炎症性肠病患者的心理健康与生活质量状况调查分析

目的 研究炎症性肠病(IBD)患者的生活质量(quality of life,QOL)及主要影响因素.方法 应用中文炎症性肠病问卷(IBDQ)、SF-36、焦虑、抑郁自评量表,对广州市4所医院的71例炎症性肠病患者的QOL进行横断面调查,通过相关分析,探讨焦虑、抑郁与患者生活质量的关系.结果 IBD患者的生活质量得分明显下降,低于肠易激综合征(IBS)组患者(P＜0.05),亦显著低于健康对照组的生活质量(P＜0.05).相关分析表明,IBD患者的焦虑、抑郁水平与生活质量呈负相关.结论 (1)我国IBD患者的生活质量水平低;(2)焦虑、抑郁水平高的IBD患者生活质量低.     

Significance of the genetic polymorphism of CYP2D6 and NAT2 in patients with inflammatory bowel diseases

BackgroundThe main types of inflammatory bowel diseases (IBD) are ulcerative colitis (UC) and Crohn's disease (CD). There is evidence that, in addition to immunological and environmental factors, genetic factors also play an important role in the pathogenesis of IBD. Determination of polymorphism of CYP2D6 and NAT2 genes encoding I and II phase enzymes of xenobiotic biotransformation may have clinical value as an indicator of individual predisposition to diseases, and also contribute to effective and safe pharmacotherapy. The aim of this study was to investigate the association between genetic polymorphism of CYP2D6 and NAT2 and the incidence of IBD, including UC and CD, among inhabitants of central Poland.MethodsThe study was performed in 258 individuals from central Poland (115 patients with IBD, including 65 patients with UC and 50 with CD; and in 143 healthy controls). The CYP2D6 genotypes of oxidation and NAT2 genotypes of acetylation were analyzed using the PCR-RFLP method.ResultsThere were no statistically significant differences in the frequency of the CYP2D6 genotypes and alleles in patients with IBD, UC and CD in comparison with the control group. The relative risk (OR) of IBD, UC and CD was higher in carriers of the allele NAT2*7 and was OR = 3.49 (p = 0.0019), OR = 3.86 (p = 0.0019), and OR = 3.02 (p = 0.0247), respectively.ConclusionsPolymorphism of the gene encoding CYP2D6 does not affect the incidence of inflammatory bowel diseases. The carriers of the NAT2*7 allele which determines slow acetylation may be more predisposed to inflammatory bowel diseases, including ulcerative colitis and Crohn's disease.     

Enkephalin degradation in serum of patients with inflammatory bowel diseases

Background

Inflammatory bowel diseases (IBD) are a group of chronic and recurrent gastrointestinal disorders that are difficult to control. Recently, a new IBD therapy based on the targeting of the endogenous opioid system has been proposed. Consequently, due to the fact that endogenous enkephalins have an anti-inflammatory effect, we aimed at investigating the degradation of serum enkephalin (Met- and Leu-enkephalin) in patients with IBD.

编制炎症性肠病病人药物自我管理测评量表

目的 为炎症性肠病病人药物自我管理水平提供测评工具.方法 通过半结构访谈、文献回顾和专家咨询形成量表初稿,采用便利抽样法对2019年2—9月江苏大学附属医院120例炎症性肠病病人进行问卷调查,测定量表的信效度.结果 炎症性肠病病人药物自我管理测评量表共包含11个条目,条目的内容效度指数0.89～1.00,量表Cronb...     

英夫力西治疗炎症性肠病与肠道菌群改变的相关性研究

目的探讨使用英夫力西(IFX)治疗炎症性肠病与肠道菌群改变的关系。方法收集104例炎症性肠病患者,其中溃疡性结肠炎(UC)52例,克罗恩病(CD)52例,使用英夫力西治疗前后测定肠道菌群数量。另取30例健康志愿者新鲜粪便,定量培养进行菌群分析,同时测定三组C反应蛋白、血沉两项数据结果,分析其与肠道细菌组成变化的相关性。结果治疗后,UC组酵母菌(1.09±0.17)、肠球菌(5.01±0.36)和消化球菌(3.99±0.23)的数量显著下降,乳酸杆菌(7.95±0.69)的数量显著上升(P<0.01);CD组酵母菌(1.06±0.19)、肠球菌(4.91±0.37)和消化球菌(3.90±0.19)的数量显著下降,乳酸杆菌(8.07±0.76)的数量显著上升(P<0.01)。治疗后,UC组CRP(10.33±4.64)、ESR(9.10±4.11)水平降低(P<0.01);CD组CRP(7.31±4.68)、ESR(9.27±3.13)水平降低(P<0.01)。结论使用英夫力西治疗炎症性肠病患者后,酵母菌、肠球菌和消化球菌数量显著降低,乳酸杆菌数量显著增加,恢复到正常水平,炎症指标CRP和ESR下降,临床症状得到有效缓解。     

慢性阻塞性肺疾病患者血清白细胞介素17的表达

目的探讨白细胞介17(IL-17)在慢性阻塞性肺疾病(COPD)发病机制中的作用。方法抽取100例COPD急性加重期(A1组)、100例稳定期患者(A2组)及100例健康人(C组)静脉血标本,采用双抗体ELISA法测定血清IL-17水平。并作肺功能检查,计算第1秒用力呼气容积比(FEV1%)。结果 A1组血清IL-17明显高于A2组[(73.1±58.4)pg/mlvs.(34.8±21.6)pg/ml](P<0.01),A2组血清IL-17高于C组[(16.4±7.6)pg/ml](P<0.01)。A1组血清IL-17与FEV1%呈负相关(P<0.05)。结论 IL-17可能参与COPD的发病。     

Anti-inflammatory action of a novel orally available peptide 317 in mouse models of inflammatory bowel diseases

BackgroundThe endogenous opioid system constitutes an attractive target in the treatment of GI disorders, including inflammatory bowel diseases (IBD). The aim of our study was to characterize the anti-inflammatory and antinociceptive effect of P-317, a novel cyclic analog of opioid peptide morphiceptin, in animal models of IBD.MethodsThe anti-inflammatory effect of P-317 after intraperitoneal (ip) and oral (po) administration was assessed in two mouse models of IBD – Crohn's disease, induced by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS) and ulcerative colitis, induced by addition of dextran sodium sulfate (DSS) into drinking water. The antinociceptive action of P-317 was characterized in mice with acute colitis using mustard oil-induced pain test. Real time RT PCR was used to assess semiquantitatively the expression of IL-1β and TNF-α mRNA in mouse colonic samples. To translate our results to clinical conditions, MOP and KOP mRNA were quantified in human colonic biopsies from IBD patients.ResultsP-317 (0.1 mg/kg, ip and 1 mg/kg, po) alleviated colonic inflammation in TNBS- and DSS-treated mice in the opioid receptor-dependent manner. The anti-inflammatory effect of P-317 was associated with the decrease in mRNA expression of proinflammatory cytokines. The antinociceptive effect of P-317 was observed after ip and po administration in mice with acute colitis.ConclusionOur results show a potent anti-inflammatory and antinociceptive effect of P-317 in mouse models of colitis upon activation of opioid receptors. The unique bioavailability of P-317 after oral administration suggests that it is a promising drug candidate for future treatment of IBD.     

Pharmacokinetics of intravenous methylprednisolone and oral prednisone in paediatric patients with inflammatory bowel disease during the acute phase and in remission

Objective: The present study was undertaken to evaluate the influence of inflammatory bowel disease on the pharmacokinetics of intravenous methylprednisolone and prednisolone (after oral administration of prednisone). Patients: Twelve children with inflammatory bowel disease, aged 12.3 years were studied during the active phase and in remission. In 6 patients the disease responded to oral prednisone while 6 did not respond. Methods: During the acute phase, intravenous methylprednisolone (2 mg · kg⁻¹) and oral prednisone (2 mg · kg⁻¹) were administered in a random order and blood was sampled over 48 h. Prednisone (2 mg · kg⁻¹) was readministered after remission. The concentrations of methylprednisolone and prednisolone were measured by high-pressure liquid chromatography. Results: During the acute phase, the systemic clearance of methylprednisolone was 0.98 (1 kg⁻¹ · h⁻¹) and the elimination half-life was 1.67 h. The area under the plasma concentration-versus-time curve of prednisolone was 4.00 and 3.20 · mg · h · l⁻¹ respectively during the active disease and remission, while its elimination half-life was 3.51 h during the acute phase and 2.42 h in remission. There were no pharmacokinetic differences between the patients who responded or did not respond to oral treatment. Conclusion: In children with inflammatory bowel disease, the initial response to corticosteroid therapy was not influenced by the pharmacokinetics of prednisolone and methylprednisolone. In addition, the pharmacokinetics of prednisolone was not modified by the inflammatory syndrome. Received: 5 December 1997 / Accepted in revised form: 14 April 1998     

Increased subsequent risk of inflammatory bowel disease association in patients with chronic pancreatitis: a nationwide population-based cohort study

Purpose: To investigate the relationship between chronic pancreatitis (CP) and inflammatory bowel disease (IBD) in a large population-based cohort study.

Methods: Data was obtained from the Taiwan National Health Insurance Research Database. The cohort study comprised 17,796 patients newly diagnosed with CP between 2000 and 2010 and 71,164 matched controls. A Cox proportional hazards model was used for evaluating the risk of IBD in the CP and comparison cohorts.

Results: When examined with a mean follow-up period of 4.87 and 6.04 years for the CP and comparison cohorts, respectively, the overall incidence of IBD was 10.3 times higher in the CP cohort than in the comparison cohort (5.75 vs. 0.56 per 10,000 person-years). Compared with the comparison cohort, the CP cohort exhibited a higher risk of IBD, irrespective of age, sex, and presence or absence of comorbidities. Moreover, the CP cohort was associated with a significantly higher risk of Crohn’s disease (adjusted hazard ratio [aHR]?=?12.9, 95% confidence interval [CI]?=?5.15–32.5) and ulcerative colitis (aHR?=?2.80, 95% CI?=?1.00–7.86).

Conclusions: This nationwide population-based cohort study revealed a significantly higher risk of IBD in patients with CP compared with control group. Clinicians should notice this association to avoid delayed diagnosis of IBD in patients with CP.     

Circulating levels of cyclosporin A in inflammatory bowel disease: relationships with lymphocyte inhibition and the age of patients

Objective To determine in the same blood sample the concentrations of cyclosporin A (CsA) and the degree of CsA-induced lymphocyte inhibition; to establish a relationship between these parameters; and to investigate the factor(s) influencing such a putative relationship.Methods Ten patients with a diagnosis of Crohns disease (n=7) or ulcerative colitis (n=3) were enrolled in the study. The patients, who had never been immunosuppressed, were treated with microemulsion CsA twice daily by the oral route; at steady-state, blood samples were collected 0, 0.5, 1, 2, 3, 5, 7 and 12 h after the morning dose. CsA blood levels were measured by means of radioimmunoassay. The percentages of lymphocytes during the S-phase were assessed by flow-cytometry on the same blood specimens, only for samples collected at 0 h and 2 h.Results An inverse relationship emerged between CsA blood concentrations and the percentage of lymphocytes during the S-phase: the latter was maximal before the beginning of treatment and minimal in association with peak CsA levels. Furthermore, a highly significant correlation was found between trough CsA levels and the age of the patient, since the percentage of inhibited lymphocytes increases with age.     

炎症性肠病的微小 RNA-377、微小 RNA-31表达及其与肠道菌群相关性

目的探讨微小 RNA-377(miR-377)、微小 RNA-31(miR-31)在炎症性肠病血清中的表达及其与肠道菌群相关性。方法选取 2016年 5月至 2019年 6月保定市第一中心医院收治的 110例炎症性肠病病人为研究组,其中活动期 69例、缓解期 41例,同时选取同院体检的健康志愿者 60例为对照组;采用 qRT-PCR法检测血清 miR-377、miR-31的表达量;根据表达量平均值将病人分为 miR-377低表达组 53例、 miR-377高表达组 57例、 miR-31低表达组 57例、 miR-31高表达组 53例,比较分析 miR-377、 miR-31表达量与肠道菌群［肠球菌( EC)、酵母菌( SB)、双歧杆菌( BL)、消化球菌( PS)、小梭菌( CD)、肠杆菌( EMB)、葡萄球菌(SP)、拟杆菌(BD)、乳杆菌(LC)、真杆菌(ES)］数量的相关性;采用 ELISA法检测血清白细胞介素 -34(IL-34)、C反应蛋白(CRP)的水平;采用电化学发光法检测血清降钙素原(PCT)的水平;采用 Pearson法分析 miR-377、miR-31表达量与 IL-34、CRP、PCT水平的相关性。结果与对照组比较,研究组血清中 miR-377、miR-31的表达水平显著升高［(0.96±0.16)(2.23±0.50)(0.97±0.24)比     

N3系脂肪酸干预对炎症性肠病病人复发风险的影响

目的 探讨N3系脂肪酸干预对炎症性肠病病人复发风险的影响。方法 前瞻性选取2018年1月至2020年5月于沧州市人民医院就诊的炎性肠病病人216例,均接受规范化治疗,按照随机数字表法分为对照组108例,予以常规饮食干预;干预组108例,在对照组基础上予以N3系脂肪酸干预;随访观察12个月,记录两组复发情况,根据病人复发情况分为复发组和非复发组,利用Cox回归分析明确N3系脂肪酸干预对炎性肠病病人复发风险的影响。结果 随访12个月,无1例失访,共75例病人出现复发,复发率34.72%;其中干预组30例复发,复发率（27.78%）较对照组45例复发,复发率（41.67%）低（log-rankχ2=6.91,P=0.009）;复发组和未复发组C-反应蛋白（CRP）、红细胞沉降率（ESR）、肿瘤坏死因子-α(TNF-α)、氧化三甲胺（TMAO）、粪便钙卫蛋白、吸烟比例比较,差异有统计学意义（P<0.05）;Cox回归分析显示：ESR[HR=1.03,95%CI:(1.01,1.05)]、TNF-α[HR=1.05,95%CI:(1.03,1.07)]、粪便钙卫蛋白[HR=1.03,95%...     

Real-world evaluation of glycemic control among patients with type 2 diabetes mellitus treated with canagliflozin versus dipeptidyl peptidase-4 inhibitors

Objective To evaluate glycemic control among patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin (CANA) vs. dipeptidyl peptidase-4 (DPP-4) inhibitors.

Methods Using integrated claims and lab data from a US health plan of commercial and Medicare Advantage enrollees, this matched-control cohort study assessed adult T2DM patients receiving treatment with CANA or DPP-4 inhibitors (1 April 2013–31 December 2013). Cohorts were chosen hierarchically; the first pharmacy claim for CANA was identified as the index date; then the first pharmacy claim for a DPP-4 inhibitor was identified and index date set. Eligible patients had 6 months of continuous health plan enrollment before the index date (baseline) and 9 months after (follow-up) and no evidence of index drug in baseline. Patients were matched 1:1 using propensity score matching. Changes in glycated hemoglobin (HbA1c) and percentages of patients with HbA1c <8% and <7% during the follow-up were evaluated.

Results The matched CANA and DPP-4 inhibitor cohorts (53.2% treated with sitagliptin) included 2766 patients each (mean age: 55.7 years). Among patients with baseline and follow-up HbA1c results, mean baseline HbA1c values were similar, 8.62% and 8.57% (p?=?0.615) for the CANA (n?=?729) and DPP-4 inhibitor (n?=?710) cohorts, respectively. Change in HbA1c was greater among patients in the CANA cohort than for those in the DPP-4 inhibitor cohort (?0.92% vs. ?0.63%, p?<?0.001), and also among the subset of patients with baseline HbA1c ≥7% (-1.07% [n?=?624] vs. ?0.79% [n?=?603], p?=?0.004). During follow-up, greater percentages of the CANA cohort relative to the DPP-4 inhibitor cohort achieved HbA1c of <8% (66.0% vs. 58.6%, p?=?0.004) and <7% (35.4% vs. 29.9%, p?=?0.022).

Limitations This study was observational and residual confounding remains a possibility.

Conclusions In this real-world study of patients with T2DM, CANA use was associated with greater HbA1c reduction and higher percentages of patients attaining HbA1c goals than those treated with DPP-4 inhibitors.     

Effect of a new De-N-acetyl-lysoglycosphingolipid on chemically-induced inflammatory bowel disease: possible mechanism of action

Summary A new, orally active de-N-acetylated lysoglycosphingolipid (WILD20) was evaluated as antiinflammatory agent using a model of chemically-induced inflammatory bowel disease (IBD) in the rat to mimic human ulcerative colitis and Chron's disease. IBD was induced by hapten trinitrobenzenesulphonic acid (TNB). WILD20, orally administered as preventive or curative, was demonstrated to be efficacious at daily dosages of 0.1–1 mg/kg for 4–5 days. Damage scores, body weight, spleen weight, colonic tissular levels of LTB₄, myeloperoxidase (MPO) and malondialdehyde (MDA) are influenced and brought into parameters of normality.Histological observation demonstrated quicker healing, better repair, reduced inflammation, and poor eosinophil degranulation.The mechanisms underlying WILD20 antinflammatory effects were investigated: whereas WILD20 fails to show a direct effect on PKC, it reduces PKC translocation to the membrane; cellular PLA₂ was consequently greatly reduced through this mechanism and thought to be responsible for WILD20 efficacy towards chemically-induced IBD.Correspondence to: E. Tubaro at the above address     

Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease

PURPOSE: The thiopurine drugs, azathioprine and 6-mercaptopurine are effective in the treatment of inflammatory bowel disease (IBD). However, their use is limited by serious adverse effects that can lead to cessation of therapy. The incidence of these adverse effects has been reported to be approximately 9% but in Christchurch it was felt that the incidence was higher. METHODS: We searched our letter database to identify all patients with IBD who had received a thiopurine drug between 1996 and 2002. The case notes were then reviewed to identify those patients who had suffered an adverse effect that required cessation of the drug. RESULTS: From a total of 216 patients with IBD taking a thiopurine drug, 56 (25.9%) had an adverse reaction requiring cessation of the drug. Adverse effects included allergic-type (25%), liver test abnormalities (34%), nausea/vomiting (6%), bone marrow suppression (7%), pancreatitis (7%) and other (9%). Males were significantly more likely than females to have an allergic-type reaction (p = 0.003). All adverse effects resolved with cessation of the drug, with a median of 7 days to resolution. Of the patients with liver test abnormalities on azathioprine, most were able to tolerate 6-mercaptopurine, however challenge with 6-mercaptopurine was not successful for most other patients. CONCLUSIONS: In Canterbury, New Zealand, patients with IBD have a high rate of therapy-limiting adverse effects to thiopurine drugs. There is a significant gender bias for allergic-type adverse effects. Mechanisms for both these observations are not clear.     

速尿、苯氧比酸、硫唑嘌呤对慢性炎症性肠病患者红细胞TPMT活性的影响

目的:研究利尿剂速尿、苯氧比酸及其硫唑嘌呤对慢性炎症性肠病患者红细胞硫嘌呤甲基转移酶(TPMT)活性的影响。方法:应用高效液相法(HPLC)测定慢性炎症性肠病患者红细胞TPMT活性,其中中等活性、正常活性、较高活性的患者各6例,依据浓度效应曲线计算每个药物的IC50。结果:速尿对TPMT活性的抑制作用较强,平均IC50为15～19μmol·L-1,在健康志愿者的正常血浆浓度范围内。苯氧比酸和硫唑嘌呤的平均IC50值分别为300～313μmol·L-1、430～532μmol·L-1,均远高于体内所能达到的血浆浓度。3种药物的IC50值在3个不同TPMT活性组间无明显差异(P>0.05)。结论:速尿可抑制红细胞TPMT活性,当速尿和硫嘌呤类药物合用时,应警惕发生不良相互作用。     

Vedolizumab does not increase risk of clostridium difficile infection in patients with inflammatory bowel disease using vedolizumab: A retrospective cohort study

IntroductionSeveral studies have shown increased incidence, recurrence, and severity of Clostridium difficile infection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies.MethodsThis was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI.ResultThere was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model.ConclusionBiologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.