Purpose: The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC). Materials and Methods: Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity. Results: Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin. Conclusion The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.

Background/Aims: Recently, 1-L polyethylene glycol-ascorbic acid (PEG-Asc) has been used to reduce the volume of preparation agents in colonoscopy. This clinical trial aimed to compare the efficacy and safety of two types of 1-L PEG-Asc (CleanViewAL ® [Tae Joon Pharmaceutical Company, Seoul, Korea] and Plenvu ® [Norgine, Harefield, United Kingdom]) in average-aged adults. Methods: This study was a prospective, randomized, non-inferiority, open-label, phase 4 clinical trial. The primary endpoint was the efficacy evaluated using the Boston bowel preparation scale (BBPS), and the secondary endpoint was clinical safety. Results: In total, 173 patients were assigned to either the CleanViewAL ® (n=84) or Plenvu ® (n=89) group. Overall cleansing successes of 97.6% (82/84) and 98.8% (88/89) were achieved in the CleanViewAL ® group and in the Plenvu ® group, respectively, showing that CleanViewAL ® has similar bowel cleansing efficacy to Plenvu ® (95% CI, -0.052 to 0.027; p=0.207). The total BBPS score was 8.67±1.00 and 8.70±0.76 in the CleanViewAL ® group and Plenvu ® group, respectively (p=0.869). The most common adverse symptom was nausea, and no adverse symptoms requiring hospitalization were reported in either group. There were no cases of critical hypernatremia and liver dysfunction exceeding the common terminology criteria for adverse events grade I. An overall satisfaction score (scale of 1 to 10) showed no difference between the two groups (p=0.289). However, the CleanViewAL ® group showed a higher taste satisfaction score (scale of 1 to 5) than the Plenvu ® group (CleanViewAL ® : 2.90±0.91, Plenvu ® : 2.60±0.86, p=0.028). Conclusions Both types of 1-L PEG-Asc, CleanViewAL ® and Plenvu ® , are effective and safe bowel cleansing agents in average-aged adults. CleanViewAL ® was preferred in terms of taste satisfaction.

Background/Aims: Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients. Methods: The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data. Results: This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively. Conclusions The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.

Background/Aims: Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients. Methods: The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data. Results: This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively. Conclusions The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.

Background: A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. Methods: C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. Results: Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. Conclusion Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.

This study performed the forensic anthropological sex estimation of Koreans in a non-metric way by reconstructing three-dimensional (3D) computed tomography (CT) images of skulls. The skull CT images used in this study were 100 (51 males, 49 females), and all CT images were taken with a slice thickness of 0.75 mm and then reconstructed into 3D images using the MIMICS 23.0 program. Using the reconstructed 3D image, measurements were repeated twice. The sex determination was male if the 4 point to 5 point was relatively more in five landmarks, and female if the points of 1 to 2 were relatively more. Results of the study show that, 88 of the 100 cases matched the actual sex. Among the 12 discrepant cases, ten cases were mismatched with the actual sex even though the estimation and repeated estimation readout of sexestimating were the same. Two cases, were “unknown,” showing different sexes in the first and repeated estimations. In conclusion, this study indicated that a forensic anthropological analysis from 3D images provided accurate point information on the landmarks of skulls, showing as high an accuracy as the sex estimation method using real bones. The ten cases of sex mismatch, except the two “Unknown” cases, are considered to be errors that did not consider differences in population groups. In further studies, further establishing a nonmetric, specifically Korean methods to increase the accuracy and reliability of sex estimation is need.

Abstract: Edible offal is easily contaminated by Escherichia coli (E. coli) and fluoroquinolone (FQ)-resistant E. coli is considered a serious public health problem, thus, this study investigated the genetic characteristics of FQ-resistant E. coli from edible offal. A total of 22 FQ-resistant E. coli isolates were tested. A double mutation in each gyrA and parC led the highest MIC. Four (18.2%) isolates carried plasmid-mediated quinolone resistance genes. The fimH, eaeA, escV, astA, and iucC genes were confirmed. Seventeen isolates (77.3%) were positive for plasmid replicons. The isolates showed high genetic heterogeneity based on pulsed-field gel electrophoresis patterns.

BACKGROUND: Stem cell engineering is appealing consideration for regenerating damaged endothelial cells (ECs) because stem cells can differentiate into EC-like cells. In this study, we demonstrate that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into EC-like cells under optimal physiochemical microenvironments.METHODS: TMSCs were preconditioned with Dulbecco's Modified Eagle Medium (DMEM) or EC growth medium (EGM) for 4 days and then replating them on Matrigel to observe the formation of a capillary-like network under light microscope. Microarray, quantitative real time polymerase chain reaction, Western blotting and immunofluorescence analyses were used to evaluate the expression of gene and protein of EC-related markers.RESULTS: Preconditioning TMSCs in EGM for 4 days and then replating them on Matrigel induced the formation of a capillary-like network in 3 h, but TMSCs preconditioned with DMEM did not form such a network. Genome analyses confirmed that EGM preconditioning significantly affected the expression of genes related to angiogenesis, blood vessel morphogenesis and development, and vascular development. Western blot analyses revealed that EGM preconditioning with gelatin coating induced the expression of endothelial nitric oxide synthase (eNOS), a mature EC-specific marker, as well as phosphorylated Akt at serine 473, a signaling molecule related to eNOS activation. Gelatin-coating during EGM preconditioning further enhanced the stability of the capillary-like network, and also resulted in the network more closely resembled to those observed in human umbilical vein endothelial cells.CONCLUSION: This study suggests that under specific conditions, i.e., EGM preconditioning with gelatin coating for 4 days followed by Matrigel, TMSCs could be a source of generating endothelial cells for treating vascular dysfunction.
Blood Vessels ; Blotting, Western ; Eagles ; Endothelial Cells ; Fluorescent Antibody Technique ; Gelatin ; Genome ; Human Umbilical Vein Endothelial Cells ; Mesenchymal Stromal Cells ; Morphogenesis ; Nitric Oxide Synthase Type III ; Palatine Tonsil ; Real-Time Polymerase Chain Reaction ; Serine ; Stem Cells

PURPOSE: The purpose of this study was to compare prognostic differentiation performances of the 7th and the 8th edition of American Joint Committee on Cancer (AJCC) staging system for gastric cancer (GC) patients. MATERIALS AND METHODS: A total of 1,633 GC patients who underwent curative D2 resection followed by adjuvant chemotherapy alone (CA) or concurrent chemo-radiotherapy (CCRT) from 2004 to 2013 were included. Concordance index (c-index) was applied to compare the discriminatory ability. RESULTS: In the 8th edition, migration of stage was detected in 248 patients (15.2%). Among them, 121 patients were up-staged while 127 patients were down-staged. Overall, there was no statistically significant difference in the discriminatory ability between the 7th and 8th editions. The new edition of staging system, however, showed a trend of better prognostic performance not only in recurrence-free survival (c-index=0.734; 95% confidence interval [CI], 0.706 to 0.762 in the 7th edition vs. c-index=0.740; 95% CI, 0.712 to 0.768 in the 8th edition; p=0.14), but also in overall survival (c-index=0.717; 95% CI, 0.688 to 0.745 in the 7th edition vs. c-index=0.722; 95% CI, 0.694 to 0.751 in the 8th edition; p=0.19), especially in stage III. This finding was repeated in the subgroup analysis regardless of adjuvant CA or CCRT. CONCLUSION: Generally, the 8th edition of AJCC staging system had failed to show a superior discriminatory ability for curatively D2 resected GC patients than the 7th edition, although there was a trend of better prognostic performance of the new edition, regardless of adjuvant treatment method.
Chemotherapy, Adjuvant ; Humans ; Joints ; Methods ; Neoplasm Staging ; Prognosis ; Radiotherapy ; Recurrence ; Stomach Neoplasms

PURPOSE: We aimed to discuss the roles of radiation and chemotherapy as adjuvant treatment in patients with staged IB GC who were enrolled in the adjuvant chemoradiotherapy in stomach tumors (ARTIST) trial. MATERIALS AND METHODS: Among the 458 patients who were enrolled in the ARTIST trial, 99 had stage IB disease. The patients were randomly assigned to receive either adjuvant chemoradiotherapy with capecitabine plus cisplatin (XP, n=50) or chemoradiotherapy (XPRT, n=49). Survival analyses were performed in accordance with the AJCC 2010 staging system. RESULTS: According to the AJCC 2010 system, stage migration from IB to II occurred in 71% of the patients; 98% of the T2 N0 cases were reclassified as T3 N0, and 42% of the T1 N1 cases were reclassified as T1 N2. When comparing survival outcomes between the XPRT and XP arms for stage IB cancer (AJCC 2002), no significant difference in 5-year disease-free survival (DFS) between the 2 arms was found. (median 5-year DFS, not reached, P=0.256). The patients classified as having stage IB cancer (AJCC 2002) and reclassified as having stage II cancer (AJCC 2010) exhibited worse prognoses than those who remained in stage IB, although the difference was not statistically significant (5-year DFS rate, 83% vs. 93%). When we compared 5-year DFS in 70 patients with stage II (AJCC 2010), the addition of radiotherapy to XP chemotherapy did not show better outcome than XP alone (P=0.137). CONCLUSIONS: The role of adjuvant chemoradiotherapy in the treatment of stage IB GC (AJCC 2002) warrants further investigation.
Arm ; Capecitabine ; Chemoradiotherapy ; Chemoradiotherapy, Adjuvant* ; Chemotherapy, Adjuvant* ; Cisplatin ; Disease-Free Survival ; Drug Therapy ; Humans ; Prognosis ; Radiotherapy* ; Stomach Neoplasms* ; Stomach*