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Background and Objectives : With increases in cancer incidence and the number of cancer survivors, the demand for cancer management is growing. However, studies on dental prosthetic treatment for patients with cancer are rare. We aim to investigate the dental prosthetic treatment in patients with cancer aged ≥65 years after expanded health insurance coverage. Materials and Methods : This retrospective study included patients who were treated with implants and removable dentures at Ulsan University Hospital in South Korea between June 2015 and June 2023. Data on age, sex, cancer location, comorbid systemic diseases, number of remaining teeth, dental prosthetic treatment history, type of dental prosthetic treatment, and insurance coverage status were extracted from patient medical records and panoramic radiographs. The influence of multiple variables on dental prosthetic treatment was analyzed using the Chi-square and Fisher's exact tests. Results : The study included 61 patients with cancer (32 men, 29 women; average age: 70.9 years). Among them, 56 (91.8%) had insurance coverage benefits, and 34 (55.7%) received treatments such as implants, removable partial dentures, or complete dentures for the first time. Treatment types included 37 (60.7%) cases of implant prostheses and 24 (39.3%) conventional removable dentures. No statistical differences were observed in the type of dental prosthetic treatment according to sex, age, cancer location, number of systemic diseases, and dental prosthetic treatment history ( p > 0.05). Patients with <10 remaining teeth received treatment with conventional removable dentures, which was statistically significant ( p < 0.001). Conclusions : Of the 61 patients, 56 (91.8%) received insurance benefits, and 34 (55.7%) underwent dental prosthetic treatment for the first time. Within the limitations of this retrospective study, the expanded health insurance coverage alleviated the unmet demand for dental prosthetic treatment. As cancer prevalence continues to increase, expanding customized health insurance coverage is crucial to meet this demand.

Background: Dizziness/vertigo is one of the most common symptoms for which people seek healthcare. However, the healthcare expenditure attributable to dizziness/vertigo in South Korea remains poorly understood. We investigated the healthcare costs due to six major disorders causing dizziness/vertigo using claims data., Methods: The healthcare costs were evaluated using all the claims data submitted to the Health Insurance Review and Assessment Service from January 1 to December 31, 2022. The six major vestibular disorders included for analysis were benign paroxysmal positional vertigo (BPPV), psychogenic/persistent postural perceptual dizziness (PPPD), vascular vertigo/dizziness (VVD), vestibular migraine (VM), Meniere's disease (MD), and vestibular neuritis (VN)., Results: During the 1-year study period, 4.1% of adults aged 20 or older visited hospitals due to dizziness/vertigo in South Korea. Compared to the general population, the patients with dizziness/vertigo were more often elderly, female, and residents of small towns. The total healthcare cost for the six major vestibular disorders was ₩547.8 billion (approximately $406.5 million). BPPV incurred the highest annual healthcare cost (₩183.5 billion, 33.5%), followed by VVD (₩158.8 billion, 29.0%), MD (₩82.2 billion, 15.0%), psychogenic/PPPD (₩60.3 billion, 11.0%), VN (₩32.9 billion, 6.0%), and VM (₩30.1 billion, 5.5%). The mean healthcare cost per hospital visit due to dizziness/vertigo was ₩96,524 (95% confidence interval, ₩96,194-₩96,855), 30% higher than the average (₩73,948) of the overall healthcare cost per hospital visit over the same period., Conclusion: Owing to higher healthcare costs for dizziness/vertigo and increased prevalence of dizziness/vertigo in the aged population, healthcare costs due to dizziness/vertigo will increase rapidly in South Korea. Thus, a guideline for cost-effective management of dizziness/vertigo should be established to reduce the healthcare costs due to these common symptoms., Competing Interests: Dr. Ji-Soo Kim serves as an Associate Editor of Frontiers in Neuro-otology and on the editorial boards of the Journal of Clinical Neurology, Frontiers in Neuro-ophthalmology, Journal of Neuro-ophthalmology, and Journal of Vestibular Research, Journal of Neurology and Medicine. The other authors have nothing to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background and Purpose: The etiological distribution of oculomotor nerve palsy has varied amongst the studies. This study aimed to define the clinical features and underlying etiologies of isolated oculomotor nerve palsy by recruiting patients from all departments in a referral-based university hospital., Methods: The medical records of 672 patients who had a confirmed diagnosis of isolated oculomotor nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020 were reviewed. A proportion of the etiology of isolated oculomotor nerve palsy was also compared with that of patients pooled from the previous studies that were searched on PubMed in May 2022., Results: The most common etiology was microvascular (n = 168, 26.5%), followed by vascular anomalies (n = 110, 17.4%), neoplastic (n = 86, 13.6%), inflammatory (n = 79, 12.5%), idiopathic (n = 60, 9.5%) and traumatic (n = 53, 8.4%). Neurologists were mainly involved in the management of microvascular and inflammatory oculomotor nerve palsies whilst ophthalmologists mainly participated in the care of idiopathic, neoplastic and traumatic palsies. Neurosurgeons mostly took care of oculomotor nerve palsy due to vascular anomalies., Conclusions: The proportion of etiologies of isolated oculomotor nerve palsy may differ according to the specialties involved in the management. The results of previous studies on the etiological distribution of isolated oculomotor nerve palsy should be interpreted with this consideration., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Hepatitis B virus reactivation (HBVr) is a well-known complication of systemic chemotherapy for particularly hematologic malignancies in HBV carriers. We performed a multicenter retrospective study to investigate the incidence and risk factors of HBVr in patients with hepatitis B surface antigen (HBsAg)-positive multiple myeloma (MM)., Methods: We included 123 patients with HBsAg-positive MM who had received systemic therapy. The primary objective of the study was to evaluate the incidence of HBVr in patients with HBsAg-positive MM., Results: The median age was 59 years, and 72 patients were male. With a median follow-up duration of 41.4 months, there were 43 instances of HBVr in 35 patients (28.5%): 29 treatment-related HBVr occurred during 424 treatments. Treatments containing antiviral prophylaxis were associated with a significantly lower incidence of HBVr compared to those without (14.4% vs. 1.9%, P < 0.001). Moreover, treatment with cyclophosphamide (P = 0.002) and doxorubicin (P = 0.053) were risk factors for HBVr; stem cell transplantation was not associated with HBVr. There was no significant difference in overall survival between patients with and without HBVr (P = 0.753) and myeloma progression was the major cause of death., Conclusion: Considering the low incidence of HBVr in patients who had received antiviral prophylaxis, HBsAg-positivity should not impede patients from receiving optimal antimyeloma treatment or participating in clinical trials., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background/aims: Based on their anatomy, cholangiocarcinomas (CCAs) are classified into intrahepatic, hilar, and distal CCAs. Although the diagnosis and treatment of each type of CCA are thought to be different, real-world data studies on the current practice are limited. Therefore, this study was designed to capture the current practice of diagnosing and treating perihilar CCA in Korea., Methods: We conducted a survey using an online platform. The questionnaire consisted of 18 questions designed to evaluate the current practice of diagnosing and treating perihilar CCA in Korea. The targets of this survey were biliary endoscopists who are members of the Korean Pancreatobiliary Association., Results: In total, 119 biliary endoscopists completed the survey. Of the respondents, 89.9% thought that the use of the International Classification of Diseases, 11th Revision (ICD-11) system is necessary to classify CCA. Approximately half of the respondents would recommend surgery or chemotherapy until patients were 80 years of age. For the pathological diagnosis of CCA, endoscopic retrograde cholangiopancreatography with biopsy was the most preferred modality. Routine preoperative biliary drainage was performed by 44.5% of the respondents. For operable CCAs, 64.7% of the respondents preferred endoscopic biliary drainage using plastic stents. For palliative biliary drainage, 69.7% of the respondents used plastic stents. For palliative endoscopic biliary drainage using metal stents, 63% of the respondents preferred the stent-in-stent method., Conclusions: A new coding system using the ICD-11 is needed for classifying CCAs. Guidelines for diagnosing and treating CCA based on the clinical situation in Korea are needed.

Background and Purpose: The etiologies of abducens nerve palsy have shown a large variability among studies. This study aimed to establish the clinical features and underlying etiologies of isolated abducens nerve palsy by recruiting patients from all departments in a referral-based university hospital., Methods: We reviewed the medical records of 807 patients with a confirmed diagnosis of isolated abducens nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. We also compared the proportion of etiology with that of the patients pooled from the previous studies., Results: The most common etiology was microvascular (n = 296, 36.7%), followed by idiopathic (n = 143, 17.7%), neoplastic (n = 115, 14.3%), vascular anomalies (n = 82, 10.2%), inflammatory (n = 76, 9.4%), and traumatic (n = 35, 4.3%). Patients were mostly managed by ophthalmologists (n = 576, 71.4%), followed by neurologists (n = 479, 59.4%), emergency physicians (n = 278, 34.4%), neurosurgeons (n = 191, 23.7%), and others (n = 72, 8.9%). The proportion of etiology significantly differed according to the age and sex of the patients and the specialties involved in the management (p < 0.001). Compared to the pooled data from the previous reports, the current study showed a higher prevalence of microvascular cause but a lower occurrence of traumatic and neoplastic causes., Conclusions: The results of previous studies on etiologic distribution of isolated abducens nerve palsy should be interpreted with consideration of the demographic features of patients recruited and the specialties involved., (© 2023 European Academy of Neurology.)

Introduction: With the availability of retrospective pharmacovigilance data, the common data model (CDM) has been identified as an efficient approach towards anonymized multicenter analysis; however, the establishment of a suitable model for individual medical systems and applications supporting their analysis is a challenge., Objective: The aim of this study was to construct a specialized Korean CDM (K-CDM) for pharmacovigilance systems based on a clinical scenario to detect adverse drug reactions (ADRs)., Methods: De-identified patient records (n = 5,402,129) from 13 institutions were converted to the K-CDM. From 2005 to 2017, 37,698,535 visits, 39,910,849 conditions, 259,594,727 drug exposures, and 30,176,929 procedures were recorded. The K-CDM, which comprises three layers, is compatible with existing models and is potentially adaptable to extended clinical research. Local codes for electronic medical records (EMRs), including diagnosis, drug prescriptions, and procedures, were mapped using standard vocabulary. Distributed queries based on clinical scenarios were developed and applied to K-CDM through decentralized or distributed networks., Results: Meta-analysis of drug relative risk ratios from ten institutions revealed that non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of gastrointestinal hemorrhage by twofold compared with aspirin, and non-vitamin K anticoagulants decreased cerebrovascular bleeding risk by 0.18-fold compared with warfarin., Conclusion: These results are similar to those from previous studies and are conducive for new research, thereby demonstrating the feasibility of K-CDM for pharmacovigilance. However, the low quality of original EMR data, incomplete mapping, and heterogeneity between institutions reduced the validity of the analysis, thus necessitating continuous calibration among researchers, clinicians, and the government., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients., Materials and Methods: Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL., Results: A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS., Conclusion: The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

Importance: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo with frequent recurrences., Objective: To determine the efficacy of a web-based diagnosis and treatment of BPPV when it recurs in patients with confirmed and treated BPPV., Design, Setting, and Participants: This randomized, controlled, parallel-group, double-blind trial took place in multiple referral-based university hospitals in South Korea between July 2017 and February 2020. Of 728 patients (age ≥20 years) with diagnosed and treated BPPV, 585 were enrolled after excluding 143 who declined participation, could not use the internet, or had spinal problems, multicanal BPPV, or cognitive dysfunction. Patients were followed up for recurrence at least for 2 years until February 2022., Interventions: Patients were randomly assigned (1:1) to the treatment or control group. The patients in the treatment group completed a questionnaire for diagnosis and received a video clip for self-administration of canalith repositioning maneuver (CRM) according to the type of BPPV diagnosed when they experienced positional vertigo again. Patients in the control group received a video clip for self-administration of CRM according to the type of BPPV that had been diagnosed on enrollment., Main Outcomes and Measures: The primary outcome was self-reported resolution of positional vertigo post-CRM. Secondary outcomes included difficulties and requirement for assistance when using the program and any falls or other adverse events related to CRM. The primary outcome was analyzed using both intention-to-treat and per-protocol methods., Results: Of 585 patients enrolled, 292 were randomized to the treatment group (mean [SD] age, 60.3 [12.8] years, 37 [64%] women) and 293 were randomized to the control group (mean [SD] age, 61.1 [13.2] years; 50 [71%] women). Overall, 128 (21.9%) had recurrence (58 in the treatment group and 70 in the control group), and 109 (85.2%) successfully used the web-based system. In the intention-to-treat analysis, 42 of 58 individuals (72.4%) in the treatment group and 30 of 70 individuals (42.9%) in the control group reported vertigo resolution (χ2 test: 95% CI, 0.13-0.46; P < .001)., Conclusions and Relevance: This trial proved the efficacy of a web-based system for the diagnosis and treatment of recurrent BPPV. Use of this system may play an important role in telemedicine for vestibular disorders., Trial Registration: Clinical Research Information Service Identifier: KCT0002364.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal., Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation., Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529)., Conclusion: In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Background and Purpose: Trochlear palsy is the most common cause of vertical diplopia. The etiologies of trochlear palsy have shown a large discrepancy among studies. This study aimed to establish the clinical features and underlying etiologies of isolated trochlear palsy by recruiting the patients from all departments in a referral-based university hospital., Methods: We reviewed the medical records of 1258 patients who had a confirmed diagnosis of isolated trochlear palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020. We also compared the proportion of etiologies with that of the patients pooled from previous studies., Results: The most common etiology was congenital (n = 330, 32.4%), followed by idiopathic (n = 256, 25.1%), microvascular (n = 212, 20.8%), and traumatic (n = 145, 14.2%). These four etiologies explained 92.5% of isolated trochlear palsy. Patients were mostly managed by ophthalmologists (n = 841, 82.5%), followed by neurologists (n = 380, 37.3%), emergency physicians (n = 197, 19.3%), neurosurgeons (n = 75, 7.4%), and others (n = 18, 1.8%). The etiologic distribution of isolated trochlear palsy in the current study did not differ from that of 2664 patients pooled from the previous studies., Conclusions: The proportion of etiologies of isolated trochlear palsy differs according to the age ranges of the patients and specialties involved in the management. The etiologic distribution of isolated trochlear palsy in the current study was comparable to the pooled result of previous reports., (© 2022 European Academy of Neurology.)

In South Korea, there are few studies to understand the current status of pulmonary rehabilitation in clinical practice and develop it. This study aimed to assess the current status and annual changes in the number and pattern of prescriptions for pulmonary rehabilitation before and after its insurance coverage. The trends of pulmonary rehabilitation before and after its insurance coverage commencement were evaluated using the data of 24,380 patients during the 3-year period from 2016 to 2018 that were archived by the National Health Information Database of the Health Insurance Review and Assessment Service in South Korea. The annual total number of patients who received pulmonary rehabilitation was stratified by the type of prescription, sex, age, type of insurance, medical institution, and region. In addition, the frequencies of pulmonary rehabilitation for various diagnoses were investigated using the major codes of the Korean Standard Classification of Disease. The patients who received pulmonary rehabilitation increased by approximately 2 times from 5936 in 2016 (before insurance coverage) to 10,474 in 2019. Before 2017, most patients underwent simple pulmonary rehabilitation coded as MM290. However, since the insurance coverage of rehabilitation exercise for pulmonary disease (MM440), the proportions of patients receiving them increased. Men underwent pulmonary rehabilitation more often than women, and >70% of the patients were aged >60 years. Most patients received pulmonary rehabilitation at tertiary hospitals in Seoul. In 2016, pulmonary rehabilitation was prescribed more frequently for cerebral infarction; after 2017, it was prescribed more frequently for lung cancer. This study summarized the current status and trends of pulmonary rehabilitation in South Korea before and after National Health Insurance Service coverage, which commenced on January 1, 2017. A significant increase in the number of pulmonary rehabilitations was confirmed after the insurance coverage., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Extensive research on the coronavirus disease 2019 (COVID-19) is underway. However, there are not many studies on the use of masks, which are essential for infection prevention. This descriptive study aimed to understand the factors influencing the use of masks by Korean adults during COVID-19. We conducted an online survey with 280 adults in South Korea between August and September 2020, analyzing the data using SPSS version 24.0. Multiple regression analyses were performed to understand the factors that influence individuals' use of masks. The participants' perceived susceptibility, perceived barriers, other people's dignity, compliance with public order, reasonable decision making, and subjective norms explained 21.6% of mask use. Mask use is expected to increase further if people perceive a personal need to wear masks, if their peers perceive the importance of mask use, and if they possess civic consciousness that considers society as a whole. This paper makes a significant contribution to the field of public health, with evidence-based recommendations for increasing mask use, going beyond simply attributing mask use to individual preferences., (© 2022 John Wiley & Sons Australia, Ltd.)

Background: Asthma and nonalcoholic fatty liver disease (NAFLD) are chronic diseases known to be associated with metabolic abnormalities. We aimed to clarify the association between NAFLD and asthma incidence in a large population-based cohort., Methods and Findings: We selected 160,603 individuals without comorbidities from the National Health Insurance Service-National Sample cohort between 2009 and 2014. NAFLD was defined using a surrogate marker, fatty liver index (FLI). During a median of 5.08 years' follow-up, 16,377 subjects (10.2%) were newly diagnosed with asthma and categorized into three groups according to FLI. The cumulative incidence of asthma was higher in subjects with higher vs. lower FLIs (FLI < 30, 10.1%; 30 ≤ FLI < 60, 10.8%; FLI ≥ 60, 10.5%). Higher FLI was associated with an increased incidence of asthma (Hazard ratios (HR)highest vs. lowest FLI, 1.25; 95% CI, 1.15-1.36). The results using another definition of NAFLD, as measured by the hepatic steatosis index (HSI), were similar to the primary results. This association was more pronounced in women than in men (HR 1.46; 95% CI, 1.13-1.64 vs. HR 1.07; 95% CI, 0.94-1.20)., Conclusions: This study demonstrated that NAFLD, as measured by FLI and HSI, may influence the incidence rates of asthma in adults, especially in women., Competing Interests: The authors have declared that no competing interests exist.

Abstract: Next generation sequencing generates copious amounts of genomics data, causing manual interpretation to be laborious and non-scalable while remaining subjective (even for highly trained specialists). We evaluated the performance of the artificial intelligence-based offering Watson for Genomics (WfG), a variant interpretation platform, in hematologic malignancies for the first time.Next generation sequencing was performed for patients treated for various hematological malignancies at Hallym University Sacred Heart Hospital, South Korea, between December 2017 and August 2020 using a 54-gene panel. Both WfG and expert manual curation were used to evaluate the performance of WfG. Acute myeloid leukemia (AML) molecular profiles were compared between Koreans and other ethnic groups using a publicly available dataset.Seventy-seven patients were analyzed (AML: 45, myeloproliferative neoplasms: 12, multiple myeloma: 7, myelodysplastic syndromes: 6, and others: 7). The concordance between the manual and WfG interpretations of 35 variants in 11 random patients was 94%. Among all patients, WfG identified 39 (51%) with at least 1 clinically actionable therapeutic alteration (i.e., a variant targeted by a United States Food and Drug Administration [US FDA]-approved drug, off-label drug, or clinical trial). Moreover, 46% of these patients (18/39) had genes that were targeted by a US FDA-approved therapy. WfG identified diagnostic or prognostic insights in 65% of the patients with no targetable alterations. In those with AML, FLT3-internal tandem duplications or tyrosine kinase domain mutations were less frequent among Koreans than among Caucasians (6.7% vs 30.2%, P < .001) or Hispanics (6.7% vs 28.3%, P = .005), suggesting ethnic differences.Variant interpretation using WfG correlated well with manually curated expert opinions. WfG provided therapeutic insights (including variant-specific drugs and clinical trials that cannot easily be provided by expert manual curation), as well as diagnostic and/or prognostic information., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The wide variability of isoniazid (INH) pharmacokinetics is mainly attributed to the trimodal N-acetyltransferase 2 (NAT2) acetylator phenotype, that is, rapid, intermediate, and slow. Consequently, a uniform INH dose in current clinical practice may lead to treatment failure and emergence of drug resistance. There is a lack of studies on specific doses of INH for different NAT2 acetylator phenotypes among tuberculosis (TB) patients. Therefore, we aimed to provide insight into the optimal dosing of INH for each NAT2 acetylator phenotype with respect to the probability of achieving a pharmacokinetic (PK)/pharmacodynamic target. PK, the NAT2 genotype, and clinical data were collected in a multicenter prospective cohort study conducted at 13 clinical centers in Korea. Population PK modeling and simulation were carried out. Data from 454 TB patients were divided into a training data set and a test data set at a ratio of 4 to 1. The PK of the training data were best described by a 2-compartment model with allometric scaling for body size effect. Importantly, NAT2 acetylator phenotypes significantly affected the apparent clearance. Our model, which provided better predictive performance compared with previously published models, was evaluated by external validation using the test set. The simulation for assessing target efficacy and toxicity indicated that the best INH dosing regimens for Korean tuberculosis patients were once-daily doses of 400, 300, and 200 mg for rapid, intermediate, and slow acetylators, respectively. In conclusion, our study provides a step forward in precision dosing for antituberculosis management., (© 2021, The American College of Clinical Pharmacology.)

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) poses an increasing clinical burden. Genome-wide association studies have revealed a limited contribution of genomic variants to the disease, requiring alternative but robust approaches to identify disease-associated variants and genes. We carried out a disease-specific expression quantitative trait loci (eQTL) screen to identify novel genetic factors that specifically act on NAFLD progression on the basis of genotype., Methods: We recruited 125 Korean patients (83 with biopsy-proven NAFLD and 42 without NAFLD) and performed eQTL analyses using 21,272 transcripts and 3,234,941 genotyped and imputed single nucleotide polymorphisms. We then selected eQTLs that were detected only in the NAFLD group, but not in the control group (i.e., NAFLD-eQTLs). An additional cohort of 162 Korean individuals with NAFLD was used for replication. The function of the selected eQTL toward NAFLD development was validated using HepG2, primary hepatocytes and NAFLD mouse models., Results: The NAFLD-specific eQTL screening yielded 242 loci. Among them, AGXT2, encoding alanine-glyoxylate aminotransferase 2, displayed decreased expression in patients with NAFLD homozygous for the non-reference allele of rs2291702, compared to no-NAFLD individuals with the same genotype (p = 4.79 × 10 -6 ). This change was replicated in an additional 162 individuals, yielding a combined p value of 8.05 × 10 -8 from a total of 245 patients with NAFLD and 42 controls. Knockdown of AGXT2 induced palmitate-overloaded hepatocyte death by increasing endoplasmic reticulum stress, and exacerbated NAFLD diet-induced liver fibrosis in mice, while overexpression of AGXT2 attenuated liver fibrosis and steatosis., Conclusions: We identified a new molecular role for AGXT2 in NAFLD. Our overall approach will serve as an efficient tool for uncovering novel genetic factors that contribute to liver steatosis and fibrosis in patients with NAFLD., Lay Summary: Elucidating causal genes for non-alcoholic fatty liver disease (NAFLD) has been challenging due to limited tissue availability and the polygenic nature of the disease. Using liver and blood samples from 125 Korean individuals (83 with NAFLD and 42 without NAFLD), we devised a new analytic method to identify causal genes. Among the candidates, we found that AGXT2-rs2291702 protects against liver fibrosis in a genotype-dependent manner with the potential for therapeutic interventions. Our approach enables the discovery of causal genes that act on the basis of genotype., Competing Interests: Conflicts of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We aimed to characterize the central positional nystagmus (CPN) observed in lesions involving the inferior cerebellar peduncle (ICP). We analyzed the clinical and neurotologic findings in six patients with an isolated unilateral ICP infarction that had been diagnosed at a university hospital in South Korea from 2003 to 2019. Patients usually presented with acute vestibular syndrome in isolation (4/6, 67%). Ipsilesional spontaneous nystagmus was observed in five while supine (5/6, 83%). Four (4/6, 67%) patients showed CPN which included apogeotropic (n = 3) or geotropic (n = 1) during head turning to either side while supine, and vertical nystagmus during straight-head hanging, Dix-Hallpike maneuvers, or up-righting (n = 3). Four patients showed contraversive ocular tilt reaction or tilt of the subjective visual vertical. Bedside and video head-impulse tests were normal in all patients. CPN is a usual finding in ICP lesions, and may be ascribed to damage of the fibers running from the nodulus/uvula onto the vestibular nucleus via the ICP., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Drug-resistance surveillance (DRS) data provide key information for building an effective treatment regimen in patients with multidrug-resistant tuberculosis (MDR-TB). This study was conducted to investigate the patterns and trends of additional drug resistance in MDR-TB patients in South Korea., Methods: Phenotypic drug susceptibility test (DST) results of MDR-TB patients collected from seven hospitals in South Korea from 2010 to 2019 were retrospectively analyzed., Results: In total, 633 patients with MDR-TB were included in the analysis. Of all patients, 361 (57.0%) were new patients. All patients had additional resistance to a median of three anti-TB drugs. The resistance rates of any fluoroquinolone (FQ), linezolid, and cycloserine were 26.2%, 0.0%, and 6.3%, respectively. The proportions of new patients and resistance rates of most anti-TB drugs did not decrease during the study period. The number of additional resistant drugs was significantly higher in FQ-resistant MDR-TB than in FQ-susceptible MDR-TB (median of 9.0 vs. 2.0). Among 26 patients with results of minimum inhibitory concentrations for bedaquiline (BDQ) and delamanid (DLM), one (3.8%) and three (11.5%) patients were considered resistant to BDQ and DLM with interim critical concentrations, respectively. Based on the DST results, 72.4% and 24.8% of patients were eligible for the World Health Organization's longer and shorter MDR-TB treatment regimen, respectively., Conclusion: The proportions of new patients and rates of additional drug resistance in patients with MDR-TB were high and remain stable in South Korea. A nationwide analysis of DRS data is required to provide effective treatment for MDR-TB patients in South Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background: Although inhaled corticosteroids (ICSs) are the recommended first-line therapy for asthma, determining whether to continue or discontinue ICS treatment in patients with mild asthma remains challenging for clinicians. Several studies have revealed that patients with mild-persistent asthma maintained a well-controlled state after ICS withdrawal. However, the long-term outcomes of ICS withdrawal have not yet been determined., Objective: To determine the possible clinical outcomes of the discontinuation of ICS in patients with well-controlled mild asthma., Methods: We investigated the clinical outcomes of discontinuing ICSs in patients with well-controlled mild asthma and compared the time to loss of control (LOC) between patients who stopped ICS treatment (ICS withdrawal group, IWG) and those who continued treatment for 3 years (continuous ICS group, CIG)., Results: A significant difference in the time to LOC was observed between the IWG and CIG (hazard ratio, 2.56; 95% confidence interval, 1.52-4.33; P < .001). Increasing fractional exhaled nitric oxide levels (P = 0.008) and sputum eosinophil counts (%) (P = 0.015) revealed a weak but significant association with LOC risk in the CIG. The sputum eosinophil counts (P = 0.039) and serum total immunoglobulin E levels (P = 0.014) were significantly higher in the LOC group than in the non-LOC group of the CIG., Conclusion: Our results suggest that the maintenance of ICS treatment may help keep patients' asthma under control. Furthermore, patients with LOC had significantly higher sputum eosinophil counts in the CIG than those in the non-LOC group. Therefore, continuous ICS use by patients with mild, well-controlled asthma could be associated with good clinical outcomes., Trial Registration: ClinicalTrials.gov Identifier: KCT0002234., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: We assessed the applicability of next-generation sequencing (NGS)-based IGH/IGK clonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time., Methods: Fifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted the IGH and IGK genes was performed using IGH FR1 and IGK primer sets., Results: Clonal IGH and IGK rearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonal IGH and/or IGK rearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells. IGHV3-9 (11.63%) and IGHV4-31 (9.30%) were the most frequently reported IGHV genes and were more common in Koreans with MM than in Western counterparts. IGHD3-10 and IGHD3-3 (13.95% each) were the most frequent IGHD genes; IGHD3-3 was more common in Koreans with MM. No IGK rearrangement was particularly prevalent, but single IGKV-J rearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts. IGKV4-1 was less frequent in Koreans regardless of light chain type. Otherwise, the usages of the IGH V, D, and J genes and of the IGK gene were like those observed in previous Western studies., Conclusion: NGS-based IGH/IGK clonality testing ought to be applicable to most Koreans with MM. The overrepresentation of IGHV3-9, IGHV4-31, and IGHD3-3 along with the underrepresentation of IGKV4-1 and the differences in IGK gene rearrangement types suggest the existence of ethnicity-specific variations in this disease., Competing Interests: No authors have competing interests.

Purpose: We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors, including a baseline mini nutritional assessment short form (MNA-SF) score, of response and survival., Patients and Methods: Between 2010 and 2018, 96 AML patients aged 65 and above who received decitabine treatment at 6 centers in Korea were retrospectively evaluated. Response rates, hematologic improvements (HI), progression-free survival (PFS), and overall survival (OS) were analyzed., Results: The median age at diagnosis was 73.9 years, and the median number of decitabine treatments administered to the patients was 4 (range, 1-29). Of 85 patients, 15 patients (17.6%) achieved complete remission (CR) or CR with incomplete blood count recovery. Twelve patients (14.1%) showed partial remission (PR), and 18 (21.2%) demonstrated HI without an objective response. The median PFS and OS were 7.0 (95% confidence interval [CI], 4.9-9.0) and 10.6 (95% CI, 7.7-13.5%) months, respectively. In multivariate analyses, MNA-SF score ≥ 8 and the absence of peripheral blood (PB) blasts were significant predictors for improved PFS and OS., Conclusions: For older patients with newly diagnosed AML, a high MNA-SF score and the absence of PB blasts were independently associated with improved survival., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to determine the etiologic distribution of dizziness and vertigo in a referral-based dizziness clinic in South Korea. We analyzed the diagnoses of 21,166 consecutive dizzy patients (12,691 women, mean age = 57.9 ± 15.7, age range = 3-97) seen from 2003 to 2019 using a registry and medical records. Overall, dizziness and vertigo were more common in women (60.0%, CI 0.59-0.61) than in men without a difference in age (57.7 ± 15.5 vs. 58.1 ± 16.1, p = 0.094). Benign paroxysmal positional vertigo (BPPV, 24.1%) was the most common cause of dizziness/vertigo, followed by psychiatric or persistent postural perceptual dizziness (20.8%), vascular disorders (12.9%), vestibular migraine (10.2%), Meniere's disease (7.2%), and vestibular neuritis (5.4%). These six disorders comprised more than 80% of all disorders. The etiology could not be determined in 5.0%, and more than one etiology was found in 14.1%. Vestibular migraine was the most common disorder in children and adolescents (< 19 years), psychiatric or persistent postural perceptual dizziness (26.3%) in the adults (19-64 years), and BPPV (28.2%) in the elderly (≥ 65 years). This etiologic distribution is similar to that reported in another country, and indicates no significant differences in the proportion of diseases causing dizziness and vertigo across different ethnic groups. This study provides valuable information to establish healthcare policy for dizziness and vertigo.

Background: Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug-drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes., Subjects, Materials, and Methods: This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first-line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first-line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi-comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment-related toxicity, and hospitalization using logistic regression and Cox regression analyses., Results: In total, 301 patients (median age 75 years; range, 70-93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0-14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18-2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment-related toxicity., Conclusion: Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period., Implications for Practice: This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug-drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer., (© AlphaMed Press 2019.)

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.

Chronic lymphocytic leukaemia (CLL) exhibits differences between Asians and Caucasians in terms of incidence rate, age at onset, immunophenotype, and genetic profile. We performed genome-wide methylation profiling of CLL in an Asian cohort for the first time. Eight Korean patients without somatic immunoglobulin heavy chain gene hypermutations underwent methyl-CpG-binding domain sequencing (MBD-seq), as did five control subjects. Gene Ontology, pathway analysis, and network-based prioritization of differentially methylated genes were also performed. More regions were hypomethylated (2,062 windows) than were hypermethylated (777 windows). Promoters contained the highest proportion of differentially methylated regions (0.08%), while distal intergenic and intron regions contained the largest number of differentially methylated regions. Protein-coding genes were the most abundant, followed by long noncoding and short noncoding genes. The most significantly over-represented signalling pathways in the differentially methylated gene list included immune/cancer-related pathways and B-cell receptor signalling. Among the top 10 hub genes identified via network-based prioritization, four (UBC, GRB2, CREBBP, and GAB2) had no known relevance to CLL, while the other six (STAT3, PTPN6, SYK, STAT5B, XPO1, and ABL1) have previously been linked to CLL in Caucasians. As such, our analysis identified four novel candidate genes of potential significance to Asian patients with CLL.

Objectives: We aimed to explore serum biomarkers for predicting survival of older patients with metastatic solid tumors who received first line palliative chemotherapy., Materials and Methods: Serum samples were prospectively collected before first-line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors. Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D were measured by ELISA and interleukin-6 (IL-6), myostatin, irisin, FGF-19, FGF-21, FGF-23 by Luminex multiplex assay. Overall survival (OS) was determined., Results: Serum samples from 138 patients (median age: 75 years, range: 70-92 years) were collected from February 2014 to December 2016. During a median follow up time of 13.8 months, 73 (52.9%) patients died. Among 13 serum markers, CRP (log-rank, P = 0.009), activin A (P = 0.007), and myostatin (P = 0.047) were significantly correlated with OS in univariate analyses. Activin A (hazard ratio [HR] 2.22, 95% confidence interval [CI] 1.32-3.72; P = 0.003) and myostatin (HR 3.02, 95% CI 1.39-6.57; P = 0.005) were significantly associated with OS after adjustment for other clinical factors. In predicting early (6-month) mortality, two inflammatory markers, IL-6 and CRP, were included in the decision-tree model., Conclusion: In older patients with cancer, high serum concentrations of activin A and myostatin were predictive of poor OS. IL-6 and CRP might be useful to select older patients at risk of early mortality. These markers could be incorporated into predictive tools for clinical decision-making and warrant further investigation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Unbiased cluster analysis has identified several asthma phenotypes. However, these phenotypes did not consistently predict disease prognosis and reflect temporal variability in airway inflammation., Objective: We aimed to identify longitudinal trajectories in terms of pulmonary function parameters and investigated whether the trajectories are associated with prognosis., Methods: Data were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). Three-year pulmonary function test results were used to apply finite mixture models for group-based trajectory in 486 patients with eligible data set., Results: Two main sets of longitudinal trajectories were identified in terms of FEV 1 % predicted, and FEV 1 variability. In the 4 trajectories determined with FEV 1 % predicted, the pulmonary function showed a consistent course in 4 stratified levels during 3 years of follow-up, which was associated with unexpected hospital visits and the use of steroid bursts due to exacerbation. The variability in pulmonary function showed 3 different patterns, and we found that higher blood and sputum eosinophil levels were associated with the higher variability in pulmonary function and more exacerbations., Conclusions: Trajectory analysis is a novel method that provides longitudinal asthma phenotypes and aids in prediction of future risk of exacerbation. Further analysis is needed to validate the usefulness of these trajectories in an independent population., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The relationship between psoriasis and cancer has not yet been established. The aim of this study was to evaluate the association of psoriasis with certain cancers using national statistics. All patients with psoriasis (n = 892 089; 51.7% male) and age- and sex-matched control subjects (n = 4 460 445) at a 5:1 ratio were enrolled using data from the National Health Insurance Service between 2007 and 2014 in Korea. In psoriatic subjects, overall cancer risk was higher than for subjects without psoriasis after adjusting for income level, diabetes, hypertension, dyslipidemia and place of residence (hazard ratio, 1.065; 95% CI, 1.049-1.081). The risk of cancer increased in the following order: prostate, thyroid, liver, ovarian, lung, leukemia, skin, multiple myeloma, lymphoma and testicular. The severity and sex of psoriatic patients also had different cancer risks. In psoriatic patients, a slightly increased risk for specific malignant neoplasms was shown. Therefore, periodic screening for cancer risk is recommended in patients with psoriasis., (© 2018 Japanese Dermatological Association.)

Background: Generally, carbohydrate antigen 19-9 (CA 19-9) is not useful for screening pancreatic cancer in the asymptomatic general population. This study aimed to evaluate the utility of CA 19-9 level as a screening indicator of pancreatic cancer in asymptomatic patients with new-onset diabetes., Methods: We retrospectively reviewed the medical records of patients who visited our health promotion center for health check-ups without cancer related symptoms from January 2005 to January 2014, and were newly diagnosed with diabetes mellitus (DM) within 2 years before their visit., Results: Of the 5111 asymptomatic patients with new-onset DM (<2 years) selected for analyses, 87 (1.7%) eventually developed pancreatic cancer after the health check-up. In the subgroup of 322 patients with high total bilirubin levels (>1.7 mg/dL) at the screening time, 42 (73.7%) of 57 patients with high CA 19-9 levels (>37 IU/mL) had been diagnosed as pancreatic cancer during follow-up period and 12 (4.5%) of 265 patients with normal CA 19-9 levels had finally developed pancreatic cancer (OR = 16.3). In the subgroup of 4789 patients with normal bilirubin levels, pancreatic cancer had been detected in 20 (3.8%) of 522 patients with high CA 19-9 level, while only 13 (0.3%) in 4267 patients with normal CA 19-9 levels (OR = 12.6), respectively., Conclusion: CA 19-9 levels after a diagnosis of new-onset DM could be a useful biomarker of pancreatic cancer, especially in patients with high serum bilirubin., (Copyright © 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background: Older patients have increased risk of toxicity from chemotherapy. Current prediction tools do not provide information on cumulative risk., Methods: Patients aged ≥ 70 years with solid cancer were prospectively enrolled. A prediction model was developed for adverse events (AEs) ≥ Grade 3 (G3), based on geriatric assessment (GA), laboratory, and clinical variables., Results: 301 patients were enrolled (median age, 75 years). Median number of chemotherapy cycles was 4. During first-line chemotherapy, 53.8% of patients experienced AEs ≥ G3. Serum protein < 6.7 g/dL, initial full-dose chemotherapy, psychological stress or acute disease in the past 3 months, water consumption < 3 cups/day, unable to obey a simple command, and self-perception of poor health were significantly related with AEs ≥ G3. A predicting model with these six variables ranging 0-8 points was selected with the highest discriminatory ability (c-statistic= 0.646), which could classify patients into four risk groups. Predicted cumulative incidence of AEs ≥ G3 was discriminated according to risk groups., Conclusions: This prediction tool could identify the risk of AEs ≥ G3 after chemotherapy and provide information on the cumulative incidence of AEs in each cycle., Clinical Trial Id: WHO ICTRP number, KCT0001071.

Episodic ataxia (EA) is a rare neurological condition characterized by recurrent spells of truncal ataxia and incoordination. Five genes (KCNA1, CACNA1A, CACNB4, SLC1A3, and UBR4) have been linked to EA. Despite extensive efforts to genetically diagnose EA, many patients remain still undiagnosed. Whole-exome sequencing was carried out in 39 Korean patients with EA to identify pathogenic mutations of the five known EA genes. We also evaluated 40 candidate genes that cause EA as a secondary phenotype or cerebellar ataxia. Eighteen patients (46%) revealed genetic information useful for establishing a molecular diagnosis of EA. In 11 patients, 16 pathogenic mutations were detected in three EA genes. These included nine mutations in CACNA1A, three in SLC1A3, and four in UBR4. Three patients had mutations in two genes, either CACNA1A and SLC1A3 or CACNA1A and UBR4, suggesting that SLC1A3 and UBR4 may act as genetic modifiers with synergic effects on the abnormal presynaptic activity caused by CACNA1A mutations. In seven patients with negative results for screening of EA genes, potential pathogenic mutations were identified in the candidate genes ATP1A2, SCN1A, TTBK2, TGM6, FGF14, and KCND3. This study demonstrates the genetic heterogeneity of Korean EA, and indicates that whole-exome sequencing may be useful for molecular genetic diagnosis of EA.

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.

Background: Combination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL)., Methods: Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m(2) on days 1-3; methotrextate 30 mg/m(2) on days 3 and 10; etoposide 100 mg/m(2) on days 1-3; and prednisolone 60 mg/m(2) per day on days 1-5) followed by involved field radiotherapy (IFRT)., Results: Overall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively., Conclusion: Due to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL., (©AlphaMed Press; the data published online to support this summary is the property of the authors.)

Background/aims: In Asia, the incidence of non-Hodgkin lymphoma (NHL) has increased in recent decades. Waldeyer's ring (WR) is the most common site of NHL involving the head and neck. In this study, the pathological distribution of WR-NHL and its clinical features were analyzed retrospectively., Methods: From January 2000 through December 2010, we analyzed the medical records of 328 patients from nine Korean institutions who were diagnosed with WR-NHL., Results: The study group comprised 197 male and 131 female patients with a median age of 58 years (range, 14 to 89). The rate of localized disease (stage I/II) was 64.9%, and that of low-risk disease (low/low-intermediate, as defined by the International Prognostic Index) was 76.8%. Diffuse large B-cell lymphoma (DLBCL; 240 patients, 73.2%) was the most common pathologic subtype, followed by peripheral T-cell lymphoma (14 patients, 4.3%) and nasal NK/T-cell lymphoma (14 patients, 4.3%). WR-NHL occurred most frequently in the tonsils (199 patients, 60.6%). Extranodal involvement was greater with the T-cell subtype (20 patients, 42.5%) compared with the B-cell subtype (69 patients, 24.5%). Multivariate analyses showed that age ≥ 62 years, T-cell subtype, and failure to achieve complete remission were significant risk factors for overall survival., Conclusions: DLBCL was found to have a higher incidence in Korea than those incidences reported by other WR-NHL studies. T-cell lymphoma occurred more frequently than did follicular lymphoma. T-cell subtype, age ≥ 62 years, and complete remission failure after first-line treatment were significant poor prognostic factors for overall survival according to the multivariate analysis.

Purpose: Pain is one of the most common and devastating symptoms in cancer patients, and misunderstandings on the patient's part can cause major obstacles in pain management., Method: We evaluated factors associated with patient's high barrier score to managing cancer-associated pain by having 201 patients complete the Korean Barriers Questionnaire II, the Brief Pain Inventory--Korean, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain Management Index (PMI) was also assessed., Results: The patients were from nine oncology clinics in university hospitals and a veterans' hospital in South Korea. The median pain score (0-10 scale) was 4, with a median percentage of pain improvement during the last 24 h of 70 %. A total of 150 patients (75 %) received strong opioids, and 177 (88 %) achieved adequate analgesia (positive PMI). Mean scores ± SD for the Barriers Questionnaire II ranged from 1.5 ± 1 to 2.8 ± 1.1, with the harmful effects subscale the highest. In the multiple regression model, depression was significantly associated with total barrier score to pain management (p < 0.0001). Pain reduction was significantly associated with the fatalism subscale., Conclusions: Depression was associated with high barrier score in patients with cancer pain. Management of cancer pain should include screening for depression, and management of depression could reduce patient-reported barriers to pain management.

We conducted a multicenter, phase II trial to investigate the efficacy and safety of rituximab plus CVP (R-CVP) combination therapy for patients with previously untreated stage III or IV marginal zone lymphoma (MZL). The treatment consisted of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2) and vincristine 1.4 mg/m(2) (maximum 2.0 mg) being given intravenously on day 1 and oral prednisolone 100 mg on days 1-5. The treatment was repeated every 3 weeks and this was continued for six or eight cycles. Forty-two patients were enrolled from 13 institutes in Korea. Among them, two patients were dropped after the first and second cycles of chemotherapy, respectively, without evaluation. The 40 patients received a total of 287 cycles of R-CVP chemotherapy. The overall response rate was 88% (95% CI, 77-98%) with 24 complete responses (60%). The median duration of response was 28.3 months. After a median follow-up of 38.2 months, the estimated 3-year progression-free survival and overall survival were 59% and 95%, respectively. There were 30/287 cycles (11%) and 5/287 cycles (2%) of grade 3 or 4 neutropenia and febrile neutropenia, respectively. The R-CVP regimen can be an effective and tolerable first-line immunochemotherapy regimen for advanced stage MZL.

Ethnic and regional differences in the epidemiology and pathological aspects of Hodgkin's lymphoma (HL) between Western and Asian patients may be associated with differences in clinical features and prognosis. We retrospectively analyzed the clinical and histopathological characteristics, therapeutic outcomes, and prognostic factors of 539 HL patients treated at 16 centers in Korea. We found that the incidence of histological subtypes of HL in Korea was similar to that in Western and other Asian countries. However, the incidence peaked between 16 and 30 years of age, unlike the bimodal age distribution seen in Western countries. In patients with stage I-IIA non-bulky disease, the complete response (CR) rate was similar between combined modality therapy and chemotherapy alone (93% vs. 84%, P = 0.44), and there was no difference in relapse-free survival (RFS) and overall survival (OS). Patients with stage I-II disease plus unfavorable factors and those with advanced-stage disease treated with combination chemotherapy regimens had an overall CR rate of 77%, with no difference between doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and non-ABVD regimens (77.2% vs. 76.8%, P = 0.95). Among those patients who achieved final CR, there was no significant difference in RFS or OS between those who achieved interim CR and PR. Only the presence of B symptoms was independently predictive of a shorter RFS. Age > 45 years, Eastern Cooperative Oncology Group 2-4, and B symptoms were independent risk factors for death. Although the incidence of HL was lower in Korea than in Western countries, the distribution of morphological subtypes, treatment outcomes, and patient prognosis were similar.

Background: The breast is a rare extranodal site of non-Hodgkin lymphoma, and primary breast lymphoma (PBL) has been arbitrarily defined as disease localized to one or both breasts with or without regional lymph nodes involvement. The aim of this study was to evaluate the clinical outcomes in patients with diffuse large B cell lymphoma (DLBCL) and breast involvement, and to find the criteria of PBL reflecting the outcome and prognosis., Methods: We retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009., Results: Median age at diagnosis was 48 years (range, 20-83 years). Forty-three (63.2%) patients were PBL according to previous arbitrary criteria, sixteen (23.5%) patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED) with or without nodal disease were 49 (72.1%), and those with multiple extranodal disease (MED) were 19 (27.9%). During median follow-up of 41.5 months (range, 2.4-186.0 months), estimated 5-year progression-free survival (PFS) was 53.7 +/- 7.6%, and overall survival (OS) was 60.3 +/- 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 +/- 8.9% vs. 27.5 +/- 11.4%, p = 0.001; 5-year OS, 74.3 +/- 7.6% vs. 24.5 +/- 13.0%, p < 0.001). In multivariate analysis, MED (hazard ratio [HR], 3.61; 95% confidence interval [CI], 1.07-12.2) and fewer than four cycles of systemic chemotherapy with or without local treatments (HR, 4.47; 95% CI, 1.54-12.96) were independent prognostic factors for worse OS. Twenty-five (36.8%) patients experienced progression, and the cumulative incidence of progression in multiple extranodal sites or other than breasts and central nervous system was significantly different between the OED group and the MED group (5-year cumulative incidence, 9.7 +/- 5.4% vs. 49.0 +/- 15.1%, p = 0.001)., Conclusions: Our results show that the patients included in OED group, reflecting different treatment outcome, prognosis and pattern of progression, should be considered as PBL in the future trial. Further studies are warranted to validate our suggested criteria.

The sorption coefficients of four rarely studied zwitterionic pharmaceuticals (benzimidazoles: fenbendazole, albendazole, thiabendazole and flubendazole) and four metabolites of fenbendazole to various dissolved organic matter surrogates (humic acid, sodium dodecyl sulfate micelle, hydroxypropyl-beta-cyclodextrin and liposomes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and sewage sludge) were measured to extend the available sorption coefficients and eventually to evaluate their environmental fate in soil and water environment. For the entire range of dissolved organic matters, the more hydrophobic fenbendazole and albendazole had higher sorption coefficients than thiabendazole and flubendazole, indicating that the traditional hypothesis of hydrophobic interaction holds for zwitterionic benzimidazole anthelmintics. However, the sorption coefficients of a given benzimidazole to selected dissolved organic matters (DOMs) varied within an order of magnitude. The measured K(oc) values decreased in the order of fenbendazole, albendazole, thiabendazole and flubendazole for sewage sludge and hydroxypropyl-beta-cyclodextrin whereas the orders were different for the other DOM surrogates, implying the hydrophilic nature of sewage sludge. This was also supported by the (N+O)/C elemental ratio of the sewage sludge sample used in this study. The correlations between log K(oc) and log K(ow) were weak (r(2)=0.28-0.64) and the magnitude of the sorption coefficients to the hydrophilic organic matters (hydroxypropyl-beta-cyclodextrin and sewage sludge) were similar to or slightly smaller than those for the hydrophobic organic matters (humic acids and liposome). This suggests that specific hydrophilic interactions also play a significant role in the sorption of moderately hydrophobic benzimidazoles to organic matters., (Copyright (c) 2010 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.)

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.)