The association between neutrophil to lymphocyte ratio and endothelial dysfunction in people living with HIV on stable antiretroviral therapy.

BACKGROUND: Residual inflammation is thought to promote endothelial dysfunction and cardiovascular disease risk among people living with HIV (PLWH) receiving antiretroviral therapy (ART). Whether the neutrophil-to-lymphocyte ratio (NLR), a putative marker of systemic inflammation, may be associated with endothelial dysfunction has not been investigated in PLWH on stable ART. RESEARCH DESIGN AND METHODS: In this cross-sectional study, 210 PLWH (mean age 49 years, 79% males, 88/7/5% Caucasians/Africans/Hispanics) on long-term ART (median ART duration 8 years) were enrolled among those who were afferent to an Infectious Diseases outpatient clinic. The association between NLR and brachial flow-mediated dilation (bFMD) was analysed. RESULTS: A curvilinear association was observed between logarithmic-NLR and logarithmic-bFMD (R square = 0.034, p = 0.027), with logarithmic-bFMD decreasing significantly with increasing logarithmic-NLR only in PLWH with high NLR (≥1.47, median NLR) (r = -0.369, p < 0.001). However, NLR had a poor accuracy in the prediction of low bFMD (≤4.55, median bFMD) in PLWH with high NLR (55% sensitivity, 80% specificity, Youden index 0.35 for NLR 2.20). CONCLUSIONS: Although there is an inverse association between NLR and bFMD among long-term ART-treated PLWH with high NLR, NLR has a low discriminatory ability toward endothelial dysfunction in this category of patients.

Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study.

Background: Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients. Methods: This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (<60 y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on young male subsets with extreme phenotype, picking up TLR7 as the most important susceptibility gene. Results: Overall, we found TLR7 deleterious variants in 2.1% of severely affected males and in none of the asymptomatic participants. The functional gene expression profile analysis demonstrated a reduction in TLR7-related gene expression in patients compared with controls demonstrating an impairment in type I and II IFN responses. Conclusions: Young males with TLR7 loss-of-function variants and severe COVID-19 represent a subset of male patients contributing to disease susceptibility in up to 2% of severe COVID-19. Funding: Funded by private donors for the Host Genetics Research Project, the Intesa San Paolo for 2020 charity fund, and the Host Genetics Initiative. Clinical trial number: NCT04549831.

Daptomycin-based aminoglycoside-sparing therapy for streptococcal endocarditis: a retrospective multicenter study.

Streptococci still represent common etiologic agents of infective endocarditis (IE). Although renal failure is frequently reported as an aminoglycoside-associated adverse event, last international guidelines recommend a beta-lactam/gentamicin combination therapy. We retrospectively evaluated the use of daptomycin-based aminoglycoside-sparing combination therapy for the treatment of streptococcal IE in seven referral hospitals in Italy. Retrospective, multicenter, observational study. All patients with streptococcal IE admitted from 2016 to 2018 were enrolled. Mortality and incidence of acute kidney injury (AKI) were compared between Group A (standard of care, SoC) and Group B (daptomycin-based aminoglycoside-sparing combination therapy). Fifty-four patients were enrolled, 33 in Group A and 21 in Group B. Mortality was 2/33 (6%) in Group A and 0 in Group B (p = 0.681); AKI incidence was 8/33 (24%) in Group A and 0 in Group B (p = 0.04). Daptomycin-based aminoglycoside-sparing combination therapy appears to be promising for the treatment of streptococcal endocarditis because of similar efficacy compared with SoC and significantly reduced incidence of AKI.

Procalcitonin, white blood cell count and C-reactive protein as predictors of S. aureus infection and mortality in infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell - WBC - count, C-reactive protein - CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. METHODS: Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. RESULTS: Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (p = 0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBC ≥ 12,800/mm3, CRP ≥ 130 mg/L, and procalcitonin ≥ 1.7 ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkers < cut-offs. AUC values for in-hospital death were 0.702, 0.725 and 0.727 for the WBC, CRP, and procalcitonin, respectively. Among inflammatory biomarkers, WBC and procalcitonin independently predicted in-hospital death. Procalcitonin refined risk stratification when added to WBC, and to the combination of WBC and CRP. Patients with WBC ≥ 10,535/mm3, CRP ≥ 85 mg/dL, and procalcitonin ≥ 0.4 ng/mL had a 27-fold higher risk of in-hospital death than patients with all biomarkers < cut-offs. CONCLUSIONS: Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.