Purpose: The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL). Materials and Methods: In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B). Results: Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33). Conclusion The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

Purpose: We investigated the efficacy of temozolomide during and after radiotherapy in Korean adultswith anaplastic gliomas without 1p/19q co-deletion. Materials and Methods: This was a randomized, open-label, phase 2 study and notably the first multicenter trial forKorean grade III glioma patients. Eligible patients were aged 18 years or older and hadnewly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative OncologyGroup performance status of 0-2. Patients were randomized 1:1 to receive radiotherapyalone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy withconcurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary endpointwas 2-year progression-free survival (PFS). Seventy patients (83.3%) were availablefor the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status. Results: The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overallsurvival (OS) did not reach to significant difference between the groups. In multivariableanalysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidenceinterval [CI], 1.04 to 4.16). The IDH1mutation was the only significant prognostic factor forPFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverseevents over grade 3 were seen in 16 patients (40.0%) in the treatment group and werereversible. Conclusion Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed nonco-deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimenneeds further analysis with long-term follow-up at least more than 10 years.

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer’s disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3′,4′-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3′,4′-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin E2 and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation. This indicates that the anti-inflammatory activities of 3′,4′-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and NF-κB signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3′,4′-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.
Animals ; Central Nervous System ; Chemokines ; Cytokines ; Dinoprostone ; Huntington Disease ; Interleukin-1beta ; Interleukin-6 ; Mice* ; Microglia* ; Neurodegenerative Diseases ; Nitric Oxide ; Parkinson Disease ; Phosphorylation ; Protein Kinases ; Tumor Necrosis Factor-alpha

PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.
Biopsy ; Chemoradiotherapy* ; Disease-Free Survival ; Follow-Up Studies ; Glioblastoma* ; Humans ; Korea* ; Methylation ; Radiotherapy ; Retrospective Studies* ; Survival Rate

Orientia tsutsugamushi (O. tsutsugamushi), which is endemic to an Asia-Pacific region, has increased its incidence and caused annually around 10 thousand patients infected with scrub typhus in Korea in the past several years. In the present study, we isolated 44 O. tsutsugamushi from the patients with febrile illness accompanied with or without an eschar in Gyeongsangnam-do, Korea. These isolates were characterized by genetic analysis of the major outer membrane protein, the 56-kDa type-specific antigen (tsa56), which is unique to O. tsutsugamushi. Two types of sequences of tsa56, designated by JJ1 and JJ2, were determined from 37 and 7 isolates of the 44 isolates, respectively. JJ1 and JJ2 showed 74.7~90.8% identity in nucleotide sequence and 66.1~90.5% identity in amino acid sequence with 33 reference strains except for Boryong and Kuroki. JJ1 and JJ2 had 100 and 99.9% nucleotide identity to Boryong strain, and 99.9 and 99.8% to Kuroki, which has been known to be similar to Boryong, respectively. In addition, they showed 77.9~ 81.4% nucleotide identity with the cluster of Gilliam-related genotypes, whereas they showed higher nucleotide identity (89.6~90.8%) with the cluster of Karp-related genotypes. To our knowledge, this is the first report to isolate O. tsutsugamushi and characterize their genotype as the Boryong in Jinju and West Gyeongsangnam-do, Korea, even though it has been reported that the Boryong was the predominant genotype in isolates from chiggers, domestic rodents, and patients in the southern part of Korea. Furthermore, our isolates could be useful source to study on the pathophysiology and epidemiology of scrub typhus in Korea.
Amino Acid Sequence ; Base Sequence ; Chungcheongnam-do ; Epidemiology ; Genotype ; Gyeongsangnam-do* ; Humans ; Incidence ; Korea* ; Membrane Proteins ; Orientia tsutsugamushi* ; Rodentia ; Scrub Typhus* ; Trombiculidae

BACKGROUND/AIMS: This study sought to characterize the current sedation practices of Korean endoscopists in real-world settings. METHODS: All active members of the Korean Society of Gastrointestinal Endoscopy were invited to complete an anonymous 35-item questionnaire. RESULTS: The overall response rate was 22.7% (1,332/5,860). Propofol-based sedation was the dominant method used in both elective esophagogastroduodenoscopy (55.6%) and colonoscopy (52.6%). The mean satisfaction score for propofol-based sedation was significantly higher than that for standard sedation in both examinations (all p<0.001). The use of propofol was supervised exclusively by endoscopists (98.6%). Endoscopists practicing in nonacademic settings, gastroenterologists, or endoscopists with <10 years of endoscopic practice were more likely to use propofol than were their counterparts (all p<0.001). In total, 27.3% of all respondents performed sedation practices without having undergone sedation training, and 27.4% did so without any formal sedation protocols. The choice of propofol as the dominant sedation method was the only significant predictor of endoscopist experience with serious sedation-related adverse events (odds ratio, 1.854; 95% confidence interval, 1.414 to 2.432). CONCLUSIONS: Endoscopist-directed propofol administration is the predominant sedation method used in Korea. This survey strongly suggests that there is much room for quality improvement regarding sedation training and patient vigilance in endoscopist-directed sedation.
Adult ; Aged ; Aged, 80 and over ; Colonoscopy/methods/psychology ; Conscious Sedation/*methods/psychology/standards ; Endoscopy, Digestive System/methods/psychology ; Endoscopy, Gastrointestinal/*methods/psychology ; Female ; Gastroenterology/methods ; Humans ; Hypnotics and Sedatives ; Male ; Middle Aged ; Patient Satisfaction ; Practice Patterns, Physicians'/standards/*statistics & numerical data ; Propofol ; Quality Improvement ; Republic of Korea ; Surveys and Questionnaires

OBJECTIVE: To evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA). METHODS: A multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m2/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed. RESULTS: TMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (> or =grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01). CONCLUSION: For recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.
Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; Lomustine ; Oligodendroglioma* ; Procarbazine ; Recurrence ; Retrospective Studies ; Salvage Therapy ; Vincristine

PURPOSE: The purpose of this study is to analyze the clinical features of distal tibia fractures and to evaluate the treatment outcomes of minimally invasive plate osteosynthesis (MIPO). MATERIALS AND METHODS: From January 2004 to December 2009, 84 cases of 81 patients treated with plate fixation for distal tibia fracture were enrolled in this retrospective review. We investigated age, sex, injury mechanism, fracture patterns, and complications, and the clinical features were analyzed. To evaluate the treatment outcomes of MIPO, we divided into two groups. MIPO group consisted of 55 patients were treated with MIPO technique and conventional group consisted of 18 patients were treated with open reduction and internal fixation with conventional anterolateral plating. The results were compared between two groups by assessing bony union time, operation time, amount of blood loss, range of ankle motion, clinical score by American Orthopaedic Foot and Ankle Society (AOFAS) score, and post-operative complications. RESULTS: The mean age of 81 patients with distal tibia fracture was 54.8 years. According to AO classification, A1:2:3 were 16, 20, 16 patients, B1:2:3 were 2, 8, 7, C1:2:3 were 1, 3, 11 patients. According to injury mechanism, slip down injury was patients, traffic accident was 26, fall from height injury was 14 patients respectively. The type A fractures were lower energy trauma and more older patients. The type C fractures were higher energy trauma and younger patients. MIPO group was better than conventional group in operative time, blood loss, bony union time, and ankle joint motion. In complications, MIPO group showed no nonunion and infection, one malunion, one skin necrosis, nine skin irritations, and one screw breakage. Conventional group showed two nonunion, four infections, two skin necrosis, and one metal failure. CONCLUSION: Distal tibial fractures caused by low energy trauma were on the increase. Minimal invasive plate osteosynthesis was shorter bony union time and operation time, less blood loss, and larger ankle motions than conventional open reduction and plate fixation.
Accidents, Traffic ; Animals ; Ankle ; Ankle Joint ; Foot ; Humans ; Necrosis ; Operative Time ; Retrospective Studies ; Skin ; Tibia ; Tibial Fractures

BACKGROUND: There are several active tuberculosis (TB) cases in Korean high schools each school year. The risk of transmission in schools is extremely high due to the considerable time spent in closed classrooms. We evaluated the control of latent tuberculosis infection in Korean high schools. METHODS: When a student was identified with active TB, tuberculin skin testing was performed on their classmates and on students in their same school grade. When a student had a positive tuberculin skin tests (TST), they underwent follow-up testing with QuantiFERON-TB Gold In-Tube (QFT). The manufacturer recommended a cut-off of 0.35 IU/mL to determine QFT positivity was applied. RESULTS: A total of 131 pulmonary tuberculosis (TB) patients were included based on the criteria for screening TB contacts in the National Tuberculosis Control Program. Seventy-five (57.2%) students tested smear positive. TST were performed on 7,109 students who were classmates of, or in the same grade as, a TB patient. Of the contacts, 1,231 students (17.3%) were TST positive and they were screened with QFT. Six hundred-sixty-six (55.0%) of the tested students returned a positive QFT result and the rate of positivity was significantly associated with the increasing size of TST indurations (p<0.0001). CONCLUSION: The use of QFT resulted in approximately 45% of TST positive students not being given chemoprophylaxis.
Chemoprevention ; Follow-Up Studies ; Humans ; Interferon-gamma ; Interferon-gamma Release Tests ; Latent Tuberculosis ; Mass Screening ; Skin ; Skin Tests ; Tuberculin ; Tuberculin Test ; Tuberculosis ; Tuberculosis, Pulmonary

Klebsiella pneumoniae(K. pneumoniae) infection has a tendency of abscess formation and it is known to be associated with diabetes mellitus. Metastatic infection was an important feature of K. pneumoniae liver abscess and bacteremia, metastatic prostate abscess was rare. We present a case of a 81-year-old man with K. pneumoniae liver abscess and metastatic prostate abscess, This patient was successfully treated with percutaneous abscess drainage of liver abscess and transurethral incisional drainage of prostate abscess.
Abscess* ; Aged, 80 and over ; Bacteremia ; Diabetes Mellitus ; Drainage ; Humans ; Klebsiella ; Klebsiella pneumoniae ; Liver Abscess* ; Liver* ; Pneumonia ; Prostate* ; Transurethral Resection of Prostate