The implementation of the Surviving Sepsis Campaign guidelines was associated with a significant decrease in mortality. The benefits depend on the number of interventions accomplished within the time limits. The 6-hr resuscitation bundle showed greater compliance and effectiveness than the 24-hr management bundle.

Summary In comparison with hip fractures, increased expression of genes in the Wnt pathway and increased Wnt activity were found in bone samples and osteoblast cultures from patients with osteoarthritis, suggesting the involvement of this pathway in subchondral bone changes. No consistent differences were found in the genetic association study.

Wnt 22 β-Catenin 23 DNA methylation 24 Fractures 25 Bone diseases 26We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in 27 osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic 28 and epigenetic mechanisms involved. 29 β-Catenin gene expression and nuclear levels were analyzed by real time PCR and confocal immunofluorescence. 30 Increased nuclear β-catenin was found in osteoblasts isolated from patients with osteoarthritis (99 ± 4 31 units vs. 76 ± 12, p = 0.01, n = 10), without differences in gene transcription, which is consistent with 32 a post-translational down-regulation of β-catenin and decreased Wnt pathway activity.33 Twenty four single nucleotide polymorphisms (SNPs) of genes showing differential expression between fractures 34 and osteoarthritis (WNT4, WNT10A, WNT16 and SFRP1) were analyzed in DNA isolated from blood of 853 pa-35 tients. The genotypic frequencies were similar in both groups of patients, with no significant differences. 36 Methylation of Wnt pathway genes was analyzed in bone tissue samples (15 with fractures and 15 with osteo-37 arthritis) by interrogating a CpG-based methylation array. Six genes showed significant methylation differences 38 between both groups of patients: FZD10, TBL1X, CSNK1E, WNT8A, CSNK1A1L and SFRP4. The DNA demethylating 39 agent 5-deoxycytidine up-regulated 8 genes, including FZD10, in an osteoblast-like cell line, whereas it down-40 regulated other 16 genes. 41 In conclusion, Wnt activity is reduced in patients with hip fractures, in comparison with those with osteoarthritis. 42 It does not appear to be related to differences in the allele frequencies of the Wnt genes studied. On the other 43 hand, methylation differences between both groups could contribute to explain the differences in Wnt activity.44

In our study MR-proADM levels correlate with increasing severity of illness and death. High MR-proADM levels offer additional risk stratification in high-risk CAP patients.