A validated web-based tool to display individualised Crohn's disease predicted outcomes based on clinical, serologic and genetic variables.

BACKGROUND: Early treatment for Crohn's disease (CD) with immunomodulators and/or anti-TNF agents improves outcomes in comparison to a slower 'step up' algorithm. However, there remains a limited ability to identify those who would benefit most from early intensive therapy. AIM: To develop a validated, individualised, web-based tool for patients and clinicians to visualise individualised risks for developing Crohn's disease complications. METHODS: A well-characterised cohort of adult patients with CD was analysed. Available data included: demographics; clinical characteristics; serologic immune responses; NOD2 status; time from diagnosis to complication; and medication exposure. Cox proportional analyses were performed to model the probability of developing a CD complication over time. The Cox model was validated externally in two independent CD cohorts. Using system dynamics analysis (SDA), these results were transformed into a simple graphical web-based display to show patients their individualised probability of developing a complication over a 3-year period. RESULTS: Two hundered and forty three CD patients were included in the final model of which 142 experienced a complication. Significant variables in the multivariate Cox model included small bowel disease (HR 2.12, CI 1.05-4.29), left colonic disease (HR 0.73, CI 0.49-1.09), perianal disease (HR 4.12, CI 1.01-16.88), ASCA (HR 1.35, CI 1.16-1.58), Cbir (HR 1.29, CI 1.07-1.55), ANCA (HR 0.77, CI 0.62-0.95), and the NOD2 frameshift mutation/SNP13 (HR 2.13, CI 1.33-3.40). The Harrell's C (concordance index for predictive accuracy of the model) = 0.73. When applied to the two external validation cohorts (adult n = 109, pediatric n = 392), the concordance index was 0.73 and 0.75, respectively, for adult and pediatric patients. CONCLUSIONS: A validated, web-based tool has been developed to display an individualised predicted outcome for adult patients with Crohn's disease based on clinical, serologic and genetic variables. This tool can be used to help providers and patients make personalised decisions about treatment options.

Increased level of stromal cell-derived factor-1 mRNA in peripheral blood mononuclear cells from children with AIDS-related lymphoma.

A common polymorphism in the 3' untranslated region of the stromal cell-derived factor 1 (also called pre-B-cell-stimulating factor) beta gene transcript, termed SDF1-3'A, has been associated with an increased risk of non-Hodgkin's lymphoma (NHL) in HIV-1-infected, but not in uninfected, individuals. Because the gene variation is located within the 3' untranslated region, the SDF1-3'A may influence the abundance of SDF-1 mRNA, possibly up-regulating the chemokine expression especially in the presence of HIV-1. In the current study, we investigated the levels of SDF-1 mRNA in peripheral blood mononuclear cells and HIV-1 viral load in 84 HIV-1-infected children (0.7 to 18 years of age; median, 5.8), including 12 children who developed NHL during their illnesses (AIDS-NHL group; 8 with SDF1-3'A, 4 with SDF1-wild-type). High level SDF-1 expression was observed in 15 of 34 children with SDF1-3'A as compared with 10 of 50 with wild type (P < 0.03). More notably, the children with AIDS-NHL had significantly elevated levels of SDF-1 mRNA in peripheral blood mononuclear cells, obtained at the time of presentation in 10 children and 8.5 to 19.4 months before (median, 15 months) in 7 children, as compared with the children in the non-NHL group (P < 0.00001). The amounts of cell-associated HIV-1 DNA and singly spliced HIV-1 mRNA were significantly greater in children with AIDS-NHL than those with non-NHL AIDS (P = 0.0052 and 0.011, respectively; stratified by antiretroviral treatment regimen), whereas their serum HIV-1 RNA levels were comparable. Overexpression of SDF-1 and aberrant HIV-1 expression in circulating lymphocytes appear to be linked to the development of AIDS-lymphoma. Additional studies are required to determine whether excessive SDF-1, together with virally encoded factors, is directly involved in the pathogenesis of AIDS-lymphoma.

Increased human immunodeficiency virus (HIV) type 1 DNA content and quinolinic acid concentration in brain tissues from patients with HIV encephalopathy.

Levels of human immunodeficiency virus type 1 (HIV-1) DNA and quinolinic acid were examined in areas of the central nervous system (CNS) and lymphoid organs (LN) from 5 AIDS patients with no clinically apparent CNS compromise (group I), 7 with CNS opportunistic diseases (group II), and 8 with HIV encephalopathy (group III). The brains from patients with HIV encephalopathy not only contained higher levels of HIV-1 DNA (cerebrum, P < .01; cerebellum, P < .05) as assessed by quantitative polymerase chain reaction but also showed a higher rate of viral pol region mutations suggestive of zidovudine or didanosine resistance than brains from patients in group I or II (P < .01). CNS quinolinic acid concentrations were significantly higher in group II and III patients than in group I (P = .03), even though quinolinic acid levels in LN were comparable among the 3 groups. These data suggest that CNS inflammatory changes associated with HIV encephalopathy may be triggered by a local productive HIV-1 infection within the CNS.

The spectrum of alleged rape.

A prospective series of 110 alleged rape victims from July through November 1974 at Denver General Hospital is presented. The victims and assailants are characterized. The laboratory established proof of recent coitus in 68%. Four-fifths of the victims presented within 12 hours of the alleged incident. The analysis of ABO vaginal antigens appears to be promising for assailant identification. Follow-up by appointment in this group was successful in only 5%. Only a minority of cases led to arrest and criminal proceedings. Suggestions are made for alternative approaches to victims based on new developments in forensic laboratory procedures.