Objective: 177 Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [ 177 Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60–90) with mCRPC from a phase I study with activity escalation design of single administration of [ 177 Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [ 177 Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion [ 177 Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

Purpose: To investigate the clinical results of vitrectomy alone as the primary treatment for rhegmatogenous retinal detachment (RD) in patients with atopic dermatitis (AD). Methods: The medical records of patients with AD treated for rhegmatogenous retinal detachment (RD) were retrospectively reviewed. We investigated the characteristics of retinal breaks and detachments, applied surgical methods, and results. Results: Twenty eyes of 14 patients with AD who presented with rhegmatogenous RD and treated by vitrectomy were included in this analysis. Sixteen eyes (80%) were treated with vitrectomy, either alone or in combination with cataract surgery, and the retina was successfully attached to 94% of the eyes. There were four cases in which vitrectomy was combined with encircling. Reoperation was needed in half of the eyes that received vitrectomy with encircling, which presented nearly total detachment, severe proliferative vitreoretinopathy, and pseudophakia. Conclusions Vitrectomy alone, in combination with cataract surgery, may be sufficient to treat rhegmatogenous RD in patients with AD. Additional encircling or buckling should still be considered in complicated cases.

Purpose: To compare the prognosis of patients with axillary adenocarcinoma from an unknown primary (ACUPax) origin with negative MRI results and those with MRI-detected primary breast cancers. Materials and Methods: The breast MRI images of 32 patients with ACUPax without signs of primary breast cancer on mammography and ultrasound (US) were analyzed. Spot compression-magnification mammography and second-look US were performed for the area of MRI abnormality in patients with positive results; any positive findings corresponding to the MRI abnormality were confirmed by biopsy. If suspicious MRI lesions could not be localized on mammography or US, MR-guided biopsy or excision biopsy after MR-guided localization was performed. We compared the prognosis of patients with negative breast MRI with that for patients with MRI-detected primary breast cancers. Results: Primary breast cancers were confirmed in 8 (25%) patients after breast MRI. Primary breast cancers were not detected on MRI in 24 (75%) patients, including five cases of false-positive MRI results. Twenty-three patients underwent axillary lymph node dissection (ALND) followed by whole breast radiation therapy (WBRT) and chemotherapy (n=17) or subsequent chemotherapy only (n=2). Recurrence or distant metastasis did not occur during follow up in 7/8 patients with MRI-detected primary breast cancers and 22/24 patients with negative MRI results. Regional recurrence or distant metastasis did not occur in any MR-negative patient who received adjuvant chemotherapy after ALND and WBRT. Conclusion The prognoses of MR-negative patients with ACUPax who received ALND and WBRT followed by chemotherapy were as good as those of patients with MRI-detected primary breast cancers.

Background/Aims: Low-level viremia (LLV) after nucleos(t)ide analog treatment was presented as a possible cause of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, detailed information on patients’ adherence in the real world was lacking. This study aimed to evaluate the effects of LLV on HCC development, mortality, and cirrhotic complications among patients according to their adherence to entecavir (ETV) treatment. Methods: We performed a retrospective observational analysis of data from 894 consecutive adult patients with treatment-naïve CHB undergoing ETV treatment. LLV was defined according to either persistent or intermittent episodes of <2,000 IU/mL detectable hepatitis B virus DNA during the follow-up period. Good adherence to medication was defined as a cumulative adherence ≥90% per study period. Results: Without considering adherence in the entire cohort (n=894), multivariate analysis of the HCC incidence showed that LLV was an independent prognostic factor in addition to other traditional risk factors in the entire cohort (P=0.031). Good adherence group comprised 617 patients (69.0%). No significant difference was found between maintained virologic response and LLV groups in terms of the incidence of liver-related death or transplantation, HCC, and hepatic decompensation in good adherence group, according to multivariate analyses. Conclusions In patients with treatment-naïve CHB and good adherence to ETV treatment in the real world, LLV during treatment is not a predictive factor for HCC and cirrhotic complications. It may be unnecessary to adjust their antiviral agent for patients with good adherence who experience LLV during ETV treatment.

OBJECTIVE: In 2002, the Korean Society for Affective Disorders developed the guidelines for the treatment of major depressive disorder (MDD), and revised it in 2006 and 2012. The third revision of these guidelines was undertaken to reflect advances in the field. METHODS: Using a 44-item questionnaire, an expert consensus was obtained on pharmacological treatment strategies for MDD 1) without or 2) with psychotic features, 3) depression subtypes, 4) maintenance, 5) special populations, 6) the choice of an antidepressant (AD) regarding safety and adverse effects, and 7) non-pharmacological biological therapies. Recommended first, second, and third-line strategies were derived statistically. RESULTS: AD monotherapy is recommended as the first-line strategy for non-psychotic depression in adults, children/adolescents, elderly adults, patient with persistent depressive disorder, and pregnant women or patients with postpartum depression or premenstrual dysphoric disorder. The combination of AD and atypical antipsychotics (AAP) was recommended for psychotic depression in adult, child/adolescent, postpartum depression, and mixed features or anxious distress. Most experts recommended stopping the ongoing initial AD and AAP after a certain period in patients with one or two depressive episodes. As an MDD treatment modality, 92% of experts are considering electroconvulsive therapy and 46.8% are applying it clinically, while 86% of experts are considering repetitive transcranial magnetic stimulation but only 31.6% are applying it clinically. CONCLUSION: The pharmacological treatment strategy in 2017 is similar to that of Korean Medication Algorithm for Depressive Disorder 2012. The preference of AAPs was more increased.
Adult ; Aged ; Antipsychotic Agents ; Biological Therapy ; Consensus ; Depression ; Depression, Postpartum ; Depressive Disorder ; Depressive Disorder, Major ; Drug Therapy ; Electroconvulsive Therapy ; Female ; Humans ; Mood Disorders ; Pregnant Women ; Premenstrual Dysphoric Disorder ; Transcranial Magnetic Stimulation

OBJECTIVE: We investigated the prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with multiple myeloma (MM). MATERIALS AND METHODS: Subjects were 76 patients with newly diagnosed myeloma and pretreatment with 18F-FDG PET/CT from four hospitals. The PET/CT features were evaluated and the clinical characteristics were reviewed. Prognostic factors related to poor progression-free survival (PFS) and overall survival (OS) were identified using a Cox proportional hazards regression model and a prediction scale was developed based on the identified factors. RESULTS: Multivariate analysis showed that the presence of 18F-FDG-avid focal bone lesions (≥ 3) was a significant and independent predictor of PFS (hazard ratio [HR] = 3.28, p = 0.007) and OS (HR = 11.78, p = 0.001). The presence of extramedullary disease on PET/CT scan was also a significant predictor of poor PFS (HR = 2.79, p = 0.006) and OS (HR = 3.89, p = 0.003). A prognostic scale was developed using these two predictors. An increase in score on the scale corresponded to a significantly increased risk of poor OS (p = 0.005). In addition, Kaplan-Meier analysis demonstrated that patient survival varied significantly according to the scale (p < 0.001 for OS and p = 0.001 for PFS). CONCLUSION: 18F-FDG-avid focal lesions and the presence of extramedullary disease on PET/CT scan are significantly associated with poor OS in MM patients. The scale developed according to these predictors represents a potential prognostic tool for evaluation of patients with MM.
Cohort Studies* ; Disease-Free Survival ; Electrons ; Fluorodeoxyglucose F18 ; Humans ; Kaplan-Meier Estimate ; Multiple Myeloma* ; Multivariate Analysis ; Positron-Emission Tomography and Computed Tomography* ; Prognosis

BACKGROUND: A subanalysis study of the ENGAGE AF-TIMI 48 trial showed that cardiac troponin I, N-terminal proB-type natriuretic peptide, and D-dimer, were powerful predictors of cerebrovascular adverse events. We aimed to evaluate D-dimer and cardiac troponin I levels during the acute period of ischemic stroke in anticoagulation-naïve patients with non-valvular atrial fibrillation (NVAF) and also studied the association between these biomarkers and stroke severity. METHODS: Consecutive anticoagulation-naïve patients with acute ischemic stroke due to NVAF were enrolled within two days after each stroke event, and all patients were stratified into either moderate-to-severe or mild neurologic deficit groups using the National Institutes of Health Stroke Scale (NIHSS) at admission. RESULTS: A total of 98 patients were enrolled in this study. The median value for the D-dimer was above the upper limit of the normal reference range, but the troponin I value was within the normal range for all patients. After adjusting for CHA2DS2-VASc risk factors, the log-transformed values for D-dimer were positively correlated with an increasing NIHSS score (r=0.233; P=0.051). In the multivariate logistic analysis, the log-transformed D-dimer was positively associated with more severe strokes (odds ratio, 30.1; 95% confidence interval [CI], 1.9–486.2 and 29.7; 95% CI, 2.0–430.8 in the upper two quartiles respectively). The log-transformed values for troponin I did not correlate with the NIHSS score. CONCLUSION: D-dimer levels were higher and an independent risk factor for severe stroke in anticoagulation-naïve patients with NVAF related stroke. In contrast, troponin I levels were normal and were not associated with stroke severity.
Atrial Fibrillation ; Biomarkers ; Humans ; National Institutes of Health (U.S.) ; Neurologic Manifestations ; Reference Values ; Risk Factors ; Stroke ; Troponin I

The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation. Among the reprogramming factors, Myc predominantly induced ERK suppression. ERK inhibition upregulated the conversion of somatic cells into iPSCs through concomitant suppression of serum response factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by ERK inhibition and negatively regulated embryonic pluripotency by inducing differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial molecular event that facilitates iPSC formation and may be a useful surrogate marker for cellular reprogramming.

OBJECTIVE: The aim of this study was to examine the validity of the Korean version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood disorder patients. METHODS: A total of 454 patients who diagnosed as mood disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32-R2 (KHCL-32-R2). RESULTS: The KHCL-32-R2 showed a three-factorial structure (eigenvalue >2) that accounted for 43.26% of the total variance. Factor 1 was labeled “active/elated” and included 16 items; factor 2, “irritable/distractible” and included 9 items; and factor 3 was labeled “risk-taking/indulging” and included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score distinguished between BD and MDD, which yielded a sensitivity of 70% and a specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15 with maximized sensitivity (0.67) and specificity (0.66). Cronbach’s alpha of KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79, respectively. Correlations between KHCL-32-R2 and Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder Questionnaire were −0.66 (p=0.41), −0.14 (p=0.9), and 0.61 (p < 0.001), respectively. CONCLUSION: The KHCL-32-R2 may be a useful tool in distinguishing between bipolar and depressive patients in clinical settings.
Bipolar Disorder ; Depression ; Depressive Disorder, Major ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Mood Disorders* ; Psychometrics* ; Sensitivity and Specificity

In this review, we compared recommendations from the Korean Medication Algorithm Project for Depressive Disorder 2017 (KMAP-DD 2017) to other global treatment guidelines for depression. Six global treatment guidelines were reviewed; among the six, 4 were evidence-based guidelines, 1 was an expert consensus-based guideline, and 1 was an amalgamation of both evidence and expert consensus-based recommendations. The recommendations in the KMAP-DD 2017 were generally similar to those in other global treatment guidelines, although there were some differences between the guidelines. The KMAP-DD 2017 appeared to reflect current changes in the psychopharmacology of depression quite well, like other recently published evidence-based guidelines. As an expert consensus-based guideline, the KMAP-DD 2017 had some limitations. However, considering there are situations in which clinical evidence cannot be drawn from planned clinical trials, the KMAP-DD 2017 may be helpful for Korean psychiatrists making decisions in the clinical settings by complementing previously published evidence-based guidelines.
Complement System Proteins ; Depression ; Depressive Disorder* ; Psychiatry ; Psychopharmacology