Increased Expression of Interleukin-13 Receptor in Ileum Associated With Nonresponse to Adalimumab in Ileal Crohn's Disease.

BACKGROUND: The terminal ileum poses a predilection for Crohn's disease (CD) but is less susceptible to undergo healing to treatment with biologics and small molecules. This study aimed to evaluate histologic features associated with endoscopic remission (ER). METHODS: This is a post hoc analysis of patients with moderately to severely active CD, defined as Crohn's disease activity index 220 to 450, and terminal ileal ulceration treated with antitumor necrosis factor (TNF)-α inhibitor adalimumab from the EXTEND trial. We studied whether baseline total Global Histologic Disease Activity Scores (GHAS), any individual histologic element, and specific immunohistochemical (IHC) markers of chronic inflammation from biopsy specimens were associated with postinduction (week 12) and maintenance (week 52) ER, defined as Simple Endoscopic Score for Crohn's Disease of 0. Multivariable logistic regression models adjusted for confounders were used to assess the relationship between histologic markers and 1-year outcomes. RESULTS: Seventy-one adult patients with CD affecting the ileum were included in this analysis. Both baseline ileal GHAS scores and individual histologic components were not found to be associated with ER at weeks 12 or 52. Increased expression of interleukin-13 receptor (IL-13R) on IHC stains was associated with reduced likelihood of achieving 1-year ER (adjusted odds ratio, 0.06; 95% CI, 0.01-0.92; P = .044). No other biomarker assessed was associated with 1-year ER. CONCLUSIONS: Ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not associated with 1-year ER. However, strong staining for IL-13 receptor in the ileum was associated with reduced odds of 1-year ER using adalimumab. Mucosal cellular disease profiles might pose an opportunity to guide treatment of CD.

In this post hoc analysis, ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not predictive of 1-year ER. However, strong staining for IL-13R in the ileum was associated with reduced odds of 1-year ER using adalimumab.

Noninvasive Methods For Assessing Inflammatory Bowel Disease Activity in Pregnancy: A Systematic Review.

Active inflammatory bowel disease (IBD) may increase the risk of adverse outcomes during pregnancy. Our aim was to systematically review the role of noninvasive fecal tests, such as fecal calprotectin (FCP) and lactoferrin (FL), and laboratory tests including C-reactive protein (CRP), hemoglobin, and albumin in the assessment of IBD during pregnancy. A systematic search of electronic databases was performed through October 2018 for studies assessing the utility of fecal and laboratory tests in predicting IBD activity in pregnant patients. Active disease was defined based on routinely used clinical criteria such as the Harvey-Bradshaw Index or Mayo score for ulcerative colitis. Noninvasive test levels were stratified by the presence of active disease and by gestational period (preconception, first trimester, second trimester, and third trimester). Thirteen studies were included. Both FCP and FL levels were significantly higher in pregnant patients with IBD compared with those without IBD. FCP levels were also significantly higher in patients with active disease compared with those with the inactive disease during all gestational periods. Furthermore, 3 studies demonstrated no consistent correlation with serum CRP and active IBD during pregnancy. Similarly, serum albumin and hemoglobin levels did not correlate with disease activity in pregnant patients with IBD. Given the lack of high-quality evidence, only FCP appears to correlate with IBD activity in all gestational periods of pregnancy. The utility of the other noninvasive tests such as serum CRP, hemoglobin, and albumin remains to be determined in this population.

First and Second Trimester Serum sFlt-1/PlGF Ratio and Subsequent Preeclampsia: A Systematic Review.

OBJECTIVE: Angiogenic biomarkers may be predictive of preeclampsia before clinical symptoms. The objective of this review was to determine the relationship between first and second trimester soluble fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) ratio and preeclampsia. METHODS: A search algorithm using appropriate medical subject headings was developed. PubMed, EMBASE, and Cochrane were searched for publications from inception to July 4, 2017. Observational studies, including prospective and retrospective cohorts, that measured serum sFlt-1/PlGF ratio at ≤24 weeks' gestation were included. Study characteristics, study design, timing of blood samples, and outcome data were systematically extracted. Study cohorts were grouped into women with low-risk and high-risk factors for preeclampsia. RESULTS: Fifteen studies were included for analysis, including 11 779 pregnancies. In studies of women with low-risk features, four subgroups from seven studies demonstrated higher sFlt-1/PlGF ratios in women who developed preeclampsia versus those who did not. In studies of women with high-risk features, six subgroups from nine studies demonstrated a higher sFlt-1/PlGF ratio in women who later developed preeclampsia. Elevated sFlt-1/PlGF ratios were especially seen in women who had early-onset or severe preeclampsia. CONCLUSION: The serum sFlt-1/PlGF ratio measured at ≤24 weeks' gestation may be elevated in select women who later develop preeclampsia, but inconsistently so.

Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery.

BACKGROUND: Atrial fibrillation is a common post-operative complication of cardiac surgery and is associated with an increased risk of post-operative stroke, increased length of intensive care unit and hospital stays, healthcare costs and mortality. Numerous trials have evaluated various pharmacological and non-pharmacological prophylactic interventions for their efficacy in preventing post-operative atrial fibrillation. We conducted an update to a 2004 Cochrane systematic review and meta-analysis of the literature to gain a better understanding of the effectiveness of these interventions. OBJECTIVES: The primary objective was to assess the effects of pharmacological and non-pharmacological interventions for preventing post-operative atrial fibrillation or supraventricular tachycardia after cardiac surgery. Secondary objectives were to determine the effects on post-operative stroke or cerebrovascular accident, mortality, cardiovascular mortality, length of hospital stay and cost of treatment during the hospital stay. SEARCH METHODS: We searched the Cochrane Central Register of ControlLed Trials (CENTRAL) (Issue 8, 2011), MEDLINE (from 1946 to July 2011), EMBASE (from 1974 to July 2011) and CINAHL (from 1981 to July 2011). SELECTION CRITERIA: We selected randomized controlled trials (RCTs) that included adult patients undergoing cardiac surgery who were allocated to pharmacological or non-pharmacological interventions for the prevention of post-operative atrial fibrillation or supraventricular tachycardia, except digoxin, potassium (K(+)), or steroids. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted study data and assessed trial quality. MAIN RESULTS: One hundred and eighteen studies with 138 treatment groups and 17,364 participants were included in this review. Fifty-seven of these studies were included in the original version of this review while 61 were added, including 27 on interventions that were not considered in the original version. Interventions included amiodarone, beta-blockers, sotalol, magnesium, atrial pacing and posterior pericardiotomy. Each of the studied interventions significantly reduced the rate of post-operative atrial fibrillation after cardiac surgery compared with a control. Beta-blockers (odds ratio (OR) 0.33; 95% confidence interval) CI 0.26 to 0.43; I(2) = 55%) and sotalol (OR 0.34; 95% CI 0.26 to 0.43; I(2) = 3%) appear to have similar efficacy while magnesium's efficacy (OR 0.55; 95% CI 0.41 to 0.73; I(2) = 51%) may be slightly less. Amiodarone (OR 0.43; 95% CI 0.34 to 0.54; I(2) = 63%), atrial pacing (OR 0.47; 95% CI 0.36 to 0.61; I(2) = 50%) and posterior pericardiotomy (OR 0.35; 95% CI 0.18 to 0.67; I(2) = 66%) were all found to be effective. Prophylactic intervention decreased the hospital length of stay by approximately two-thirds of a day and decreased the cost of hospital treatment by roughly $1250 US. Intervention was also found to reduce the odds of post-operative stroke, though this reduction did not reach statistical significance (OR 0.69; 95% CI 0.47 to 1.01; I(2) = 0%). No significant effect on all-cause or cardiovascular mortality was demonstrated. AUTHORS' CONCLUSIONS: Prophylaxis to prevent atrial fibrillation after cardiac surgery with any of the studied pharmacological or non-pharmacological interventions may be favored because of its reduction in the rate of atrial fibrillation, decrease in the length of stay and cost of hospital treatment and a possible decrease in the rate of stroke. However, this review is limited by the quality of the available data and heterogeneity between the included studies. Selection of appropriate interventions may depend on the individual patient situation and should take into consideration adverse effects and the cost associated with each approach.

Prognostic importance of preoperative anti-PF4/heparin antibodies in patients undergoing cardiac surgery. A systematic review.

It was the objective of this study to obtain best estimates of the prevalence of anti-PF4/heparin antibodies in patients not suspected to have clinical heparin-induced thrombocytopenia (HIT) prior to undergoing cardiac surgery and to determine whether preoperative antibody status and antibody class is predictive of postoperative thromboembolic outcomes, non-thromboembolic outcomes, length of stay, and mortality. PubMed and EMBASE online databases were searched up to July 2011, and we included studies involving adults undergoing cardiac surgery examining the relationship between preoperative anti-PF4/heparin antibodies (ELISA) and postoperative clinical outcomes. Five studies involving a combined total of 2,332 patients met our inclusion criteria. Preoperative anti-PF4/heparin antibodies were detected in 5-22% of patients. No study demonstrated an association between preoperative anti-PF4/heparin antibodies and postoperative thromboembolic outcomes or mortality. Three studies demonstrated a statistically significant association between preoperative anti-PF4/heparin antibodies and length of stay while two showed an association with non-thromboembolic complications. In the one study that examined outcomes by anti-PF4/heparin antibody class, IgM antibodies predicted non-thromboembolic complications and length-of-stay. None of the studies reported prior heparin exposure, and most studies did not examine the relationship of the absolute value of antibody titres (ELISA OD) and risk, nor the incidence of true/clinical HIT in preoperative positive or negative patients. In conclusion, pre-formed anti-PF4/heparin antibodies are common in patients undergoing cardiac surgery, but the available literature does not support that they predict postoperative thromboembolic complications or death. There does appear to be an association between anti-PF4/heparin antibodies and non-thromboembolic adverse events, but a causal relationship is unlikely.