Supplementary Data are available at NAR Online: Supplementary Figures S1-S9.  Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis BACKGROUND: Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome. METHOD: We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission. RESULTS: Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome. CONCLUSION: The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients. Community-acquired pneumonia (CAP) is considered the leading cause of death from infectious disease in developed countries [1] . In Mexico, the annual estimated incidence is100 to 230 cases per 100, 000 inhabitants, causing an alarming impact on public health since 25% of these cases require hospitalization [2] . Severity assessment scores help identify high-risk patients that need hospital therapy; however, the lack of specific and valid pathophysiologic severity markers affects early effective interventions. The recent H1N1 influenza pandemic (p2009A H1N1 or S-OIV) was associated with an increase in cases of CAP that required hospitalization and continues to be a national public health threat [3] [4] [5] [6] . Although the mortality rate was only 1.8%, 31% of patients with severe disease were admitted to an intensive care unit, and 14%-46% died [7] [8] [9] [10] . The first 18 cases, seen from March 24 to April 24, 2009 were reported at the National Institute of Respiratory Diseases in Mexico City. More than half of the patients were between 13 and 47 years of age. Twelve patients required mechanical ventilation and seven died (38%) [3] . Increased mortality was associated with systemic manifestations and complications of CAP with sepsis being the most common and challenging.