Incidence and risk factors for venous thrombosis among patients with inflammatory bowel disease in China: a multicenter retrospective study

Background/Aims@#Risk of venous thrombosis is increased in patients with inflammatory bowel disease (IBD); data on Asian IBD patients is limited and status quo of thrombosis screening and prophylaxis are unknown. Therefore, we aimed to investigate the incidence, screening, prophylaxis, and risk factors for venous thrombosis among Asian IBD patients. @*Methods@#Medical files of patients with Crohn’s disease (CD) and ulcerative colitis (UC) from 17 hospitals across China between 2011 and 2016 were reviewed for venous thrombosis, use of screening and prophylaxis. A case-control study was performed among hospitalized patients with venous thrombosis and their age-, sex-matched IBD controls hospitalized around the same period; disease characteristics and known provoking factors of venous thrombosis were recorded. Risk factors were analyzed in both univariate and logistic regression analyses. @*Results@#A total of 8,459 IBD patients were followed for 12,373 person-year. Forty-six patients (0.54%) had venous thrombosis, yielding an incidence of 37.18 per 10,000 person-year. Incidence increased with age, especially among CD. Less than 20% of patients received screening tests and 35 patients (0.41%) received prophylaxis. Severe disease flare was an independent risk factor for venous thrombosis (odds ratio [95% confidence interval]: CD, 9.342 [1.813– 48.137]; UC, 5.198 [1.268–21.305]); past use of steroids and extensive involvement were 2 additional risk factors in CD and UC, respectively. @*Conclusions@#Incidence of venous thrombosis in China was 37.18 per 10,000 person-year (0.54%). Use of screening and prophylaxis were rare. Severe disease flare was an independent risk factor for thrombosis among hospitalized patients.

Incidence and risk factors for venous thrombosis among patients with inflammatory bowel disease in China: a multicenter retrospective study

Background/Aims@#Risk of venous thrombosis is increased in patients with inflammatory bowel disease (IBD); data on Asian IBD patients is limited and status quo of thrombosis screening and prophylaxis are unknown. Therefore, we aimed to investigate the incidence, screening, prophylaxis, and risk factors for venous thrombosis among Asian IBD patients. @*Methods@#Medical files of patients with Crohn’s disease (CD) and ulcerative colitis (UC) from 17 hospitals across China between 2011 and 2016 were reviewed for venous thrombosis, use of screening and prophylaxis. A case-control study was performed among hospitalized patients with venous thrombosis and their age-, sex-matched IBD controls hospitalized around the same period; disease characteristics and known provoking factors of venous thrombosis were recorded. Risk factors were analyzed in both univariate and logistic regression analyses. @*Results@#A total of 8,459 IBD patients were followed for 12,373 person-year. Forty-six patients (0.54%) had venous thrombosis, yielding an incidence of 37.18 per 10,000 person-year. Incidence increased with age, especially among CD. Less than 20% of patients received screening tests and 35 patients (0.41%) received prophylaxis. Severe disease flare was an independent risk factor for venous thrombosis (odds ratio [95% confidence interval]: CD, 9.342 [1.813– 48.137]; UC, 5.198 [1.268–21.305]); past use of steroids and extensive involvement were 2 additional risk factors in CD and UC, respectively. @*Conclusions@#Incidence of venous thrombosis in China was 37.18 per 10,000 person-year (0.54%). Use of screening and prophylaxis were rare. Severe disease flare was an independent risk factor for thrombosis among hospitalized patients.

Clinical analysis of 18 primary intestinal T cell lymphoma misdiagnosed as Crohn′s disease / 中华消化杂志

Objective To analyze clinical features and prognosis of primary intestinal T cell lymphoma (ITCL)which was misdiagnosed as Crohn′s disease (CD),and summarized the key points of differentiation between ITCL and CD.Methods From January 2003 to January 2014,clinical data of patients with ITCL once misdiagnosed as CD were retrospectively analyzed,which included demographic,clinical,pathological and prognostic data.The data of 177 patients diagnosed as CD from January 2012 to January 2014 were collected. The demographic,clinical,pathological and prognostic data of these two groups were analyzed and compared. The continuous variables were compared with t test or Mann-WhitneyU test,and the differences of classification variables between two groups were analyzed by Chi-square test or Fisher exact probability method.Results A total of 18 patients (17 males and one female)with ITCL misdiagnosed as CD were enrolled in the study,and the median age at diagnosis was 38.5 (28.8 to 42.5)years and the median duration of diagnosis was 6.00 (3.75 to 13.25)months.The common primary symptoms were abdominal pain (12/18),diarrhea (13/18)and anemia (13/18).Intestinal perforation was primary symptom in two cases (2/18).However,B symptoms of lymphoma was observed in 16 patients,which included fever in 13 patients,weight loss in 16 patients and night sweat in one patient.One or more serious complications appeared in 12 patients,which included intestinal perforation in nine patients,severe gastrointestinal bleeding in seven patients and intestinal obstruction in two patients.In 177 patients with CD,104 patients were male (58.8%),and the median age at diagnosis was 22.0 (18.0 to 29.0) years.The primary symptoms were abdominal pain (88.7%,157/177),diarrhea (55.9%,99/177),anemia (63.8%,113/177),fever (33.3%,59/177)and weight loss (59.9%,106/177).During the disease course,30 patients (16.9%)had intestinal perforation (mainly chronic),12 patients (6.8%)had intestinal obstruction and seven patients (4.0%)had severe gastrointestinal bleeding.Compared to CD patients,male patients were more common in ITCL (χ2 =8.837,P <0.01),age at diagnosis was older (χ2 =314.5,P <0.01),the disease course was shorter (U=385.0,P <0.01),weight loss (χ2 =5.867,P <0.05)and fever (χ2 =10.609,P <0.01)were more common in clinical symptoms and intestinal perforation and severe gastrointestinal bleeding were more common in complications (χ2 =9.185,24.908,both P <0.01).The lesions of ITCL were multiple lesions, small bowel involved in eight cases,colon involved in 14 cases and one case with esophagus involved.Under endoscopy examination,most lesions appeared as ulcerations and were segmentally distributed.Compared to CD, lymphocyte proliferation was more common in the intestinal histopathological findings of ITCL (17/18 vs 19.7%(35/177);χ2 =42.844,P <0.01)and granuloma was rare (0 vs 42.8%(76/177),χ2 =12.665,P <0.01). Among 18 patients with ITCL,nine received chemotherapy and the median survival time was two months. Conclusions Primary ITCL had non-specific symptoms and was easily misdiagnosed as CD.More attention should be paid to the differential diagnosis of the two disease.

Analysis of body composition in patients with Crohn's disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the differences in body composition between Crohn's disease(CD) patients and healthy subjects as well as the characteristics of human body composition in various types of CD.</p><p><b>METHODS</b>A total of 57 CD patients were prospectively selected from the Sixth Affiliated Hospital of Sun Yat-sen University as the study group, while 51 healthy subjects as the control group. Protein content, mineral content, fat content, lean body mass, waist circumference, and hip circumference in the two groups were measured by body composition analyzer. Characteristics of CD at different location and different disease activity index were investigated as well.</p><p><b>RESULTS</b>Intracellular fluid, extracellular fluid, weight, protein content, fat content, lean body mass, muscle weight, body fat ratio, waist hip ratio, body weight ratio, arm muscle circumference, arm circumference, quality of cells, BMI and basal metabolic rate in CD patients were significantly lower than those in control group(all P<0.05). Proportion of protein-deficiency patients and fat-deficiency patients were 66.7% and 47.4% respectively. Protein content, fat content, and lean body mass in ileocolic CD patients were lower than those with small bowel and colonic CD(all P<0.05). Protein content, fat content, lean body mass in patients with high disease activity index were lower than those in patients with low and medium index, but higher basal metablic rate was found in the former group(all P<0.05).</p><p><b>CONCLUSIONS</b>The human body composition in patients with CD are different from healthy people. Disease location and disease activity index have an impact on protein content, fat content, and lean body mass.</p>

Initial study on the combined therapy of cyclophosphamide and thalidomide in the treatment of fifteen cases of refractory Crohn's disease / 中华消化杂志

Objective To investigate the efficacy and safety of the combined therapy of cyclophosphamide and thalidomide in the treatment of refractory Crohn's disease (CD).Methods This study was a prospective and open study.A total of 15 patients with refractory CD were enrolled.All patients received intravenous cyclophosphamide 200 mg every other day for two weeks,then followed by intravenous 400 mg once a week until the cumulative dose reached 6 to 8 g.when the cyclophosphamide treatment started,at the same time thalidomide was taken 25 to 75 mg every night according to the tolerance of patients.Before the treatment,two weeks' after the treatment and at the time when the cumulative dose of cyclophosphamide reached 6 to 8 g,Crohn's disease activity index (CDAI),hemoglobin (Hb),white blood cell (WBC) count,erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP) were recorded.Endoscopy examination was conducted before the treatment and at the time when the cumulative dose of cyclophosphamide reached 6 to 8 g.The condition of mucosa healing was observed and scored by simple endoscopic score for crohn's disease (SES-CD).Adverse effects of all patients were monitored.Paired t test was performed for statistical analysis.Results Before the treatment,the CDAI of 15 patients with refractory CD was 235.87±59.87,two weeks after the treatment the CDAI declined to 135.33 ± 29.23,and the difference was statistically significant (t=7.50,P＜0.01).Before the treatment,ESR and hs-CRP was (42.13±22.80) mm/1 h and (13.73± 2.18) mg/L.Two weeks after treatment they declined to (23.80±16.63) mm/1 h and (5.77±4.77) mg/L,and the differences were statistically significant (t=2.43 and 6.17,both P＜0.05).After two-week treatment,10 patients achieved clinical remission.After the cumulative dose of cyclophosphamide reached 6 to 8 g combined therapy,CDAI of patients was 108.14 ± 47.10,which decreased significantly compared with that before treatment (t=6.30,P＜0.01).ESR,hs-CRP and WBC count was (19.35± 19.18) mm/1 h,(6.16± 5.02) mg/L and (6.28 ± 3.42) × 109/L,respectively,which decreased compared with those before treatment,and the differences were statistically significant (t=5.90,5.40 and 3.71,all P＜0.01).Twelve patients achieved clinical remission.And the lesions of 12 patients improved under endoscope,furthermore,the mucosa of four patients healed.Before the treatment,SES-CD was 9.14 ± 5.39,which declined to 5.07 ± 4.58 after the treatment,and the difference was statistically significant (t =3.14,P ＜ 0.01).During the treatment,five patients had adverse effects.Alanine aminotransferases (ALT) increased in three patients,WBC count decreased in one patient and one patient got a severe urinary infection.Conclusions Patients with refractory CD could achieve clinical remission,mucosa healing under endoscopy and better efficacy with the combined therapy of cyclophosphamide and thalidomide.However,adverse effects should be monitored during the treatment.

Role of miR-19a in ulcerative colitis in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the role of miR-19a in ulcerative colitis (UC) in mice.</p><p><b>METHODS</b>The target gene of miR-19a was predicted by bioinformatics analysis. The expression of the target protein in UC colon was detected by immunohistochemistry and Western blotting. The target gene was further identified by enhanced green fluorescent protein (EGFP) report vector system.</p><p><b>RESULTS</b>The target gene of miR-19a was TNF-α as predicted by bioinformatics analysis. TNF-α expression was highly expressed in the colonic tissue of UC mice. MiR-19a could inhibit the report gene activity of TNF-α-3'UTR-WT but no that of TNF-α-3'UTR-Mut.</p><p><b>CONCLUSION</b>The target gene of miR-19a is TNF-α, and the binding site is TNF-α 3'UTR. The possible role of miR-19a in UC pathogenesis involves regulation of TNF-α expression in the colon.</p>

Preliminary efficacy of thalidomide in refractory Crohn's disease treatment / 中华消化杂志

Objective To observe the efficacy and safety of thalidomide in refractory Crohn's disease (CD).Methods A total of 21 moderate or severe active CD patients were enrolled,who had no response to glucocorticoid and azathioprine treatment or steroid-dependent.The patients were administrated with thalidomide 100 mg/d before sleep and followed up for one year.The clinical efficacy,endoscopic findings and safety were evaluated.Results Among 21 refractory CD patients,six patients stopped medication due to adverse effect and two because of ineffectiveness,three patients continued medication not completed one year follow-up,10 patients completed one year follow-up.The clinical remission,effective and ineffective rates were 23.8％(5/21),19.0％(4/21) and 57.1％(12/21) respectively.Under endoscope,the mucosal healing,improvement and no improvement rates were 9.5％(2/21),14.3％(3/21) and 76.2％ (16/21) respectively.The adverse effect rate was 71.4％ (15/21) including rash,conspitation,sommolence,numbness of hands and feet,leucopenia and muscular soreness.The mean time of the adverse effects onset was 3.4 weeks.Conclusions Thalidomide is effective in refractory CD treatment and could be used in patients unwilling to use biological medication or receive surgery.But the adverse effects should be noted.

The clinical and endoscopic efficacy of step-up and top-down infliximab therapy in Crohn's disease / 中华内科杂志

ObjectiveTo compare the efficacy of step-up and top-down infliximab therapy on patients with Crohn's disease (CD).MethodsA prospective and open-label study was performed by the First Affiliated Hospital of SUN Yat-sen University during September 2007 to December 2010.Active CD patients who were refractory to steroid/immunomodulator or who were steroid-dependent were enrolled into step-up group.Active CD patients who had no steroid or immunomodulator therapy before were enrolled into top-down group. All patients were intravenously infused with infliximab of 5 mg/kg body weight in an induction regimen of 3 doses at week 0,2 and 6,followed by maintenance dosing every 8 weeks beginning at week 14.The clinical and endoscopic follow up lasted 30 weeks.Clinical symptoms and mucosal healing status under endoscopy were evaluated by follow-up at week 10 and 30.Results Forty-one CD patients were enrolled,with 24 in step-up group and 17 in top-down group. There were significant differences in disease duration (P =0.006),combination therapy (P ＜ 0.001 ) and severity of disease ( P =0.011 ) in baseline between step-up and top-down groups.At week 10 and 30 during treatment,the clinical remission rates in step-up group were 45.8％ (11/24) and 58.3％ (14/24) respectively; the mucosal healing rates in step-up group were 33.3％ (8/24) and 54.2％ (13/24) respectively; the clinical remission rates in topdown group were 70.6％ ( 12/17)and 82.4％ (14/17) respectively; and the mucosal healing rates in topdown group were 35.3％ (6/17) and 52.9％ (9/17) respectively.No significant differences in clinical remission and mucosal healing rates at both week 10 and 30 were observed between the two groups.The prevalences of adverse events in step-up and top-down group were 41.7％ (10/24) and 29.4％ (5/17)respectively ( P =0.422).ConclusionBoth step-up and top-down infliximab therapy can induce remission in more than half of CD patients,while top-down therapy might be more benefitiary to symptom and endoscopic remission.

Clinical and colonoscopic characteristics of Crohn disease and intestinal tuberculosis / 中华消化内镜杂志

ObjectiveTo unify the definitions of colonoscopic characteristics of Crohn disease (CD) and intestinal tuberculosis ( ITB),and to evaluate colonoscopic and clinical features in the differential diagnosis of CD and ITB.MethodsA collaborative group composed of 10 experts from 5 hospitals voted to identify and confirm the colonoscopic characteristics.Clinical and colonoscopic characteristics were analyzed,thereafter,characteristics were scored based on different diagnostic specificity.ROC curve was used for determining the cutoff point to differentiate CD from ITB.ResultsFirstly,standard endoscopic images and descriptions were determined.Secondly,colonoscopic parameters which were significantly different between the CD and ITB patients included the follows:involvement of more than four intestinal segments,anorectal involvement,longitudinal ulcers,cobblestone appearance and transverse ulcers.Clinical findings which were significantly different between the CD and ITB patients included active pulmonary tuberculosis,PPD-test strong positive,anal fistula/perianal abscess and extra-intestinal manifestations in CD.4.4％(6/136) patients were confirmed by histological evidence of caseating granulomas.By using our scoring system,39.7％ (54/136) confirmed diagnoses and 18.4％ (25/136) suspected diagnoses were made in patients without histological evidence.ConclusionIdentification of colonoscopic characteristics and unification of the colonscopic diagnostic criteria were helpful in the differential diagnosis between CD and ITB.The differential diagnosis rate could he improved by using the scoring system.Half cases could not be confirmed even with combined pathology and the scoring system,so a more comprhensive scoring system would be warranted.

Clinical and endoscopic follow-up of infliximab with azathioprine combination therapy in Crohn's disease / 中华消化杂志

Objective To inspect the efficacy and mucosa healing condition of infliximab with azathioprine combination therapy in Crohn's disease (CD) and its correlation with prognosis.Methods A total of 20 active CD patients who received infliximab and azathioprine combination therapy at The First Affiliated Hospital of Sun Yat-sen University were objects of this study.The clinical efficacy was evaluated at 10 weeks,30 weeks,54 weeks and 2 years respectively according to CD activity index.The efficacy was evaluated under endoscopy at 10 weeks,30 weeks,54 weeks and 2 years respectively according to mucosal response situation under endoscopy.The data were analyzed by analysis of variance or Fisher's exact test between two groups.The factor affecred mucosal healing was analyzed by Logistic regression analysis.Results The clinical remission rate of patients without steroid at week 10,30,54 and 2 year were 12/20,16/20,15/20 and 15/20 respectively.Mucosal healing rate at week 10,30 and 54 weeks were 8/20,12/20 and 10/20 respectively.Logistic regression analysis indicated that age was the only factor affected mucosal healing at 30 weeks (OR =0.774,95％ CI:0.630 to 0.950).There was significant differences in clinical remission between mucosa response patients and invalid under endoscopy at 30 weeks and 2 years without steroid (at 30 weeks:14/14 vs 2/6; at 2 years:14/14 vs 1/6; all P＜0.01).Infliximab were withdrawn in 4 of 16 patients who was in non-steroid clinical remission at 30 weeks,and the other 12 patients were continued with infliximab therapy.There was no significant difference in non-steroid clinical remission rate (4/4 vs 11/12) and mucosa healing rate (2/4 vs 7/12) between withdrawal and continue of infliximab therapy (all P＞0.05).Conclusions Infliximab with azathioprine combination therapy can effectively promote and maintain mucosa healing in CD.The mucosa response patients can maintain long time non-steroid clinical remission.

The correlation of fecal calprotectin and lactoferrin with intestinal mucosa lesions in Crohn′s disease patients / 中华消化杂志

Objective To study the correlation of fecal calprotectin and lactoferrin with intestinal mucosa lesions in Crohn′s disease (CD). Methods Eighty-eight cases of diagnosed CD patients were selected as study group and 35 irritable bowel syndrome (IBS) patients were as controls. Fecal samples of CD patients were collected in one week before colonoscopy examination and of IBS patients were collected of CD patients, CD activity index (CDAI) was calculated at same visit, and CD endoscopic index (CDEI) was calculated in the subsequent endoscopic examination. The level of fecal calprotectin and lactoferrin were tested by ELISA method. Results The median levels of facal calprotectin and lactoferrin in CD patients were 277.16 mg/kg (from 96.85 to 693.57 mg/kg) and 59.68 mg/kg (from 10.75 to 100.58 mg/kg) respectively, which were significantly higher than those of IBS patients (7.6mg/kg, from 5.54 to 32.3 mg/kg and 0.65 mg/kg from 0.23 to 4.34 mg/kg), (Z=-8.301 and -7.986, respectively both P =0.000). There were no significant difference of calprotectin and lactoferrin level between CD patients with colon pathological changes and without colon pathological changes (Z=-0.424 and -0.699,P=0.672 and 0.485, respectively). There was no significant difference of calprotectin and lacoferrin level between remission and active periods in CD patients (Z=-1.491 and -1.075, P=0.136 and 0.283, respectively). The median values of calprotectin and lactoferrin of patients in moderate and severe active period judged under endoscopy were 663.11 mg/kg (from 263.45 to 2015.63 mg/kg) and 105.64 mg/kg (from 56.52 to 187.44) mg/kg respectively, in mild active period were 344.54 mg/kg (from 132.03 to 722.67 mg/kg) and 86.68 mg/kg (from 21.07 to 100.55 mg/kg) accordingly, and in remission period were 133.94 mg/kg (from 60.54 to 583.33 mg/kg) and 45.31 mg/kg (from 7.59 to 48.31 mg/kg, respectively). Both calprotectin and lactoferrin levels were significantly higher in active period than in remission period (χ2=10.63 and 8.18, while, P=0.005 and 0.017, respectively). Conclusions The level of fecal calprotectin and lactoferrin can reflect the pathological changes and severity of the intestinal mucosa.

Clinical and endoscopic evaluation of anti-tuberculosis trial for differentiation between intestinal tuberculosis and Crohn's disease / 中华消化内镜杂志

Objective To investigate the evaluation standard and proper time point of anti-tuberculosis trial for differential diagnosis between intestinal tuberculosis (ITB) and Crohn's disease (CD). Methods Clinical data and endoscopic changes of 28 patients with confirmed ITB and 11 with confirmed CD,who underwent anti-tuberculosis trail, were retrospectively analyzed. Results No significant difference could be found in clinical characteristics of ITB and CD patients on baseline, such as active pulmonary tuberculosis, strong positive skin test and anal fistula/perianal abscess. Clinical symptoms were relieved in both groups right after anti-tuberculosis treatment. After 3 months of treatment, the no-improvement rate in ITB group was 0, whereas that of CD group was 27.3% (P =0. 004). The disappearance rate plus improvement rate of ulcer in ITB group was 90. 9% (20/22) plus 9. 1% (2/22) and 100% ( 28/28 ) plus 0 at 3 and 6 months of treatment, respectively. The disappearance rate plus improvement rate of nodular lesion was 58. 8% (10/17) plus 41.2% (7/17) and 76. 5% (13/17) plus 23.5% (4/17), respectively. There was no obvious improvement of active ulcer or nodular transformation in CD group at any time point ( P ＜ 0. 01 ).Conclusion With deficiency of special index for differential diagnosis of ITB and CD, some cases hard to differentiate still have to accept anti-tuberculosis treatment. Three months of anti-tuberculosis treatment is a proper time point to evaluate the efficacy. Disappearance of active ulcer and nodular transformation, together with cure or obvious improvement in clinic are taken as effective for treatment trail.

The impact of 5-aminosalicylic acid on bone marrow suppression caused by thiopurines / 中华消化杂志

Objective To evaluate the effect and mechanism of 5-aminosalicylic acid (5-ASA) on bone marrow suppression caused by thiopurines, and to explore the proper dosage of thiopurines when combined with 5-ASA for inflammatory bowel diseases (IBD) patients.MethodsThe clinical data of IBD patients who took thiopurines were retrospectively analyzed. Thiopurine methyltransferase (TPMT) activity and 6-thioguanine nucleotide (6-TGN) concentration were tested.In prospective study, patients firstly treated with azathioprine (AZA) of 50 mg/d for 4 weeks, then combined with 5-ASA of 3 g/d for another 4 weeks.The concentration of 6-TGN in red blood cells (RBC) was analyzed at the end of 4th and 8th week.Results In retrospective study, there were 45 cases in AZA/6-mercaptopurine (MP) combined with 5-ASA group, 94 patients were in AZA/6-MP.alone group.The incidence of bone marrow suppression in these two groups were 46.7％ and 16.0％, respectively.Multivariates regression analysis indicated co-administration of 5-ASA was the only risk factor of increasing bone marrow suppression incidence (OR=3.45,95％ CI 1.31 ～ 9.04).There was no significant difference of TPMT activity between AZA/6-MP combined with 5-ASA group and AZA/6-MP alone group(t=-0.351 ,P=0.734).The 6-TGN concentration was significantly higher in AZA/6-MP combined with 5-ASA group than that of AZA/6-MP alone group (the median concentration was 384.9 pmol/8× 108 RBC and 286.4 pmol/8× 108 RBC,F=29.15,P=0.00).Prospective study was completed in 8 patients.After treated with AZA of 50 mg/d for 4 weeks, the 6-TGN concentration of 7 patients was lower than 230 pmol/8 × 108 RBC.After added with 5-ASA of 3 g/d for another 4weeks, the 6-TGN concentration of 7 patients was over 230 pmol/8 × 108 RBC, three patients of those was even higher than 420 pmol/8 × 108 RBC, and bone marrow suppression occurred in 2 patients.ConclusionsThe incidence of bone marrow suppression increased in Chinese IBD patients treated with recommended routine dossage of AZA/6-MP when conbined with 5-ASA.The mechanism may be related with the increased concentration of 6-TGN in RBC.To reduce the AZA dosage may possibly keep the efficacy while decrease the incidence of bone marrow suppression.

An open prospective trial of azathioprine in treatment of patients with active Crohn's disease / 中华消化杂志

Objective To evaluate the efficacy and safety of azathioprine (AZA) in long term treatment of patients with active Crohn's disease (CD) in China. Methods Sixty patients with active CD,who needed to be treated with systemic steroids, were recruited. All patients initially received AZA combined with steroids therapy and AZA was maintained for treatment after withdrawal of steroids. Clinical efficacy, endoscopic healing of mucosa and adverse events were assessed at the end of the 12th, 24th, 48th, 72th and 96th weeks. Results The complete remission (CR) of the patients at the 12th, 24th, 48th, 72th and 96th weeks was 55.0%, 66. 7%, 61. 7%, 53. 3% and 53. 3%,respectively. Endoscopic examination was performed in 25 patients before treatment and at the end of the 48th week. Eight of them achieved mucosal healing that was kept to the end of 96th week (8/8).Whereas only 9 out of 17 patients without mucosal healing achieved CR at the end of 96th week (9/17,P=0. 026). The clinical features were compared between CR group and non-CR group at the end of 48th week. Logistic regression analysis showed that regaining of hs-CRP was the only independent factor for maintaining remission by AZA treatment ( P= 0. 009,OR 10.1,95 % CI 1.8 ～ 57.9). Sixteen patients (26.7 % ) had adverse events. Ten (16.7 % ) of them had to halt treatment because of serious adverse events. Leucopenia was the most common adverse event and could be occurred at any time during the treatment. Conclusion AZA combined with steroid therapy can effectively induce remission of active CD. Long term steroid-free remission is also effectively maintained by AZA treatment. The most common adverse event is leucopenia and some patients can get mucosal healing. Those who get mucosal healing may have longer duration of remission.

The prevalence of non-acidic reflux and its relation with heartburn symptoms in patients with gastroesophageal reflux disease / 中华消化杂志

Objective To investigate the prevalence of non-acidic reflux in patients with gastroesophageal reflux disease and its correlation extent with heartburn symptom by 24-hour combined multichannel intraluminal impedance-pH (MII-pH) monitoring. Methods Consecutive patients with chief complain of heartburn in gastrointestinal specialty clinic were enrolled. Patients were divided into erosive esophagitis (EE) group, non-erosive reflux disease (NERD) group after upper gastrointestinal endoscope, further diagnosed with 24-hour combined MII-pH monitoring and rabeprazole test. The MII-pH parameters were compared in these two groups. Results 36 cases of EE and 62 of NERD were enrolled. There was significant difference in acidic reflux frequency and acidic reflux time percentage between these two groups (P=0. 001 and 0. 002). The frequency of non-acidic reflux in EE and NERD groups was 37.3% (663/1777) and 44.3% (1220/2754) respectively (x2 =21. 723,P = 0. 000). The percentage of heartburn symptom positive index in patients with acidic reflux, non-acidic reflux , and total reflux in EE group was 36.1 % (13/36), 19.4 % (7/36) and 55.6%(20/36) respectively, while in NERD group was 27. 4% (17/62), 6.4 % (4/62) and 33.8% (21/62).Conclusion The percentage of non-acidic reflux in EE and NERD groups was 37.3% and 44.3%respectively, and the non-acidic reflux was highly related to heartburn symptom.

Association between polymorphism of interleukin-17F A7488G and gastric cancer in Guangdong province of China / 中华消化杂志

Objective To elucidate the association of interleukin (IL)-17F A7488G (p.His161Arg) polymorphism with gastric cancer susceptibility,clinicopathological features and survival.Methods DNA from 927 unrelated patients with gastric cancer and 777 age and gendermatched healthy controls was typed for IL-17F A7488G polymorphism by polymerase chain reactionrestriction fragment length polymorphism.Logistic regression analyses and Cox proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility,clinicopathological features and survival.Results There was significant difference between healthy controls and patients with gastric cancer with respect to frequencies of IL-17FA7488G genotypes (X2= 16.55,P<0.01).After adjusted for age and gender,IL-17F A7488G GA and GG genotypes were associated with an increased risk of gastric cancer compared with the AA genotype (OR=1.51;95% CI:1.22-1.87 for GA;OR=1.61,95% CI:1.03-2.51 for GG).In comparison with AA genotype carriers,the risk of gastric cancer increased in those with GA or GG genotypes (OR= 1.53,95 % CI:1.25- 1.87,P<0.01 ).Further stratification analyses indicated that the effect of IL-17F A7488G GA genotype was especially noteworthy in gastric cancer patients of noncardia,intestinal type,poorly and moderately differentiated,and lymph node metastasis.Whereas there was no significant difference in survival among subjects with different polymorphisms of IL-17F A7488G gene (P= 0.534).Conclusions Genetic polymorphism of IL-17F A7488G involves in susceptibility to gastric cancer,which also influences certain subtypes of gastric cancer according to clinicopathological features,however,it is not the independent risk factor for prognosis of gastric cancer patients.

Evaluation of thiopurine methyltransferase genotyping and enzyme activity detection in treatment of patients with inflammatory bowel disease / 中华消化杂志

Objective To assess the predictive value of thiopurine methyltransferase genotyping and enzyme activity in relation to side effects in patients with inflammatory bowel disease (IBD) who were treated with azathioprine (AZA). Methods One hundred and eleven IBD patients (26 with ulcerative colitis and 86 with Cronh's disease) with indication of AZA administration between April 2004 and Dec. 2009 were enrolled. All patients received 2 mg/kg of AZA daily. Polymerase chain reaction and high performance liquid chromatography were used to genotype the TPMT * 2, * 3A, * 3B, * 3C and to detect TPMT activity, respectively. The association of TPMT genotype and activity with side effects was analyzed in patients treated with AZA for 24 weeks or more, or in those discontinued AZA because of adverse effects. Results Adverse effects were reported in 38(33. 9%) patients, the most frequent being myelosuppression (20. 5%). The frequency of TPMT * 3C heterozygous mutation was 0. 9% (1/112). The TPMT activity was (12. 9±4. 8) U/ml RBC with unimodal distribution. One patient with TPMT * 3C heterozygous mutation developed myelosuppression at the 4th week after AZA treatment. The TPMP genotype myelosuppression patients. Conclusions TPMT genotype mutation and low enzyme activity can be used to predict myelosuppression with high specifically and low sensitivity. In patients treated with AZA, co-administration of 5-ASA results in a high frequency of myelosuppression with no effect on TPMT activity.

Correlates of health-care seeking behavior in patients with irritable bowel syndrome / 中华全科医师杂志

Objective To explore correlates of health-care seeking behavior in patients with irritable bowel syndrome (IBS).Methods Four thousand permanent residents were recruited from eight urban communities and rural villages in Guangzhou and Huizhou, Guangdong province during 2009 by cluster stratified sampling for face-to-face questionnaire survey, including symptoms of bowel disease,behavior of seeking for health-care, demographic characteristics, coping style, life events and medical history.IBS was identified based on the Rome Ⅱ Criteria.Patient with IBS were divided into two groups,one seeking health-care at hospitals or clinics and the other non-seeking health-care.Univariate and multivariate logistic regression analysis was used to compare difference between the two groups and explore its related factors.Results A total of 237 IBS patients were identified based on the Rome Ⅱ Criteria, 53 of them (22.4% ) had sought health-care due to their symptoms.Results of multivariate logistic regression analysis showed that preference in seeking for health-care, abdominal pain lasting for more than one hour in each episode and extra-gastrointestinal symptoms were main factors related to their seeking for health-care,adjusted for age and gender, with odds ratios (ORs) of 1.81 (95% CI: 1.27 -2.58), 1.41 (95% CI:1.01 - 5.14 ) and 2.14 ( 95% CI: 1.06 - 4.33 ), respectively.Conclusions Extra-gastrointestinal symptoms and abdominal pain lasting for more than one hour in each episode correlate their health-care seeking behavior in patients with IBS, as well as their preferences in seeking for health-care.

Value of combined multichannel intralumminal impedance-pH monitoring in the diagnosis of gastroesophageal reflux disease / 中华消化杂志

Objective To investigate the role of combined multichannel intralumminal impedanee-pH (MII-pH) monitoring in the diagnosis of gastroesophageal reflux disease (GERD). Methods Forty-four consecutive patients, who had heartburn symptom and without esophageal mucosal lesion, underwent combined MII-pH monitoring. Then rabeprazole test was performed for 14 days with 10 mg twice daily. Rabeprazole test was defined as positive if patients were totally heartburn symptom free in the second week. The normal values from 70 healthy volunteers who underwent MII-pH monitoring were served as controls. Results Conventional esophageal pH monitoring showed that 20 patients (45.5%) had pathologic esophageal acid exposure or positive acid reflux associated symptom index. MII-pH monitoring revealed that 2 patients were positive for weakly acidic reflux related to symptom index, thus increased the diagnostic yield to 50% (22/44). Furthermore, rabeprazole test demonstrated that 4 patients were positive which increased the diagnostic yield to 54.5%(24/44). Conclusion The detective rate of GERD will be elevated if combined with MII-pH monitoring in diagnosis.

Effect of esomeprazole with different dosage and usage on intragastric pH of healthy volunteers / 中华消化杂志

Objective To evaluate the effect of csomeprazole with different dosage and usage regimes on intragastric pH of healthy volunteers. Methods It was a randomized, open-label, three-way crossover study. Fifteen healthy volunteers received esomeprazole with 3 different dosages (20 mg or 40 mg once daily or 20 mg twice daily) with 5 days each. Twenty-four continuous ambulatory intragastric pH was recorded at day 5 of each regime. Results The mean time of intragastric pH above 4 was higher in regime of 20 mg twice daily [(21.16 ±2.45) hours ] than that in regimes of 20 mg once daily [(18. 70±4.19) hours] and 40 mg once daily [(19.27±2.68 ) hours] (P<0.05). The percentages of the sleeping and active period that pH remained above 3,4,5 were significantly higher in regime of 20 mg twice daily(day time:95.0%±7.5% ,92.0%±10.6% ,86.7% ± 14.5% ;night time:93.2%± 13.1% ,87.8%±20.3% ,78.6%±28. 9 % )compared with regimes of 40 mg once daily(day time:87.9%±9.5% ,83.5%±11.7%,75.6%±15.50%, night time:75. 7%±20. 8%,66. 9%±23. 8%,53. 3%±30. 3%) and 20 mg once daily(day time: 85.1 % ± 16.3 %, 81.1 %± 18. 1%, 71.5 % ± 20.3 % ; night time: 72.9 % ± 30.5 %,67.2 % ± 31.9 %, 55.7 % ± 31.8 % ) (P< 0.05 ). Esomeprazole maintained intragastric pH above these pH thresholds for a similar propotion of sleeping and active periods with 40 mg once daily and 20 mg once daily.Conclusions Esomeprazole has strong inhibitory effect on intragastric acid. The regime of 20 mg twice daily is superior to 40 mg once daily and 20 mg once daily in both day and night time acid inhibition.There is no difference between esomeprazole 40 mg once daily and 20 mg once daily.