Abstract Background Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal condition characterized by immune dysregulation driven by microbiome dysbiosis, with a reduction of beneficial bacteria such as Faecalibacterium, a dominant commensal bacterium comprising 5-10% of the human gut microbiome. Its depletion is a hallmark of Crohn's disease and other autoimmune-related conditions, making it an emerging candidate as a next-generation probiotic. Methods CJRB-201 was selected using our BI platform (Ez-Mx), based on more than 500 metagenomic datasets from IBD patients and healthy controls. The immune regulatory efficacy of CJRB-201 was evaluated through in vitro and ex vivo assays, focusing on key cytokine ratios (IL-10/IL-1β, IL-10/TNF, IL-10/IFN-γ) in macrophages and T cells. The induction of T regulatory (T reg) cell populations was evaluated ex vivo and in germ-free (GF) mice. Three pathogenetically different IBD animal models (DSS-induced, IL-10 KO GF, T cell transfer) were examined to assess its efficacy. Lastly, the SHIME system (Simulator of the Human Intestinal Microbial Ecosystem) was applied to test various fibers that promote the growth of CJRB-201. Results Among 34 tested anti-inflammatory strains, including those from CJ Bioscience, 4D Pharma, and our Ez-Mx platform, CJRB-201 emerged as one of the most effective. Notably, CJRB-201 and its conforming species showed the highest induction of T reg populations ex vivo among the sixty Faecalibacterium strains, primarily driven by its cell pellet form rather than the supernatant. Administration of CJRB-201 resulted in successful colonization in the colon of GF mice, leading to an enhanced T reg cell population. In the three IBD models with both preventative and therapeutic approaches, CJRB-201 demonstrated significant improvements across five key disease features (body weight, disease activity index, colon length, histopathology, and inflammatory markers such as cytokines and fecal lipocalin-2). Interestingly, CJRB-201 outperformed other potential single and consortia strains and demonstrated efficacy comparable to the α-IL-12p40 antibody, particularly in the T cell transfer model (Figure 1). Lastly, we identified the fiber that stabilizes the engraftment of CJRB-201 in the SHIME system. Conclusion CJRB-201 exhibits superior anti-inflammatory efficacy in multiple immune assays and IBD animal models, significantly improving preclinical and inflammatory markers. Given its ability to enhance T reg populations and the promising potential of the identified fiber in supporting its colonization, CJRB-201 holds strong promise as a microbiome-based therapeutic for IBD patients. References 1.Current Biology 30, 4932–4943, 2020 2.J Antimicrob Chemother 65, 2556-2565, 2010 3.Nat Rev Immunol 14, 329–342, 2014 4.Cell Mol Gastroenterol Hepatol 1, 154-170, 2005
Background Hyperuricemia is particularly common in patients with chronic kidney disease (CKD). Its role, however, as a risk factor for renal outcomes of CKD is debated and those data in gout patients with CKD are rare. Objectives This aim of study was to evaluate long-term effect of serum uric acid (SUA) level on progression of CKD in gout patients with uric acid lowering treatment. Methods All patients who had a first visit for gout with CKD at Samsung Medical Center between 1995 and 2003, and follow-up until December 2012 or expired during follow-up period were included and retrospective analyzed. CKD was defined as an estimated glomerular filtration rate GFR) of <60 mL/min/1.73m2 via the Modification of Diet in Renal Disease Study equation more than 3 months according to the Kidney Disease Outcome Quality Initiative CKD classification. All serum creatinine and matched SUA taken during follow-up period were analyzed by using mixed effect model to determine the effect of SUA level on renal outcome. Results One-hundred eleven gout patients with CKD were observed. The mean age of the patients at diagnosis of gout was 51.3 and mean follow-up duration was 13 years. Baseline estimated GFR and serum creatinine were 47.7 mL/min/1.73m2 and 1.62 mg/dL, respectively. Eight (7.2%) patients revealed CKD stage 4 and the rest of patients (92.8%) were CKD stage 3. Maintaining the SUA below 6 mg/dL showed protective effect on serum creatinine and estimated GFR compared with maintaining SUA more than 6 mg/dL (p <0.0001 and p =0.02, respectively). The elevation of SUA as a continuous variable was also related to poor renal outcome in gout patients with CKD (p <0.0001). This effect of SUA on progression of CKD was not changed after adjusting for duration of gout and age at baseline, time-dependent hypertension, diabetes mellitus, hyperlipidemia, obesity, intrinsic renal diseases, and obstructive renal diseases. In particular, for every 1 mg/dL increase of the SUA, serum creatinine revealed to be increased by 0.019 mg/dL in group with SUA more than 6 mg/dL. Hypertension, diabetes mellitus and intrinsic renal disease were independent risk factors for progression of CKD in gout patients (p <0.0001, p <0.0001 and p =0.014, respectively). Conclusions Our long term follow-up data demonstrated the SUA level was independent risk factor for progression of CKD in gout patients with uric acid lowering treatment. Maintaining of SUA level below 6 mg/dL would be essential to protect renal function in gout patients with CKD. Disclosure of Interest None declared
Background Peroxisome proliferator-activated receptor gamma (PPARγ) agonist has anti-inflammatory properties, which has known to reduce inflammatory cytokine production in RA. Cysteine-rich angiogenic inducer 61 (Cyr61) is associated with diseases related to chronic inflammation. Cyr61, pro-inflammatory factor, has been shown to be increased in the synovial tissues of patients with RA. However the action mechanisms between Cyr61 and PPARγ are unknown. Objectives The aim of this study was to investigate mechanism of PPARγ and its relation to Cyr61 in pathogenesis of RA. Methods All synovial tissue were obtained from RA patients undergoing total joint replacement. RA-FLS were cultured with TNFα, and Cyr61 in the presence or absence of PPARγ agonist. Expression of the Cyr61 was estimated by RT-PCR and western blotting. The Cell migration and invasion was assessed by wound repair assays and transwell system. Results Cyr61 protein was expressed on RA-FLS, and its expression was increased by TNFα. Moreover, Cyr61 directly promotes RA-FLS migration (p<0.01) and invasion (p<0.01) compared to the untreated RA-FLS. RSG significantly decreased TNFα-induced Cyr61 protein expression. Furthermore, not only did RSG inhibit TNFα induced RA-FLS migration distance (p<0.01) and invasion (p=0.018), but also decreased Cyr61 treated RA-FLS invasion (p<0.01). However, RSG did not affect Cyr61 gene expression in RA-FLS. Conclusions Our result show that PPARγ agonist may have beneficial effects on migration and invasion of RA-FLS via down-regulation of Cyr61. Therefore, PPARγ agonist could be a potential treatment of RA. References Jie LG, Huang RY, Sun WF, Wei S, Chu YL, Huang QC, et al. Role of cysteinerich angiogenic inducer 61 in fibroblastlike synovial cell proliferation and invasion in rheumatoid arthritis. Mol Med Rep 2015 Feb;11(2):917-923. Pang X, Wei Y, Zhang Y, Zhang M, Lu Y, Shen P. Peroxisome proliferator-activated receptor-gamma activation inhibits hepatocellular carcinoma cell invasion by upregulating plasminogen activator inhibitor-1 Cancer Sci 2013 Jun;104(6):672-680. Disclosure of Interest None declared
It is known that triplet pregnancies (TP) have adverse obstetric and perinatal outcomes. The purpose of this study was to evaluate recent perinatal outcomes in TP according to chorionicity. This retrospective study included 164 women with TP who delivered in Seoul National University Hospital between Nov. 1997 and Mar. 2014. Among the 164 cases, pregnancies associated with lethal congenital malformations, fetal reduction, spontaneous abortion or at least 1 fetal death before 20 weeks' gestation were excluded (n = 12). One hundred and fifty-two TP were used for analysis: monochorionic triamniotic (MCTA), 7 cases (4.6%); dichorionic triamniotic (DCTA), 35 cases (23%); trichorionic triamniotic (TCTA), 110 cases (72.4%). Chorionicity was confirmed by ultrasonographic finding at early gestational age. Composite morbidity was defined as one of following complications; bronchopulmonary dysplasia, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, neonatal seizure, germinal matrix hemorrhage. Fisher's exact, Kruskal-Wallis and Mann-Whitney test were used for statistical analysis. There were no significant differences in clinical characteristics among the 3 groups. The occurrence of pre-eclampsia was significantly different among the 3 groups (p < 0.032). Also, MCTA resulted in a higher rate of postpartum transfusion than TCTA (p <0.038). MCTA had a higher rate of composite neonatal morbidity than DCTA and TCTA (table 1). OP11.07: Table 1. MCTA triplets had worse perinatal outcomes than DCTA and TCTA triplets. Although DCTA TP had a monochorionic pair, DCTA and TCTA can be expected to have comparable outcomes.
The purpose of this study was to evaluate the inter-observer and intra-observer reliability of the two grading systems for fetal hydronephrosis which were suggested by Society for Fetal Urology (SFU) and Onen, respectively. This is a retrospective study of the perinatal outcomes of the patients who were diagnosed prenatally with fetal hydronephrosis between 2005 and 2013. The beginner and expert were asked to evaluate the prenatal sonography of fetal hydronephrosis by the two grading systems to compare whether an intra-observer or an inter-observer reliability exists. Cohen's kappa statistics was used to estimate both the intra-observer and inter-observer reliability with SFU and Onen. A total of 104 pregnancies with fetal hydronephrosis were recruited. Inter-observer reliability of SFU grading system (right K 0.486, 95%CI 0.542–0.430, Left K 0.477, 95%CI 0.533–0.420) was better than that of Onen grading system (right K 0.375, 95%CI 0.431–0.312, Left K 0.477, 95%CI 0.537–0.417). Intra-observer reliability for SFU grading system (right K 0.962, 95%CI 0.983–0.941, Left K 0.899, 95%CI 0.931–0.866) and Onen grading system (right K 0.925, 95%CI 0.953–0.897, Left K 0.921, 95%CI 0.950–0.891) showed no significant difference from the analysis by the beginner and the expert. The kappa values of both SFU and Onen substantially indicate almost perfect agreement with the intra-observer reliability test. Inter-observer reliability correlates better with SFU than with Onen. This study suggests that the beginners need substantial time to learn the grading system for fetal hydronephrosis the need for learning curve of Onen grading.
To evaluate the impact of two grading systems for hydronephrosis what were suggested by the Society for Fetal Urology (SFU) and Onen. This is a retrospective study of perinatal outcomes among patients that were diagnosed fetal hydronephrosis by sonography form 2005–2013. We defined a primary outcome as perinatal mobidity consisting hospital care for urinary tract infection, outpatient care for urinary tract infection, whether an operation is conducted or not(Op.), and creatine level of after birth. Logistic regression was used to calculate the odd ratio (OR) and corresponding 95% confidence intervals (CIs) for perinatal outcomes. The predictive ability of SFU and Onen were compared using receiver-operating characteristics (ROC) curves. A total of 104 pregnancies with fetal hydronephrosis were recruited. A significant linear association was shown between the two grading systems and the two perinatal outcomes which are the outpatient care for urinary tract infection(OR 1.381, 95%CI 1.079-1.768 (SFU) vs. OR 1.549, 95%CI 1.156-2.066 (Onen)) and Op.(OR 0.768, 95%CI 0.603-0.979 (SFU) vs. OR 0.727, 95%CI 0.548-0.962 (Onen)). There was no significant linear association between the hospital care for urinary tract infection(OR 1.229, 95%CI 0.875-1.723 (SFU) vs. OR 1.349, 95%CI 0.927-1.958 (Onen)) and the creatinine level of post-partum(OR 1.160, 95%CI 0.881-1.527 (SFU) vs. OR 1.127, 95%CI 0.822-1.545 (Onen)). Onen grading system was more predictive than SFU grading system on two perinatal outcomes, which are the outpatient care for urinary tract infection (AUC 0.650 (SFU) vs 0.660 (Onen)) and the fact that whether an operation is conducted or not (AUC 0.376 (SFU) vs 0.379 (Onen)) by ROC curve area analysis. Onen grading system is more predictable for outpatient care for urinary tract infection than SFU grading system. However, for the prediction of other prenatal outcomes, we will need further studies to reveal other factors in addition to SFU and Onen grading system.
The influence of chorionicity on pregnancy complications in triplet pregnancies has been studied, whereas the influence of zygosity has not. The purpose of this study was to find out difference of zygosity and the pregnancy complications according to the mode of conception in triplet pregnancies. One hundred and thirty-four triplets were delivered at Seoul National University Hospital from 1997 to 2013. Among them, zygosity was confirmed in 110 cases by DNA analysis of umbilical cord blood using 16 STR marker (PowerPlex 16, ABI, USA). We reviewed medical records to confirm mode of conception and pregnancy complications. Eighteen cases (16.4%) were conceived by natural pregnancy (NP), 9 cases (8.2%) by ovulation induction (OI), 14 cases (12.7%) by controlled ovarian hyperstimulation (COH), and 69 cases (62.7%) by in vitro fertilization and embryo transfer (IVF-ET). There was statistical difference of zygosity distribution according to mode of conception (p<0.001). However, there were no significant differences in prevalence of pregnancy complications including preterm premature rupture of membranes (PPROM), preterm labour (PTL), gestational diabetes mellitus (GDM), and pre-eclampsia (PE) among 4 groups. P18.05: Table 1. Zygosity and pregnancy complications according to mode of conception in triplet pregnancy Zygosity distribution was different according to mode of conception in triplet pregnancy. Although the rate of monozygotic triplets (MZT) was remarkably higher in NP group than other groups, there were no differences in pregnancy complications in all 4 groups.
The purpose of this study is to evaluate the feasibility of Volume NTTM, a new technique that automatically archives mid-sagittal plane views and measures the maximum NT (Nuchal Translucency) distance, by comparing Herman score of NT measurements with the conventional two- (2D) and three-dimensional (3D) techniques. The study population consisted of 100 consecutive singletons undergoing NT screening at 11-13 + 6 weeks gestation. Fetuses with enlarged NT and multiple anomalies were excluded. Volume NTTM, 2D, and 3D techniques were performed with Accuvix V20 Prestige (Samsung Medison Co). Four experienced operators participated in this study. Each operator manually measured the NT according to Herman score, FMF (Fetal Medicine Foundation) and with in to in assessment. Then through an approximated mid-sagittal section determined by conventional B-mode ultrasound, the operator obtained an NT automatically using Volume NT™ software. One less experienced operator blinded to 2D and 3D measurements of experts examined archive images of patients and obtained automatic measurement of the NT with Volume NT™ from in to in of the two echogenic lines delineating the NT. Among the 100 cases initially included in this study, 24 cases were excluded from analysis because of exclusion criteria (NT increased and multiple abnormalities n = 6) or missing data (n = 18). Median measure of 2D NT (1.3 mm (0.7 to 3.4)) was higher than in 3D (1.2 mm (0.6 to 3)) without significant difference, probably due to “In to In” assessement. 25 cases of 2D NT measurements were associated with a low Herman score (<6). 23 of these 25 cases were associated with better Herman score (≥6) using Volume NT and even those measured by the least experienced operator (p = 0.035). Volume NTTM helps to improve Herman score, whenever 2D NT assessment is difficult to get, by obtaining a better sagittal plane, even in the hands of a less experienced operator.
In neonates with single ventricle congenital heart disease, several clinical findings of neonates such as systemic outflow obstruction and ventricular systolic dysfunction are known risk factors for adverse outcomes. The objective of this study was to determine if the antenatal ultrasound findings and cord blood biomarkers for heart failure can predict neonatal mortality in single ventricle congenital heart disease. A total of 44 cases of single ventricle congenital heart disease were enrolled. The presence of antenatal ultrasound findings suggesting systemic outflow obstruction (ascending aorta < 2.5 percentile) or ventricular dysfunction (the presence of cardiomegaly or hydrops) were evaluated, and the total number of abnormal findings was converted to a numeric score, which was named as “cardiac profile score”. In addition, N-terminal pro-B-type natriuretic peptide (NT pro-BNP) and cardiac troponin T (cTnT) was measured in cord blood which was taken at the time of delivery. The rate of neonatal mortality (within 28 days after birth) was 27% (12/44). The antenatal ultrasound findings of systemic outflow obstruction or ventricular dysfunction were detected more frequently and the cord blood concentrations of NT pro-BNP and cTnT were elevated in cases who are destined to neonatal death. The presence of either abnormal ultrasound findings (cardiac profile score ≥ 2) or elevated concentrations of NT pro-BNP or cTnT was associated with the risk of neonatal death (neonatal death risk: 6% in cases without these finding vs. 41% in cases with at least one of these findings, p < 0.05). The antenatal ultrasound findings and cord blood biomarkers for heart failure can predict neonatal death in single ventricle congenital heart disease. OC02.05: Table 1.
The aim of this study was to correlate prenatal renal parenchymal thickness with postnatal outcome of severe fetal hydronephrosis in order to establish the predictability of prenatal renal parenchymal thickness for surgical treatment and to apply this parameter to reach a better follow-up outcome of prenatal hydronephrosis. From January 2008 to August 2012, we retrospectively reviewed 108 cases of fetal hydronephrosis in which pelvic anteroposterior diameter (PAPD) of greater than 15mm occured. Renal parenchymal thickness (RPT), PAPD and renal anteroposterior diameter (RAPD) were measured on midtransverse plane at prenatal ultrasound. The ability of these parameters to predict who would require surgical treatment was examined. The difference of these parameters was compared using the Two-sample t test, Chi-square test (or Fisher's exact test), ROC analysis. 66.7% of fetuses with a renal parenchymal thickness lesser than 8mm and 71.4% of fetuses with a renal parenchymal thickness smaller than 6mm required surgical treatment. 33.3% of fetuses with an PAPD greater than 12mm and 45% of fetuses with an PAPD greater than 15mm required surgical treatment. 60% of fetuses with a ratio of PAPD/RAPD greater than 0.4 and 70% of fetuses with an ratio of PAPD/RAPD greater than 0.5 required surgical treatment. This study shows that RPT could be used as a useful parameter in the prediction of requirement of postnatal surgical treatment of fetal hydronephrosis, in addition to the size of PAPD and the ratio of PAPD/RAPD which have been assumed to be one of the most important parameters. Future prospective studies with a large cohort of patients will be needed in order to determine the most appropriate parameters and management of infants with prenatal hydronephrosis.