A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Background: Survival and post-cardiac arrest care vary considerably by hospital, region, and country. In the current study, we aimed to analyze mortality in patients who underwent cardiac arrest by hospital level, and to reveal differences in patient characteristics and hospital factors, including post-cardiac arrest care, hospital costs, and adherence to changes in resuscitation guidelines. Methods: We enrolled adult patients (≥ 20 years) who suffered non-traumatic cardiac arrest from 2006 to 2015. Patient demographics, insurance type, admission route, comorbidities, treatments, and hospital costs were extracted from the National Health Insurance Service database. We categorized patients into tertiary hospital, general hospital, and hospital groups according to the level of the hospital where they were treated. We analyzed the patients' characteristics, hospital factors, and mortalities among the three groups. We also analyzed post-cardiac arrest care before and after the 2010 guideline changes. The primary end-point was 30 days and 1 year mortality rates. Results: The tertiary hospital, general hospital, and hospital groups represented 32.6%, 49.6%, and 17.8% of 337,042 patients, respectively. The tertiary and general hospital groups were younger, had a lower proportion of medical aid coverage, and fewer comorbidities, compared to the hospital group. Post-cardiac arrest care, such as percutaneous coronary intervention, targeted temperature management, and extracorporeal membrane oxygenation, were provided more frequently in the tertiary and general hospital groups. After adjusting for age, sex, insurance type, urbanization level, admission route, comorbidities, defibrillation, resuscitation medications, angiography, and guideline changes, the tertiary and general hospital groups showed lower 1-year mortality (tertiary hospital vs. general hospital vs. hospital, adjusted odds ratios, 0.538 vs. 0.604 vs. 1; P < 0.001). After 2010 guideline changes, a marked decline in atropine use and an increase in post-cardiac arrest care were observed in the tertiary and general hospital groups. Conclusion The tertiary and general hospital groups showed lower 30 days and 1 year mortality rates than the hospital group, after adjusting for patient characteristics and hospital factors. Higher-level hospitals provided more post-cardiac arrest care, which led to high hospital costs, and showed good adherence to the guideline change after 2010.

Background: Survival and post-cardiac arrest care vary considerably by hospital, region, and country. In the current study, we aimed to analyze mortality in patients who underwent cardiac arrest by hospital level, and to reveal differences in patient characteristics and hospital factors, including post-cardiac arrest care, hospital costs, and adherence to changes in resuscitation guidelines. Methods: We enrolled adult patients (≥ 20 years) who suffered non-traumatic cardiac arrest from 2006 to 2015. Patient demographics, insurance type, admission route, comorbidities, treatments, and hospital costs were extracted from the National Health Insurance Service database. We categorized patients into tertiary hospital, general hospital, and hospital groups according to the level of the hospital where they were treated. We analyzed the patients' characteristics, hospital factors, and mortalities among the three groups. We also analyzed post-cardiac arrest care before and after the 2010 guideline changes. The primary end-point was 30 days and 1 year mortality rates. Results: The tertiary hospital, general hospital, and hospital groups represented 32.6%, 49.6%, and 17.8% of 337,042 patients, respectively. The tertiary and general hospital groups were younger, had a lower proportion of medical aid coverage, and fewer comorbidities, compared to the hospital group. Post-cardiac arrest care, such as percutaneous coronary intervention, targeted temperature management, and extracorporeal membrane oxygenation, were provided more frequently in the tertiary and general hospital groups. After adjusting for age, sex, insurance type, urbanization level, admission route, comorbidities, defibrillation, resuscitation medications, angiography, and guideline changes, the tertiary and general hospital groups showed lower 1-year mortality (tertiary hospital vs. general hospital vs. hospital, adjusted odds ratios, 0.538 vs. 0.604 vs. 1; P < 0.001). After 2010 guideline changes, a marked decline in atropine use and an increase in post-cardiac arrest care were observed in the tertiary and general hospital groups. Conclusion The tertiary and general hospital groups showed lower 30 days and 1 year mortality rates than the hospital group, after adjusting for patient characteristics and hospital factors. Higher-level hospitals provided more post-cardiac arrest care, which led to high hospital costs, and showed good adherence to the guideline change after 2010.

Background: This study investigated the relationships of thigh and waist circumference with the hemoglobin glycation index (HGI) and carotid atherosclerosis in patients with type 2 diabetes. Methods: This observational study included 3,075 Korean patients with type 2 diabetes, in whom anthropometric measurements and carotid ultrasonography were conducted. HGI was defined as the measured hemoglobin A1c (HbA1c) level minus the predicted HbA1c level, which was calculated using the linear relationship between HbA1c and fasting plasma glucose levels. Carotid atherosclerosis was defined as a clearly isolated focal plaque or focal wall thickening >50% of the surrounding intima-media thickness. Results: The frequency of a positive HGI decreased with increasing thigh circumference in men and increased with increasing waist circumference in women after adjusting for potential confounding variables. Thigh and waist circumference had a combined augmentative effect on the likelihood of positive HGI, which was dramatically higher in patients in higher waist-to-thigh ratio quartiles (adjusted odds ratios for the highest compared to the lowest quartile: 1.595 in men and 1.570 in women). Additionally, the larger the thigh circumference, the lower the risk of carotid atherosclerosis, although in women, this relationship lacked significance after adjustment for potential confounders. Conclusion HGI was associated with thigh circumference in men and waist circumference in women. In addition, the combination of low thigh circumference and high waist circumference was strongly associated with a higher HGI in Korean patients with type 2 diabetes. In particular, thigh circumference was associated with carotid atherosclerosis in men. However, further longitudinal studies are warranted.

BACKGROUND: Lower-limb varicose veins (VVs) are common and known to have a higher prevalence among people who work in occupations requiring prolonged standing. In the Republic of Korea, however, VV-related occupational factors have seldom been examined. This study was conducted to assess the prevalence of VVs among nurses, an occupational group considered to be at high risk of VVs, and determine the occupational risk factors of prolonged standing. METHODS: Between March and August 2014, a questionnaire survey coupled with Doppler ultrasonography was conducted on the nurses working at a university hospital. RESULTS: A total of 414 nurses participated in the survey and diagnostic testing. From the survey analysis and test results, the prevalence of VVs in nurses was estimated to be 16.18%. Significant factors for venous reflux were age [odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.03–1.10], pregnancy (OR = 2.15, 95% CI = 1.17–3.94), and delivery (OR = 2.02, 95% CI = 1.08–3.78). The statistical significance of these factors was verified after risk adjustment for sociodemographic factors (OR = 3.40, 95% CI = 1.27–9.09). CONCLUSION: Factors significantly associated with venous reflux were increasing age and prolonged working hours (≥ 4 hours) in a standing position (OR = 2.80, 95% CI = 1.08–7.25), even after risk adjustment for sociodemographic factors. This study is significant in that an objective diagnosis of VVs preceded the analysis of the risk factors for VV incidence, thus verifying objectively that VVs are associated with occupations requiring prolonged hours of working in a standing position.
Diagnosis ; Diagnostic Tests, Routine ; Humans ; Incidence ; Occupational Groups ; Occupations ; Posture ; Pregnancy ; Prevalence* ; Republic of Korea ; Risk Adjustment ; Risk Factors* ; Ultrasonography, Doppler ; Varicose Veins*

PURPOSE: We evaluated the results of allograft reconstruction following wide resection of malignant bone tumors in long bone, retrospectively. MATERIALS AND METHODS: Seven patients were included. The mean age was 44 years old. Male was 4 cases, and female was 3 cases. Mean follow-up period was 38 months. The mean Musculoskeletal Tumor Society (MSTS) score at final follow-up was evaluated. Postoperative complications were evaluated via periodic radiologic follow-up. Oncologic results were analyzed at final follow-up. RESULTS: The primary malignancies occurred at femur in 5 cases, humerus in 1 case and tibia in 1 case. Pathologic diagnoses were osteosarcoma in 4 cases, multiple myeloma in 2 cases and adamantinoma in 1 case. Mean length of allograft was 165 mm. Fixations of allograft were intramedullary nailing with additional plate in 4 cases, intramedullary nailing in 2 cases, and screw fixation in 1 case. Mean time to union was 14.5 weeks. Mean MSTS score at final follow-up was 20 (67%). Postoperative complications were nonunion in 3 cases, implant failure in 1 case, and infection in 1 case. Oncologic outcomes were continuous disease free in 5 cases and alive with disease in 2 cases at final follow-up. Autologous bone graft and hemi-cortical onlay graft were performed in 2 cases of nonunion. CONCLUSION: Allograft reconstruction following wide resection of malignant bone tumors in long bone was effective surgical option. However, the possibility of nonunion between host bone and allograft should be considered.
Adamantinoma ; Allografts* ; Diagnosis ; Female ; Femur ; Follow-Up Studies ; Fracture Fixation, Intramedullary ; Humans ; Humerus ; Inlays ; Male ; Multiple Myeloma ; Osteosarcoma ; Postoperative Complications ; Retrospective Studies ; Tibia ; Transplants

PURPOSE: This study compared the oncologic impact of postoperative chemotherapy and chemoradiotherapy on patients with rectal cancer without preoperative chemoradiation. METHODS: This retrospective study analyzed 713 patients with a mean follow-up of 58 months who had undergone radical resection for stage II/III rectal cancer without preoperative treatment in nine hospitals from January 2004 to December 2009. The study population was categorized a chemotherapy group (CG, n = 460) and a chemoradiotherapy group (CRG, n = 253). Five-year overall survival (OS) and disease-free survival (DFS) were analyzed, and independent factors predicting survival were identified. RESULTS: The patients in the CRG were significantly younger (P < 0.001) and had greater incidences of low rectal cancer (P < 0.001) and stage III disease (P < 0.001). Five-year OS (P = 0.024) and DFS (P = 0.012) were significantly higher in the CG for stage II disease; however, they were not significantly different for stage III disease. In the multivariate analysis, independent predictive factors were male sex, low rectal cancer and stage III disease for OS and male sex, abdominoperineal resection, stage III disease and tumor-positive circumferential margin for DFS. However, adjuvant therapy type did not independently affect OS (hazard ratio [HR], 1.243; 95% confidence interval [CI], 0.794–1.945; P = 0.341) and DFS (HR, 1.091; 95% CI, 0.810–1.470; P = 0.566). CONCLUSION: Adjuvant therapy type did not affect survival of stage II/III rectal cancer patients without neoadjuvant chemoradiotherapy. These results suggest that adjuvant therapy can be chosen based on the patient’s condition and the policies of the surgeons and hospital facilities.
Chemoradiotherapy ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Incidence ; Male ; Multivariate Analysis ; Rectal Neoplasms* ; Retrospective Studies* ; Surgeons

The National Health Information Standards Committee was established in 2004 in Korea. The practical subcommittee for laboratory test terminology was placed in charge of standardizing laboratory medicine terminology in Korean. We aimed to establish a standardized Korean laboratory terminology database, Korea-Logical Observation Identifier Names and Codes (K-LOINC) based on former products sponsored by this committee. The primary product was revised based on the opinions of specialists. Next, we mapped the electronic data interchange (EDI) codes that were revised in 2014, to the corresponding K-LOINC. We established a database of synonyms, including the laboratory codes of three reference laboratories and four tertiary hospitals in Korea. Furthermore, we supplemented the clinical microbiology section of K-LOINC using an alternative mapping strategy. We investigated other systems that utilize laboratory codes in order to investigate the compatibility of K-LOINC with statistical standards for a number of tests. A total of 48,990 laboratory codes were adopted (21,539 new and 16,330 revised). All of the LOINC synonyms were translated into Korean, and 39,347 Korean synonyms were added. Moreover, 21,773 synonyms were added from reference laboratories and tertiary hospitals. Alternative strategies were established for mapping within the microbiology domain. When we applied these to a smaller hospital, the mapping rate was successfully increased. Finally, we confirmed K-LOINC compatibility with other statistical standards, including a newly proposed EDI code system. This project successfully established an up-to-date standardized Korean laboratory terminology database, as well as an updated EDI mapping to facilitate the introduction of standard terminology into institutions.

PURPOSE: We analyzed the surgical result of schwannoma occurring in the major peripheral nerves of the extremity and factors that influence these surgical results. MATERIALS AND METHODS: Fifty-one patients, who were followed for more than 1 year, were included. The mean age was 51 years. There were 23 male cases and 28 female cases. There were 27 cases of schwannoma in the upper extremity and 24 cases in the lower extremity. The involved nerves were classified. The maximal diameter of excised tumors was measured. Clinical and neurological symptoms were analyzed at preoperative, postoperative, and final follow-up. Risk factors of neurological complications were also analyzed. RESULTS: The mean follow-up period was 20 months. The average maximal diameter of tumors was 2.9 cm. The most affected nerve in the upper extremity was the ulnar nerve in 10 cases, and tibial nerve in the lower extremity in 10 cases. The most prevalent preoperative symptom was Tinel in 38 cases. Clinical symptoms were improved in more than 90% of patients following the surgery. There were 13 cases with preoperative sensory deficits. Symptom improvement after surgery was observed in 9 cases; and symptoms persisted in 4 cases following surgery. At the final follow-up, sensory deficits disappeared in 2 cases and persisted in 2 cases. There were 2 cases of preoperative motor deficits. There was improvement in 1 case following the surgery and persisted in 1 case until the final follow-up. There was a statistical significance between maximal diameter of schwannoma and postoperative neurological deficits (p<0.05). CONCLUSION: Schwannoma at the major peripheral nerves of the extremity can be excised with acceptable risk for neurological deficits. Meticulous dissection is required to avoid injuries of the involved nerves.
Extremities* ; Female ; Follow-Up Studies ; Humans ; Lower Extremity ; Male ; Neurilemmoma* ; Peripheral Nerves* ; Risk Factors ; Tibial Nerve ; Ulnar Nerve ; Upper Extremity

PURPOSE: To analyze the results of surgical treatment for pathological fractures at the proximal femur. MATERIALS AND METHODS: Nineteen patients with a pathological fracture were included. The mean age was 65.7 years old. The patients comprised 8 males and 11 females. Primary tumors, types of pathological fractures, surgical procedures, and postoperative complications were recorded. Musculoskeletal Tumor Society (MSTS) functional score was used for functional evaluation. A Kaplan-Meier survival analysis was used to determine survival rate. RESULTS: The primary malignancies were 6 cases of breast cancer, 3 cases of lung cancer, 3 cases of renal cell carcinoma, 2 cases of cholangiocarcinoma, 2 cases of hepatocellular carcinoma, 1 case of esophageal cancer, 1 case of colon cancer, and 1 case of ovarian cancer. Pathological fractures included 8 cases of pertrochanteric fractures and 11 cases of subtrochanteric fractures. Intramedullary nailing was performed in 10 cases, and joint replacement surgery was performed in 9 cases. Postoperative complications included local recurrence in 1 case, infection in 1 case, and nail breakage in 1 case. The mean postoperative MSTS score was 21. The mean survival period was 10.6 months. Patient survival rates were 42.1% after 6 months, 26.3% after 12 months, and 10.5% after 24 months. CONCLUSION: Surgical treatment of pathological fractures at the proximal femur provided early ambulation, and excellent pain relief. The surgery was well tolerated emotionally. Surgery is necessary for improving the quality of life in such patients; however, more cases of pathological fractures in these regions should be subjected to detailed analysis.
Adult ; Aged ; Aged, 80 and over ; Bone Nails ; Bone Neoplasms/*secondary/surgery ; Female ; Femoral Fractures/etiology/pathology/*surgery ; Fracture Fixation, Intramedullary/*methods ; Fracture Healing ; Fractures, Spontaneous/pathology/*surgery ; Hip Fractures/surgery ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local/surgery ; Neoplasms/complications/pathology/*surgery ; Postoperative Complications ; Quality of Life ; Survival Rate ; Treatment Outcome