Multiple myeloma (MM), a hematological malignancy, is characterized by malignant plasma cell proliferation in the bone marrow. Recent treatment advances have significantly improved patient outcomes associated with MM.In this study, we aimed to develop comprehensive, evidence-based guidelines for the diagnosis, prognosis, and treat‑ ment of MM. We identified 12 key clinical questions essential for MM management, guiding the extensive literature review and meta-analysis of the study. Our guidelines provide evidence-based recommendations by integrating patient preferences with survey data. These recommendations include current and emerging diagnostic tools, thera‑ peutic agents, and treatment strategies. By prioritizing a patient-centered approach and rigorous data analysis, these guidelines were developed to enhance MM management, both in Korea and globally.

Objective: Spontaneous remission may influence the outcome of clinical trials and evaluation of antidepressant efficacy, as it is associated with placebo effects and false remission rates. However, the characteristics of spontaneous remission and its biological mechanisms remain poorly understood. This study aimed to explore the metabolic signatures and underlying biological mechanisms of spontaneous remission using metabolomics. Methods: This study conducted untargeted and targeted metabolomic analyses in a discovery cohort (n = 16) comprising patients with major depressive disorder (MDD) and those who were spontaneously remitted without medication.Findings were validated in an independent cohort (n = 185), comprising drug-treated patients and healthy controls. Results: Acetylcarnitine levels were significantly increased in spontaneous remission compared to depression, whereas glycerophosphocholine levels were decreased in spontaneous remission. Both metabolites showed the highest concentration in the control group, followed by the remission group, and the lowest concentration in the depression group, regardless of medication status. These changes suggest alterations in mitochondrial and membrane lipid metabolism. Conclusion Altered levels in acetylcarnitine and glycerophosphocholine may reflect key pathogenic mechanisms of MDD. These findings offer new insight into spontaneous remission as a distinct clinical subtype of depression and may highlight the potential of these metabolites as biomarkers for treatment monitoring in MDD.

Background: This study aims to analyze the outcomes of living donor liver transplantation (LDLT) using grafts with multiple hepatic arteries (HAs), compared to those with a single HA. Methods: A retrospective analysis was conducted on 1,059 LDLT patients from July 2005 to December 2022 at Severance Hospital, South Korea. Patients were categorized into multiple-HA and single-HA groups. Propensity score matching was employed to balance baseline characteristics, with primary outcomes being graft survival and secondary outcomes including HA, biliary, and total vascular complications. Results: The study included 27 patients in the multiple-HA group and 925 in the single-HA group before matching. After propensity score matching, no significant difference in 5-year graft survival rates was observed between the groups (60.4% for multiple-HA vs. 72.8% for single-HA, p=0.172). However, the multiple-HA group exhibited a higher incidence of bile duct complications (80.0% vs. 48.3%, p=0.038).Multivariable Cox regression analysis did not find multiple HAs to be a significant predictor of graft loss but confirmed their association with increased bile duct complications. Conclusion LDLT using grafts with multiple HAs does not adversely affect overall graft survival compared to single-HA grafts. Nevertheless, the increased risk of bile duct complications associated with multiple HAs necessitates careful surgical planning and postoperative management to mitigate this risk.

Purpose: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. Results: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). Conclusion Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Purpose: Classical swine fever (CSF) reemerged on CSF-free Jeju Island where vaccination is not practiced by the unintentional injection of a live attenuated vaccine (modified live attenuated vaccines–low-virulence Miyagi [MLV-LOM]) in 2014. Since the Jeju provincial authority is considering adopting a voluntary immunization policy using a CSF-E2 subunit vaccine to combat LOM-derived CSF endemic, this study aimed to evaluate in Jeju herds. Materials and Methods: Two vaccination trials using the Bayovac CSF-E2 vaccine licensed for use in South Korea assessed the safety and humoral immunity of the CSF-E2 vaccine in breeding (trial 1) and nursery animals (trial 2) under farm application conditions. Results: Neither local nor systemic (including reproductive) adverse effects were objectively observed in pregnant sows and young piglets following a respective vaccination regime at pregnancy or weaning, respectively. Trial 1 showed that sows immunized with the CSF-E2 vaccine possessed high and consistent E2-specific and neutralizing antibody levels. The CSF-E2 vaccine-immunized pregnant sows subsequently conferred appropriate and steady passive immunity to their offspring. In trial 2, a double immunization scheme of the CSF-E2 vaccine in piglets at 40 and 60 days of age could elicit a consistent and long-lasting adequate antibody response. Additionally, the two trials detected no E rns -specific antibody responses, indicating that CSF-E2 vaccine can differentiate infected from vaccinated animals (DIVA). Conclusion Our trial data collectively provide invaluable information on applying the CSFE2 subunit vaccine to circumvent the possible drawbacks associated with the MLV-LOM concerning the safety, efficacy, and DIVA, in the LOM-endemic field farms and contribute to advanced CSF eradication on Jeju Island.

To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K+(Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an halfinhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06.Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapineinduced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentrationand use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapineinduced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

Purpose: The aim of the current study was to evaluate the adverse clinical impact of intraoperative conversion during laparoscopic pancreaticoduodenectomy (LPD). Materials and Methods: The medical records of patients who underwent pancreaticoduodenectomy (PD) were retrospectively reviewed. Perioperative clinical variables were compared between patients who underwent converted PD (cPD) and initially planned open PD (OPD) to investigate the clinical impact and predictive factors of intraoperative conversion during LPD. Results: A total of 171 patients were included. Among them, 31 patients (19.3%) were found to have intraoperative conversion during LPD. Failure of progression due to severe adhesion (12 patients, 7%) and major vessel invasion (7 patients, 4%) were the two most frequent reasons for conversion. On multivariate analysis, age [Exp(β)=1.044, p=0.044] and pancreatic texture [Expa(β)=2.431, p=0.039) were found to be independent factors for predicting intraoperative conversion during LPD. In comparative analysis with the OPD group, the cPD group had a longer operation time (516.8 min vs. 449.9 min, p=0.001), higher rate of postoperative hemorrhage (12.1% vs. 0.85%, p=0.008), higher reoperation rate (9.1% vs. 0%, p=0.01), and higher cost (21886.4 USD vs. 17168.9 USD, p=0.018). Conclusion Intraoperative conversion during LPD can have an adverse clinical impact on the postoperative course following LPD. Appropriate patients selection and improvement of surgical techniques will be crucial for unnecessary intraoperative conversion and safe LPD.

Purpose: The aim of the current study was to evaluate the adverse clinical impact of intraoperative conversion during laparoscopic pancreaticoduodenectomy (LPD). Materials and Methods: The medical records of patients who underwent pancreaticoduodenectomy (PD) were retrospectively reviewed. Perioperative clinical variables were compared between patients who underwent converted PD (cPD) and initially planned open PD (OPD) to investigate the clinical impact and predictive factors of intraoperative conversion during LPD. Results: A total of 171 patients were included. Among them, 31 patients (19.3%) were found to have intraoperative conversion during LPD. Failure of progression due to severe adhesion (12 patients, 7%) and major vessel invasion (7 patients, 4%) were the two most frequent reasons for conversion. On multivariate analysis, age [Exp(β)=1.044, p=0.044] and pancreatic texture [Expa(β)=2.431, p=0.039) were found to be independent factors for predicting intraoperative conversion during LPD. In comparative analysis with the OPD group, the cPD group had a longer operation time (516.8 min vs. 449.9 min, p=0.001), higher rate of postoperative hemorrhage (12.1% vs. 0.85%, p=0.008), higher reoperation rate (9.1% vs. 0%, p=0.01), and higher cost (21886.4 USD vs. 17168.9 USD, p=0.018). Conclusion Intraoperative conversion during LPD can have an adverse clinical impact on the postoperative course following LPD. Appropriate patients selection and improvement of surgical techniques will be crucial for unnecessary intraoperative conversion and safe LPD.

40 years or new hires with less than 1 year of service.]]>
Brain ; Cardiovascular Diseases ; Cohort Studies ; Firefighters ; Follow-Up Studies ; Health Surveys ; Hospitals, University ; Humans ; Killer Cells, Natural ; Korea ; Magnetic Resonance Imaging ; Mental Disorders ; Mental Health ; Neuropsychological Tests ; Polycyclic Hydrocarbons, Aromatic ; Prospective Studies ; Republic of Korea ; Risk Factors

Objective: Little is known about factors influencing of hippocampal metabolism (HM) in mild cognitive impairment (MCI). Our objective was to determine whether HM in patients with amnestic MCI (aMCI) is decreased than non-amnestic MCI (naMCI). Methods: Overall, 32 MCI patients underwent 18F-fluorodeoxyglucose-positron emission tomography. They were characterized as aMCI (n=18) or naMCI (n=14) according to comprehensive neuropsychological criteria. Analysis of variances were used to assess differences on HM between aMCI and naMCI after controlling age, sex, education and Korean version of Mini Mental Status Examination. Results: We found that HM was more decreased in aMCI than naMCI. This result was not changed after controlling hippocampal volume. Conclusion Our findings suggest that aMCI is associated with decreased HM in MCI.