1.Gut microbiome and metabolome signatures in liver cirrhosis-related complications
Satya Priya SHARMA ; Haripriya GUPTA ; Goo-Hyun KWON ; Sang Yoon LEE ; Seol Hee SONG ; Jeoung Su KIM ; Jeong Ha PARK ; Min Ju KIM ; Dong-Hoon YANG ; Hyunjoon PARK ; Sung-Min WON ; Jin-Ju JEONG ; Ki-Kwang OH ; Jung A EOM ; Kyeong Jin LEE ; Sang Jun YOON ; Young Lim HAM ; Gwang Ho BAIK ; Dong Joon KIM ; Ki Tae SUK
Clinical and Molecular Hepatology 2024;30(4):845-862
Background/Aims:
Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis.
Methods:
Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased).
Results:
Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites.
Conclusions
Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.
2.Botulinum Toxin A Ameliorates Neuroinflammation in the MPTP and 6-OHDA-Induced Parkinson’s Disease Models
Hyeon Joo HAM ; In Jun YEO ; Seong Hee JEON ; Jun Hyung LIM ; Sung Sik YOO ; Dong Ju SON ; Sung-Su JANG ; Haksup LEE ; Seung-Jin SHIN ; Sang Bae HAN ; Jae Suk YUN ; Jin Tae HONG
Biomolecules & Therapeutics 2022;30(1):90-97
Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson’s disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.
3.Dynamics of viral load and anti-SARS-CoV-2 antibodies in patients with positive RT-PCR results after recovery from COVID-19
Kyoung-Ho SONG ; Dong-Min KIM ; Hyunju LEE ; Sin Young HAM ; Sang-Min OH ; Hyeonju JEONG ; Jongtak JUNG ; Chang Kyung KANG ; Ji Young PARK ; Yu Min KANG ; Ji-Yeon KIM ; Jeong Su PARK ; Kyoung Un PARK ; Eu Suk KIM ; Hong Bin KIM
The Korean Journal of Internal Medicine 2021;36(1):11-14
Recently, the number of patients with coronavirus disease 2019 (COVID-19) who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), via the reverse transcription polymerase chain reaction (RT-PCR) test, after recovery has increased; this has caused a dilemma regarding the medical measures and policies. We evaluated the dynamics of viral load and anti-SARSCoV-2 antibodies in four patients with positive RT-PCR results after recovery. In all patients, the highest levels of immunoglobulin G (IgG) and IgM antibodies were reached after about a month of the onset of the initial symptoms. Then, the IgG titers plateaued, and the IgM titers decreased, regardless of RT-PCR results.The IgG and IgM levels did not increase after the post-negative positive RT-PCR results in any of the patients. Our results reinforced that the post-negative positive RT-PCR results may be due to the detection of RNA particles rather than reinfection in individuals who have recovered from COVID-19.
4.Factors Associated with Clinical Outcomes of Palliative Stenting for Malignant Colonic Obstruction
Sang-Jae KWON ; Jiyoung YOON ; Eun Hye OH ; Jeongseok KIM ; Nam Seok HAM ; Sung Wook HWANG ; Sang Hyoung PARK ; Byong Duk YE ; Jeong-Sik BYEON ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Dong-Hoon YANG
Gut and Liver 2021;15(4):579-587
Background/Aims:
Self-expandable metal stents (SEMSs) can be applied to relieve colorectal obstruction secondary to incurable primary colorectal cancer or extracolonic malignancy. We aimed to identify factors associated with clinical success and the reintervention-free survival (RFS) after palliative stenting.
Methods:
Cases of palliative SEMS placement between 2005 and 2019 were retrieved from the institutional database and reviewed retrospectively. Logistic regression and log-rank testing followed by Cox proportional hazard analyses were performed to investigate the predictors of the clinical success of palliative stenting and factors associated with RFS, respectively.
Results:
A total of 593 patients underwent palliative stenting for malignant colonic obstruction (MCO). The technical and clinical success rates were 92.9% and 83.5%, respectively. Peritoneal carcinomatosis was a predictor of clinical failure (odds ratio, 0.33; 95% confidence interval [CI], 0.17 to 0.65) in the multivariate analysis. Peritoneal carcinomatosis (hazard ratio [HR], 2.48; 95% CI, 1.69 to 3.64) and stent expansion >90% on day 1 (HR, 1.62; 95% CI, 1.05 to 2.50) were associated with a shorter RFS. Neither clinical success nor RFS was associated with extracolonic malignancy. Re-obstruction, stent migration, and perforation were responsible for most reinterventions after clinically successful palliative stenting.
Conclusions
In patients requiring palliative stenting for MCO, peritoneal carcinomatosis was associated with both clinical failure and short RFS. Stent expansion >90% on postprocedural day 1 was another predictor of a short RFS after clinically successful stenting. A large prospective study is warranted to establish factors associated with RFS after successful palliative stenting for MCO.
5.Factors Associated with Clinical Outcomes of Palliative Stenting for Malignant Colonic Obstruction
Sang-Jae KWON ; Jiyoung YOON ; Eun Hye OH ; Jeongseok KIM ; Nam Seok HAM ; Sung Wook HWANG ; Sang Hyoung PARK ; Byong Duk YE ; Jeong-Sik BYEON ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Dong-Hoon YANG
Gut and Liver 2021;15(4):579-587
Background/Aims:
Self-expandable metal stents (SEMSs) can be applied to relieve colorectal obstruction secondary to incurable primary colorectal cancer or extracolonic malignancy. We aimed to identify factors associated with clinical success and the reintervention-free survival (RFS) after palliative stenting.
Methods:
Cases of palliative SEMS placement between 2005 and 2019 were retrieved from the institutional database and reviewed retrospectively. Logistic regression and log-rank testing followed by Cox proportional hazard analyses were performed to investigate the predictors of the clinical success of palliative stenting and factors associated with RFS, respectively.
Results:
A total of 593 patients underwent palliative stenting for malignant colonic obstruction (MCO). The technical and clinical success rates were 92.9% and 83.5%, respectively. Peritoneal carcinomatosis was a predictor of clinical failure (odds ratio, 0.33; 95% confidence interval [CI], 0.17 to 0.65) in the multivariate analysis. Peritoneal carcinomatosis (hazard ratio [HR], 2.48; 95% CI, 1.69 to 3.64) and stent expansion >90% on day 1 (HR, 1.62; 95% CI, 1.05 to 2.50) were associated with a shorter RFS. Neither clinical success nor RFS was associated with extracolonic malignancy. Re-obstruction, stent migration, and perforation were responsible for most reinterventions after clinically successful palliative stenting.
Conclusions
In patients requiring palliative stenting for MCO, peritoneal carcinomatosis was associated with both clinical failure and short RFS. Stent expansion >90% on postprocedural day 1 was another predictor of a short RFS after clinically successful stenting. A large prospective study is warranted to establish factors associated with RFS after successful palliative stenting for MCO.
6.Immunological measurement of aspartate/alanine aminotransferase in predicting liver fibrosis and inflammation
Hyun Jeong KIM ; Sang Yeol KIM ; Suk Pyo SHIN ; Young Joo YANG ; Chang Seok BANG ; Gwang Ho BAIK ; Dong Joon KIM ; Young Lim HAM ; Eui Yul CHOI ; Ki Tae SUK
The Korean Journal of Internal Medicine 2020;35(2):320-330
Background/Aims:
Enzymatic analysis of aspartate/alanine aminotransferase (AST/ALT) does not exactly represent the progression of liver fibrosis or inflammation. Immunoassay for AST (cytoplasmic [c] AST/mitochondrial [m] AST) and ALT (ALT1/ALT2) has been suggested as one alternatives for enzymatic analysis. The objective of this study was to evaluate the efficacy of immunoassay in predicting liver fibrosis and inflammation.
Methods:
A total of 219 patients with chronic hepatitis B (CHB) who underwent hepatic venous pressure gradient (HVPG) and liver biopsy before antiviral therapy were recruited. Serum samples were prepared from blood during HVPG. Results of biochemical parameters including enzymatic AST/ALT and immunological assays of cAST, mAST, ALT1, and ALT2 through sandwich enzyme-linked immunosorbent assay (ELISA) immunoassay with fluorescence labeled monoclonal antibodies were compared with the results of METAVIR stage of live fibrosis and the Knodell grade of inflammation.
Results:
METAVIR fibrosis stages were as follows: F0, six (3%); F1, 52 (24%); F2, 88 (40%); F3, 45 (20%); and F4, 28 patients (13%). Mean levels of AST and ALT were 121 ± 157 and 210 ± 279 IU/L, respectively. Mean HVPG score of all patients was 4.7 ± 2.5 mmHg. According to the stage of liver fibrosis, HVPG score (p < 0.001, r = 0.439) and ALT1 level (p < 0.001, r = 0.283) were significantly increased in all samples from patients with CHB. ALT (p < 0.001, r = 0.310), ALT1 (p < 0.001, r = 0.369), and AST (p < 0.001, r = 0.374) levels were positively correlated with Knodell grade of inflammation.
Conclusions
ALT1 measurement by utilizing sandwich ELISA immunoassay can be useful method for predicting inf lammation grade and fibrosis stage in patients with CHB.
7.Long-term Outcomes of Adalimumab Therapy in Korean Patients with Ulcerative Colitis: A Hospital-Based Cohort Study
Eun Hye OH ; Jeongseok KIM ; Namseok HAM ; Sung Wook HWANG ; Sang Hyoung PARK ; Dong-Hoon YANG ; Jeong-Sik BYEON ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Byong Duk YE
Gut and Liver 2020;14(3):347-356
Background/Aims:
Studies on long-term outcomes of adalimumab therapy in non-Caucasian patients with ulcerative colitis (UC) are lacking.
Methods:
We analyzed long-term outcomes of Korean UC patients treated with adalimumab at the Asan Medical Center, Seoul, Korea.
Results:
Between July 2013 and October 2018, adalimumab therapy was started in a total of 100 patients with UC (65 males [65.0%]; median age, 39.5 years [interquartile range, 23.3 to 49.8 years]; and median disease duration, 3.0 years [interquartile range, 1.0 to 7.0 years]). The median duration of adalimumab therapy was 13.5 months (interquartile range, 4.0 to 32.0 months). Eight of 100 patients (8.0%) received induction therapy only, four (4.0%) of whom ultimately underwent colectomy. Of 92 patients who received adalimumab maintenance therapy, 30 (30.0%) stopped adalimumab therapy due to loss of response, and one patient (1.0%) was lost to follow-up. Among the 92 patients who received adalimumab maintenance therapy, the cumulative proportions of patients remaining on adalimumab maintenance therapy were 70.0% at 1 year and 48.9% at 5 years. High partial Mayo score after 8 weeks of adalimumab therapy (hazard ratio [HR], 1.217; 95% confidence interval [CI], 1.040 to 1.425; p=0.014) and a history of exposure to two biologic agents before adalimumab therapy (HR, 4.722; CI, 1.033 to 21.586; p=0.045) were predictors of adalimumab discontinuation.
Conclusions
Long-term outcomes of adalimumab therapy in Korean UC patients appear to be comparable to those in previously published Western studies. Furthermore, previous exposure to multiple biologic agents before adalimumab therapy and disease activity after 8 weeks of adalimumab therapy were predictors of adalimumab discontinuation.
8.Prospective Randomized Controlled Study on the Efficacy of Multimedia Informed Consent for Patients Scheduled to Undergo Green-Light High-Performance System Photoselective Vaporization of the Prostate.
Dong Yeub HAM ; Woo Suk CHOI ; Sang Hoon SONG ; Young Joon AHN ; Hyoung Keun PARK ; Hyeong Gon KIM ; Hwancheol SON
The World Journal of Men's Health 2016;34(1):47-55
PURPOSE: The aim of this study was to evaluate the efficacy of a multimedia informed consent (IC) presentation on the understanding and satisfaction of patients who were scheduled to receive 120-W green-light high-performance system photoselective vaporization of the prostate (HPS-PVP). MATERIALS AND METHODS: A multimedia IC (M-IC) presentation for HPS-PVP was developed. Forty men with benign prostatic hyperplasia who were scheduled to undergo HPS-PVP were prospectively randomized to a conventional written IC group (W-IC group, n=20) or the M-IC group (n=20). The allocated IC was obtained by one certified urologist, followed by a 15-question test (maximum score, 15) to evaluate objective understanding, and questionnaires on subjective understanding (range, 0~10) and satisfaction (range, 0~10) using a visual analogue scale. RESULTS: Demographic characteristics, including age and the highest level of education, did not significantly differ between the two groups. No significant differences were found in scores reflecting the objective understanding of HPS-PVP (9.9±2.3 vs. 10.6±2.8, p=0.332) or in subjective understanding scores (7.5±2.1 vs. 8.6±1.7, p=0.122); however, the M-IC group showed higher satisfaction scores than the W-IC group (7.4±1.7 vs. 8.4±1.5, p=0.033). After adjusting for age and educational level, the M-IC group still had significantly higher satisfaction scores. CONCLUSIONS: M-IC did not enhance the objective knowledge of patients regarding this surgical procedure. However, it improved the satisfaction of patients with the IC process itself.
Education
;
Humans
;
Informed Consent*
;
Male
;
Multimedia*
;
Prospective Studies*
;
Prostate*
;
Prostatic Hyperplasia
;
Surgical Procedures, Operative
;
Volatilization*
9.Discordance between location of positive cores in biopsy and location of positive surgical margin following radical prostatectomy.
Ji Won KIM ; Hyoung Keun PARK ; Hyeong Gon KIM ; Dong Yeub HAM ; Sung Hyun PAICK ; Yong Soo LHO ; Woo Suk CHOI
Korean Journal of Urology 2015;56(10):710-716
PURPOSE: We compared location of positive cores in biopsy and location of positive surgical margin (PSM) following radical prostatectomy. MATERIALS AND METHODS: This retrospective analysis included patients who were diagnosed as prostate cancer by standard 12-core transrectal ultrasonography guided prostate biopsy, and who have PSM after radical prostatectomy. After exclusion of number of biopsy cores <12, and lack of biopsy location data, 46 patients with PSM were identified. Locations of PSM in pathologic specimen were reported as 6 difference sites (apex, base and lateral in both sides). Discordance of biopsy result and PSM was defined when no positive cores in biopsy was identified at the location of PSM. RESULTS: Most common location of PSM were right apex (n=21) and left apex (n=15). Multiple PSM was reported in 21 specimens (45.7%). In 32 specimens (69.6%) with PSM, one or more concordant positive biopsy cores were identified, but 14 specimens (28%) had no concordant biopsy cores at PSM location. When discordant rate was separated by locations of PSM, right apex PSM had highest rate of discordant (38%). The discordant group had significantly lower prostate volume and lower number of positive cores in biopsy than concordant group. CONCLUSIONS: This study showed that one fourth of PSM occurred at location where tumor was not detected at biopsy and that apex PSM had highest rate of discordant. Careful dissection to avoid PSM should be performed in every location, including where tumor was not identified in biopsy.
Aged
;
Biopsy, Large-Core Needle/methods
;
Humans
;
Male
;
Middle Aged
;
Neoplasm Grading
;
Neoplasm Staging
;
Prostatectomy/*methods
;
Prostatic Neoplasms/*pathology/*surgery/ultrasonography
;
Retrospective Studies
;
Ultrasonography, Interventional/methods
10.Molecular Characterization of Norovirus and Rotavirus in Outbreak of Acute Gastroenteritis in Seoul.
Se Ah OH ; Sang Hun PARK ; Hee Jin HAM ; Hyun Jung SEUNG ; Jung Im JANG ; Sang Won SUH ; Suk Ju JO ; Sung Min CHOI ; Hae Sook JEONG
Journal of Bacteriology and Virology 2013;43(4):307-316
Norovirus and rotavirus are important causes of acute nonbacterial gastroenteritis in communities worldwide. Genotypes of norovirus and rotavirus in stool samples, which were collected from patients, was determined by RT-PCR and ELISA. A total 4,484 stool samples (461 outbreak cases) collected during January 2010-April 2013 were analyzed. Four hundred thirty eight of samples were positive for norovirus. Twelve samples were positive for Rotavirus. Norovirus genotypes identified were nine kinds of G I genotype (G I -1, G I -2, G I -3, G I -4, G I -6, G I -7, G I -9, G I -12, G I -13) and nine kinds of G II genotype(G II -2, G II -4, G II -5, G II -6, G II -7, G II -11, G II -12, G II -15, G II -16). Rotavirus genotypes were G2P[4]. The results might be useful information for evaluating the epidemiological status of viral diarrhea in Seoul, and providing a strategy to prevent human norovirus, rotavirus and other threats to public health in Korea.
Diarrhea
;
Enzyme-Linked Immunosorbent Assay
;
Gastroenteritis*
;
Genotype
;
Humans
;
Korea
;
Norovirus*
;
Public Health
;
Rotavirus*
;
Seoul*

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