Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea,2010-2018

BACKGROUND Inflammatory bowel disease(IBD)was previously regarded as a Western disease;however,its incidence is increasing in the East.The epidemiology of IBD in Asia differs significantly from the patterns in the West.AIM To comprehensively investigate the epidemiology of IBD in South Korea,inclu-ding its incidence,prevalence,medication trends,and outcomes.METHODS We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases(RIDs),operated by the National Health Insurance Service of South Korea.Patients with IBD were identified based on the International Classification of Diseases,Tenth Revision,and RID diagnostic codes for Crohn’s disease(CD)and ulcerative colitis(UC)from 2010 to 2018.RESULTS In total,14498 and 31409 patients were newly diagnosed with CD and UC,respectively,between 2010 and 2018.The annual average incidence of CD was 3.11 cases per 105 person-years,and that of UC was 6.74 cases per 10^(5) person-years.Since 2014,the incidence rate of CD has been stable,while that of UC has steadily increased,shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018.The CD and UC prevalence increased consistently over the study period;the use of 5-aminosali-cylates and corticosteroids gradually decreased,while that of immunomodulators and biologics steadily increased in both CD and UC.The clinical outcomes of IBD,such as hospitalization and surgery,decreased during the study period.CONCLUSION The CD incidence has been stable since 2014,but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018.IBD clinical outcomes improved over time,with increased use of immunomodu-lators and biologics.

Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease

AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors(PPAR)-δ agonist treatment in nonalcoholic fatty liver disease(NAFLD) models.METHODS: Male C57BL/6J mice were classified according to control or high fat diet(HFD) with or without PPAR-δ agonist(GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide(LPS), HFD + LPS + GW group]. Hep G2 cells were exposed to palmitic acid(PA) and/or LPS in the absence or presence of GW.RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin(IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In Hep G2 cells, PA and LPS treatment markedly increased m RNA of several nucleotide-binding andoligomerization domain-like receptor family members(NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α.CONCLUSION: PPAR-δ agonist reduces fatty acidinduced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.

Correlations between endoscopic and clinical disease activity indices in intestinal Behcet's disease

AIM:To develop a novel endoscopic severity model of intestinal Behcet's disease(BD) and to evaluate its feasibility by comparing it with the actual disease activity index for intestinal Behcet's disease(DAIBD).METHODS:We reviewed the medical records of 167 intestinal BD patients between March 1986 and April 2011.We also investigated the endoscopic parameters including ulcer locations,distribution,number,depth,shape,size and margin to identify independent factors associated with DAIBD.An endoscopic severity model was developed using significant colonoscopic variables identified by multivariate regression analysis and its correlation with the DAIBD was evaluated.To determine factors related to the discrepancy between endoscopic severity and clinical activity,clinical characteristics and laboratory markers of the patients were analyzed.RESULTS:A multivariate regression analysis revealed that the number of intestinal ulcers(≥ 2,P = 0.031) and volcanoshaped ulcers(P = 0.001) were predictive factors for the DAIBD.An endoscopic severity model(Y) was developed based on selected endoscopic variables as follows:Y = 47.44 + 9.04 × non-Ileocecal area + 11.85 ×≥ 2 of intestinal ulcers + 5.03 × shallow ulcers + 12.76 × deep ulcers + 4.47 × geographicshaped ulcers + 26.93 × volcano-shaped ulcers + 8.65 ×≥ 20 mm of intestinal ulcers.However,endoscopic parameters used in the multivariate analysis explained only 18.9% of the DAIBD variance.Patients with severe DAIBD scores but with moderately predicted disease activity by the endoscopic severity model had more symptoms of irritable bowel syndrome(21.4% vs 4.9%,P = 0.026) and a lower rate of corticosteroid use(50.0% vs 75.6%,P = 0.016) than those with severe DAIBD scores and accurately predicted disease by the model.CONCLUSION:Our study showed that the number of intestinal ulcers and volcano-shaped ulcers were predictive factors for severe DAIBD scores.However,the correlation between endoscopic severity and DAIBD(r = 0.434) was weak.

Periodontitis combined with smoking increases risk of the ulcerative colitis: A national cohort study

BACKGROUND Periodontitis is a chronic inflammation of periodontal tissues.The effect of periodontitis on the development of inflammatory bowel disease(IBD)remains unclear.AIM To assessed the risk of IBD among patients with periodontitis,and the risk factors for IBD related to periodontitis.METHODS A nationwide population-based cohort study was performed using claims data from the Korean National Healthcare Insurance Service.In total,9950548 individuals aged≥20 years who underwent national health screening in 2009 were included.Newly diagnosed IBD[Crohn’s disease(CD),ulcerative colitis(UC)]using the International Classification of Disease 10th revision and rare intractable disease codes,was compared between the periodontitis and nonperiodontitis groups until 2017.RESULTS A total of 1092825 individuals(11.0%)had periodontitis.Periodontitis was significantly associated with older age,male gender,higher body mass index,quitting smoking,not drinking alcohol,and regular exercise.The mean age was 51.4±12.9 years in the periodontitis group and 46.6±14.2 years in the nonperiodontitis group(P<0.01),respectively.The mean body mass index was 23.9±3.1 and 23.7±3.2 in the periodontitis and non-periodontitis groups,respectively(P<0.01).Men were 604307(55.3%)and 4844383(54.7%)in the periodontitis and non-periodontitis groups,respectively.The mean follow-up duration was 7.26 years.Individuals with periodontitis had a significantly higher risk of UC than those without periodontitis[adjusted hazard ratio:1.091;95%confidence interval(CI):1.008-1.182],but not CD(adjusted hazard ratio:0.879;95%confidence interval:0.731-1.057).The risks for UC were significant in the subgroups of age≥65 years,male gender,alcohol drinker,current smoker,and reduced physical activity.Current smokers aged≥65 years with periodontitis were at a 1.9-fold increased risk of UC than non-smokers aged≥65 years without periodontitis.CONCLUSION Periodontitis was significantly associated with the risk of developing UC,but not CD,particularly in current smokers aged≥65 years.

Trends and risk factors of elderly-onset Crohn’s disease: A nationwide cohort study

BACKGROUND The incidence of inflammatory bowel disease(IBD)is increasing in Asia.Numerous risk factors associated with IBD development have been investigated.AIM To investigate trends and environmental risk factors of Crohn’s disease(CD)diagnosed in persons aged≥40 years in South Korea.METHODS Using the National Health Insurance Service database,a total of 14060821 persons aged>40 years who underwent national health screening in 2009 were followed up until December 2017.Patients with newly diagnosed CD were enrolled and compared with non-CD cohort.CD was identified according to the International Classification of Diseases 10th revision and the rare/intractable disease registration program codes from the National Health Insurance Service database.The mean follow-up periods was 7.39 years.Age,sex,diabetes,hypertension,smoking,alcohol consumption,regular exercise,body mass index,anemia,chronic kidney disease(CKD)and dyslipidemia were adjusted for in the multivariate analysis model.RESULTS During the follow-up,1337(1.33/100000)patients developed CD.Men in the middle-aged group(40-64 years)had a higher risk than women[adjusted hazard ratio(aHR)1.46,95%confidence interval(CI):1.29-1.66];however,this difference tended to disappear as the age of onset increases.In the middle-aged group,patients with a history of smoking[(aHR 1.46,95%CI:1.19-1.79)and anemia(aHR 1.85,95%CI:1.55-2.20)]had a significantly higher CD risk.In the elderly group(age,≥65 years),ex-smoking and anemia also increased the CD risk(aHR 1.68,95%CI:1.22-2.30)and 1.84(95%CI:1.47-2.30,respectively).Especially in the middle-aged group,those with CKD had a statistically elevated CD risk(aHR 1.37,95%CI:1.05-1.79).Alcohol consumption and higher body mass index showed negative association trend with CD incidence in both of the age groups.[Middle-aged:aHR 0.77(95%CI:0.66-0.89)and aHR 0.73(95% CI:0.63-0.84),respectively][Elderly-group:aHR 0.57(95% CI:0.42-0.78)and aHR 0.84(95%CI 0.67-1.04),respectively].For regular physical activity and dyslipidemia,negative correlation between CD incidences was proved only in the middle-aged group[aHR 0.88(95%CI:0.77-0.89)and aHR 0.81(95%CI:0.68-0.96),respectively].CONCLUSION History of cigarette smoking,anemia,underweight and CKD are possible risk factors for CD in Asians aged>40 years.

Cardiac mucosa at the gastroesophageal junction:An Eastern perspective

AIM:To investigate the nature and origin of cardiac mucosa(CM).METHODS:Biopsy samples from sixty-one individuals were included in this study. The specimens were taken "at","just below",or "just above" the gastroesophageal junction,including the histologic squamocolumnar junction. Clinical data were obtained by reviewing electronic medical records for each patient. Patients with a history of stomach adenoma or carcinoma and esophageal carcinoma were excluded,and cases that were endoscopically suspicious of Barrett's esophagus or a polyp were also ruled out. Histologic and endoscopic reviews were performed blinded to the patient's clinical data. Histologic evaluation wasconducted by two pathologists,and endoscopic review was performed by a endoscopist with wide experience in the field. Histologically,the columnar epithelium of squamocolumnar junction,presence and severity of acute and chronic inflammation,atrophy,intestinal metaplasia,and presence of carditis were evaluated. Endoscopically,reflux esophagitis was evaluated by Los Angeles(LA) classification,hiatal hernias were classified by Hill grade,and gastroesophageal flap valves were assessed. RESULTS:Fifty-nine of the 61(96.7%) patients were Korean; 65.6%(40/61) of the patients underwent endoscopy according to the schedule of the National Health Insurance Program as a screening inspection. Of these,only 20.0%(8/40) of cases had reflux s y m p t o m s. C M w a s p r e s e n t i n 4 1 / 6 1( 6 7. 2 %) individuals,and its presence was associated with older age compared to oxyntocardiac mucosa/oxyntic mucosa(60.59 ± 2.02 years vs 51.55 ± 3.35 years; P = 0.018). The presence of CM was associated with endoscopic diagnosis of esophagitis according to the LA classification(P = 0.022). CM was associated with mononuclear cell infiltration and neutrophilic infiltration,which were statistically significant(P = 0.001,and P = 0.004,respectively). The inflammation of CM,"carditis",showed a statistically significant association with endoscopic diagnosis of reflux esophagitis according to the LA classification(P = 0.008). CONCLUSION:CM at the gastroesophageal junction is a common histologic finding in biopsy specimens,though not always present,and associated with gastroesophageal reflux disease and carditis severity.

Tonsil-derived stem cells as a new source of adult stem cells

Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, TSCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.

Clinical outcomes and predictive factors in oral corticosteroid-refractory active ulcerative colitis

AIM:To evaluate the clinical outcomes and prognostic factors after intravenous corticosteroids following oral corticosteroid failure in active ulcerative colitis patients.METHODS:Consecutive patients with moderate to severe ulcerative colitis who had been treated with a course of intravenous corticosteroids after oral corticosteroid therapy failure between January 1996 and July 2010 were recruited at Severance Hospital,Seoul,South Korea.The disease activity was measured by the Mayo score,which consists of stool frequency,rectal bleeding,mucosal appearance at flexible sigmoidoscopy,and Physician Global Assessment.We retrospectively evaluated clinical outcomes at two weeks,one month,three months,and one year after the initiation of intravenous corticosteroid therapy.Two weeks outcomes were classified as responders or non-responders.One month,three month and one year outcomes were classified into prolonged response,steroid dependency,and refractoriness.RESULTS:Our study included a total of 67 eligible patients.At two weeks,56(83.6%) patients responded to intravenous corticosteroids.At one month,complete remission was documented in 18(32.1%) patients and partial remission in 26(46.4%).Eleven patients(19.7%) were refractory to the treatment.At three months and one year,we found 37(67.3%) and 25(46.3%) patients in prolonged response,ten(18.2%) and 23(42.6%) patients in corticosteroid dependency,8(14.5%) and 6(11.1%) patients with no response,respectively.Total 9 patients were underwent elective proctocolectomy within 1 year.The duration of oral corticosteroid therapy(> 14 d vs ≤ 14 d,P = 0.049) and lower hemoglobin level(≤ 11.0 mg/dL vs >11.0 mg/dL,P = 0.02) were found to be poor prognostic factors for response at two weeks.For one year outcome,univariate analysis revealed that only a partial Mayo score(≥ 6 vs <6,P = 0.057) was found to be associated with a poor response.CONCLUSION:The duration of oral corticosteroid therapy and lower hemoglobin level were strongly associated with poor outcome.

Effect of Dioscorea batatas on longitudinal bone growth rate in adolescent female rats

OBJECTIVE The root of Dioscorea batatas,rich in steroidal saponins,alkaloids,tannins,phytosterols,and starch,is an herbal medicine of tonifying qi and nourishing stomach after invigorating spleen with a long history of safe use for treatment of chronic dysentery and weakness of the spleen and stomach in Korea.This study was aimed to investigate the effect of D.batatas on longitudinal bone growth rate in adolescent female rats.METHODS D.batatas was extracted with 30% EtOH for 3h at 90℃in a reflux apparatus.In two groups,we administered a twice daily dosage of D.batatas extract(at 30 and 300mg·kg-1,respectively)per os for 4d,and in a control group,we administered vehicle only under the same conditions.Recombinant human growth hormone(rhGH)was subcutaneously injected once daily.All rats were born at same day(33d-old).On day 3,tetracycline was injected intraperitoneally to form a fluorescent band on the growth plates.RESULTS The bone growth rate in groups administered D.batatas 300mg·kg-1 and rhGH was significantly increased to 343.8±20.7,and 359.6±30.2μm·d-1 respectively from control group,320.7±23.2μm·d-1.No difference was observed in the amount of food intake or mean body weight among all groups during the acclimation or administration period.CONCLUSION These results suggest that D.batatas extracts have the potential to induce height increase;however,further research,including clinical trials,is necessary.

Effects of Angelica sinensis on longitudinal bone growth rate in adolescent female rats

OBJECTIVE To investigate the effect of A.sinensis on longitudinal bone growth rate in adolescent female rats.METHODS A.sinensis was extracted with 30% EtOH for 3h at 90℃in a reflux apparatus.Female Sprague-Dawley rats(33d-old)were randomly divided into three groups:control(vehicle),recombinant human growth hormone(rhGH;20μg·kg-1·d-1),and A.sinensis(300mg·kg-1·d-1).A.sinensis extracts or vehicle was administered orally twice daily for 4d.Longitudinal bone growth rate in newly synthesized bone was observed using tetracycline labeling(20mg·kg-1,intraperitoneally).RESULTS A.sinensis significantly increased longitudinal bone growth rate in adolescent female rats at 300mg·kg-1(6.1%,357.34±32.67μm·d-1)compared to control group(336.80±14.47μm·d-1).CONCLUSION A.sinensis extract significantly increased longitudinal bone growth rate and growth plate height in adolescent female rats.These results suggest that A.sinensis could be helpful for increasing bone growth rate in children who have growth retardation.

Applications of scaffolds:Tools for enhancing the immunomodulation of mesenchymal stromal cells

Exogenously delivered mesenchymal stromal cells(MSCs)are therapeutically beneficial owing to their paracrine effect;they secrete various cytokines,nucleic acids,and proteins.Multiple bioengineering techniques can help MSC cultures to release secretomes by providing stem cell niche-like conditions(both structurally and functionally).Various scaffolds mimic the natural extracellular matrix(ECM)using both natural and synthetic polymers,providing favorable environments for MSC proliferation and differentiation.Depending on material properties,either topographically or elastically structured scaffolds can be fabricated.Three-dimensional scaffolds have tunable substrate rigidities and structures,aiding MSC cultivation.Decellularized ECM-derived hydrogels are similar to the natural ECM,thus improving the paracrine effects of MSCs.Here,we discuss recent research on the application of scaffolds to maximize the immunomodulatory function of MSCs.

Intravenous Anesthesia for the aneurysm coiling

Objective All aneurysm coiling procedures were performed with Intravenous(IV) anesthesia in our department. We have reviewed our clinical experiences. Material and Methods Since June 1996 aneurysm coiling was attempted with IV anesthesia in 542 procedures. From June 1996 to Feb 2002 only propofol administrated for anesthesia (362 case) after Feb 2002 to June 2004 alfentanil combinded (180 case). Target-controlled infusion (TCI) of alfentanil concentration 0.2 μg/kg/min and propofol at rates were varied up and down depending on systolic blood pressure (Bolus dosage: 6 μg/kg/min Loading dosage: 40-100 μg/kg/min). Systolic and diastolic blood pressure, heart rate, respiratory depression (SpO2<95%), involuntary movement were checked during the operation. Mean infusion rates of alfentanil were 0.1-0.2 μg/kg/min and propofol were 30-70 μg/kg/min. Mean anesthesia time takes 2hours. Conclusions Aneurysm coiling performed using IV anesthesia is a feasible and effective method.