Mary Beth Barry

T Cell Responses Are Better Correlates of Vaccine Protection in the Elderly

It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-γ:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults.

Granzyme B: Correlates with protection and enhanced CTL response to influenza vaccination in older adults.

This study compared serum antibody titers and granzyme B (GrzB) levels in virus-stimulated peripheral blood mononuclear cells following influenza vaccination. Twelve of 239 older adults who subsequently developed laboratory-diagnosed influenza illness (LDI) had significantly lower GrzB levels compared to subjects without LDI (p=0.004). Eight subjects with LDI in the previous year showed an enhanced GrzB response to vaccination (p=0.02). Serum antibody titers following vaccination did not distinguish those older adults who developed LDI from those who did not. These results suggest that GrzB levels could be combined with antibody titers to more effectively predict vaccine efficacy in older adults.

Advances in clinical laboratory tests for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a generic term that refers to Crohns disease and chronic ulcerative colitis (UC). The CD and UC are considered to be distinct forms of IBD; but there is a subgroup of CD with a UC-like presentation. The genetic factors play a significant role in IBD. IBD is associated with a strong familial pattern. Recent studies support the hypothesis that IBD patients have a dysregulated immune response to endogenous bacteria in the gastrointestinal tract. The serologic responses seen in Crohns disease include antibodies to Saccharomyces cerevisiae, mycobacteria, bacteroides and E. coli. The pANCA antibody seen in UC and CD has been demonstrated to react with epitopes of H1 histone, Bacteroides caccae (Ton-B linked outer membrane protein), Pseudomonas fluorescens-associated bacterial protein I-2, mycobacterial histone 1 homologue called Hup B. In recent years, several serologic markers have been found to be useful for the diagnosis and differentiation of CD and UC. These markers include the following antibodies: (a) pANCA, (b) ASCA, (c) anti-pancreatic antibody, (d) OmpC antibody and (e) I-2 antibody and antibodies to anaerobic coccoid rods. The application of a panel of markers with the use of an algorithm (i.e. IBD First Step) can identify specific subtypes of IBD that have different clinical courses and progression of the diseases. The serologic markers are useful for the diagnosis and management of CD and UC patients.

Correlation of B-type natriuretic peptide level to 6-min walk test performance in patients with left ventricular systolic dysfunction

BACKGROUND B-type natriuretic peptide (BNP) is a neurohormone that can be measured in blood and is useful in patients with congestive heart failure (CHF). We compared whole blood BNP concentrations to distance walked during a 6-min walk test in patients with CHF. METHODS Forty-four patients with CHF underwent a 6-min walk test. The distance walked was compared to the BNP concentration on blood collected prior to the walk test. Patients were followed for 16 +/- 2.8 months after testing. RESULTS A significant correlation was observed between the BNP concentration and the distance walked (r = -0.47, p < 0.001). One patient without congestion died suddenly. Two patients died of progressive heart failure, and two other patients underwent cardiac transplantation. Each of the latter four patients had high BNP concentrations (median 1080 ng/l) and walked short distances (median 183 m). This study indicates that the BNP concentration in blood correlates inversely with the degree of physical capability of patients with heart failure. CONCLUSIONS The BNP concentration could be used as an alternative to the 6-min walk test to assess the severity of heart failure. The assay for BNP is non-invasive, inexpensive, and results are available at the bedside or in a heart failure clinic.

Preventability of 30-Day Readmissions for Heart Failure Patients Before and After a Quality Improvement Initiative

The objective of this study was to estimate the frequency of heart failure (HF) readmissions that can be prevented through a quality improvement (QI) program. All HF patients at the University of Connecticut Health Center who had a readmission within 30 days of discharge in the year before (2008) and the year after (2011) a QI program were studied. Through chart review, the percentage of patients who had preventable readmissions in each year was estimated. Prior to the QI initiative, chart reviewers identified that 20% to 30% of readmissions were preventable. The decrease in readmissions after the QI program was similar at 28%. Fewer readmissions after the QI initiative were deemed preventable compared with before. In conclusion, this study found a percentage of preventable readmissions similar to the actual 28% reduction in readmissions after a QI program was launched. Preventable readmissions were less common after the QI program was in place.