Background and Objectives: In chronic heart failure (HF), natriuretic peptide (NP) levels are higher in atrial fibrillation (AF) compared to sinus rhythm (SR). However, due to the loss of atrial contraction, AF patients are prone to hemodynamic decompensation at earlier stages.Since NP levels reflect disease severity, acutely decompensated AF patients may exhibit lower NP levels compared to SR patients, who retain greater hemodynamic reserve. Methods: We analyzed 5,048 patients with acute HF from the Korea Acute Heart Failure registry with available NP data. NP levels and echocardiographic parameters were compared between AF and SR patients. The association of NP levels with in-hospital and one-year mortality was also assessed according to cardiac rhythm. Results: Brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured in 2,027 and 3,021 patients, respectively. NP levels were lower in AF than in SR (median BNP, 740 vs. 1,044 pg/mL; median NT-proBNP, 4,420 vs. 5,198 pg/mL), particularly in HF with reduced or mildly reduced ejection fraction. A similar trend was observed regardless of HF onset or etiology. AF patients had smaller left ventricular (LV) end-diastolic diameter and larger left atrial size compared to SR patients. Higher NP tertiles were associated with increased in-hospital and one-year mortality in both groups. Conclusions In acute HF, NP levels are lower in AF than in SR. AF patients also exhibited smaller LV chamber sizes. Nevertheless, NP levels remain strong predictors of outcomes in both AF and SR patients.

With advancements in both pharmacologic and non-pharmacologic treatments, significant changes have occurred in heart failure (HF) management. The previous Korean HF registries, namely the Korea Heart Failure Registry (KorHF-registry) and Korean Acute Heart Failure Registry (KorAHF-registry), no longer accurately reflect contemporary acute heart failure (AHF) patients. Our objective is to assess contemporary AHF patients through a nationwide registry encompassing various aspects, such as clinical characteristics, management approaches, hospital course, and long-term outcomes of individuals hospitalized for AHF in Korea. This prospective observational multicenter cohort study (KorHF III) is organized by the Korean Society of Heart Failure. We aim to prospectively enroll 7,000 or more patients hospitalized for AHF at 47 tertiary hospitals in Korea starting from March 2018. Eligible patients exhibit signs and symptoms of HF and demonstrate either lung congestion or objective evidence of structural or functional cardiac abnormalities in echocardiography, or isolated right-sided HF. Patients will be followed up for up to 5 years after enrollment in the registry to evaluate long-term clinical outcomes. KorHF III represents the nationwide AHF registry that will elucidate the clinical characteristics, management strategies, and outcomes of contemporary AHF patients in Korea.

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl-2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

Background: Dermatophyte infection is one of the most common skin diseases affecting the skin, hair, and nails. Despite widespread recognition of the disease, missing details and misperceptions are commonplace in the general population. Objective: This study aimed to investigate the public perception and behavior regarding dermatophytosis of the hands and feet. Methods: This results from an online survey conducted between July 2022 and August 2022. The survey included 1,000 Korean participants aged 20 to 69 years, of whom 60% experienced symptoms of tinea pedis or onychomycosis. The questionnaire focused on the awareness and personal experience of tinea pedis and perception of the treatment of dermatophytosis. Results: Of the 1,000 participants, nearly 80% regarded tinea pedis as a common skin condition by which anyone can be affected. Furthermore, 88.4% had heard that the treatment of tinea pedis could be harmful, causing skin rash (60.4%) and worsening liver function (48.5%). Among 896 participants who noticed suspicious symptoms, 81.2% did not visit the clinic because it was not severe (50.1%) and seemed easily manageable (25.7%). Of the respondents, 84.4% preferred to meet dermatologists rather than non-dermatologist doctors regarding skin diseases, mainly because of trust in experts and belief in a faster cure. Conclusion Providing accurate and detailed information via online media, educational campaigns, and medical papers can rectify misconceptions and improve patient appliance, contributing to public skin health.

Purpose: This study aimed to compare treatment outcomes and toxicity profile between imaged-guided brachytherapy (IGBT) versus conventional brachytherapy (CBT) performed by the same practitioner during the same time period. Materials and Methods: Medical records of 104 eligible patients who underwent brachytherapy for locally advanced cervical cancer were retrospectively reviewed. Fifty patients (48.1%) underwent IGBT, and 54 (51.9%) patients underwent CBT. All patients underwent concurrent chemoradiation with cisplatin. High-dose-rate intracavitary brachytherapy with dose prescription of 25-30 Gy in 4-6 fractions was performed for all patients. Late lower gastrointestinal (GI) and urinary toxicities occurred more than 3 months after the end of brachytherapy were included for comparative and dosimetric analyses. Results: The median follow-up period was 18.33 months (range, 3.25 to 38.43 months). There were no differences in oncologic outcomes between the two groups. The IGBT group had lower rate of actuarial grade ≥ 3 toxicity than the CBT group (2-year, 4.5% vs. 25.7%; p=0.030). Cumulative equieffective D2cc of sigmoid colon was significantly correlated with grade ≥ 2 lower GI toxicity (p=0.033), while equieffective D2cc of rectum (p=0.055) and bladder (p=0.069) showed marginal significance with corresponding grade ≥ 2 toxicities in the IGBT group. Half of grade ≥ 3 lower GI toxicities impacted GI tract above the rectum. Optimal thresholds of cumulative D2cc of sigmoid colon and rectum were 69.7 Gy and 70.8 Gy, respectively, for grade ≥ 2 lower GI toxicity. Conclusion IGBT showed superior toxicity profile to CBT. Evaluating the dose to the GI tract above rectum by IGBT might prevent some toxicities.

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.

Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR) + ILC3s in the lung.Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR + ILC3 frequencies and microbial diversity in the lung. Sputum NCR + ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR + ILC3s may contribute to a healthy commensal diversity and normal lung function.

Purpose: In this study, we investigated the frequencies of mutations in DNA damage repair genesincluding BRCA1, BRCA2, homologous recombination genes and TP53 gene in ovarian highgradeserous carcinoma, alongside those of germline and somatic BRCA mutations, withthe aim of improving the identification of patients suitable for treatment with poly(ADPribose)polymerase inhibitors. Materials and Methods: Tissue samples from 77 Korean patients with ovarian high-grade serous carcinoma weresubjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repairgenes and TP53 gene and their relationships with patient survival were examined. Additionally,we analyzed BRCA germline variants in blood samples from 47 of the patients forcomparison. Results: BRCA1, BRCA2, and TP53 mutations were detected in 28.6%, 5.2%, and 80.5% of the 77patients, respectively. Alterations in RAD50, ATR, MSH6, MSH2, and FANCA were also identified.At least one mutation in a DNA damage repair gene was detected in 40.3% of patients(31/77). Germline and somatic BRCA mutations were found in 20 of 47 patients (42.6%),and four patients had only somatic mutations without germline mutations (8.5%, 4/47).Patients with DNA damage repair gene alterations with or without TP53mutation, exhibitedbetter disease-free survival than those with TP53 mutation alone. Conclusion DNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma,with somatic BRCAmutations in the absence of germline mutation in 8.5%. Somaticvariant examination, along with germline testing of DNA damage repair genes, has potentialto detect additional candidates for PARP inhibitor treatment.

BACKGROUND AND OBJECTIVES: Impaired recovery from left ventricular (LV) dysfunction is a major prognostic factor after myocardial infarction (MI). Because P2Y12 receptor blockade inhibits myocardial injury, ticagrelor with off-target properties may have myocardial protection over clopidogrel. In animal models, ticagrelor vs. clopidogrel protects myocardium against reperfusion injury and improves remodeling after MI. We aimed to investigate the effect of ticagrelor on sequential myocardial remodeling process after MI. METHODS: High platelet inhibition with ticagrelor to improve LV remodeling in patients with ST-segment elevation MI (HEALING-AMI) is an investigator-initiated, randomized, open-label, assessor-blinded, multi-center trial done at 10 sites in Korea. Patients will be enrolled if they have ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention and a planned duration of dual antiplatelet treatment of at least 6 months. Screened patients will be randomly assigned (1:1) using an internet-based randomization with a computer-generated blocking with stratification across study sites to either ticagrelor or clopidogrel treatment. The co-primary primary endpoints are LV remodeling index with three-dimensional echocardiography and the level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) at 6 months representing post-MI remodeling processes. Changes of LV end-systolic/diastolic volume indices and LV ejection fraction between baseline and 6-month follow-up will be also evaluated. Analysis is per protocol. CONCLUSIONS: HEALING-AMI is testing the effect of ticagrelor in reducing adverse LV remodeling following STEMI. Our trial would show the benefit of ticagrelor vs. clopidogrel related to the recovery of post-MI LV dysfunction beyond potent platelet inhibition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02224534
Blood Platelets ; Echocardiography, Three-Dimensional ; Follow-Up Studies ; Humans ; Korea ; Models, Animal ; Myocardial Infarction ; Myocardium ; Natriuretic Peptide, Brain ; Percutaneous Coronary Intervention ; Random Allocation ; Reperfusion Injury ; Ventricular Remodeling

BACKGROUND AND OBJECTIVES: Impaired recovery from left ventricular (LV) dysfunction is a major prognostic factor after myocardial infarction (MI). Because P2Y12 receptor blockade inhibits myocardial injury, ticagrelor with off-target properties may have myocardial protection over clopidogrel. In animal models, ticagrelor vs. clopidogrel protects myocardium against reperfusion injury and improves remodeling after MI. We aimed to investigate the effect of ticagrelor on sequential myocardial remodeling process after MI. METHODS: High platelet inhibition with ticagrelor to improve LV remodeling in patients with ST-segment elevation MI (HEALING-AMI) is an investigator-initiated, randomized, open-label, assessor-blinded, multi-center trial done at 10 sites in Korea. Patients will be enrolled if they have ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention and a planned duration of dual antiplatelet treatment of at least 6 months. Screened patients will be randomly assigned (1:1) using an internet-based randomization with a computer-generated blocking with stratification across study sites to either ticagrelor or clopidogrel treatment. The co-primary primary endpoints are LV remodeling index with three-dimensional echocardiography and the level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) at 6 months representing post-MI remodeling processes. Changes of LV end-systolic/diastolic volume indices and LV ejection fraction between baseline and 6-month follow-up will be also evaluated. Analysis is per protocol. CONCLUSIONS HEALING-AMI is testing the effect of ticagrelor in reducing adverse LV remodeling following STEMI. Our trial would show the benefit of ticagrelor vs. clopidogrel related to the recovery of post-MI LV dysfunction beyond potent platelet inhibition.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02224534