Liappis, Angelike P.

Background: Persistent inflammation and incomplete immune recovery among persons with HIV (PHIV) are associated with increased disease risk. We hypothesized that the angiotensin receptor blocker (ARB) losartan would reduce inflammation by mitigating nuclear factor (NF)κB responses and promote T-cell recovery via inhibition of transforming growth factor-beta (TGFβ)-mediated fibrosis. Methods: Losartan (100 mg) versus placebo over 12 months was investigated in a randomized (1 : 1) placebo-controlled trial, among PHIV age at least 50 years, receiving antiretroviral therapy (ART), with HIV RNA less than 200 copies/ml and CD4+ cell count 600 cells/μl or less. Inflammation, fibrosis and myocardial biomarkers were measured in blood using ELISA, electrochemiluminescence and immunoturbidimetric methods, and T-cell and monocyte phenotypes were assessed with flow cytometry among a subset of participants. Changes over follow-up in (log-2 transformed) biomarkers and cell phenotypes (untransformed) were compared between losartan and placebo arms using linear mixed models. Results: Among 108 PHIV (n = 52 to losartan; n = 56 to placebo), 97% had a month 12 visit. Median age was 57 years and baseline CD4+ cell count was 408 cells/μl. Losartan treatment was not associated with an improvement in interleukin-6 levels, or other blood measures of inflammation, immune activation, fibrosis activity or myocardial function. CD4+ and CD8+ T cells also did not differ by treatment group. Losartan reduced SBP and DBP by 6 and 5 mmHg, respectively. Conclusion: Among older PHIV with viral suppression, losartan did not improve blood measures of inflammation nor T-cell immune recovery. Losartan treatment is unlikely to reduce inflammation associated comorbidities to a clinically meaningful degree, beyond the benefits from lowering blood pressure. ClinicalTrials.gov: NCT02049307.

AbstractBackgroundCefazolin is used as standard preoperative prophylaxis for a variety of surgical procedures that involve the skin. In contrast, vancomycin is recommended for a minority of patients, specifically those with an IgE‐mediated allergy to beta‐lactams and considered in patients with known colonization with methicillin‐resistant Staphylococcus aureus or at high risk for such. Vancomycin, however, has been overprescribed, has nephrotoxicity risk, and may be less effective due to its inferior coverage of methicillin‐susceptible S. aureus and lack of Gram‐negative coverage. This study was performed to assess whether vancomycin use was associated with an increased incidence of cardiovascular implantable electronic device infection (CIEDI) as compared to that of cefazolin or other antistaphylococcal beta‐lactam antibiotics.MethodsThe VA Informatics and Computing Infrastructure database, which included all veterans who underwent CIED placement or revision between 2008 and 2015, was used. A logistic regression model was constructed to estimate the adjusted odds of CIEDI.ResultsOverall, 10,454 CIED procedures were included, and 98% of them were performed in men with a mean age of 71 ± 12 years. The logistic regression analysis showed that vancomycin use alone or in combination with other antibiotics was associated with an increased risk of CIEDI (odds ratio 2.99 [1.76–5.06], P‐value < 0.001), after controlling for other effects.ConclusionsOur study revealed that among patients who received surgical site infection prophylaxis for CIED placement or revision, there was: (1) an unanticipated high rate of vancomycin use, and (2) a threefold increase in the incidence of subsequent CIEDI among vancomycin recipient

AbstractBackgroundThe rate of cardiovascular implantable electronic device infection (CIEDI) has increased, despite the use of perioperative antibiotics at the time of device placement or revision. This is due, in part, to the presence of multiple comorbid conditions in an elderly population, in general, who require CIED. Statins may have an antibacterial effect, although there is currently no evidence that the likelihood of CIEDI has been impacted by statin use.MethodsA retrospective cohort study was performed to assess whether statins are associated with a reduced risk of CIEDI. The VA Informatics and Computing Infrastructure (VINCI) database, which includes all veterans who underwent CIED placement between 2008 and 2015, was used. A logistic regression model was constructed to estimate the adjusted risk of CIEDI among patients who were receiving statins after adjusting for confounding factors.ResultsOverall, 18,970 CIED procedures were included, and 98% of them were performed in men with a mean age of 71 ± 11 years. The rate of diabetes mellitus, heart failure, advanced chronic kidney diseases, CIEDI, positive methicillin‐resistant Staphylococcus aureus nasal colonization, and statin use were 23%, 15.7%, 3.3%, 1.14%, 12.6%, and 56%, respectively. The logistic regression analysis showed that statins were significantly associated with a reduced risk of CIEDI; after controlling for other effects, the reduction was 66% (odds ratio 0.34 [0.2–0.59], P‐value < 0.001). The effect of statins was confirmed by propensity score analysis.ConclusionsOur study showed that among patients receiving statins who had undergone CIED placement, there was a 66% reduction in subsequent CIEDI.