Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

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.

Erosive adenomatosis of the nipple (EAN), also known as nipple adenoma, florid papillomatosis, or papillary adenoma of the nipple, is a benign neoplasm originating from a lactiferous duct of the breast. Although the potential for malignant change is invariably negligible, the nature of the disease is quite intractable despite several treatment methods. Surgical excision is known as the treatment of choice, but this invasive approach is generally not acceptable to the vast majority of patients due to the cosmetic outcomes. Cryosurgery could be an alternative choice to preserve the structure of the nipple-areola complex, though its application has not been studied due to the paucity of cases. A 22-year-old female presented with a unilateral, crater-like erosion of the left nipple with serosanguineous discharge. The skin biopsy revealed proliferation of tubular structures, which corresponded to EAN. She was treated with 4 sessions of cryosurgery (open cryospray with liquid nitrogen) over 6 months, and the skin lesion resolved completely without any recurrence for 12 months. Although further study is required to determine the optimal treatment regimen for EAN, cryosur-gery should be considered as an effective option to surgical excision.

Purpose: With changing fungal epidemiology and azole resistance in Aspergillus species, identifying fungal species and susceptibility patterns is crucial to the management of aspergillosis and mucormycosis. The objectives of this study were to evaluate performance of panfungal polymerase chain reaction (PCR) assays on formalin-fixed paraffin embedded (FFPE) samples in the identification of fungal species and in the detection of azole-resistance mutations in the Aspergillus fumigatus cyp51A gene at a South Korean hospital. Materials and Methods: A total of 75 FFPE specimens with a histopathological diagnosis of aspergillosis or mucormycosis were identified during the 10-year study period (2006–2015). After deparaffinization and DNA extraction, panfungal PCR assays were conducted on FFPE samples for fungal species identification. The identified fungal species were compared with histopathological diagnosis. On samples identified as A. fumigatus, sequencing to identify frequent mutations in the cyp51A gene [tandem repeat 46 (TR46), L98H, and M220 alterations] that confer azole resistance was performed. Results: Specific fungal DNA was identified in 31 (41.3%) FFPE samples, and of these, 16 samples of specific fungal DNA were in accord with a histopathological diagnosis of aspergillosis or mucormycosis; 15 samples had discordant histopathology and PCR results. No azole-mediating cyp51A gene mutation was noted among nine cases of aspergillosis. Moreover, no cyp51A mutations were identified among three cases with history of prior azole use. Conclusion Panfungal PCR assay with FFPE samples may provide additional information of use to fungal species identification. No azole-resistance mediating mutations in the A. fumigatus cyp51A gene were identified among FFPE samples during study period.

Background: The value of the Fracture Risk Assessment Tool (FRAX) and the trabecular bone score (TBS) for assessing osteoporotic fracture risk has not been fully elucidated in Koreans. We conducted this study to clarify the predictive value of FRAX adjusted by TBS for osteoporotic fractures in Korean women. Methods: After screening 7,192 eligible subjects from the Ansung cohort, 1,165 women aged 45 to 76 years with available bone mineral density (BMD) and TBS data were enrolled in this study. We assessed their clinical risk factors for osteoporotic fractures and evaluated the predictive value of FRAX with or without BMD and TBS. Results: During the mean follow-up period of 7.5 years, 99 (8.5%) women suffered major osteoporotic fractures (MOFs) and 28 (2.4%) experienced hip fractures. FRAX without BMD, BMD-adjusted FRAX, and TBS-adjusted FRAX were significantly associated with the risk of MOFs (hazard ratio [HR] per percent increase, 1.08; 95% confidence interval [CI], 1.03 to 1.14; HR, 1.09; 95% CI, 1.03 to 1.15; and HR, 1.07; 95% CI, 1.02 to 1.13, respectively). However, BMD-adjusted FRAX and TBS-adjusted FRAX did not predict MOFs better than FRAX without BMD based on the Harrell’s C statistic. FRAX probabilities showed limited value for predicting hip fractures. The cut-off values of FRAX without BMD, FRAX with BMD, and FRAX with BMD adjusted by TBS for predicting MOFs were 7.2%, 5.0%, and 6.7%, respectively. Conclusion FRAX with BMD and TBS adjustment did not show better predictive value for osteoporotic fractures in this study than FRAX without adjustment. Moreover, the cut-off values of FRAX probabilities for treatment might be lower in Korean women than in other countries.

PURPOSE: To report a case of recurrent intraocular hemorrhage due to type A hemophilia in a female patient without any previous medical history.CASE SUMMARY: A 51-year-old female patient without any previous medical history was referred to our clinic due to blurred vision in her left eye. Slit lamp microscopy of the anterior segment was nonspecific. Fundus examination revealed vitreous hemorrhage with retinal tear in her left eye. Vitrectomy and cataract surgery were performed. One day after surgery, hyphema and vitreous hemorrhage recurred. A coagulation disorder was suspected and further serological evaluation was conducted. Coagulation factor analyses showed that the activity of coagulation factors 8 and 12 decreased to 25% and 47%, respectively. Genetic sequence analyses were conducted, and a missense mutation of C6724G> A] was found in exon 25, and type A hemophilia was confirmed. CONCLUSIONS In patients who tend to show persistent bleeding even after proper treatment, hematological evaluation including coagulation factor assays, and the possibility of rare diseases such as hemophilia should be considered.

The number of persons infected by HIV/AIDS has consistently increased in Korea since the first case of HIV/AIDS infection in 1985 and reached 15,208 by 2016. About 1,100 new patients with HIV/ AIDS infections have emerged every year since 2013. In Korea, the Korea HIV/AIDS Cohort Study was established for the evidenced-based prevention, treatment, and effective management of patients infected with human immunodeficiency virus (HIV) in December 2006. This study monitored 1,438 patients, who accounted for about 10% of all patients with HIV/AIDS in Korea, for 10 years with the following aims: (1) to develop an administrative system for the establishment of a HIV/AIDS cohort-based study; (2) to standardize methodologies and the case report forms; and (3) to standardize multi-cohort data and develop a data cleaning method. This study aims to monitor at least 1,000 patients (excluding those for whom investigation had been completed) per year (estimated number of patients who can be monitored by January 2018: 939). By December 2016, the sex distribution was 93.3% for men, and 6.7% for women (gender ratio, 13.9:1.0), and 98.9% of all participants were Korean. More than 50.0% of the participants were confirmed as HIV positive after 2006. This study reports competitive, long-term research that aimed to develop policies for the prevention of chronic infectious diseases for patients with HIV. The data collected over the last decade will be used to develop indices for HIV treatment and health promotion.