RESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is associated with complications, frequent hospitalizations, surgery and death. The introduction of biologic drugs into the therapeutic arsenal in the last two decades, combined with an expansion of immunosuppressant therapy, has changed IBD management and may have altered the profile of hospitalizations and in-hospital mortality (IHM) due to IBD. AIM: To describe hospitalizations from 2008 to 2018 and to analyze IHM from 1998 to 2017 for IBD in Brazil. METHODS: This observational, retrospective, ecological study used secondary data on hospitalizations for IBD in Brazil for 2008-2018 to describe hospitalizations and for 1998-2017 to analyze IHM. Hospitalization data were obtained from the Hospital Information System of the Brazilian Unified Health System and population data from demographic censuses. The following variables were analyzed: Number of deaths and hospitalizations, length of hospital stay, financial costs of hospitalization, sex, age, ethnicity and type of hospital admission. RESULTS: There was a reduction in the number of IBD hospitalizations, from 6975 admissions in 1998 to 4113 in 2017 (trend: y = -0.1682x + 342.8; R2 = 0.8197; P < 0.0001). The hospitalization rate also decreased, from 3.60/100000 in 2000 to 2.17 in 2010. IHM rates varied during the 20-year period, between 2.06 in 2017 and 3.64 in 2007, and did not follow a linear trend (y = -0.0005049x + 2.617; R2 = 0,00006; P = 0.9741). IHM rates also varied between regions, increasing in all but the southeast, which showed a decreasing trend (y = -0.1122x + 4.427; R2 = 0,728; P < 0.0001). The Southeast region accounted for 44.29% of all hospitalizations. The Northeast region had the highest IHM rate (2.86 deaths/100 admissions), with an increasing trend (y = 0.1105x + 1.110; R2 = 0.6265; P < 0.0001), but the lowest hospitalization rate (1.15). The Midwest and South regions had the highest hospitalization rates (3.27 and 3.17, respectively). A higher IHM rate was observed for nonelective admissions (2.88), which accounted for 81% of IBD hospitalizations. The total cost of IBD hospitalizations in 2017 exhibited an increase of 37.5% compared to 2008. CONCLUSION: There has been a notable reduction in the number of hospitalizations for IBD in Brazil over 20 years. IHM rates varied and did not follow a linear trend.
RESUMO
CBA mice macrophages (MØ) control infection by Leishmania major and are susceptive to Leishmania amazonensis, suggesting that both parasite species induce distinct responses that play important roles in infection outcome. To evaluate the MØ responses to infection arising from these two Leishmania species, a proteomic study using a Multidimensional Protein Identification Technology (MudPIT) approach with liquid chromatography tandem mass spectrometry (LC-MS/MS) was carried out on CBA mice bone-marrow MØ (BMMØ). Following SEQUEST analysis, which revealed 2,838 proteins detected in BMMØ, data mining approach found six proteins significantly associated with the tested conditions. To investigate their biological significance, enrichment analysis was performed using Ingenuity Pathway Analysis (IPA). A three steps IPA approach revealed 4 Canonical Pathways (CP) and 7 Upstream Transcriptional Factors (UTFs) strongly associated with the infection process. NRF2 signatures were present in both CPs and UTFs pathways. Proteins involved in iron metabolism, such as heme oxigenase 1 (HO-1) and ferritin besides sequestosome (SQSMT1 or p62) were found in the NRF2 CPs and the NRF2 UTFs. Differences in the involvement of iron metabolism pathway in Leishmania infection was revealed by the presence of HO-1 and ferritin. Noteworty, HO-1 was strongly associated with L. amazonensis infection, while ferritin was regulated by both species. As expected, higher HO-1 and p62 expressions were validated in L. amazonensis-infected BMMØ, in addition to decreased expression of ferritin and nitric oxide production. Moreover, BMMØ incubated with L. amazonensis LPG also expressed higher levels of HO-1 in comparison to those stimulated with L. major LPG. In addition, L. amazonensis-induced uptake of holoTf was higher than that induced by L. major in BMMØ, and holoTf was also detected at higher levels in vacuoles induced by L. amazonensis. Taken together, these findings indicate that NRF2 pathway activation and increased HO-1 production, together with higher levels of holoTf uptake, may promote permissiveness to L. amazonensis infection. In this context, differences in protein signatures triggered in the host by L. amazonensis and L. major infection could drive the outcomes in distinct clinical forms of leishmaniasis.
