Abstract Background Recently, lower estimates of influenza vaccine effectiveness (VE) against A(H3N2) virus illness among those vaccinated during the previous season or multiple seasons have been ...reported; however, it is unclear whether these effects are due to differences in immunogenicity. Methods We performed hemagglutination inhibition antibody (HI) assays on serum collected at preseason, ∼30 days post-vaccination, and postseason from a prospective cohort of healthcare personnel (HCP). Eligible participants had medical and vaccination records for at least four years (since July, 2006), including 578 HCP who received 2010-11 trivalent inactivated influenza vaccine IIV3, containing A/Perth/16/2009-like A(H3N2) and 209 HCP who declined vaccination. Estimates of the percentage with high titers (≥40 and > 100) and geometric mean fold change ratios (GMRs) to A/Perth/16/2009-like virus by number of prior vaccinations were adjusted for age, sex, race, education, household size, hospital care responsibilities, and study site. Results Post-vaccination GMRs were inversely associated with the number of prior vaccinations, increasing from 2.3 among those with 4 prior vaccinations to 6.2 among HCP with zero prior vaccinations ( F 4,567 = 9.97, p < .0005). Thirty-two percent of HCP with 1 prior vaccination achieved titers >100 compared to only 11% of HCP with 4 prior vaccinations (adjusted odds ratio = 6.8, 95% CI = 3.1 – 15.3). Conclusion Our findings point to an exposure-response association between repeated IIV3 vaccination and HI for A(H3N2) and are consistent with recent VE observations. Ultimately, better vaccines and vaccine strategies may be needed in order to optimize immunogenicity and VE for HCP and other repeated vaccinees.
Abstract Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited, life-threatening, metabolic disorder of low-density lipoprotein (LDL) receptor function characterized by elevated serum ...LDL cholesterol (LDL-C) and rapidly progressive atherosclerotic cardiovascular disease (ACVD). Since LDL receptors are predominantly found on hepatocytes, orthotopic liver transplantation (OLT) has emerged as a viable intervention for HoFH because LDL receptor activity is restored. This study assessed the effects of OLT on ACVD and ACVD risk factors in pediatric patients with HoFH. We analyzed lipids, lipoproteins, body mass index, glucose, blood pressure and cardiovascular imaging in 8 pediatric patients who underwent OLT for HoFH. Total serum cholesterol, LDL-C, lipoprotein(a) and apolipoprotein B/apolipoprotein A1 ratio decreased to normal values in all subjects (p values <0.001) at 1 month after OLT and were maintained for the length of follow up (2- 6 years). There were few complications related to surgery or immunosuppressive therapy. Two patients developed mild hypertension. In the first 4 subjects monitored for 4-6 years after OLT, coronary artery disease (CAD) did not develop or progress except in 1 minor artery in 1 subject, and actually regressed in 2 subjects with >50% stenosis. However, aortic valve stenosis progressed in 2 of 4 subjects. In conclusion, OLT is an effective therapeutic option for HoFH patients with CAD and persistently elevated serum LDL-C despite maximum medical therapy. Aortic valvular disease may progress. Long-term data are needed to evaluate the true risk-benefit ratio of this surgical approach.
Mitral regurgitation (MR) is common with coronary artery disease as altered myocardial substrate can affect valve performance. Single-photon emission computed tomography myocardial perfusion imaging ...(MPI) enables assessment of myocardial perfusion alterations. This study examined perfusion pattern in relation to MR. A total of 2,377 consecutive patients with known or suspected coronary artery disease underwent stress MPI and echocardiography within 1.6 ± 2.3 days. MR was present on echocardiography in 34% of patients, among whom 13% had advanced (moderate or more) MR. MR prevalence was higher in patients with abnormal MPI (44% vs 29%, p <0.001), corresponding to increased global ischemia (p <0.001). Regional perfusion varied in left ventricular segments adjacent to each papillary muscle: adjacent to the anterolateral papillary muscle, magnitude of baseline and stress-induced anterior/anterolateral perfusion abnormalities was greater in patients with MR (both p <0.001). Adjacent to the posteromedial papillary muscle, baseline inferior/inferolateral perfusion abnormalities were greater with MR (p <0.001), whereas stress inducibility was similar (p = 0.39). In multivariate analysis, stress-induced anterior/anterolateral and rest inferior/inferolateral perfusion abnormalities were independently associated with MR (both p <0.05) even after controlling for perfusion in reference segments not adjacent to the papillary muscles. MR severity increased in relation to magnitude of perfusion abnormalities in each territory adjacent to the papillary muscles, as evidenced by greater prevalence of advanced MR in patients with at least moderate anterior/anterolateral stress perfusion abnormalities (10.7% vs 3.6%), with similar results when MR was stratified based on rest inferior/inferolateral perfusion (10.4% vs 3.0%, both p <0.001). In conclusion, findings demonstrate that myocardial perfusion pattern in left ventricular segments adjacent to the papillary muscles influences presence and severity of MR.
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