Are faecal markers good indicators of mucosal healing in inflammatory bowel disease?

AIM: To review the published literature concerning the accuracy of faecal inflammatory markers for identifying mucosal healing. METHODS: Bibliographical searches were performed in MEDLINE electronic database up to February 2015,using the following terms: "inflammatory bowel disease","Crohn′s disease","ulcerative colitis","faecal markers","calprotectin","lactoferrin","S100A12","endoscop*","mucosal healing","remission". In addition,relevant references from these studies were also included. Data were extracted from the published papers including odds ratios with 95%CI,P values and correlation coefficients. Data were grouped together according to each faecal marker,Crohn's disease or ulcerative colitis,and paediatric compared with adult study populations. Studies included in this review assessed mucosal inflammation by endoscopic and/or histological means and compared these findings to faecal marker concentrations in inflammatory bowel diseases(IBD) patient cohorts. Articles had to be published between 1990 and February 2015 and written in English. Papers excluded from the review were those where the faecal biomarker concentration was compared between patients with IBD and controls or other disease groups,those where serum biomarkers were used,those with a heterogeneous study population and those only assessing post-operative disease. RESULTS: The available studies show that faecal markers,such as calprotectin and lactoferrin,are promising non-invasive indicators of mucosal healing. However,due to wide variability in study design,especially with regard to the definition of mucosal healing and evaluation of marker cut offs,the available data do not yet indicate the optimal roles of these markers. Thirty-six studies published between 1990 and 2014 were included. Studies comprised variable numbers of study participants,considered CD(15-164 participants) or UC(12-152 participants) separately or as a combined group(11-252 participants). Eight reports included paediatric patients. Several indices were used to document mucosal inflammation,encompassing elevenendoscopic and eight histologic grading systems. The majority of the available reports focused on faecal calprotectin(33 studies),whilst others assessed faecal lactoferrin(13 studies) and one study assessed S100A12. Across all of the biomarkers,there is a wide range of correlation describing the association between faecal markers and endoscopic disease activity(r values ranging from 0.32 to 0.87,P values ranging from 0.0001 to 0.7815). Correlation coefficients are described in almost all studies and are used more commonly than outcome measures such as sensitivity,specificity,PPV and/or NPV. Overall,the studies that have evaluated faecal calprotectin and/or faecal lactoferrin and their relationship with endoscopic disease activity show inconsistent results. CONCLUSION: Future studies should report the results of faecal inflammatory markers in the context of mucosal healing with clear validated cut offs.     

Aging increases the susceptibility of cisplatin-induced nephrotoxicity

Cisplatin (CDDP) nephrotoxicity is one of the most common side effects in cancer treatment, causing the disruption of chemotherapy. In this study, we analyzed the influence of nongenetic factors on CDDP-induced nephrotoxiciy using the data from 182 CDDP-treated and 52 carboplatin (CBP)-treated patients. The mean change of eGFR (100 % to baseline) in CDDP-treated patients was −9.2 %, which was significantly lower than that in the population with CBP therapy. By using the chi-squared test and multivariate logistic regression analysis, age (≥50 years) is found associated with CDDP-induced nephrotoxicity, with odds ratio (OR) of 9.167 and 11.771, respectively. Three- and 18-month-old mice were employed to study the age-dependent susceptibility of CDDP-induced nephrotoxicity. Biochemical parameters, histopathogical examination, and mRNA biomarkers indicated that old mice were subjected to more severe kidney injury. In addition, old mice accumulated more CDDP in kidney than young mice, and the protein level of CDDP efflux transporter, MATE1, in aged mice kidney was 35 % of that in young mice. Moreover, inflammatory receptor TLR4 was higher in the kidney of old mice, indicating the alteration of inflammatory signaling in old mice. After CDDP administration, the induced alterations of TNF-α, ICAM-1, and TLR4 were more extensive in old mice. To summarize, aging increased the susceptibility of CDDP-induced renal function decline or nephrotoxicity.

Electronic supplementary material

The online version of this article (doi:10.1007/s11357-015-9844-3) contains supplementary material, which is available to authorized users.     

Does the level of reproductive knowledge specific to inflammatory bowel disease predict childlessness among women with inflammatory bowel disease?

BACKGROUND:

Women with inflammatory bowel disease (IBD) may choose to remain childless due to a lack of IBD-specific reproductive knowledge.

OBJECTIVES:

To examine the effects of IBD-specific reproductive knowledge and discussion of family planning with a physician on childlessness among women with IBD.

METHODS:

Female IBD patients 18 to 45 years of age completed the Crohn’s and Colitis Pregnancy Knowledge questionnaire (CCPKnow), and answered questions regarding reproductive history, plans to have children and discussion of family planning with a physician. CCPKnow scores were grouped according to poor (0 to 7), adequate (8 to 10), good (11 to 13) and very good (14 to 17).

RESULTS:

Of 434 eligible women, 248 (57.1%) completed the questionnaires. Of these 248 women, 51.6% were childless and, among these, 12.9% were voluntarily childless and 12.1% were trying to become pregnant. Childless women had a lower median CCPKnow score than women with children (6.0 versus 8.0; P=0.001). After adjusting for current age and marital status, each one point increase in the CCPKnow score corresponded to 8% lower odds of childlessness (OR 0.92 [95% CI 0.86 to 0.99]), 9% lower odds of voluntary child-lessness (OR 0.91 [95% CI 0.79 to 1.0]) and 20% higher odds of trying to become pregnant (OR 1.2 [95% CI 1.0 to 1.4]). Discussion of family planning with a gastroenterologist corresponded to 72% lower odds of a poor CCPKnow score (OR 0.28 [95% CI 0.15 to 0.53]) and of voluntary childlessness (OR 0.28 [95% CI 0.057 to 1.3]).

CONCLUSION:

In the present study, higher IBD-specific reproductive knowledge lowered the odds of childlessness among women with IBD. Discussion of family planning with a physician was associated with higher CCPKnow scores and lower odds of voluntary childlessness.     

凉血通瘀方对脑缺血大鼠血液系统及脑损伤的影响

目的探讨凉血通瘀方对实验性脑缺血大鼠血液系统及脑损伤的影响。方法采用插线阻断大鼠脑中动脉法制备脑缺血模型,观察凉血通瘀方低、中、高剂量对脑缺血模型大鼠的行为学评分、脑梗死率,血浆中活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB),血清中组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活物抑制因子(PAI)-1、β血小板球蛋白(TG)、血小板因子(PF)4等指标的影响。结果凉血通瘀方中、高剂量能减轻模型大鼠脑损伤;延长血浆APTT、PT、TT,降低血浆中FIB含量;增加血清中t-PA含量,降低血清中PAI-1、β-TG、PF4含量。结论凉血通瘀方能改善脑缺血大鼠凝血-抗凝血-纤溶系统功能,减轻缺血引起的脑损伤。     

机械通气联合盐酸氨溴索对老年急性呼吸窘迫综合征患者氧合指标和炎性因子的影响

目的探讨机械通气与盐酸氨溴索联合治疗老年急性呼吸窘迫综合征(ARDS)的临床疗效。方法将2013年2月至2014年2月该院就诊的52例老年ARDS患者随机分为实验组和对照组,两组均采用抗炎、营养、脱水和吸痰等支持治疗,对照组仅采用机械通气治疗,实验组采用机械通气与盐酸氨溴索联合治疗。对比两组治疗前及治疗后1 w体内氧合指标及炎性因子浓度。结果两组患者经1 w治疗后,与治疗前相比,血清白细胞介素(IL)-10浓度、动脉血氧饱和度(Sa O2)、脉血氧分压(Pa O2)、氧合指数(Pa O2/Fi O2)均上升,血清IL-6和肿瘤坏死因子(TNF)-α浓度均降低(均P0.05);且实验组以上各指标较对照组改善更明显(均P0.05)。结论机械通气与盐酸氨溴索联合治疗ARDS可改善患者体内的氧合指标,调节细胞因子水平,增强患者抗炎能力,提高疗效。     

Inflammatory Bowel “Cardiac” Disease: Point Prevalence of Atrial Fibrillation in Inflammatory Bowel Disease Population

Background/Aim:

Proinflammatory markers such as interleukin (IL)-6 have been closely associated with atrial fibrillation (AF). These markers are characteristically elevated in chronic inflammatory bowel disease (IBD) and positively correlate with disease activity. Although IBD and AF have similar pathogenesis, there have been very limited studies looking at their association. The aim of this study is to determine the prevalence of AF in patients with IBD.

Patients and Methods:

Medical records of patients with biopsy proven IBD (n = 203, both in and outpatient) were retrospectively reviewed. One hundred and forty-one IBD patients with documentary evidence of electrocardiograms (ECG''s) were included. The “Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA)” study, a large cross-sectional study (n = 1.89 million) done to evaluate the prevalence of AF among the US population, was our control population. All ECGs available till December 2010 for each IBD patient were reviewed carefully for evidence of AF. We studied the prevalence of AF among IBD population and compared it to that of control (ATRIA) population.

Results:

The prevalence of AF was significantly higher among IBD patients compared with the ATRIA study patients (11.3% vs 0.9%, P < 0.0001). Additionally, the IBD patient population were much younger compared with the controls (64.4 ± 10.7 vs 71.2 ± 12.2, P = 0.02).

Conclusion:

AF has an overall higher prevalence across all age groups in IBD compared with the subjects of ATRIA study, which could be due to the chronic inflammatory state of IBD. Further studies are needed to study the association in detail.     

Systemic inflammatory response following acute myocardial infarction

Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial infarction, and heart failure) in patients with AMI.