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.

Purpose: Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC). Materials and Methods: A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017. Results: Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1. Conclusion NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

PURPOSE: An association between endocrine treatment-related symptoms and breast cancer recurrence has been suggested previously; however, conflicting results have been reported. We performed a meta-analysis of published studies to clarify this relationship. METHODS: We systematically searched PubMed, Embase, Scopus, and the Cochrane database for studies investigating the association between endocrine treatment-related symptoms and patient survival. Random-effects meta-analysis was conducted with recurrence rate as the primary outcome. RESULTS: Out of 7,713 retrieved articles, six studies were included. In patients who received endocrine treatment, the presence of any endocrine treatment-related symptom was found to be associated with a lower recurrence rate in comparison to an absence of any symptoms (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.66–0.87). This relationship persisted in patients presenting with only vasomotor or only musculoskeletal symptoms (HR, 0.74, 95% CI, 0.63–0.87; HR, 0.69, 95% CI, 0.55–0.86, respectively). At both time-points of symptom evaluation (3 months and 12 months), patients with endocrine treatment-related symptoms had a lower recurrence rate (HR, 0.74, 95% CI, 0.66–0.84; HR, 0.79, 95% CI, 0.69–0.90, respectively). This association was also significant in pooled studies including patients with and without baseline symptoms (HR, 0.73, 95% CI, 0.54–0.99; HR, 0.76, 95% CI, 0.69–0.85, respectively). CONCLUSION: Endocrine treatment-related symptoms are significantly predictive of lower recurrence rate in breast cancer patients, regardless of the type of symptoms, time-point of evaluation, or inclusion of baseline symptoms. These symptoms could be biomarkers for the prediction of long-term responses to endocrine treatment in patients with breast cancer.
Biomarkers ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Recurrence ; Symptom Assessment

PURPOSE: The American College of Surgeons Oncology Group Z0011 trial reported that complete dissection of axillary lymph nodes (ALNs) may not be warranted in women with clinical T1-T2 tumors and one or two involved ALNs who were undergoing lumpectomy plus radiation followed by systemic therapy. The present study was conducted to identify preoperative imaging predictors of ≥ 3 ALNs. MATERIALS AND METHODS: The training set consisted of 1,917 patients with clinical T1-T2 and node negative invasive breast cancer. Factors associated with ≥ 3 involved ALNs were evaluated by logistic regression analysis. The validation set consisted of 378 independent patients. The nomogram was applied prospectively to 512 patients who met the Z0011 criteria. RESULTS: Of the 1,917 patients, 204 (10.6%) had ≥ 3 positive nodes. Multivariate analysis showed that involvement of ≥ 3 nodes was significantly associated with ultrasonographic and chest computed tomography findings of suspicious ALNs (p < 0.001 each). These two imaging criteria, plus patient age, were used to develop a nomogram calculating the probability of involvement of ≥ 3 ALNs. The areas under the receiver operating characteristic curve of the nomogram were 0.852 (95% confidence interval [CI], 0.820 to 0.883) for the training set and 0.896 (95% CI, 0.836 to 0.957) for the validation set. Prospective application of the nomogram showed that 60 of 512 patients (11.7%) had scores above the cut-off. Application of the nomogram reduced operation time and cost, with a very low re-operation rate (1.6%). CONCLUSION: Patients likely to have ≥ 3 positive ALNs could be identified by preoperative imaging. The nomogram was helpful in selective intraoperative examination of sentinel lymph nodes.
Breast Neoplasms* ; Breast* ; Female ; Humans ; Logistic Models ; Lymph Nodes* ; Mastectomy, Segmental ; Multivariate Analysis ; Nomograms* ; Prospective Studies ; ROC Curve ; Surgeons ; Thorax

PURPOSE: To evaluate the 3-month natural course of recurrent macular edema secondary to branch retinal vein occlusion (BRVO) treated with intravitreal bevacizumab. METHODS: This retrospective, observational study included 36 eyes with macular edema secondary to BRVO. All patients were initially treated with intravitreal bevacizumab for macular edema. Recurrence of macular edema was either not treated (untreated group) or treated with a single intravitreal bevacizumab injection (treated group). Central foveal thickness (CFT) and best-corrected visual acuity (BCVA) were compared at the time of recurrence and 3 months later. RESULTS: At the time of recurrence, the mean CFT and logarithm of the minimum angle of resolution BCVA were 484.9 ± 124.1 µm and 0.58 ± 0.26 in the untreated group (n = 19) and 456.3 ± 126.8 µm and 0.51 ± 0.21 in the treated group (n = 17), respectively. Three months later, the mean CFT and BCVA had changed to 493.7 ± 123.9 µm and 0.62 ± 0.29 in the untreated group and 294.7 ± 104.4 µm and 0.40 ± 0.24 in the treated group, respectively. The differences in CFT and BCVA between the two time points were not significant in the untreated group (p = 0.106 and p = 0.687, respectively), whereas statistically significant differences were noted in the treated group (p = 0.002 and p < 0.001, respectively). CONCLUSIONS: Unlike the first episode of macular edema following BRVO, recurrent macular edema following intravitreal bevacizumab therapy did not spontaneously resolve, suggesting the potential benefit of prompt treatment.
Bevacizumab* ; Curriculum* ; Humans ; Macular Edema* ; Natural History ; Observational Study ; Recurrence ; Retinal Vein Occlusion* ; Retinal Vein* ; Retinaldehyde* ; Retrospective Studies ; Visual Acuity

Health risk appraisal (HRA) is a systematic approach for collecting information regarding individual risk factors, predicting the probability of disease occurrence and death, and linking patients with interventions to promote health and prevent disease. Because the risk factors of cardiovascular disease are well established, several cardiovascular disease risk prediction models have been developed over multiple decades. The health risk appraisal prediction model of the Korean national health screening program will be revised and updated using the latest well-validated studies to reflect the current characteristics of the Korean population and to improve the effectiveness of education and behavioral modifications. It is necessary to provide various tools such as a web page and smartphone application to increase the utility of this program in the future.
Behavior Control ; Cardiovascular Diseases* ; Education ; Health Status Indicators* ; Humans ; Mass Screening* ; Risk Factors ; Smartphone

PURPOSE: Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. MATERIALS AND METHODS: This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. RESULTS: A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. CONCLUSION: Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.
Breast Neoplasms* ; Breast* ; Comorbidity ; Diagnosis ; Disease-Free Survival ; Humans ; Retrospective Studies ; Survival Rate ; Time-to-Treatment ; Triple Negative Breast Neoplasms

PURPOSE: To decide the optimal treatment for breast cancer patients with locoregional recurrence (LRR), it is important to determine which group has the highest risk of subsequent distant metastasis (DM). We aimed to investigate the factors associated with DM in patients with LRR. METHODS: We reviewed the data of 208 patients with LRR as the first event after primary surgery for breast cancer at our institution between 1997 and 2010, to identify significant factors associated with DM. Subsequently, Kaplan-Meier curves and the Cox regression method were used to analyze the correlation between clinical factors and survival. RESULTS: DM occurred in 33.2% (68/208) of LRR patients. The median DM-free interval was 23 months. Some clinical factors were associated with DM in univariate analysis, including the type of primary surgery (p=0.026), tumor size (p=0.005), nodal status (p=0.011), and administration of initial adjuvant chemotherapy (p=0.001). In addition, regional rather than local recurrence and a disease-free interval (DFI; duration between primary surgery and LRR) < or =30 months were also significant (p<0.001 for both). However, only a shorter DFI reached significance in multiple logistic regression analysis. Cox regression analysis of DM-free survival showed that both a shorter DFI and regional recurrence were significant factors with hazard ratios of 2.1 (95% confidence interval [CI], 1.21-3.65) and 1.85 (95% CI, 1.04-3.28), respectively. CONCLUSION: DFI was the most important factor associated with subsequent DM in patients with LRR as a first event of failure.
Breast Neoplasms* ; Chemotherapy, Adjuvant ; Humans ; Logistic Models ; Neoplasm Metastasis* ; Neoplasm Recurrence, Local ; Prognosis ; Recurrence* ; Risk Factors*

PURPOSE: To identify the risk factors of retinal breaks in patients with symptoms of floaters and to determine the associations between those risk factors and retinal breaks. METHODS: A retrospective chart review of patients who visited with the symptom of vitreous floaters between July 2012 and October 2012 was performed. Patient information, such as age, sex, symptoms (e.g., multiple floaters and flashing), duration of symptoms, refractive error, and complete eye examination were recorded. The patients were divided into 2 groups: the control group had symptoms of floaters with no retinal breaks and the retinal breaks group had symptoms of floaters with retinal breaks. The chi-square test and univariate logistic regression were used for statistical analysis. RESULTS: A total of 1744 eyes were examined in this study, including 1706 eyes in the control group and 38 eyes in the retinal breaks group. Univariate analysis revealed that patients with high myopia and multiple floaters showed increased risk of retinal breaks by 3.4 and 4.4 times, respectively, when compared to patients with a single floater alone. Lattice degeneration and vitreous or retinal hemorrhage increased the risk of retinal breaks by 10.8 and 37.5 times when compared to eyes that did not have lattice degeneration or vitreous or retinal hemorrhage. During the follow-up period after laser photocoagulation, a new retinal tear was found in 2 patients (2/38, 5.3%). CONCLUSIONS: Vitreous or retinal hemorrhage, lattice degeneration, multiple floaters, and high myopia are risk factors of retinal breaks in patients with the symptom of floaters. Therefore, it is important for ophthalmologists to be aware of these risk factors and the patients at risk should be encouraged to attend follow-up examinations.
Follow-Up Studies ; Humans ; Light Coagulation ; Logistic Models ; Myopia ; Refractive Errors ; Retinal Hemorrhage ; Retinal Perforations* ; Retrospective Studies ; Risk Factors* ; Vitreous Hemorrhage