Objective: Low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive brain stimulation modality with high spatial selectivity and the ability to reach deep brain areas. The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder. Methods: Participants were recruited in an outpatient clinic and randomly assigned to either the verum tFUS or sham stimulation group. The intervention group received six sessions of tFUS stimulation to the left dorsolateral prefrontal cortex over two weeks. Neuropsychological assessments were conducted before and after the sessions. Resting-state functional magnetic resonance imaging (rsfMRI) was also performed to evaluate changes in functional connectivity (FC). The primary outcome measure was the change in depressive symptoms, assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS). Results: The tFUS stimulation sessions were well tolerated without any undesirable side effects. The analysis revealed a significant main effect of session sequence on the MADRS scores and significant interactions between the session sequences and groups. The rsfMRI analysis showed a higher FC correlation between the right superior part of the subgenual anterior cingulate cortex (sgACC) and several other brain regions in the verum group compared with the sham group. Conclusion Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion. This randomized, sham-controlled clinical trial, the first study of its kind, demonstrated the safety and probable efficacy of tFUS stimulation for the treatment of depression.

Background: The most important aspect of a retrospective cohort study is the operational definition (OP) of the disease. We developed a detailed OP for the detection of sodiumglucose cotransporter-2 inhibitors (SGLT2i) related to diabetic ketoacidosis (DKA). The OP was systemically verified and analyzed. Methods: All patients prescribed SGLT2i at four university hospitals were enrolled in this experiment. A DKA diagnostic algorithm was created and distributed to each hospital;subsequently, the number of SGLT2i-related DKAs was confirmed. Then, the algorithm functionality was verified through manual chart reviews by an endocrinologist using the same OP. Results: A total of 8,958 patients were initially prescribed SGLT2i. According to the algorithm, 0.18% (16/8,958) were confirmed to have SGLT2i-related DKA. However, based on manual chart reviews of these 16 cases, there was only one case of SGLT2i-related DKA (positive predictive value = 6.3%). Even after repeatedly narrowing the diagnosis range of the algorithm, the effect of a positive predictive value was insignificant (6.3–10.0%, P > 0.999). Conclusion Owing to the nature of electronic medical record data, we could not create an algorithm that clearly differentiates SGLT2i-related DKA despite repeated attempts. In all retrospective studies, a portion of the samples should be randomly selected to confirm the accuracy of the OP through chart review. In retrospective cohort studies in which chart review is not possible, it will be difficult to guarantee the reliability of the results.

Tumor localization is challenging in the context of ductal carcinoma in situ (DCIS) treated with breast-conserving surgery. Conventional localization methods are generally performed under the guidance of ultrasonography or mammography and are rarely performed with magnetic resonance imaging (MRI), which is more sensitive than the aforementioned modalities in detecting DCIS. Here, we report the application of MRI-based individualized 3-dimensional (3D)-printed breast surgical guides (BSGs) for patients with breast cancer.We successfully resected indeterminate and suspicious lesions that were only detected using preoperative MRI, and the final histopathologic results confirmed DCIS with clear resection margins. MRI guidance combined with 3D-printed BSGs can be used for DCIS localization, especially for lesions easily detectable using MRI only.

Tumor localization is challenging in the context of ductal carcinoma in situ (DCIS) treated with breast-conserving surgery. Conventional localization methods are generally performed under the guidance of ultrasonography or mammography and are rarely performed with magnetic resonance imaging (MRI), which is more sensitive than the aforementioned modalities in detecting DCIS. Here, we report the application of MRI-based individualized 3-dimensional (3D)-printed breast surgical guides (BSGs) for patients with breast cancer.We successfully resected indeterminate and suspicious lesions that were only detected using preoperative MRI, and the final histopathologic results confirmed DCIS with clear resection margins. MRI guidance combined with 3D-printed BSGs can be used for DCIS localization, especially for lesions easily detectable using MRI only.

Objectives: Despite growing attention to anxiety in bipolar disorder (BD), little research has assessed anxiety symptoms in the course of BD. The current prospective follow-up study examines the influence of subjectively and objectively measured anxiety symptoms on the course of BD. Methods: A total of 49 patients with BD were followed-up prospectively for average of one year at an average of four months interval. The Korean version of the Beck Anxiety Inventory (K-BAI), the Hamilton Anxiety Rating Scale, heart rate variability (HRV) were used to measure anxiety subjectively, objectively and physiologically. Participants were divided into high and low anxiety groups based on their K-BAI scores. Kaplan-Meier survival analysis was performed to compare the recurrence of mood episode, suicide attempt, emergency room visit, and psychiatric hospitalization between two groups. Mediators were investigated with Cox proportional hazards models. Results: Compared to the low anxiety group, the high anxiety group reported significantly higher impulsiveness (p = 0.016) and lower high frequency component on HRV (p = 0.007) after controlling for severity of BD. Regarding survival analysis, the high anxiety group showed hastened depressive episode recurrence (p = 0.048) and suicidal ideation was the mediator of the hazard ratio (HR) 1.089 (p = 0.029) in the Cox model. Moreover, the high anxiety group showed a tendency of accelerated suicide attempt (p = 0.12) and impulsivity was the risk factor of suicide attempt (HR = 1.089, p = 0.036). Conclusions This interim analysis of prospective study suggests that high anxiety level in BD may anticipate unfavorable course.Further studies are needed to understand the multifactorial mechanism of anxious bipolar patients.

Objectives: Despite growing attention to anxiety in bipolar disorder (BD), little research has assessed anxiety symptoms in the course of BD. The current prospective follow-up study examines the influence of subjectively and objectively measured anxiety symptoms on the course of BD. Methods: A total of 49 patients with BD were followed-up prospectively for average of one year at an average of four months interval. The Korean version of the Beck Anxiety Inventory (K-BAI), the Hamilton Anxiety Rating Scale, heart rate variability (HRV) were used to measure anxiety subjectively, objectively and physiologically. Participants were divided into high and low anxiety groups based on their K-BAI scores. Kaplan-Meier survival analysis was performed to compare the recurrence of mood episode, suicide attempt, emergency room visit, and psychiatric hospitalization between two groups. Mediators were investigated with Cox proportional hazards models. Results: Compared to the low anxiety group, the high anxiety group reported significantly higher impulsiveness (p = 0.016) and lower high frequency component on HRV (p = 0.007) after controlling for severity of BD. Regarding survival analysis, the high anxiety group showed hastened depressive episode recurrence (p = 0.048) and suicidal ideation was the mediator of the hazard ratio (HR) 1.089 (p = 0.029) in the Cox model. Moreover, the high anxiety group showed a tendency of accelerated suicide attempt (p = 0.12) and impulsivity was the risk factor of suicide attempt (HR = 1.089, p = 0.036). Conclusions This interim analysis of prospective study suggests that high anxiety level in BD may anticipate unfavorable course.Further studies are needed to understand the multifactorial mechanism of anxious bipolar patients.

BACKGROUND/OBJECTIVES: Numerous school-based weight control programs have been initiated for weight loss among adolescents. However, the relationship between these programs and inappropriate weight control efforts, dietary habits and behavior of students, have not been investigated sufficiently. This study was undertaken to investigate the association between body mass index (BMI) of adolescents, and their health status and inappropriate weight-control efforts. We further examined the relationship between attendance to school-based weight-control programs and attempting inappropriate weightcontrol efforts, dietary habits, and behavior. SUBJECTS/METHODS: A survey of 1,742 students was conducted in Korea. Logistic regression was used to assess differences in the health status (grouped by BMI and improper weight control) and dietary habits, based on attendance to the weight-control programs. RESULTS: Obese students were significantly more dissatisfied with physical, mental and spiritual health. Students who attended weight-control programs were likely to be underweight (P < 0.001), whereas those who did not attend weight-control programs were likely to attempt weight control improperly (P < 0.001). Students who participated in the program also had relatively healthy dietary habits (P < 0.001–0.027), and students who did not attend had comparatively unhealthy dietary habits (P < 0.001–0.008). Students who attended weight-control programs were likely to be underweight (P < 0.001) with relatively healthy dietary habits (P < 0.001–0.027), whereas students who did not attend the programs were likely to attempt weight control improperly (P < 0.001) and had comparatively unhealthy dietary habits (P < 0.001–0.008). CONCLUSIONS Attending school-based weight-control programs was significantly associated with not attempting inappropriate weight-control efforts, as well as following healthy dietary habits. Our data indicates that offering school-based weight-control programs is valuable to student health, and is anticipated to reducing the public health burden.

BACKGROUND/OBJECTIVES: Numerous school-based weight control programs have been initiated for weight loss among adolescents. However, the relationship between these programs and inappropriate weight control efforts, dietary habits and behavior of students, have not been investigated sufficiently. This study was undertaken to investigate the association between body mass index (BMI) of adolescents, and their health status and inappropriate weight-control efforts. We further examined the relationship between attendance to school-based weight-control programs and attempting inappropriate weightcontrol efforts, dietary habits, and behavior. SUBJECTS/METHODS: A survey of 1,742 students was conducted in Korea. Logistic regression was used to assess differences in the health status (grouped by BMI and improper weight control) and dietary habits, based on attendance to the weight-control programs. RESULTS: Obese students were significantly more dissatisfied with physical, mental and spiritual health. Students who attended weight-control programs were likely to be underweight (P < 0.001), whereas those who did not attend weight-control programs were likely to attempt weight control improperly (P < 0.001). Students who participated in the program also had relatively healthy dietary habits (P < 0.001–0.027), and students who did not attend had comparatively unhealthy dietary habits (P < 0.001–0.008). Students who attended weight-control programs were likely to be underweight (P < 0.001) with relatively healthy dietary habits (P < 0.001–0.027), whereas students who did not attend the programs were likely to attempt weight control improperly (P < 0.001) and had comparatively unhealthy dietary habits (P < 0.001–0.008). CONCLUSIONS Attending school-based weight-control programs was significantly associated with not attempting inappropriate weight-control efforts, as well as following healthy dietary habits. Our data indicates that offering school-based weight-control programs is valuable to student health, and is anticipated to reducing the public health burden.

Background: Obesity and dental caries have common risk factors such as food intake, eating habits, and lifestyle. Nevertheless, there has been no consensus on the significant association between obesity and dental caries, and additional studies are needed.We investigated the relationship between obesity and dental caries in some college students in this pilot study. Methods: Forty-two obese college students (body mass index [BMI]≥25) registered at a University Obesity Clinic and 19 normal students (18.5≤BMI＜25) were recruited. Oral examinations were conducted, and anthropometric data and blood samples were collected. The blood concentrations of low-density lipoprotein (LDL), high-density lipoprotein, and triglyceride were also measured. After controlling for dental plaque index, a univariate analysis of dental caries indicators related to obesity was performed; partial correlation analysis was also conducted. A nonparametric test was used for the analysis of gender-related trends due to the limited number of participants. Results: The obese group had significantly fewer missing teeth (p=0.014), missing surfaces (p=0.035), filled surfaces (p=0.038), and decayed-missing-filled surfaces (p=0.020) than the normal group. There was no difference between the males in the normal and obese groups. The females in the obese group had significantly fewer missing teeth (p=0.003), missing surfaces (p=0.003), and decayed-missing-filled surfaces (p=0.046). Partial correlation analysis showed a weak negative correlation (r=−0.256) between the blood LDL concentration and decayed-missing-filled teeth. The other obesity and dental caries indicators were not correlated. Conclusion The blood cholesterol concentration had a negative relationship with dental caries, and there were fewer cases of dental caries in the obese group in this study. However, it is important to clarify the relationship between obesity and dental caries through a dietary survey or additional investigations considering other confounding factors.

Purpose: Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. Methods This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy.We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.