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

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

Factors and outcome used to predict individual patient outcome.

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

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

Newly recruited macrophages in the liver during colitis predispose it to inflammation.

<p>WT mice were treated under SPF conditions with 2% DSS for 5 days and subsequently with water for 2 days (<i>n</i> = 5 mice per group). The Fas-activating antibody, Jo2, was injected i.p. into mice. (<b>A</b>) Changes in body weight are expressed as a percentage of original weight. Values are presented as the mean ± SEM for each group. Data are representative of two independent experiments. (<b>B</b>) Macroscopic view of livers from water- (left) and DSS-treated mice. (<b>C</b>) Levels of aspartate aminotransferase (left) and alanine aminotransferase (right) in water- and DSS-treated mice 6 h after Jo2 injection.</p

Immune dysregulation in the liver independent of T cell accumulation in the liver.

<p>(<b>A</b>) Numbers of hepatic mononuclear cells. Data are presented as the mean ± SEM for each group. RAG-2^−/− mice (<i>n</i> = 4) and RAG-2^−/− LP CD4⁺ mice (<i>n</i> = 4). (<b>B</b>) Representative data from flow cytometry analysis of Th cells in each organ. Dead cells were excluded by 7AAD staining. (<b>C</b>) Numbers of hepatic CD3⁺ CD4⁺ Th cells and non-T cells. (<b>D</b>) Representative data from flow cytometry analysis of pDCs and Mφs in the liver of each experimental group. Dead cells were excluded using 7AAD staining. Scatter plots for CD11b⁻CD11c^int and CD11b⁺CD11c⁻ cells are shown in the middle and bottom rows, respectively. (<b>E</b>) Proportion of PDCA-1⁺CD11b⁻CD11c^int pDCs and F4/80⁺CD11b⁺CD11c⁻ Mφs among whole mononuclear cells. Data are representative of three independent experiments. Values are presented as the mean ± SEM from seven mice in each group. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.005.</p