HOW to Optimize eLDerly systolic BP (HOWOLD-BP) is a prospective, multicenter, open-label, randomized clinical trial that aims to compare intensive (target systolic blood pressure [SBP] ≤ 130 mmHg) with standard (target SBP ≤ 140 mmHg) treatment to reduce cardiovascular events in older hypertensive Korean patients aged ≥ 65 years. Data were analyzed through a screening assessment of 2,085 patients recruited from 11 university hospitals. Demographic, functional (physical and cognitive), medical history, laboratory data, quality of life, and medication history of antihypertensive drugs were assessed. Results: The mean age was 73.2 years (standard deviation ± 5.60), and 48.0% (n = 1,001) were male. Prevalent conditions included dyslipidemia (66.5%), obesity (body mass index ≥ 25 kg/m 2 , 53.6%), and diabetes (28.9%). Dizziness and orthostatic hypotension were self-reported by 1.6% (n = 33) and 1.2% (n = 24), respectively. The majority of patients were on two antihypertensive drugs (48.4%), while 27.5% (n = 574) and 20.8% (n = 433) were on 1 and 3 antihypertensive medications, respectively. Frail to pre-frail patients were older and also tended to have dependent instrumental activities of daily living, slower gait speed, weaker grip strength, lower quality of life, and lower cognitive function. The frail to pre-frail group reported more dizziness (2.6% vs. 1.2%, P < 0.001) and had concerning clinical factors, including lower glomerular filtration rate, more comorbidities such as diabetes, stroke, and a history of admission. Frail to pre-frail older hypertensive patients used slightly more antihypertensive medications than robust older hypertensive patients (1.95 vs. 2.06, P = 0.003). Pre-frail to frail patients often chose beta-blockers as a third medication over diuretics. Conclusion This study described the general clinical characteristics of older hypertensive patients in Korea. Frail hypertensive patients face challenges in achieving positive clinical outcomes because of multifactorial causes: they are older, have more morbidities, decreased function, lower quality of life and cognitive function, and take more antihypertensive medications. Therefore, it is essential to comprehensively evaluate and monitor diseaserelated or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Objective: To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline. Methods: In all, 20 participants with Alzheimer’s dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer’s dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion The higher the GR, the lower the prevalence of Alzheimer’s dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer’s dementia and cognitive decline.

Background/Aims: The optimal systolic blood pressure (SBP) goal for elderly patients with hypertension, especially to reduce cardiovascular disease (CVD) incidence and improve outcome, is unclear. This study aimed to evaluate the beneficial effects of intensive treatment for hypertension on the incidence of CVD in elderly Korean patients. Methods: The HOW to Optimize eLDerly systolic Blood Pressure (HOWOLD-BP) trial is a multicenter, parallel-design, open-label, randomized controlled trial designed to evaluate whether intensive treatment (SBP ≤ 130 mmHg) will provide more benefits in lowering the incidence and mortality associated with CVD than standard treatment (SBP ≤ 140 mmHg) in elderly patients with hypertension aged ≥ 65 years. For this study, eleven university hospitals in Korea will enroll approximately 3,176 elderly patients with hypertension between 2019 and 2022. Patients will be requested to visit the clinic every 4 months for the first year and every 6 months thereafter for 36 months. Parameters, including clinic and home blood pressure, anthropometric and laboratory findings, and frailty assessments, will be collected according to the standardized protocol. The primary outcome is a composite of CVD (acute coronary syndrome, stroke, and heart failure) incidence and cardiovascular deaths. Results: As of December 2021, 1,655 participants had been enrolled in the study, including 831 patients in the standard group and 824 patients in the intensive group. Conclusions The HOWOLD-BP trial is the first study performed in Korea to evaluate the beneficial effects of intensive blood pressure treatment on CVD in elderly patients with hypertension. The results of this study will help clarify the appropriate target SBP for this population.

Background/Aims: Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC. Methods: In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment. Results: For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p<0.001). The 2- and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037). Conclusions FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient’s general condition and clinical status.

Background/Aims: Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC. Methods: In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment. Results: For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p<0.001). The 2- and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037). Conclusions FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient’s general condition and clinical status.

Objectives: The Korea Centers for Disease Control and Prevention has published “A Guideline for Unknown Disease Outbreaks (UDO).” The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future. Methods: The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced. Results: Since September 9th , 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen. Conclusion Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 - 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.

OBJECTIVE: To find out whether levels of fibrin degradation products (FDP) and D-dimer are increased in breast cancer-related lymphedema (BCRL) as in many vascular diseases. FDP and D-dimer have been used in blood tests to help differentiate deep vein thrombosis in the diagnosis of lymphedema. Levels of FDP and D-dimer are often elevated in patients with BCRL. METHODS: Patients with BCRL (group I), non-lymphedema after breast cancer treatment (group II), and deep venous thrombosis (group III) from January 2012 to December 2016 were enrolled. Levels of FDP and D-dimer were measured in all groups and compared among groups. RESULTS: Mean values of FDP and D-dimer of group I were 5.614±12.387 and 1.179±2.408 μg/μL, respectively. These were significantly higher than their upper normal limits set in our institution. Levels of FDP or D-dimer were not significantly different between group I and group II. However, values of FDP and D-dimer in group III were significantly higher than those in group I. CONCLUSION: Values of FDP and D-dimer were much higher in patients with thrombotic disease than those in patients with lymphedema. Thus, FDP and D-dimer can be used to differentiate between DVT and lymphedema. However, elevated levels of FDP or D-dimer cannot indicate the occurrence of lymphedema.
Breast Neoplasms ; Breast ; Diagnosis ; Fibrin Fibrinogen Degradation Products ; Fibrin ; Hematologic Tests ; Humans ; Lymphedema ; Vascular Diseases ; Venous Thrombosis