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Inflammation is a common process involved in aging, multiple sclerosis (MS), and age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), but there is limited evidence for the effects of aging on inflammation in the central nervous system. We collected cerebrospinal fluid (CSF) from 105 healthy control subjects representing a wide age range (23–86), and analyzed levels of cytokines associated innate immunity (TNF-α) and different T-helper subtypes: interferon–gamma induced protein 10 (IP-10) for Th1, interleukin-10 (IL-10) for Th2, and interleukin 8 (IL-8/CXCL8) for Th17. We show that CSF levels of TNF-α, IP-10, and IL-8 all increased linearly with age, but levels of IL-10 demonstrated a U-shaped relationship with age. We further found greater age-related increases in TNF-α, IL-10, and IL-8 relative to increases in IP-10 levels, consistent with a shift from Th1 to other inflammatory phenotypes. Finally, when we analyzed the same four cytokines in people with neurological disorders, we found that MS and AD, but not PD or dementia with Lewy bodies, further accentuated the age-related shift from Th1- to non-Th1-related cytokines. We propose that CSF cytokine levels represent powerful surrogates of brain inflammation and aging, and some, but not all, neurological disorders accelerate the shift away from Th1 phenotypes.

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BackgroundAcute kidney injury (AKI) occurs frequently in hospitalized patients and has been associated with the administration of certain medications. Concerns have been raised in recent reports that the antibiotic combination of vancomycin and piperacillin/tazobactam (combV/P) may be more associated with AKI than monotherapy with either drug.MethodsTo compare the incidence of and risk factors for AKI in patients receiving combV/P versus monotherapy with either drug, a retrospective study was conducted in non-critically ill inpatients at a large urban teaching hospital. AKI was defined as either: (1) Increase in serum creatinine ≥0.5 mg/dl OR (2) ≥1.5-fold creatinine increase from admission baseline. In addition to standard multivariable regression adjustment, propensity score weighting was used as a robust approach to reduce the effects of covariate confounding when estimating the adjusted odds of AKI.ResultsA total of 228 patients were evaluated. The overall incidence of AKI was 11.8 % (27 of 228 patients). AKI occurred in 4 of 101 patients in the vanc group (4.0 %), 4 of 26 patients in the piptazo group (15.4 %), and 19 of 101 patients in the combV/P group (18.8 %). The univariable odds of AKI was significantly lower in the vanc group compared to both the combV/P group (OR 0.178, 95 % CI 0.058–0.544, p = 0.003) and piptazo (OR 0.227, 95 % CI 0.053–0.978, p = 0.047) group. A multivariable model accounting for baseline characteristics again showed that vanc monotherapy was associated with lower odds of AKI than combV/P (OR 0.14, 95 % CI 0.04–0.52, p = 0.004). Male sex was also associated with lower odds of AKI (OR 0.28, 95 % CI 0.10–0.79, p = 0.02) in the multivariable model. In the propensity score analysis using inverse probability of treatment weighting (IPTW), vanc monotherapy and male sex were again associated with lower odds of AKI (OR 0.17; 95 % CI 0.04–0.62, p = 0.008 and OR 0.28, 95 % CI 0.09–0.89, p = 0.03, respectively).ConclusionThis study substantiates recent reports that combV/P may be more associated with AKI than vanc monotherapy in hospital inpatients. AKI also appears to be more likely in females during therapy with these antimicrobials. While severity of illness is difficult to account for, these findings are further justification for narrowing antibiotic coverage when possible after this combination has been initiated in hospitalized patients.