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OBJECTIVES: To provide an evaluation of predictors of 6-month mortality in incident Staphylococcus aureus bacteraemia cases. METHODS: A retrospective population-based study of 541 adult residents of Olmsted County, MN with monomicrobial S. aureus bacteraemia from 1 January 2006 through 31 December 2020. Multivariable Cox regression was used to investigate risk factors of 6-month mortality. RESULTS: The median (interquartile range [IQR]) age of 541 patients with S. aureus bacteraemia was 66.8 (54.4–78.5) years and 39.6% were female. The median (IQR) Charlson Comorbidity Index was 6 (3–9). Overall, 144 patients died during the six-month period following their initial episode (30-day and 6-month mortality = 16.5% and 26.7%, respectively). In a multivariable analysis, older age, ICU admission, and unknown source of infection were significant predictors of increased 6-month mortality. In contrast, having an infectious diseases (ID) consultation was associated with reduced mortality in the first 2 weeks of follow-up. Secondary analyses revealed an early benefit of ID consultation during the first 30 days of follow-up and that infective endocarditis was an additional predictor of 6-month mortality. CONCLUSIONS: To our knowledge, this investigation represents the only US population-based study evaluating predictors of mortality in patients with S. aureus bacteraemia. The finding of a short-term survival benefit associated with early ID consultation may be due to more extensive diagnostic efforts.

OBJECTIVE: Women who are currently using menopausal hormone therapy (MHT) have higher cerebrovascular reactivity when compared with postmenopausal women who are not taking MHT; however the effect of cessation of MHT on cerebrovascular reactivity is not known. Given that MHT can have structural and activational effects on vascular function, this study was performed to characterize cerebrovascular reactivity following cessation of MHT in women at low risk for cerebrovascular disease. METHODS: Cerebrovascular reactivity measured in a subset of women from the Kronos Early Estrogen Prevention Study (KEEPS) three years after the cessation of the study drug [oral conjugated equine estrogen (oCEE); transdermal 17-β estradiol (tE2); or placebo (PLA)]. RESULTS: Age, body mass index, and blood pressure were comparable among groups. At rest, middle cerebral artery velocity (MCAv), cerebrovascular conductance index (CVCi), mean arterial pressure (MAP) and cerebral pulsatility index did not differ among groups. Slope-based summary measures of cerebrovascular reactivity did not differ significantly among groups. However, utilizing repeated measures modeling, there was a significant upward shift in MCAv responses (p=0.029) in the combined MHT group compared with PLA group. CONCLUSION: MHT has a marginal sustained effect on cerebrovascular reactivity when measured three years after cessation of hormone treatment.

Beta-haemolytic streptococcal (BHS) endocarditis is rare, but well-recognised for its high morbidity and mortality. This study sought to further characterise clinical features, management and outcomes of BHS endocarditis.Retrospective review of all adultpatients (≥ 18 years old) with BHS endocarditis treated at the Mayo Clinic from 1 January 2000 to 31 December 2014.Forty-nine cases of BHS endocarditis were identified with a mean (± SD) age of 64 (± 14.9) years and 65% were males. The infection was community acquired in 92% of the cases, with a median (IQR) time to diagnosis from symptom onset of 6 days (5-10). Associated conditions included the presence of a prosthetic valve (41%), malignancy (33%) and diabetes mellitus (DM) (31%). Median (IQR) vegetation size was 12 mm (9-17 mm). In a univariate analysis patients with DM had larger vegetations, median (IQR) = 17 mm (10.5-26 mm) compared to non-diabetic patients, median (IQR) = 11 mm (8-15 mm) (p = 0.01). Septic brain emboli occurred in 43% of cases. Eighteen patients (37%) underwent early (within 30 days) surgery. All-cause 1 month and 6 month mortality rates were 25% and 31%, respectively.BHS endocarditis has an acute onset and is complicated by relatively large vegetations with a high rate of systemic embolisation. DM was the second most common associated medical condition and patients with DM had larger vegetations. Despite medical and surgical advances, mortality due to BHS endocarditis remains high, particularly within 30 days of diagnosis.

Activated platelets serve as a catalyst for thrombin generation and a source of vasoactive and mitogenic factors affecting vascular remodeling. Oral menopausal hormone treatments (MHT) may carry greater thrombotic risk than transdermal products. This study compared effects of oral and transdermal MHT on platelet characteristics, platelet proteins, and platelet-derived microvesicles (MV) in recently menopausal women. Platelets and MV were prepared from blood of a subset of women (n = 117) enrolled in the Kronos Early Estrogen Prevention Study prior to and after 48 months of treatment with either oral conjugated equine estrogen (0.45 mg/day), transdermal 17β-estradiol (50 µg/day), each with intermittent progesterone (200 mg/day for 12 days a month), or placebo pills and patch. Platelet count and expression of platelet P-selectin and fibrinogen receptors were similar across groups. An aggregate measure of 4-year change in vasoactive and mitogenic factors in platelet lysate, by principle component analysis, indicated significantly lower values in both MHT groups compared to placebo. Increases in numbers of tissue factor positive and platelet-derived MV were significantly greater in the transdermal compared to placebo group. MHT was associated with significantly reduced platelet content of vasoactive and mitogenic factors representing a potential mechanism by which MHT may affect vascular remodeling. Various hormonal compositions and doses of MHT could differentially regulate nuclear transcription in bone marrow megakaryocytes and non-genomic pathways in circulating platelets thus determining numbers and characteristics of circulating MV. Thrombotic risk associated with oral MHT most likely involves liver-derived inflammatory/coagulation proteins rather than circulating platelets per se.

Cardiovascular disease and osteoporosis increase in women after menopause. While aortic calcification is associated with bone loss in women, a similar relationship for coronary arterial calcification (CAC), a risk factor for coronary artery disease in women, is less clear. This study was designed to examine the relationship between CAC and volumetric bone mineral density (vBMD) in women (n=137) who were within a median of 18 months past their last menses at screening for the Kronos Early Estrogen Prevention Study (KEEPS).CAC was measured using 64-slice computed tomography; vBMD was measured from these images using the Spine Cancer Assessment program. Concentrations of osteocalcin, bone alkaline phosphatase, tartrate-resident acid phosphatase-5b and osteopontin as bone matrix protein in serum and plasma were evaluated by ELISA.CAC scores ranged from 0 to 327.6 Agatston Units (AU); 113 women had a score of 0 AU, 20 had a CAC score between 0 and 50 AU, and four had a CAC score50 AU. Although not statistically significant, there was a trend toward decreasing central density of thoracic T9 with increasing CAC. On average, levels of markers of bone turnover were within the normal range but did not correlate with age or with months past menopause.Clinically significant CAC and spine vBMD are quantifiable from the same scans within the first 3 years of menopause. Additional work is needed to determine how these measurements change with increasing age or with estrogenic treatments.