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Background: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers., Research Design and Methods: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness., Results: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response., Conclusions: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH., Methods: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009-2020 were enrolled., Results: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed., Conclusion: These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens., Competing Interests: Jin Seok Kim has received honoraria and consulting fees from Handok Inc. Jun Ho Jang has received research support from Alexion, AstraZeneca Rare Disease. Sung-Soo Yoon has received research funding from Chong Kun Dang Pharm, JW Pharmaceutical, Kyowa Kirin, Roche-Genentech, and Yuhan Pharmaceutical; has served on the advisory board for Amgen, Antengene, Astellas, Celgene, Janssen, Merck, Novartis, and Takeda; and has received consulting fees from Ticaros Therapeutics. BokJin Hyun, HyunSun Nam, and Eunhye Kim are employees of Handok Inc. Min Joo Kwak and Yong Kyun Won were an employee of Handok Inc. at the time of study. Jong Wook Lee has served on advisory boards and has received honoraria and research grants from Alexion, AstraZeneca Rare Disease. Deog-Yeon Jo, Seo-Yeon Ahn, Je-Hwan Lee, Sung-Hyun Kim, Chul Won Choi, Ho-Jin Shin, Min-Kyoung Kim, Jae Hoon Lee, Yeung-Chul Mun, and Jee Hyun Kong have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background/aim: Ixazomib, lenalidomide, and dexamethasone (IRd) have proven efficacy and an excellent safety profile in relapsed and/or refractory multiple myeloma (RRMM). However, there are limited reports on the real-world safety and effectiveness of IRd regimens in Asian patients with RRMM., Patients and Methods: This was a retrospective study of 60 patients with RRMM who were treated with IRd., Results: The median patient age was 68 years. Forty percent of patients did not meet the eligibility criteria for the TOURMALINE-MM1 trial. Patients received a median of one prior line of therapy. Non-hematologic adverse events (AEs) were more common than hematologic AEs. The most common AE was skin rash, followed by gastrointestinal toxicities. Most grade 3 or higher AEs were observed in less than 5% of the patients, except for skin rashes and infections. IRd therapy did not aggravate peripheral neuropathy (PN) in 20 of the 24 patients with pre-existing peripheral neuropathy. The overall response rate was 85%. After a median follow-up of 26.3 months, the median progression-free survival was 25.9 months and overall survival was not reached., Conclusion: Ixazomib and Rd combination therapy had a comparable toxicity profile and effectiveness in real-world RRMM patients., (© 2022. Japanese Society of Hematology.)

Introduction: Acquired haemophilia A (AHA) treatment involves the haemostatic treatment for acute haemorrhage and immunosuppressive therapy (IST) to eradicate FVIII inhibitory antibodies., Aim: We assessed the clinical features of AHA and analysed treatment outcomes in Korea. We further identified prognostic factors affecting treatment outcomes., Methods: Medical records of 55 patients with AHA from 18 institutions were reviewed retrospectively. Logistic and Cox regression analyses were performed to elucidate clinical factors affecting the achievement of complete remission (CR). The primary endpoint was time to CR after IST, and secondary endpoints were time to haemostasis, the achievement of CR, and overall survival (OS)., Results: Among the 55 patients, 50 (91%) had bleeding symptoms. Bleeding was severe in 74% of patients. Thirty-six (72%) patients received haemostatic therapy. Of the 42 patients who received IST, 23 (52%) received steroid alone, with a 52% response rate, and 10 (25%) received a combination of steroid and cyclophosphamide, with an 83% response rate. Five (16%) patients relapsed after a median duration of 220 days. There were eight deaths. In the Cox regression analysis, the FVIII inhibitor titre ≥ 20 BU/mL was the only significant prognostic factor affecting time to CR and haemostasis. No significant difference was observed in OS based on the inhibitor titre., Conclusion: The present study demonstrated the demographic data of AHA in Korea and showed that FVIII inhibitory antibody titre was a predictor of time to achieve CR after IST., (© 2021 John Wiley & Sons Ltd.)

Carfilzomib, lenalidomide, and dexamethasone (KRd) effectively improve survival in patients with relapsed and refractory multiple myeloma (RRMM). However, the outcome of KRd treatment in Asian patients reflecting a general RRMM population outside of a clinical trial has not been reported. Fifty-five RRMM patients who were treated with carfilzomib in combination with Rd from the time of the first approval of KRd in the Republic of Korea were analyzed. The median age was 61 years. The percentage of patients with an ECOG performance status ≥ 3, creatinine clearance < 50 mL/min, high-risk cytogenetics, and ≥ 4 lines of prior treatment were 9%, 22%, 31%, and 27%, respectively. Forty-one patients started treatment with KRd, whereas the remaining 14 patients (25%) were added carfilzomib during the Rd treatment. In the whole cohort, the overall response rate was 73% and progression-free survival was 8.8 months. The addition of carfilzomib in patients who were refractory or had disease progression during Rd treatment reattained a response in half of the patients. The advantage of carfilzomib with Rd was significant in patients in the first relapse. Toxicity profile was acceptable, excluding severe infections. Carfilzomib in combination with Rd is effective and has a reasonable adverse event rate in Asian patients with RRMM., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

This study aimed to demonstrate pharmacokinetic (PK) equivalence of a single dose of the proposed adalimumab biosimilar CT-P17 to United States-licensed adalimumab (US-adalimumab) and European Union-approved adalimumab (EU-adalimumab). This double-blind, parallel-group, phase I trial (clinicaltrials.gov NCT03970824) was conducted at 10 hospitals (Republic of Korea), in which healthy subjects (1:1:1) were randomized to receive a single 40 mg (100 mg/ml) subcutaneous injection of CT-P17, US-adalimumab, or EU-adalimumab. Primary end points were PK equivalence in terms of: area under the concentration-time curve from time zero to infinity (AUC 0-inf ); AUC from time zero to the last quantifiable concentration (AUC 0-last ); and maximum serum concentration (C max ). PK equivalence was concluded if 90% confidence intervals (CIs) for percent ratios of geometric least squares means (GLSMs) for pairwise comparisons were within the equivalence margin of 80-125%. Additional PK end points, safety, and immunogenicity were evaluated. Of the 312 subjects who were randomized (103 CT-P17; 103 US-adalimumab; 106 EU-adalimumab), 308 subjects received study drug. AUC 0-inf , AUC 0-last , and C max were equivalent among CT-P17, US-adalimumab, and EU-adalimumab, because 90% CIs for the ratios of GLSMs were within the 80-125% equivalence margin for each pairwise comparison. Secondary PK end points, safety, and immunogenicity were similar between treatment groups. In conclusion, PK equivalence for single-dose administration of CT-P17, EU-adalimumab, and US-adalimumab was demonstrated in healthy adults. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previous reports for adalimumab biosimilars., (© 2021 Celltrion, Inc. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Background: Dasatinib is administered at a fixed starting dosage of 100 mg once daily regardless of patient-specific factors. However, such fixed dosing may not be optimal for the treatment of Asian patients with chronic myeloid leukemia in chronic phase (CP-CML)., Patients and Methods: The dose-limiting toxicities (DLTs) and molecular responses (MRs) of dasatinib therapy were evaluated using clinical data obtained from 102 patients newly diagnosed with CP-CML at 17 hospitals in South Korea., Results: By 36 months after the initiation of a fixed dose regimen of dasatinib 100 mg once daily as the first-line therapy, 55.9% of patients experienced at least one type of DLT. The 3 most frequent DLTs were thrombocytopenia (45.5%), pericardial or pleural effusion (30.9%), and anemia (7.3%). Patients with higher dasatinib dose adjusted for body weight (Dose/BW) had a greater rate of DLT occurrence (logit [P] = 1.58 × [Dose/BW] - 2.27, P = .03). As median Dose/BW increased from 1.23 to 2.00 mg/kg, the rate of DLT occurrence increased from 43.5% to 66.7% (P = .03). However, Dose/BW did not affect the achievement rate of major MR (60.9% to 69.6%, P = .92)., Conclusion: The starting dosage of dasatinib may need to be reduced (eg, 80 mg once daily or lower) for Asian patients with CP-CML, especially with lighter BW, to alleviate the risk of DLT occurrence without compromising the achievement of MR., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A new species of cumacean belonging to the genus Diastylis Say, 1818 was collected from the Nokdo Island, Korea. The new species, Diastylis uniplicata sp. nov., can be distinguished from all other Diastylis species by the combination of the smooth carapace surface with a transverse ridge and a pair of oblique ridges, and telson 1.7 times as long as pleonite 6, with 5-6 short stout simple setae laterally. Full illustrations of the new species, including the mouthparts, are given in this paper. Also, a key to the Korean species of Diastylis is provided.

Precise allergy diagnosis and effective allergen specific immunotherapy are largely dependent on the quality of allergen extract. A new extract of Dermatophagoides farinae was commercially developed by Prolagen. The allergenic properties of the new extract were compared with those of other commercial products. The allergenic properties of the new extract were compared according to protein concentration, protein profiles, major allergen (Der f 1) contents, and allergenic potency to those for three commercially available extracts imported in Korea (Jubilant HollisterStier Allergy, Lofarma S.p.A., and Stallergenes Greer). Protein concentrations varied up to 2.62-fold (0.404 to 1.057 mg/mL), and Der f 1 contents varied up to 11.3-fold (3.597 to 40.688 μg/mL). Protein profiles of the extracts showed no major discrepancies, although there were some differences in SDS-PAGE band intensities, reflecting protein concentrations. Allergen potency ranged from 37038 to 60491 PAU/mL. The Prolagen product was highest in terms of protein concentration and allergen potency. The Lofarma product displayed Der f 1 content similar to that in Prolagen (19.4 μg/mg vs. 19.3 μg/mg). Endotoxin levels varied 8.9-fold (1020 to 8985 EU/mL). The newly developed house dust mite extract showed equal or better allergenic properties than available commercial extracts. This new product may be useful for better diagnostics and allergen-specific immunotherapeutics., Competing Interests: JD Kim, KY Jeong, KH Park, JH Lee, and JW Park share equivalents of Prolagen, Ltd. JW Park reports serving as an unpaid chief technology officer for Prolagen. KY Jeong is a Technical Advisor of Prolagen. JT Kim and JD Kim are co-chief executive officers. HH Kim, SH Kim, DJ Kim, and YJ Shin are employees of Prolagen. The interests of these authors did not influence the academic fairness in conducting this study, analyzing results, and writing a paper. Other authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2021.)

Three new species of Cumacea belonging to the genus Bodotria were collected from the Yellow Sea in Korea. Among them, Bodotria (Bodotria) hwanghaensis sp. nov. and Bodotria (Bodotria) pseudomaculosa sp. nov. share the dorso-lateral carina on the carapace and uniarticulated uropod endopod with other Korean Bodotria species. In contrast, the last one, Bodotria (Atlantobodotria) incarinata sp. nov. lacks the dorso-lateral carina on the carapace and has a biarticulated uropod endopod. The new species B. (A.) incarinata sp. nov. can be distinguished from all other Bodotria species by the combination of carapace without dorso-lateral carina or ridge, dorso-median carina marked over whole length of carapace, antero-lateral corner of carapace rounded, antennal notch shallow, maxilliped 3 merus and carpus dilated, pereopod 1 carpus not dilated, and pereopod 2 basis with plumose seta. The new species B. (B.) hwanghaensis sp. nov. can be distinguished from all other Bodotria species by the combination of carapace almost ovoid in dorsal view, carapace lower edge of mid-lateral depression forming a faint ridge, pereopod 1 carpus not dilated, and pereopod 2 basis without plumose seta. The new species B. (B.) pseudomaculosa sp. nov. can be distinguished from all other Bodotria species by the combination of carapace surface covered with coarse squamosa-reticulate patterning formed by large, shallow pits, carapace lower edge of mid-lateral depression forming an angular ridge, pereopod 1 carpus little dilated, and pereopod 2 basis with plumose seta. We described with full illustrations, including mouthparts for the three new species. Also, a key to the Korean Bodotria species is provided.

Purpose: The benefits of reirradiation for head and neck cancer (HNC) have not been determined. This study evaluated the efficacy of reirradiation using intensity-modulated radiotherapy (IMRT) for recurrent or second primary HNC (RSPHNC) and identified subgroups for whom reirradiation for RSPHNC is beneficial., Materials and Methods: A total of 118 patients from seven Korean institutions with RSPHNC who underwent IMRT-based reirradiation between 2006 and 2015 were evaluated through retrospective review of medical records. We assessed overall survival (OS) and local control (LC) within the radiotherapy (RT) field following IMRT-based reirradiation. Additionally, the OS curve according to the recursive partitioning analysis (RPA) suggested by the Multi-Institution Reirradiation (MIRI) Collaborative was determined., Results: At a median follow-up period of 18.5 months, OS at 2 years was 43.1%. In multivariate analysis, primary subsite, recurrent tumor size, interval between RT courses, and salvage surgery were associated with OS. With regard to the MIRI RPA model, the class I subgroup had a significantly higher OS than class II or III subgroups. LC at 2 years was 53.5%. Multivariate analyses revealed that both intervals between RT courses and salvage surgery were prognostic factors affecting LC. Grade 3 or more toxicity and grade 5 toxicity rates were 8.5% and 0.8%, respectively., Conclusion: IMRT-based reirradiation was an effective therapeutic option for patients with RSPHNC, especially those with resectable tumors and a long interval between RT courses. Further, our patients' population validated the MIRI RPA classification by showing the difference of OS according to MIRI RPA class.

A new species of Cumacea belonging to the genus Iphinoe Bate was collected from the Yellow Sea in Korea. The new speices Iphinoe indenticulata sp. nov. resembles I. sagamiensis Gamô, 1962 in the shape of carapace and the type of setae on the uropod peduncle. However, the new species is distinguished from congeners by having only setules on dorso-median carina of carapace. Also, the number of setae of uropodal peduncle and endopod is different from the I. sagamiensis. The new species is described with full illustration including mouthparts. A key to the Korean Iphinoe species is also provided.

This study on Korean cumaceans is based on the specimens collected from Geomun Island in Korea. The one species of the Genus Bodotria (Bodotriidae) is identified as new species, Bodotria paraspinifera sp. nov., which is similar to B. spinifera Gamô, 1986 in having the spinulose on body, dorso-lateral carina of carapace well-developed, carapace almost rectangular in dorsal view, carpus of pereopod 1 dilated, pereopod 2 without ischium, and uropod endopod uniarticulate. However, shape of carapace anterior portion, spinulose distribution pattern, and setae patterns and segment ratios of appendages are characteristics which serve to distinguish the new species from B. spinifera. Herein we described with full illustration containing information of the mouthparts for the new species. Also, a key to the Korean Bodotria species is provided.

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.

Objective: We aimed to evaluate the effect of stem cell source and dose on the survival of various donor subgroups, such as matched sibling donor (MSDs) and alternative donors (ADs), upon bone marrow (BM) or peripheral blood stem cell (PBSC) infusion in aplastic anemia (AA)., Methods: We retrospectively investigated the effects of stem cell source and dose on allogeneic hematopoietic stem cell transplantation (alloHSCT) in AA., Results: A total of 267 patients were included in this analysis. The BM-treated group showed an association with low incidence of any-grade acute graft versus host disease (GvHD) (p < 0.001). A higher stem cell dose was related with a low incidence of extensive chronic GvHD in MSDs (p = 0.025). Multivariate analysis for overall survival (OS) revealed that only age at alloHSCT <31 years (p = 0.010) and prior platelet transfusion <86 U (p = 0.046) in MSDs and higher stem cell dose (hazard ratio = 2.596, p = 0.045) in ADs were favorable prognostic factors., Conclusion: PBSCs could be preferred in AD because high stem cell dose may be easily achieved to improve the OS at the expense of acute GvHD. However, BM stem cells are preferred in MSDs., (© 2019 S. Karger AG, Basel.)

Background: Kimchi, a Korean food, is now produced and consumed in many other countries. In this study, the macro, trace, and toxic element content in varieties of kimchi from Korea and China was evaluated. A health-risk assessment, involving the calculation of estimated dietary intake values, was undertaken. To discriminate among samples with different origins, linear discriminant analysis (LDA) and principal component analysis (PCA) were applied., Results: The analytical methods used for analyses were successfully validated. In the quantification of elements, no significant differences were detected in the concentrations of the elements that were analyzed. Based on the fresh weight of kimchi, among the macro elements, the concentrations of Na and K were relatively high, with values of 4181.9-9919.8 mg kg -1 and 1661.8-6623.5 mg kg -1 , respectively. Among the trace elements that were analyzed, zinc in Korean samples, and strontium in Chinese samples showed the highest concentrations, at 2.67 and 2.98 mg kg -1 , respectively. Concentration levels of the toxic trace elements were within permissible limits. The amount of daily intake and provisional daily intake of each element calculated based on kimchi intake confirmed its safety for consumption. Linear discriminant analysis and PCA successfully discriminated among the samples of Chinese and Korean origin., Conclusion: The provisional daily intake of the toxic elements was within provisional tolerable daily intake values. The normal intake of kimchi could not pose a threat upon consumption. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Background/aims: Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients., Methods: In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/ metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication., Results: Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died., Conclusion: Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.

Background: Whether or not short-term exposure to particulate matter <2.5 μm in diameter (PM 2.5 ) increases the risk of psychiatric emergency diseases is unclear., Methods: The study was performed in a metropolis from January 2015 to December 2016. The exposure was PM 2.5 , and the confounders were weather (temperature and humidity) and other pollutants (PM 10 , SO 2 , CO, O 3 , and NO 2 ). The outcomes were emergency department (ED) visits with psychiatric disease codes (F00-F99 in ICD10 codes). General additive models were used for the statistical analysis to calculate the adjusted relative risks (ARRs) and 95% confidence intervals (95% CIs) for the daily number of ED visits with a lag of 1 to 3 days following a 10 μg/m 3 increase in PM 2.5 ., Results: During the study period, a total of 67,561 ED visits for psychiatric diseases were identified and tested for association with PM 2.5 . Daily ED visits for all psychiatric diseases were not associated with PM 2.5 in the model that was not adjusted for other pollutants. The ARR (95% CI) in the model adjusted for SO 2 was 1.011 (1.002-1.021) by 10 μg/m 3 of PM 2.5 on Lag 1 for all psychiatric diseases (F00-F99). The ARR (95% CI) in the model adjusted for O 3 was 1.015 (1.003-1.029) by 10 μg/m 3 of PM 2.5 on Lag 1 for F40-F49 (Neurotic, stress-related and somatoform disorders)., Conclusion: An increase in PM 2.5 showed a significant association with an increase in ED visits for all psychiatric diseases (F00-F99) and for neurotic, stress-related and somatoform disorders (F40-F49) on lag day 1., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Intrahepatic cholangiocarcinoma is a malignancy of the intrahepatic biliary tree. Although surgical resection is the mainstay of treatment for this tumor, the impact of lymph node dissection during hepatectomy is controversial. In this study, we evaluated the impact of lymph node dissection during surgical resection for intrahepatic cholangiocarcinoma., Methods: Records from 170 patients who underwent radical hepatectomy for intrahepatic cholangiocarcinoma from January 2000 to December 2014 were retrospectively reviewed. Twenty-two patients who underwent R1 resection or had distant metastasis at the time of surgery were excluded. Using propensity score matching (matched factors: differentiation, lymphovascular invasion, perineural invasion, and T stage), the patients were divided into two groups: no dissection (n = 34) or lymph node dissection (n = 34). Disease-free survival and overall survival were compared between groups., Results: There was a marginally significant difference between the two groups with respect to the disease-free survival (no dissection vs. lymph node dissection: 20.0 [4.2-35.8] months vs. 64.0 [27.3-120.8] months, p = 0.077). Overall survival was significantly longer in the lymph node dissection group (no dissection vs. lymph node dissection: 44.0 [31.1-56.9] months vs. 90.0 [51.1-158.9] months, p = 0.027)., Conclusion: Radical surgery including an adequate lymph node dissection area and suitable harvested lymph nodes appears to improve oncologic outcomes for intrahepatic cholangiocarcinoma.

Blinatumomab, a bispecific T cell-engaging antibody, has demonstrated efficacy for relapsed or refractory acute lymphoblastic leukemia (ALL). In this study, we evaluated the efficacy and toxicity of blinatumomab in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL. A total of 50 patients received blinatumomab treatment between June 2016 and August 2017 in Korea. The median number of prior therapy was one (range, 1-4). Among the 49 evaluable patients, 22 (44.9%) achieved complete response (CR) or CR with incomplete blood count recovery, and 16 of whom subsequently underwent allogenic stem cell transplantation. Although no statistically significant differences were observed, patients with extramedullary disease and poor performance status had lower responses to blinatumomab treatment. In addition, the use of high-dose dexamethasone prior to blinatumomab treatment did not affect the response to blinatumomab. The median event-free survival and overall survival of the responders were 7.5 and 8.1 months, respectively. For non-hematologic toxicities, the most common toxicity was infection. The incidences of severe cytokine release syndrome and neurologic toxicity each was 4%. In conclusion, blinatumomab was an effective and tolerable therapy in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL.

Background/aims: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System., Methods: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed., Results: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS., Conclusion: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

Objective: To investigate the association between sarcopenia, sarcopenic obesity (SO), metabolic syndrome (MetS), and occupational history., Methods: Using data from the Korea National Health and Nutrition Examination Survey, men more than or equal to 65 years of age (n = 679) were grouped according to occupation., Results: Mean skeletal muscle mass index was higher and mean body fat mass was lower in agribusiness and low-level (AL) workers than white-collar (WC), blue-collar (BC), and pink-collar (PC) workers. The risk of sarcopenia was highest in BC, followed by WC, PC, and AL. The risk of SO was higher in WC than AL and MetS was higher in WC and BC than AL., Conclusions: The development of sarcopenia, SO, and MetS is related to lifetime occupation, with BC workers being most affected by sarcopenia and WC workers being most affected by SO and MetS.

Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML-CP). We investigated the 2-year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open-label, multi-institutional phase 4 study, 110 Philadelphia chromosome-positive CML-CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24-month cumulative MR 4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per-patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow-up of 22.2 months, the 24-month cumulative MR 4.5 rate was 56.2% (95% confidence interval, 44.0%-8.3%), and the median time to MR 4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR 4 , and MR 4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML-CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Recently, cabbage kimchi has occasionally been associated with the foodborne diseases of enteric viruses such as human norovirus (HuNoV). This study aimed to evaluate the correlation between microbial/physicochemical properties and persistence of HuNoV in experimentally contaminated cabbage kimchi fermented and stored at 4°C or 10°C for 28 days. Changes in organic acid content, lactic acid bacteria (LAB), acidity, pH, and salinity were analyzed. The recovery of structurally intact HuNoV was examined for up to 28 days post-inoculation, using a NoV GII.4 monoclonal antibody-conjugated immuno-magnetic separation method combined with quantitative real-time reverse transcription polymerase chain reaction. On day 0, LAB loads were 4.70 log 10 colony forming units/g and HuNoV GII.4 titers were 2.57 log 10 genomic copies/μl, at both temperatures. After 28 days, intact HuNoV titers decreased to 1.58 (4°C) and 1.04 (10°C) log 10 genomic copies/μl, whereas the LAB density increased. This correlated with a gradual increase in lactic acid and acetic acid at both temperatures. Our findings support a statistical correlation between changes in physicochemical properties and the recovery of structurally intact HuNoV GII.4. Moreover, we determined that the production of organic acid and low pH could affect HuNoV GII.4 titers in cabbage kimchi during fermentation. However, HuNoV GII.4 was not completely eliminated by microbial/physicochemical factors during fermentation, although HuNoV GII.4 was reduced. Based on this, we speculate that the persistence of HuNoV GII.4 may be affected by the continually changing conditions during kimchi fermentation.

Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM.Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS).Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered. Overall response rate (ORR) was 72.9%, and complete response (CR) rate was 20.3%. With a median follow-up of 11.9 months, median PFS was 17 months. The 2-year PFS and overall survival (OS) rates were 29.2% and 80.0%, respectively. Median OS was not reached. PFS was significantly different depending on performance status (Eastern Cooperative Oncology Group < 2 vs. ≥ 2; p = 0.0002), β2-microglobulin level (< 5.5 vs. ≥ 5.5 mg/L; p = 0.0481), and cumulative dose of bortezomib (< 35.1 vs. ≥ 35.1 mg/m2; p < 0001). The common adverse events (AEs) were in line with the well-known toxicity profiles associated with VMP.In conclusion, VMP is a feasible and effective front-line treatment for transplant-ineligible older patients with MM in Korea. Continuing therapy with prompt adjustment of treatment according to AEs may be important to improve outcomes of elderly patients.

The aim of this study is to report general and age-specific risk factors for pterygium prevalence in the Korean population.This in an observational case series study.Data from total 24,812 participants (age 40 years or older) from the Korean National Health and Nutrition Examination Surveys conducted from 2010 to 2012 were retrieved. After applying exclusion criteria, data from 13,204 participants (821 with pterygium and 12,383 without) were used for univariate and multivariate analyses. General risk factors were identified and participants were grouped by decade: 40 s, 50 s, 60 s, 70 s, and 80+. Age-specific risk factors were investigated for each group.After univariate analysis, 2 multiple regression models were constructed. Model 1: age + sex + spherical equivalent (SE) + sun exposure hours + occupation (indoor vs outdoor) + residency area (rural vs urban) + education level; model 2: age + sex + SE + sun exposure hours. In model 1, older age (odds ratio [OR]: 1.05 95% confidence interval [CI]: 1.05-1.06), male gender (OR: 1.28, 95% CI: 1.01-1.61), and longer sun exposure hours (OR: 1.47, 95% CI: 1.11-1.94) were significant risk factors for pterygium prevalence whereas higher level of education (elementary school vs college, OR: 3.98, 95% CI: 2.24-7.06) and urban residency (vs rural residency, OR: 0.56, 95% CI: 0.45-0.70) were protective factors. Higher SE (OR 1.11, 95% CI: 1.03-1.19) refractive error was considered a risk factor when using model 2 for the analysis. Age-specific risk factors were different in each age group. Male gender was associated with higher pterygium prevalence in younger age groups while longer sun exposure (5+ hours/day) increased pterygium prevalence in older age groups.Previously characterized risk factors were also found in this large population study. However, we found that risk factors may vary according to the age group. Myopic eyes were found to have lower prevalence than hyperopic eyes.

This study was designed to evaluate the prevalence of chromosomal abnormalities and to identify the specific abnormalities associated with poor prognosis. A total of 2,474 patients whose conventional cytogenetics were available at the time of diagnosis were evaluated via a nationwide registry. Normal metaphase cytogenetics was observed in 2,012 patients (81.3%). Among the 462 patients with chromosomal abnormalities, there were 161 (34.8%) patients with hyperdiploidy, 197 (42.6%) with pseudodiploidy, 79 (17.1%) with hypodiploidy, and 25 (5.5%) with near-tetraploidy. Deletion 13 (Δ13) in metaphase was observed in 167 patients (6.8%). Fluorescent in situ hybridization (FISH) was carried out in 967 patients (39.1%), and 66 (13.7%) out of 482 and 63 (10.3%) out of 611 patients were positive for t(4;14) and del(17p), respectively. With a median follow-up duration of 25.1 months, the median overall survival (OS) was 51.2 months (95% confidence interval, 46.5-55.9 months). In univariate analysis, the following four chromosomal abnormalities were significantly associated with a poor survival outcome: Δ13, hypodiploidy, del(13q) in FISH, and del(17p) in FISH. In the subsequent multivariate analysis, in which del(13q) and del(17p) in FISH were excluded due to a relatively low number of patients, Δ13 and hypodiploid status were independently associated with a poor survival outcome after adjusting for important clinical factors, including age, sex, performance, beta2-microglobulin, albumin, and lactate dehydrogenase (LDH). Using conventional metaphase cytogenetics, we confirmed that both Δ13 and hypodiploid status were robust poor prognostic factors. The metaphase karyotyping should remain the primary cytogenetic tool and an essential investigation for risk stratification in newly diagnosed multiple myeloma patients.

In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.

Purpose: To identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies., Materials and Methods: Three hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled., Results: The overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) ≥2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (≥4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity., Conclusion: We concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole.

Background: Essential thrombocythemia (ET) is classified as a Philadelphia chromosome-negative classic myeloproliferative neoplasm. ET is a clonal stem cell disorder that is often associated with JAK2 mutations and shares phenotypic and pathogenetic similarities with other myeloproliferative neoplasms. Hemorrhagic complications and arterial and venous thrombosis are common in patients with ET. The aim of this retrospective analysis was to assess the cumulative incidence rate and risk factors for thrombohemorrhagic events in patients with ET based on a multicenter study in Korea., Patients and Methods: A total of 239 patients with ET, from February 1995 to April 2011, were retrospectively analyzed from 4 Korean academic institutions. Data were collected through the review of medical records, and vascular events were confirmed by diagnostic procedures for establishing thrombosis and hemorrhagic complications., Results: Of the patients (median age, 61 years; median follow-up, 51.8 months), 32 (13.4%) experienced thrombohemorrhagic complications. The 10-year cumulative incidence rate showed a 20.6% incidence of thrombohemorrhagic events. In univariate analysis, the presence of JAK2 mutations, high-risk group, previous thrombohemorrhagic events, and >60 years old were shown to have higher incidences of vascular events than any other factors. In multivariate analysis, previous thrombotic events and JAK2 mutations were independent risk factors for vascular events (hazard ratio, 2.907 [95% CI, 1.142-7.406], P =.025; and 4.146 [95% CI 1.227-14.018], P = 0.022)., Conclusion: Previous thrombotic history and the JAK2 V617F mutation were associated with a higher 10-year cumulative incidence rate of thrombohemorrhagic events., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We determined the somatic mutations in the mitochondrial genomes of 70 lung cancer patients by pair-wise comparative analyses of the normal- and tumor-genome sequences acquired using Affymetrix Mitochondrial Resequencing Array 2.0. The overall mutation rates in lung cancers were Approximately 100 fold higher than those in normal cells, with significant statistical correlation with smoking (p=0.00088). Total of 532 somatic mutations were evenly distributed in 499 positions with very low overall frequency (1.07/bp), but the non-synonymous mutations causing amino acid substitution occurred more frequently (1.83/bp), particularly at two positions, 8701 and 10398 (10.5/bp) that code for ATPase6 and NADH dehydrogenase 3, respectively. Despite the randomness or even distribution of the mutations, these two mutations occurred together in 86% of the cases. The linkage between the two most frequent mutations suggests that they were selected together, possibly due to their cooperative role during cancer development. Indeed, the mutation at 10398 was shown by Canter, Pezzotti, and their colleagues in 2009, as a risk factor for breast cancer. In this study, we identified two potential biomarkers that might be functionally linked together during the development of cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to improve the predictive power of the WHO classification-based prognostic scoring system (WPSS) by including age in patients with the myelodysplastic syndrome (MDS)., Patients and Methods: 136 Korean patients with de novo MDS between 1995 and 2008 were evaluated retrospectively. All patients were reclassified according to WHO criteria. 114 patients were included in the final analysis. An individualized age-adapted scoring system was developed to improve the accuracy of prognosis of the WPSS., Results: The WPSS was significantly associated with the prediction of survival and the leukemia-free survival. While the risk of a patient with the WPSS was best represented by the values 0 (very low), +1 (low), +2 (intermediate), +3 (high), and +4 (very high), these values were found to vary between -1.0 and 4.2 in the same patients when age was included as a factor. The WPSS may vary according to age, <55 or ≥55 years. The estimated difference in median survival was more prominent in the lower risk groups of the WPSS than in the higher-risk groups., Conclusion: In addition to the WPSS, age was found to significantly influence the prognosis of patients with MDS and provided a more individualized prognosis for the patients with MDS., (Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.)

Over its long survival duration, marginal zone B-cell lymphoma (MZL) routinely involves frequent relapses. In this study, we conducted a retrospective analysis to identify the clinical features and outcomes of relapsed or refractory MZL. From 1995 to 2008, a total of 92 patients with relapsed MZL were retrospectively analyzed. The median age of our subjects was 53.5 years (range: 23-82 years). The most common primary sites of involvement were the orbit and ocular adnexa (28.3%) followed by the lymph node and lymphatic organs (23.9%), and multiple mucosa-associated lymphoid tissue (MALT) sites (13.0%). The median time to relapse from initial diagnosis was 25.5 months. Of the 53 patients with Stage I or II at diagnosis, 42 patients (79.2%) evidenced locoregional recurrence. Among these locoregional relapsed patients, 27 patients achieved CR (54.1%) or PR (18.9%). In addition to the 39 patients initially in advanced Stage III or IV, a total of 50 patients were in advanced stage at relapse. Among those patients with advanced stage at relapse, 44 patients were treated. The overall response rate was 54.5% (24 patients), with 18 CRs and 6 PRs. The median time to progression (TTP) was 34.1 months (95% CI: 11.3-56.9 months) and the estimated 5-year overall survival (OS) was 84.3%. The majority of them was controlled well with salvage treatment, and could achieve prolonged survival. However, patients' refractory to initial therapy and advanced relapse evidenced shorter TTP and OS. Thus, we need to consider more aggressive treatment in cases of refractory MZL or advanced relapsed MZL., ((c) 2009 Wiley-Liss, Inc.)

OBJECTIVE. Although endoscopic treatment for early gastric cancer (EGC) is an accepted therapy in South Korea and Japan, long-term outcomes remain unknown. We evaluated the clinical outcome of endoscopic submucosal dissection (ESD) for gastric dysplasia and EGC. MATERIAL AND METHODS. A total of 402 patients with gastric dysplasia and EGC were treated with ESD at a single hospital from January 2004 to December 2007. The patients underwent ESD and then received periodic endoscopic follow-up and metastatic surveys for 9-49 months (median 30 months). Resectability (en bloc or piecemeal resection), curability (complete or incomplete), local recurrence, and disease-free survival rates were estimated. RESULTS. There were 107 patients with low-grade dysplasia (LGD), 97 with high-grade dysplasia (HGD) and 198 with EGC. In EGC patients, en bloc resection was achieved in 89.7% (177/198), the complete resection rate was 87.9% (174/198), and the local recurrence rate was 5.1% (10/198). Tumor size >20 mm was significantly associated with local recurrence (odds ratio 6.45; 95% CI 1.20-20.11; p=0.001). There were significant correlations between the incidences of a piecemeal or incomplete resection and that of local recurrence (odds ratio 5.23; 95% CI 1.02-18.34; p=0.001; and odds ratio 6.99; 95% CI 1.22-21.65; p=0.002, respectively). The 3-year cancer-free survival rate was 94.9%. CONCLUSIONS. Curative treatment with successful en bloc resection can reduce the local recurrence of gastric neoplastic lesions after ESD. Clinical outcome may be excellent, although longer follow-up studies are warranted.

Aim: The Korean Multiple Myeloma Working Party performed a nationwide registration of multiple myeloma patients via a web-based data bank system., Methods: We retrospectively analyzed registered data from 3,209 patients since 1999., Results: The median overall survival (OS) was 50.13 months (95% confidence interval: 46.20-54.06 months). Patients < or =40 years demonstrated a longer OS than patients >65 years of age (median OS 71.13 vs. 36.73 months, p < 0.001). Patients who received novel agents at any time during their treatments showed a longer OS than patients who did not (median OS 42.23 vs. 55.50 months, p < 0.001). Response to treatment was associated with OS, with tandem autologous stem cell transplantation (SCT) producing longer OS than single autologous SCT., Conclusions: We demonstrated associations between survival outcomes and treatment modalities as well as baseline disease characteristics in a registry of multiple myeloma patients using a web-based data analysis., (Copyright 2009 S. Karger AG, Basel.)