Atypical Presentation of Bacteremia in Older Patients Is a Risk Factor for Death.

BACKGROUND: The absence of fever in bacteremia in patients who are older is known to delay diagnosis. Our objective was to determine whether atypical presentation was associated to mortality as a result of bacteremia in this patient cohort as well as possible factors associated with this atypical presentation. METHODS: We conducted an observational prospective study in 2 French university hospitals in 2016-2017 including patients ages ≥75 years with bacteremia. Atypical presentation was defined as the absence of a temperature ≥38.3°C or <36°C, chills, or hypotension. Mortality and dependence for activities of daily living (ADL) were recorded at 1 week (D7) and 3 months (D90). RESULTS: Among the 151 patients (mean age 85.4±5.8 years) enrolled, atypical presentation prevalence was 21.2%. D7 and D90 mortality rates were 7.9% and 40.0%, respectively. Atypical presentation was independently associated with D7 (odds ratio (OR) 4.46, 95% confidence interval (CI) 1.04-19.24) and D90 mortality (OR 3.76, 95% CI 1.30-10.92) after controlling for other prognostic factors. Patients with diabetes and those infected with Staphylococcus aureus were more likely to have atypical signs of infection. ADL score decreased from 3.6±2.0 before bacteremia to 2.8±2.1 at D90 (P <0.001). CONCLUSION: Patients who are older with bacteremia have poor vital and functional prognoses in the short and long terms. The absence of typical signs of infection is associated with mortality. Blood culture should be considered for patients who are older, especially with diabetes with acute unexplained clinical manifestations.

Multimorbidity, age-related comorbidities and mortality: association of activation, senescence and inflammation markers in HIV adults.

BACKGROUND: The widespread introduction of combination antiretroviral therapy (cART) has increased survival of HIV-infected patients. However, the prevalence of age-related comorbidities remains higher than that of the general population, suggesting that individuals with HIV suffer from accelerated aging. Immune activation, senescence and inflammation could play an important role in this process. METHODS: The CIADIS (Chronic Immune Activation anD Senescence) sub-study analyzed biomarkers of activation, differentiation and senescence of T cells in a cellular-CIADIS-weighted score, whereas biomarkers of inflammation were analyzed in a soluble CIADIS-weighted score using principal component analysis. Adjusted logistic regression and Cox proportional hazard models were used to determine the association between CIADIS-weighted scores and the presence of multimorbidity, time to occurrence of the first new age-related comorbidity and time to death, over a 3-year follow-up period. RESULTS: Of 828 patients with an undetectable viral load, a higher cellular-CIADIS-weighted score and higher TNFRI levels were independently associated with the presence of multimorbidity (OR 1.3; 95% CI 1.0-1.6; P = 0.02), but the soluble CIADIS-weighted score was not (OR = 1.1; 95% CI 0.9-1.3; P = 0.33). A higher cellular CIADIS-weighted score (hazard ratio 2.2; P < 0.01), higher levels of CD8 activation and a lower CD4/CD8 ratio were associated with a higher risk of age-related comorbidities. Only TNFRI was associated with mortality in a 3-year period. CONCLUSION: The cellular CIADIS-weighted score was independently associated with both multimorbidity at inclusion and the risk of new age-related comorbidity during a 3- year follow-up. TNFRI was associated a higher risk for mortality.

Mitochondria as Molecular Platforms Integrating Multiple Innate Immune Signalings.

The immune system of vertebrates confers protective mechanisms to the host through the sensing of stress-induced agents expressed during infection or cell stress. Among them, the first line of host defense composed of the innate immune sensing of these agents by pattern recognition receptors enables downstream adaptive immunity to be primed, mediating the body's appropriate response to clear infection and tissue damage. Mitochondria are «bacteria within¼ that allowed the emergence of functional eukaryotic cells by positioning themselves as the cell powerhouse and an initiator of cell death programs. It is striking to consider that such ancestral bacteria, which had to evade host defense at some point to develop evolutionary endosymbiosis, have become instrumental for the modern eukaryotic cell in alerting the immune system against various insults including infection by other pathogens. Mitochondria have indeed become critical regulators of innate immune responses to both pathogens and cell stress. They host numerous modulators, which play a direct role into the assembly of innate sensing machineries that trigger host immune response in both sterile and non-sterile conditions. Several lines of evidence indicate the existence of a complex molecular interplay between mechanisms involved in inflammation and metabolism. Mitochondrial function seems to participate in innate immunity at various stages as diverse as the transcriptional regulation of inflammatory cytokines and chemokines and their maturation by inflammasomes. Here, we review the mechanisms by which mitochondria orchestrate innate immune responses at different levels by promoting a cellular metabolic reprogramming and the cytosolic immune signaling cascades.