Mechanism of Action and Pharmacokinetics of Approved Bispecific Antibodies.

Bispecific antibodies represent a significant advancement in therapeutic antibody engineering, offering the ability to simultaneously target two distinct antigens. This dual-targeting capability enhances therapeutic efficacy, especially in complex diseases, such as cancer and autoimmune disorders, where drug resistance and incomplete target coverage are prevalent challenges. Bispecific antibodies facilitate immune cell engagement and disrupt multiple signaling pathways, providing a more comprehensive treatment approach than traditional monoclonal antibodies. However, the intricate structure of bispecific antibodies introduces unique pharmacokinetic challenges, including issues related to their absorption, distribution, metabolism, and excretion, which can significantly affect their efficacy and safety. This review provides an in-depth analysis of the structural design, mechanisms of action, and pharmacokinetics of the currently approved bispecific antibodies. It also highlights the engineering innovations that have been implemented to overcome these challenges, such as Fc modifications and advanced dimerization techniques, which enhance the stability and half-life of bispecific antibodies. Significant progress has been made in bispecific antibody technology; however, further research is necessary to broaden their clinical applications, enhance their safety profiles, and optimize their incorporation into combination therapies. Continuous advancements in this field are expected to enable bispecific antibodies to provide more precise and effective therapeutic strategies for a range of complex diseases, ultimately improving patient outcomes and advancing precision medicine.

Potential role of ANGPTL4 in cancer progression, metastasis, and metabolism: a brief review.

Angiopoietin-like 4 (ANGPTL4) has been identified as an adipokine involved in several non-metabolic and metabolic diseases, including angiogenesis, glucose homeostasis, and lipid metabolism. To date, the role of ANGPTL4 in cancer growth and progression, and metastasis, has been variable. Accumulating evidence suggests that proteolytic processing and posttranslational modifications of ANGPTL4 can significantly alter its function, and may contribute to the multiple and conflicting roles of ANGPTL4 in a tissue-dependent manner. With the growing interest in ANGPTL4 in cancer diagnosis and therapy, we aim to provide an up-to-date review of the implications of ANGPTL4 as a biomarker/oncogene in cancer metabolism, metastasis, and the tumor microenvironment (TME). In cancer cells, ANGPTL4 plays an important role in regulating metabolism by altering intracellular glucose, lipid, and amino acid metabolism. We also highlight the knowledge gaps and future prospect of ANGPTL4 in lymphatic metastasis and perineural invasion through various signaling pathways, underscoring its importance in cancer progression and prognosis. Through this review, a better understanding of the role of ANGPTL4 in cancer progression within the TME will provide new insights into other aspects of tumorigenesis and the potential therapeutic value of ANGPTL4. [BMB Reports 2024; 57(8): 343-351].

The Protective Role of Magnoliae Flos in Preventing Ovotoxicity and Managing Ovarian Function: An In Vitro and In Vivo Study.

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.

Feasibility of Extended Postoperative Follow-Up in Patients With Gastric Cancer.

Importance: Conventional research and guidelines on postgastrectomy follow-up for gastric cancer often restrict their focus to the first 5 years after surgery. Objective: To evaluate the association of extended regular follow-up after 5 years postgastrectomy in patients with gastric cancer with overall and postrecurrence survival rates. Design, Setting, and Participants: This population-based, retrospective cohort study used Korean National Health Insurance claims data extracted between January 1, 2005, and December 31, 2014, with follow-up data examined until December 31, 2021. Patients without recurrence or other cancers at 5 years postgastrectomy were divided into 2 groups: those who had extended regular follow-up visits and those who did not. The data were analyzed between August 15 and November 15, 2023. Exposures: Regular follow-up vs irregular follow-up after 5 years postgastrectomy. Main Outcomes and Measures: The main outcome was whether extended regular follow-up after 5 years postgastrectomy was independently associated with overall and postrecurrence survival rates using Cox proportional hazards regression. Postrecurrence survival rates were also compared across different follow-up methods and intervals. Results: A total of 40 468 patients with gastric cancer were included, with 14 294 in the regular follow-up group (mean [SD] age, 61.3 [11.7] years; 9669 male [67.8%]) and 26 174 in the irregular follow-up group (mean [SD] age, 58.1 [11.1] years; 18 007 male [68.8%]). Late recurrence or gastric remnant cancer (GRC) was identified in 3138 patients (7.8%), including 1610 of 40 468 patients (4.0%) between 5 and 10 years postgastrectomy and 1528 of 16 287 (9.4%) patients after 10 years postgastrectomy. Regular follow-up was associated with a significantly decreased overall mortality rate after 5 years postgastrectomy (from 49.4% to 36.9% in 15-year mortality rate; P < .001), as well as significant improvement of postrecurrence survival rate after occurrence of late recurrence or GRC (from 32.7% to 71.1% in 5-year postrecurrence survival rate; P < .001). Comparison of follow-up methods revealed that the combination of endoscopy and abdominopelvic computed tomography (CT) (only abdominopelvic CT in total gastrectomy subgroup) yielded the highest 5-year postrecurrence survival rate (endoscopy alone vs abdominopelvic CT alone vs a combination of both, 54.5% vs 47.1% vs 74.5%, respectively). A time interval of more than 2 years between previous endoscopy or abdominopelvic CT and late recurrence and GRC diagnosis was associated with a significantly reduced postrecurrence survival rate (hazard ratio, 1.72 [95% CI, 1.45-2.04] and 1.48 [95% CI, 1.25-1.75], respectively). Conclusions and Relevance: These findings suggest that extended regular follow-up after 5 years postgastrectomy should be implemented clinically and that current practice and value of follow-up protocols in postoperative care of patients with gastric cancer be reconsidered.

Temporal Trends in Clinical Characteristics and Outcomes for Peripartum Cardiomyopathy: The Nationwide Multicenter Registry Over 20 Years.

BACKGROUND: Although peripartum cardiomyopathy (PPCM) is a fatal disease affecting young patients and fetuses, little is known about its recent prognosis and risk factors. This study investigated temporal trends in clinical characteristics and outcomes for PPCM in a nationwide multicenter registry. METHODS AND RESULTS: The study population comprised 340 patients (mean age, 33 years) who were diagnosed with PPCM between January 2000 and September 2022 in 26 tertiary hospitals in South Korea. PPCM was defined as heart failure with left ventricular ejection fraction ≤45% and no previously known cardiac disease. The main study outcomes included time to the first occurrence of all-cause death, heart transplantation, and cardiovascular hospitalization. The diagnosis of PPCM cases increased notably during the study period (P<0.001). However, clinical outcomes showed no significant improvement (all-cause death for 10 years: 0.9% [2000-2010] versus 2.3% [2011-2022], P=0.450; all-cause death and heart transplantation for 10 years: 3.6% [2000-2010] versus 3.0% [2011-2022] P=0.520; all-cause death, heart transplantation, and cardiovascular hospitalization for 10 years: 11.7% [2000-2010] versus 19.8% [2011-2022], P=0.240). High body mass index (hazard ratio [HR], 1.106 [95% CI, 1.024-1.196]; P=0.011), the presence of gestational diabetes (HR, 5.346 [95% CI, 1.778-16.07]; P=0.002), and increased baseline left ventricular end-diastolic dimension (HR, 1.078 [95% CI, 1.002-1.159]; P=0.044) were significant risk factors for poor prognosis. CONCLUSIONS: While the incidence of PPCM has increased over the past 20 years, the prognosis has not improved significantly. Timely management and close follow-up are necessary for high-risk patients with PPCM with high body mass index, gestational diabetes, or large left ventricular end-diastolic dimension.

Development and psychometric evaluation of the adjuvant endocrine therapy beliefs scale for breast cancer survivors.

PURPOSE: Adjuvant endocrine therapy has a vital role in reducing breast cancer mortality. The beliefs in adjuvant endocrine therapy is a very important factor in the medication adherence of breast cancer survivors. Therefore, it is necessary to develop a standardized scale for assessment of adjuvant endocrine therapy. The purpose of this study was to identify the attributes of adjuvant endocrine therapy beliefs, and to evaluate adjuvant endocrine therapy beliefs scale psychometric properties. METHODS: A hybrid model was applied to identify the concept of adjuvant endocrine therapy beliefs and measurement question were developed by the scale development process. Statistical analysis using validity analysis and Rasch analysis based on item response theory were performed. A total of 228 breast cancer survivors in South Korea participated in the study. RESULTS: The finally developed adjuvant endocrine therapy beliefs scale consisted of 22 items. The items extracted by 4 factors explained 59.72% of the total variance. The model fit showed an acceptable level. The adjuvant endocrine therapy beliefs scale was excellent in convergent and discriminant validity with reliability. CONCLUSION: This scale is expected to be practical and useful in identifying adjuvant endocrine therapy beliefs and developing intervention strategies to promote adjuvant endocrine therapy adherence. In addition, continuous education and support should be accompanied so that breast cancer survivors can maintain positive beliefs in adjuvant endocrine therapy adherence.

Association Between Lifestyle Behaviors and Obesity Among Stroke Survivors.

AIM: The aim was to investigate factors influencing obesity among stroke survivors based on demographics and lifestyle behaviors. BACKGROUND: Stroke survivors are more likely to experience stroke recurrence within a few years. As obesity is a traditional risk factor for stroke, obesity should be managed in stroke survivors to prevent stroke recurrence. METHODS: A cross-sectional secondary data analysis analyzed data from the 2017 United States Behavioral Risk Factor Surveillance System (BRFSS) survey. Demographics, frequency of vegetable and fruit intake, smoking, alcohol use, physical activity, and sleep were examined. RESULTS: Among 1032 stroke survivors, 57.8% were obese. Advanced age, female sex, veteran status, at least once-daily fruit intake, current smoking, and lack of physical activity were associated with obesity. CONCLUSION: Stroke survivors should be encouraged to pursue healthy behaviors to manage obesity. Appropriate transitional care, including diet education and tailored exercise, can be an effective strategy.

Continuity of care between dyslipidemia patients and multiple providers: A cohort study.

OBJECTIVE: This study aimed to investigate the impacts of continuity of care (COC) between patients and multiple providers, i.e., doctors and community pharmacists, on clinical and economic outcomes. METHODS: This is a retrospective cohort study and analyzed Korean national claims data for ambulatory care setting between 2007 and 2018. Patients with dyslipidemia newly diagnosed in 2008 were identified. COC between providers and patients was computed using the continuity of care index (COCI). Based on COCIs, the study patients were allocated to four groups: HM/HP, HM/LP, LM/HP, and LM/LP. Each symbol represents H for high, L for low, M for doctor, and P for pharmacist. The primary study outcome was the incidence of atherosclerotic cardiovascular disease (ASCVD). RESULTS: 126,710 patients were included. Percentages of patients in the four study groups were as follows: HM/HP 35%, HM/LP 19%, LM/HP 12%, and LM/LP 34%. During the seven-year outcome period, 8,337 patients (6.6%) developed an ASCVD, and percentages in the study groups were as follows; HM/HP 6.2%, HM/LP 6.3%, LM/HP 6.8%, and LM/LP 7.1%. After adjusting for confounding covariates, only the LM/LP group had a significantly higher risk of ASCVD than the reference group, HM/HP (aHR = 1.16 [95% confidence interval = 1.10~1.22]). The risk of inappropriate medication adherence gradually increased 1.03-fold in the HM/LP group, 1.67-fold in the LM/HP, and 2.26-fold in the LM/LP group versus the HM/HP group after adjusting for covariates. Disease-related costs were lower in the HM/HP and LM/HP groups. CONCLUSIONS: The study shows that patients with high relational care continuity with doctors and pharmacists achieved better clinical results and utilized health care less, resulting in reduced expenses. Further exploration for the group that exhibits an ongoing relationship solely with pharmacists is warranted.

Effectiveness of calcipotriol/betamethasone dipropionate aerosol foam in patients with small versus large plaque psoriasis in routine practice in South Korea.

Small plaque psoriasis is the typical form of chronic plaque psoriasis affecting adults in South Korea. The effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) aerosol foam for large and small psoriasis plaques has not previously been examined. We performed a post hoc analysis of a recent, 4-week observational study of Cal/BD aerosol foam use in routine clinical practice in South Korea. Investigator Global Assessment response ([IGA] 0/1 at week 4), Patient Global Assessment response ([PaGA] 0/1 at week 4), change in Psoriasis Area and Severity Index (PASI), changes in psoriasis symptom scores, change in the Dermatology Life Quality Index (DLQI), and the proportion of patients achieving DLQI ≤5 were analyzed for patients with small (≤5 cm; n = 131) or large (>5 cm; n = 35) baseline plaque size. IGA response rates were similar for patients with small and large plaques (59.5% and 51.4% respectively). Similarly, there was no significant difference between the small and large groups in mean change in PASI (-2.20 vs -3.34), the proportions of patients with DLQI ≤5 (62.3% vs 54.3%) or PaGA 0/1 (29.2% vs 40.0%). Mean improvements in DLQI (-4.04 vs -6.20) and in psoriasis symptoms including itching (-1.50 vs -2.83), sleep loss (-0.67 vs -1.89), dryness (-1.57 vs -2.97), scaling (-1.21 vs -3.57), and redness (-1.17 vs -3.11) were greater in patients with large plaques than those with small plaques. Itching and DLQI differences were not statistically significant after adjustment for baseline characteristics. Stratification by body surface area affected eliminated statistically significant differences between the groups for most outcomes. In conclusion, this analysis suggests that Cal/BD aerosol foam is an effective, well-accepted treatment for adult patients with the small plaques typical of chronic plaque psoriasis in South Korea, as well as for those with large plaques.

Effect of hemoglobin A1c change on 24-month clinical outcomes in patients with diabetes after acute myocardial infarction.

BACKGROUND: The average glycated hemoglobin (HbA1c) may not accurately reflect glycemic control status during the mid-term after acute myocardial infarction (AMI). We aimed to evaluate changes in HbA1c and their effect on mid-term clinical outcomes in patients with diabetes and AMI. METHODS: We enrolled patients with diabetes ( n  = 967) who underwent HbA1c measurement in the Korean nationwide registry. These patients were categorized into three groups based on changes in HbA1c from index admission to the 1-year follow-up visit: a decrease in HbA1c > 1%, changes in HbA1c within 1%, and an increase in HbA1c > 1%. Clinical outcomes at 24 months were examined. RESULTS: The baseline HbA1c levels were 8.55 ±â€…0.85, 7.00 ±â€…0.98 and 7.07 ±â€…1.05 ( P  = 0.001) and HbA1c levels after 1 year were 6.62 ±â€…0.73, 7.05 ±â€…0.98 and 9.26 ±â€…1.59 ( P  = 0.001) for patients with 3 groups, respectively. Patients with a 1% decrease in HbA1c had significantly lower incidence of major adverse cardiovascular events (MACE), cardiac death, and rehospitalization after 24 months than those with a 1% increase in HbA1c. However, in the Cox regression analysis, a >1% decrease in HbA1c change was not an independent factor for MACE, cardiac death, and rehospitalization. CONCLUSIONS: Our analysis indicates that an HbA1c decrease of >1% within the first 12 months was not an independent prognostic factor until the 24-month mark. Therefore, standard diabetic control is recommended for patients with diabetes and AMI for up to 2 years.

Relationship of high-fidelity simulation experience, clinical reasoning, and clinical competence of new nurses: A cross-sectional study.

AIM: This study aimed to determine which high-fidelity simulation (HFS) experiences were associated with clinical reasoning and clinical competence among new nurses. BACKGROUND: HFS has been actively used in nursing education. It is necessary to verify the effects of HFS transfer to the clinical environment. DESIGN: A cross-sectional study reported following STROBE criteria. METHODS: Data were collected on new nurses (n = 224) who experienced HFS in their fourth-year undergraduate courses. The number of HFSs, the inclusion of simulation elements, the importance of elements to learning, clinical reasoning, and clinical competence were measured. Hierarchical regression models examined factors associated with clinical reasoning and clinical competence. RESULTS: Feedback was the most sufficiently included element of the HFS learning, and participants perceived it as the most important. A significant factor associated with clinical competence was clinical reasoning, and HFS design indirectly affected clinical competence through clinical reasoning. CONCLUSIONS: HFS learning is one of the best ways to improve clinical reasoning. Improving students' clinical reasoning should be an important goal of HFS learning in undergraduate courses to prepare students to be clinically competent nurses. IMPLICATIONS FOR NURSING: The ultimate goal of nursing education is to prepare nursing students to be competent nurses. Validating the outcomes of nursing education in the clinical environment setting is an essential task to improve clinical practice. IMPLICATIONS FOR NURSING POLICY: Nurse educators and leaders can increase nurses' clinical competence by emphasizing education to foster nurses' clinical reasoning in nursing education policies.

Girdling behavior of the longhorn beetle modulates the host plant to enhance larval performance.

BACKGROUND: Preingestive behavioral modulations of herbivorous insects on the host plant are abundant over insect taxa. Those behaviors are suspected to have functions such as deactivation of host plant defenses, nutrient accumulation, or modulating plant-mediated herbivore interactions. To understand the functional consequence of behavioral modulation of insect herbivore, we studied the girdling behavior of Phytoecia rufiventris Gautier (Lamiinae; Cerambycidae) on its host plant Erigeron annuus L. (Asteraceae) that is performed before endophytic oviposition in the stem. RESULTS: The girdling behavior significantly increased the larval performance in both field monitoring and lab experiment. The upper part of the girdled stem exhibited lack of jasmonic acid induction upon larval attack, lowered protease inhibitor activity, and accumulated sugars and amino acids in compared to non-girdled stem. The girdling behavior had no effect on the larval performance of a non-girdling longhorn beetle Agapanthia amurensis, which also feeds on the stem of E. annuus during larval phase. However, the girdling behavior decreased the preference of A. amurensis females for oviposition, which enabled P. rufiventris larvae to avoid competition with A. amurensis larvae. CONCLUSIONS: In conclusion, the girdling behavior modulates plant physiology and morphology to provide a modulated food source for larva and hide it from the competitor. Our study implies that the insect behavior modulations can have multiple functions, providing insights into adaptation of insect behavior in context of plant-herbivore interaction.

A dietary commensal microbe enhances antitumor immunity by activating tumor macrophages to sequester iron.

Innate immune cells generate a multifaceted antitumor immune response, including the conservation of essential nutrients such as iron. These cells can be modulated by commensal bacteria; however, identifying and understanding how this occurs is a challenge. Here we show that the food commensal Lactiplantibacillus plantarum IMB19 augments antitumor immunity in syngeneic and xenograft mouse tumor models. Its capsular heteropolysaccharide is the major effector molecule, functioning as a ligand for TLR2. In a two-pronged manner, it skews tumor-associated macrophages to a classically active phenotype, leading to generation of a sustained CD8+ T cell response, and triggers macrophage 'nutritional immunity' to deploy the high-affinity iron transporter lipocalin-2 for capturing and sequestering iron in the tumor microenvironment. This process induces a cycle of tumor cell death, epitope expansion and subsequent tumor clearance. Together these data indicate that food commensals might be identified and developed into 'oncobiotics' for a multi-layered approach to cancer therapy.

Association Between Orthostatic Hypertension and Frailty Among Older Patients With Hypertension.

BACKGROUND: Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension. METHODS: Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and handgrip strength. Orthostatic hypertension was defined as a ≥20-mm Hg increase in systolic blood pressure within 3 minutes of standing and upright systolic blood pressure of ≥140 mm Hg. RESULTS: We analyzed the data of 2065 participants who had been enrolled until December 31, 2022. The mean age was 73.2±5.6 years, and 52.0% were female. The mean blood pressure was 137.1±14.9/75.1±9.7 mm Hg. Among the participants, 1886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life. In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension. CONCLUSIONS: Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low quality of life in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.

An Antibody-CRISPR/Cas Conjugate Platform for Target-Specific Delivery and Gene Editing in Cancer.

The CRISPR/Cas system has been introduced as an innovative tool for therapy, however achieving specific delivery to the target has been a major challenge. Here, an antibody-CRISPR/Cas conjugate platform that enables specific delivery and target gene editing in HER2-positive cancer is introduced. The CRISPR/Cas system by replacing specific residues of Cas9 with an unnatural amino acid is engineered, that can be complexed with a nanocarrier and bioorthogonally functionalized with a monoclonal antibody targeting HER2. The resultant antibody-conjugated CRISPR/Cas nanocomplexes can be specifically delivered and induce gene editing in HER2-positive cancer cells in vitro. It is demonstrated that the in vivo delivery of the antibody-CRISPR/Cas nanocomplexes can effectively disrupt the plk1 gene in HER2-positive ovarian cancer, resulting in substantial suppression of tumor growth. The current study presents a useful therapeutic platform for antibody-mediated delivery of CRISPR/Cas for the treatment of various cancers and genetic diseases.

Characteristics According to Frailty Status Among Older Korean Patients With Hypertension.

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/m², 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 disease-related or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003787.