Which PCDAI Version Best Reflects Intestinal Inflammation in Pediatric Crohn Disease?

INTRODUCTION: There is increasing interest in measuring mucosal inflammation in Crohn disease (CD), but there are minimal data correlating the Pediatric Crohn's Disease Activity Index (PCDAI) versions (PCDAI, weighted Pediatric Crohn's Disease Activity Index [wPCDAI], abbreviated Pediatric Crohn's Disease Activity Index [abbrPCDAI], and the short Pediatric Crohn's Disease Activity Index [shPCDAI]) with mucosal inflammation. METHODS: We aimed to compare the 4 PCDAI versions head to head with endoscopic degree of inflammation as measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD), fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and to explore cut-off values that are associated with mucosal healing. We used the prospectively collected data from the ImageKids study on 100 children with CD undergoing colonoscopy and from the Growth Relapse and Outcomes with Therapy study (n = 222), in which 145 children had calprotectin data at week 12 after diagnosis. RESULTS: All 4 PCDAI versions had fair correlation with the SES-CD (r = 0.42-0.45, all P < 0.001) and CRP (r = 0.32-0.45, all P < 0.01); the wPCDAI and PCDAI were superior to the shorter versions when comparing the blood tests. All versions had poor correlation with calprotectin, and only the wPCDAI reached significance (r = 0.26, P = 0.002 vs r = 0.15, P = 0.07 for PCDAI; r = 0.08, P = 0.37 for shPCDAI; r = 0.06, P = 0.5 for abbrPCDAI). The best cut-off to identify endoscopic mucosal healing was <12.5 points for the wPCDAI (sensitivity 58% and specificity 84%) and <10 for PCDAI (sensitivity 63% and specificity 77%). CONCLUSIONS: The more feasible wPCDAI and the PCDAI had comparable correlation with measures of endoscopic inflammation. These were slightly superior to the other 2 shorter versions, but still none of the PCDAI versions can give a valid assessment of mucosal healing.

Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells.

In non-small cell lung carcinoma (NSCLC), stimulation of toll-like receptor 7 (TLR7), a receptor for single stranded RNA, is linked to tumor progression and resistance to anticancer chemotherapy. However, the mechanism of this effect has been elusive. Here, using a murine model of lung adenocarcinoma, we demonstrate a key role for TLR7 expressed by malignant (rather than by stromal and immune) cells, in the recruitment of myeloid derived suppressor cells (MDSCs), induced after TLR7 stimulation, resulting in accelerated tumor growth and metastasis. In adenocarcinoma patients, high TLR7 expression on malignant cells was associated with poor clinical outcome, as well as with a gene expression signature linked to aggressiveness and metastastic dissemination with high abundance of mRNA encoding intercellular adhesion molecule 1 (ICAM-1), cytokeratins 7 and 19 (KRT-7 and 19), syndecan 4 (SDC4), and p53. In addition, lung tumors expressing high levels of TLR7 have a phenotype of epithelial mesenchymal transition with high expression of vimentin and low abundance of E-cadherin. These data reveal a crucial role for cancer cell-intrinsic TLR7 expression in lung adenocarcinoma progression.