Additional file 1: Table S1. of Smoking influences the need for surgery in patients with the inflammatory bowel diseases: a systematic review and meta-analysis incorporating disease duration

Search strategy. (DOCX 84 kb

Additional file 2: Figure S1. of Smoking influences the need for surgery in patients with the inflammatory bowel diseases: a systematic review and meta-analysis incorporating disease duration

Study flow diagram. (DOCX 108 kb

Additional file 6: Table S5. of Smoking influences the need for surgery in patients with the inflammatory bowel diseases: a systematic review and meta-analysis incorporating disease duration

Sensitivity analysis substituting age-specific smoking-surgery analyses into the overall estimate. (DOCX 75 kb

mRNA expression of FPR2/ALX in colonic mucosal biopsies from healthy subjects without(Ctrl) or with a prior history (Hx) of UC, or UC patients with active disease (Active) or medically-induced remission (Rem).

<p> Increased expression of FPR2/ALX was detected in biopsies from individuals with UC. Data are expressed as fold change relative to Ctrl (**<i>P</i><.01, n = 5–12).</p

Quantitative Metabolomic Profiling of Serum, Plasma, and Urine by ¹H NMR Spectroscopy Discriminates between Patients with Inflammatory Bowel Disease and Healthy Individuals

Serologic biomarkers for inflammatory bowel disease (IBD) have yielded variable differentiating ability. Quantitative analysis of a large number of metabolites is a promising method to detect IBD biomarkers. Human subjects with active Crohn’s disease (CD) and active ulcerative colitis (UC) were identified, and serum, plasma, and urine specimens were obtained. We characterized 44 serum, 37 plasma, and 71 urine metabolites by use of ¹H NMR spectroscopy and “targeted analysis” to differentiate between diseased and non-diseased individuals, as well as between the CD and UC cohorts. We used multiblock principal component analysis and hierarchical OPLS-DA for comparing several blocks derived from the same “objects” (e.g., subject) to examine differences in metabolites. In serum and plasma of IBD patients, methanol, mannose, formate, 3-methyl-2-oxovalerate, and amino acids such as isoleucine were the metabolites most prominently increased, whereas in urine, maximal increases were observed for mannitol, allantoin, xylose, and carnitine. Both serum and plasma of UC and CD patients showed significant decreases in urea and citrate, whereas in urine, decreases were observed, among others, for betaine and hippurate. Quantitative metabolomic profiling of serum, plasma, and urine discriminates between healthy and IBD subjects. However, our results show that the metabolic differences between the CD and UC cohorts are less pronounced

Figure 1

<p>Expression of HNE and CD68 in colonic mucosal biopsies from healthy subjects without (Ctrl) or with a prior history (Hx) of UC, or UC patients with active disease (Active) or medically-induced remission (Rem) (<b>A</b>). HNE expression (Upper), used to detect PMNs was elevated in UC patients with active disease. CD68 expression (Lower), a pan macrophage marker, was elevated in active disease as well as in medically-induced remission. Cumulative analysis (mean counts/field) of HNE (<b>B</b>) and CD68 expression (<b>C</b>)<b>.</b> Dual-staining of macrophage populations with CD68 and CD206, markers for alternatively activated (M2) macrophages (<b>D</b>), Data are expressed as mean ± SEM (*<i>P</i><.05, ***<i>P</i><.001, n = 4). Magnification bar = 100μm.</p

Figure 2

<p>Colonic mucosal lipoxin A₄ levels (<b>A</b>) in biopsies from healthy subjects without (Ctrl) or with a prior history (Hx) of UC, or UC patients with active disease (Active) or medically-induced remission (Rem). Lipoxin A₄ levels were significantly elevated in the samples from patients who were in medically-induced remission compared with healthy subjects and those with a prior history of UC (>4 years disease-free). Quantitative RT-PCR analysis of 5-LO (<b>B</b>), 12-LO (<b>C</b>) and 15-LO (<b>D</b>) expression revealed an increase of 5-LO expression in patients with active disease. This correlated with an increase in the number of 5-LO-positive cells as assessed by immunohistochemistry (<b>E</b>). Data are expressed as fold change relative to Ctrl (*<i>P</i><.05, **<i>P</i><.01 ***<i>P</i><.001, n = 5–20). Magnification bar = 100 μm.</p

Quantitative Metabolomic Profiling of Serum, Plasma, and Urine by ¹H NMR Spectroscopy Discriminates between Patients with Inflammatory Bowel Disease and Healthy Individuals

Serologic biomarkers for inflammatory bowel disease (IBD) have yielded variable differentiating ability. Quantitative analysis of a large number of metabolites is a promising method to detect IBD biomarkers. Human subjects with active Crohn’s disease (CD) and active ulcerative colitis (UC) were identified, and serum, plasma, and urine specimens were obtained. We characterized 44 serum, 37 plasma, and 71 urine metabolites by use of ¹H NMR spectroscopy and “targeted analysis” to differentiate between diseased and non-diseased individuals, as well as between the CD and UC cohorts. We used multiblock principal component analysis and hierarchical OPLS-DA for comparing several blocks derived from the same “objects” (e.g., subject) to examine differences in metabolites. In serum and plasma of IBD patients, methanol, mannose, formate, 3-methyl-2-oxovalerate, and amino acids such as isoleucine were the metabolites most prominently increased, whereas in urine, maximal increases were observed for mannitol, allantoin, xylose, and carnitine. Both serum and plasma of UC and CD patients showed significant decreases in urea and citrate, whereas in urine, decreases were observed, among others, for betaine and hippurate. Quantitative metabolomic profiling of serum, plasma, and urine discriminates between healthy and IBD subjects. However, our results show that the metabolic differences between the CD and UC cohorts are less pronounced

Quantitative Metabolomic Profiling of Serum, Plasma, and Urine by ¹H NMR Spectroscopy Discriminates between Patients with Inflammatory Bowel Disease and Healthy Individuals

Serologic biomarkers for inflammatory bowel disease (IBD) have yielded variable differentiating ability. Quantitative analysis of a large number of metabolites is a promising method to detect IBD biomarkers. Human subjects with active Crohn’s disease (CD) and active ulcerative colitis (UC) were identified, and serum, plasma, and urine specimens were obtained. We characterized 44 serum, 37 plasma, and 71 urine metabolites by use of ¹H NMR spectroscopy and “targeted analysis” to differentiate between diseased and non-diseased individuals, as well as between the CD and UC cohorts. We used multiblock principal component analysis and hierarchical OPLS-DA for comparing several blocks derived from the same “objects” (e.g., subject) to examine differences in metabolites. In serum and plasma of IBD patients, methanol, mannose, formate, 3-methyl-2-oxovalerate, and amino acids such as isoleucine were the metabolites most prominently increased, whereas in urine, maximal increases were observed for mannitol, allantoin, xylose, and carnitine. Both serum and plasma of UC and CD patients showed significant decreases in urea and citrate, whereas in urine, decreases were observed, among others, for betaine and hippurate. Quantitative metabolomic profiling of serum, plasma, and urine discriminates between healthy and IBD subjects. However, our results show that the metabolic differences between the CD and UC cohorts are less pronounced

Detection of annexin-A1 NH₂-terminal-intact and -cleaved fragments in biopsies from healthy subjects without(Ctrl) or with a prior history (Hx) of UC, or UC patients with active disease (Active) or medically-induced remission (Rem).

<p>Annexin-1 was overexpressed in colonic mucosal biopsies of patients with UC compared to healthy patients with a prior history of UC (<b>A</b>). Alongside the native 37 kDa fragment, a NH₂-terminal cleaved isoform (33 kDa) could also be visualized, indicating specific degradation in response to externalization from activated cells. Analysis of relative intensity, where annexin-A1 immunoreactivity was normalized against β-actin (<b>B</b>). Data are expressed as mean ± SEM (**<i>P</i><.01, n = 5–11).</p