Computer-Aided Prediction of Long-Term Prognosis of Patients with Ulcerative Colitis after Cytoapheresis Therapy

<div><p>Cytoapheresis (CAP) therapy is widely used in ulcerative colitis (UC) patients with moderate to severe activity in Japan. The aim of this study is to predict the need of operation after CAP therapy of UC patients on an individual level using an artificial neural network system (ANN). Ninety UC patients with moderate to severe activity were treated with CAP. Data on the patients’ demographics, medication, clinical activity index (CAI) and efficacy of CAP were collected. Clinical data were divided into training data group and validation data group and analyzed using ANN to predict individual outcomes. The sensitivity and specificity of predictive expression by ANN were 0.96 and 0.97, respectively. Events of admission, operation, and use of immunomodulator, and efficacy of CAP were significantly correlated to the outcome. Requirement of operation after CAP therapy was successfully predicted by using ANN. This newly established ANN strategy would be used as powerful support of physicians in the clinical practice.</p></div

The sensitivity and specificity provided by ANN.

<p>The sensitivity and specificity provided by ANN.</p

The sensitivity and specificity provided by ANN.

<p>The sensitivity and specificity provided by ANN.</p

Factors and outcome used to predict individual patient outcome.

<p>Factors and outcome used to predict individual patient outcome.</p

Characteristics of patients.

<p>Continuous data are expressed as mean with range or number in parentheses. CAI: Clinical activity index, CAP: Cytoapheresis, PSL: Prednisolone</p><p>Characteristics of patients.</p

Relative weights of input factors for ANNs.

<p>Data are expressed as the mean±SD for member networks.</p

Accumulation of mononuclear cells in the liver develops in chronic colitis models.

<p>(<b>A</b>) H&E specimens of the liver (left) and colon (right) derived from WT, IL-10^−/− mice, and RAG-2^−/− RB^high mice. Magnification: ×100 (left) and ×400 (right). (<b>B</b>) Absolute number of hepatic mononuclear cells. FACS data are representative of three independent experiments. Values are expressed as means ± SEM for each group. WT (<i>n</i> = 5), IL-10^−/− mice (<i>n</i> = 7) and RAG-2^−/− RB^high mice (<i>n</i> = 4). *<i>P</i><0.05.</p

Accumulation of liver macrophages in acute colitis models.

<p>(<b>A</b>) H&E specimens of the colon taken from mice treated with water (left) or 2% DSS (right). Magnification, ×40 (<b>B</b>) H&E specimens of livers from mice treated with water (left) and DSS (right). Magnification, ×100 (<b>C</b>) The number of liver mononuclear cells from water- and DSS-treated mice. (<b>D</b>) The absolute number of PDCA-1⁺CD11b⁻CD11c^int pDCs and CD11b⁺CD11c⁻ Mφs among whole mononuclear cells. Data are representative of three independent experiments. (<b>E</b>) Levels of mRNA transcripts for IFN-γ, TNF, and IL-6 in the liver. Values are presented as the mean ± SEM for each group (<i>n</i> = 4, water-treated group; <i>n</i> = 5, DSS-treated group). *<i>P</i><0.05. N.S., no significant difference. (<b>F–H</b>) Hepatic DSS Mφs induce a Th1 inflammatory response. (<b>F</b>) Proliferation of naïve CFSE-labeled splenic CD4⁺ T cells. (<b>G</b>) Intracellular IFN-γ and IL-17A expression in naïve CFSE-unlabeled splenic CD4⁺ T cells from OT-II mice that were co-cultured with or without hepatic Mφs from DSS-treated WT mice in the presence of OVA. Dead cells were excluded with 7AAD staining, and CD4⁺ T cells gated on CD3⁺ CD4⁺ cells are shown. Data are representative of two independent experiments. (<b>H</b>) Representative cytokine concentrations in culture supernatants from two independent experiments. Each experiment was performed using duplicate samples.</p

Hepatic infiltration of Macrophages are obserbed in DSS-treated RAG-2^−/− mice.

<p>(<b>A</b>) H&E specimens of colon from mice treated with water (left) or 4% DSS (right). Magnification, ×100 (<b>B</b>) H&E specimens of liver from water- (left) and DSS-treated (right) mice. Magnification, ×200 (<b>C</b>) The number of liver mononuclear cells for each group of mice. (<b>D</b>) Proportion and (<b>E</b>) absolute number of PDCA-1⁺CD11b⁻CD11c^int pDCs and CD11b⁺CD11c⁻ macrophages among whole mononuclear cells. Data are representative of two independent experiments. Values are presented as the mean ± SEM for each group (<i>n</i> = 4, water-treated group; <i>n</i> = 4, DSS-treated group). *<i>P</i><0.05. N.S., no significant difference.</p

Chronic intestinal inflammation was associated with reciprocal changes in the balance of APCs.

<p>(<b>A</b>) Flow cytometry results related to mononuclear cells isolated from the livers of WT (left column), IL-10^−/− (middle), and RAG-2^−/− RB^high (right) mice. Dead cells were excluded with 7AAD staining, followed by proper use of a FSC/SSC gate. CD11b⁻, CD11b⁺CD11c^high, and CD11b⁺CD11c^low cells were gated from the cells shown in the first row. CD11b⁻ cells are shown in the second row and PDCA-1⁺CD11b⁻CD11c^int cells were analyzed. The expression of F4/80 in CD11b⁺CD11c^high cells and CD11b⁺CD11c^low cells are analyzed in the third row and the fourth row. (<b>B</b>) Proportion of PDCA-1⁺CD11b⁻CD11c^int pDCs and F4/80⁺CD11b⁺ Mφ/cDCs among whole mononuclear cells. (<b>C</b>) Proportion of F4/80⁺ CD11b⁺CD11c^high Mφ/cDCs and F4/80⁺ CD11b⁺CD11c^low Mφ/cDCs among whole mononuclear cells. (<b>D</b>) Flow cytometry analysis of mononuclear cells isolated from the colons of WT (left column), IL-10^−/− (middle), and RAG-2^−/− RB^high (right) mice. (<b>E</b>) Proportion of PDCA-1⁺CD11b⁻CD11c⁺ pDCs and F4/80⁺CD11b⁺CD11c⁻ Mφ/cDCs among whole mononuclear cells. FACS data are representative of three independent experiments expressed as means ± SEM for each group. WT (<i>n</i> = 4), IL-10^−/− (<i>n</i> = 4) and RAG-2^−/− RB^high (<i>n</i> = 3) mice. *<i>P</i><0.05.</p