Patient self-reported symptoms using visual analog scales are useful to estimate endoscopic activity in ulcerative colitis

Background/Aims In clinical practice, colonoscopy has been regarded as the gold standard for the evaluation of disease severity as well as mucosal healing in ulcerative colitis (UC). Some activity indices incorporating patient symptoms as parameters have been shown to reflect the endoscopic activity of UC. The aim of this study was to examine whether self-reported symptoms with visual analog scales (VAS) can predict endoscopic activity. Methods A cross-sectional study of 150 UC patients who underwent colonoscopy with submission of VAS scores of 4 symptoms: general condition, bloody stools, stool form, and abdominal pain (0: no symptoms, 10: the most severe symptoms). Each VAS score was compared with colonoscopic activity assessed with the Mayo endoscopic subscore (MES). Results All VAS scores were significantly correlated with the endoscopic severity (Spearman correlation coefficients of general condition, bloody stools, stool form, and abdominal pain: 0.63, 0.64, 0.58, and 0.43, respectively). Mucosal healing defined as MES 0 alone was predicted by VAS score <1.5 on general condition or 0 on bloody stools with sensitivity of 0.84 and 0.76 and specificity of 0.66 and 0.76, respectively. Additionally, VAS score <2.5 on stool form predicted active lesions in distal colorectum alone with sensitivity of 0.67 and specificity of 0.66, suggesting that this item could predict the indication of topical therapy. Conclusions Self-reported VAS scores on symptoms were correlated with endoscopic activity of UC. To clarify the relationship between VAS and mucosal healing, further validation studies are needed

Excessive Cytokine Response to Rapid Proliferation of Highly Pathogenic Avian Influenza Viruses Leads to Fatal Systemic Capillary Leakage in Chickens

Highly pathogenic avian influenza viruses (HPAIVs) cause lethal infection in chickens. Severe cases of HPAIV infections have been also reported in mammals, including humans. In both mammals and birds, the relationship between host cytokine response to the infection with HPAIVs and lethal outcome has not been well understood. In the present study, the highly pathogenic avian influenza viruses A/turkey/Italy/4580/1999 (H7N1) (Ty/Italy) and A/chicken/Netherlands/2586/2003 (H7N7) (Ck/NL) and the low pathogenic avian influenza virus (LPAIV) A/chicken/Ibaraki/1/2005 (H5N2) (Ck/Ibaraki) were intranasally inoculated into chickens. Ty/Italy replicated more extensively than Ck/NL in systemic tissues of the chickens, especially in the brain, and induced excessive mRNA expression of inflammatory and antiviral cytokines (IFN-γ, IL-1β, IL-6, and IFN-α) in proportion to its proliferation. Using in situ hybridization, IL-6 mRNA was detected mainly in microglial nodules in the brain of the chickens infected with Ty/Italy. Capillary leakage assessed by Evans blue staining was observed in multiple organs, especially in the brains of the chickens infected with Ty/Italy, and was not observed in those infected with Ck/NL. In contrast, LPAIV caused only local infection in the chickens, with neither apparent cytokine expression nor capillary leakage in any tissue of the chickens. The present results indicate that an excessive cytokine response is induced by rapid and extensive proliferation of HPAIV and causes fatal multiple organ failure in chickens

Comparison of HPAIVs and LPAIV proliferation.

<p>After 10^6.0 EID₅₀ of Ty/Italy, Ck/NL, or Ck/Ibaraki was intranasally inoculated into chickens, peripheral blood (<b>A</b>), brains (<b>B</b>), lungs (<b>C</b>), and spleens (<b>D</b>) were collected every 24 h, and infectivity titers were determined by inoculation of 10-day-old embryonated eggs. The mean values with corresponding standard errors from 3 chickens are shown. * <i>p</i><0.05 between Ty/Italy and Ck/NL, ** <i>p</i><0.05 between Ty/Italy and Ck/Ibaraki, + <i>p</i><0.05 between Ck/NL and Ck/Ibaraki.</p

IL-6 mRNA in the brain detected using <i>in</i><i>situ</i> hybridization.

<p>IL-6 mRNA expressing cells in the brains of the chickens infected with Ty/Italy was determined by <i>in situ</i> hybridization. IL-6 signals, represented as red color, were mainly localized to the microglial nodules on the section at 48 (<b>a</b>) and 96 hpi (<b>c</b>). The IL-6 mRNA was not detected in the brains of the Ck/NL-infected chickens (<b>e</b> and <b>g</b>), nor in those of the Ck/Ibaraki-infected chickens (<b>i</b> and <b>k</b>). The consecutive sections of HE staining (<b>b</b>, <b>d</b>, <b>f</b>, <b>h</b>, <b>j</b>, <b>l</b>) were examined by <i>in situ</i> hybridization (<b>a</b>, <b>c</b>, <b>e</b>, <b>g</b>, <b>i</b>, <b>k</b>), respectively. Original magnification, ×400.</p

Comparison of cytokine mRNA expression.

<p>Tissues were collected from 3 chickens per group every 24 h after inoculation with 10^6.0 EID₅₀ of HPAIVs or LPAIV, and cytokine mRNA expression in the brain (<b>A</b>), lungs (<b>B</b>), and spleen (<b>C</b>) was analyzed using real-time PCR. Data are expressed as mean fold changes with standard errors relative to β-actin mRNA. Data of dead chickens was eliminated from the results. * <i>p</i><0.05 between Ty/Italy and Ck/NL, ** <i>p</i><0.05 between Ty/Italy and Ck/Ibaraki, + <i>p</i><0.05 between Ck/NL and Ck/Ibaraki.</p

Survival rates of the chickens inoculated with Ty/Italy or Ck/NL.

<p>Chickens were intranasally inoculated with 10^6.0 EID₅₀ of Ty/Italy or Ck/NL and were observed for 12 days.</p

Extravasation of EB dye in the tissues of the chickens.

<p>Four days after infection, EB dye was intravenously injected into the chickens, and tissues were collected 3 h later. Photographs show brains of the chickens inoculated with Ty/Italy (<b>A</b> and <b>B</b>) or Ck/Ibaraki (<b>C</b>) and hearts of the chickens inoculated with Ty/Italy (<b>D</b>) or Ck/Ibaraki (<b>E</b>).</p