Search PubMed⌕ Search

Biomedical subjects

Sowmya R Rao

Publications and source records attributed to Sowmya R Rao.

4 recordsLinked to original sources
PubMed2025

Antibody responses in Klebsiella pneumoniae bloodstream infection: a prospective cohort study.

BACKGROUND: Klebsiella pneumoniae is a leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive K pneumoniae. We sought to determine whether the O-specific polysaccharide antigen is immunogenic in humans with K pneumoniae bloodstream infection. We also sought to define the cross-reactivity of human antibody responses among structurally related K pneumoniae O-specific polysaccharide subtypes and to assess the effect of capsule production on O-specific polysaccharide-targeted antibody binding and function. METHODS: In this prospective cohort study, we compared plasma antibody responses to O-specific polysaccharide in a cohort of consecutively enrolled patients with K pneumoniae bloodstream infection with controls, specifically a cohort of healthy individuals and a cohort of individuals with Enterococcus spp bloodstream infection. Patients were enrolled at the Massachusetts General Hospital, a tertiary hospital with affiliated clinics in the USA. We excluded patients whose isolates were not confirmed to be K pneumoniae by whole-genome sequencing. The primary outcome was the measurement of plasma IgG, IgM, and IgA antibody responses. We performed flow cytometry to measure the effects of K pneumoniae capsule production on O-specific polysaccharide antibody binding and O-specific polysaccharide antibody-mediated complement deposition, using patient isolates with variable levels of capsule production and isogenic capsule-deficient strains derived from these isolates. FINDINGS: We enrolled 129 consecutive patients with suspected K pneumoniae bloodstream infection between July 24, 2021, and August 4, 2022, of whom 69 patients (44 [64%] male and 25 [36%] female) with confirmed K pneumoniae bloodstream infection were eligible for immunological evaluation. Common O-specific polysaccharide serotypes (O1, O2, O3, and O5) accounted for 57 (83%) of 69 infections. O-specific polysaccharide was immunogenic in patients with K pneumoniae bloodstream infection, and peak O-specific polysaccharide-IgG antibody responses in patients were ten-fold to 30-fold higher than antibody responses detected in healthy controls, depending on the serotype. There was cross-reactivity among similar O-specific polysaccharide subtypes, including the O1v1 and O1v2, O2v1 and O2v2, and O3 and O3b subtypes, as well as between the O1 and O2 types. Capsule produced by both hyperencapsulated and non-hyperencapsulated K pneumoniae inhibited O-specific polysaccharide-targeted antibody binding and function. INTERPRETATION: O-specific polysaccharide was immunogenic in patients with K pneumoniae bloodstream infection, supporting its potential as a candidate vaccine antigen. The cross-reactivity observed between similar O-specific polysaccharide subtypes in patients with K pneumoniae bloodstream infection suggests that it might not be necessary to include all subtypes in an O-specific polysaccharide-based vaccine. However, these observations are tempered by the fact that capsule production, even in non-highly encapsulated strains, has the potential to interfere with O-specific polysaccharide antibody binding. This finding could limit the effectiveness of vaccines that exclusively target O-specific polysaccharide. FUNDING: National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Humans↗
PubMed2005

Breast cancer trends among black and white women in the United States.

PURPOSE: Overall US breast cancer mortality rates are higher among black women than white women, and the disparity is widening. To investigate this disparity, we examined incidence data and changes in mortality trends according to age, year of death (calendar period), and date of birth (birth cohort). Calendar period mortality trends reflect the effects of new medical interventions, whereas birth cohort mortality trends reflect alterations in risk factors. PATIENTS AND METHODS: Incidence data were obtained from the Connecticut and National Cancer Institute Surveillance, Epidemiology, and End Results registries and mortality data were obtained from the National Center for Health Statistics. Changes in age, period, and cohort mortality trends were analyzed with Poisson regression. RESULTS: For both races, breast cancer incidence rates for localized and regional disease diverged in the late 1970s. Almost concurrently, overall mortality rates diverged among blacks and whites. For both races, mortality increases with age, but blacks have higher mortality at age younger than 57. The calendar period curves revealed declining mortality for whites over the entire study period. For blacks, calendar period mortality declined until the late 1970s, and then sharply increased. After 1994, calendar period mortality declined for both. For women born between 1872 and 1950, trends in mortality were similar for blacks and whites. For women born after 1950, mortality decreased more rapidly for blacks. CONCLUSION: The widening racial disparity in breast cancer mortality seems attributable to calendar period rather than birth cohort effects. Thus, differences in response or access to newer medical interventions may largely account for these trends.

Adult↗
PubMed2003

Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention.

BACKGROUND: The Breast Cancer Prevention Trial demonstrated that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer among women at elevated risk for the disease. The U.S. Food and Drug Administration (FDA) subsequently approved tamoxifen for women aged 35 years or older with a 5-year breast cancer risk of 1.67% or higher for breast cancer chemoprevention. However, tamoxifen use has been associated with adverse outcomes, and not all eligible women have a positive benefit/risk ratio. METHODS: We used weighted data from the year 2000 National Health Interview Survey Cancer Control Module to estimate the total number of U.S. women, aged 35-79 years, who were eligible for tamoxifen chemoprevention based on the FDA eligibility criteria. We also estimated the numbers of white and black women who would benefit from tamoxifen chemoprevention on the basis of a positive benefit/risk index developed by Gail et al. RESULTS: Of the 65,826,074 women aged 35-79 years without reported breast cancer in the United States in 2000, 10,232 816 women (15.5%, 95% confidence interval [CI] = 14.7% to 16.3%) would be eligible for tamoxifen chemoprevention. The percentage of U.S. women who would be eligible varied dramatically by race, with 18.7% (95% CI = 17.8% to 19.7%) of white women, 5.7% (95% CI = 4.3% to 7.5%) of black women, and 2.9% (95% CI = 2.1% to 3.9%) of Hispanic women being eligible. Of the 50,104,829 white U.S. women aged 35-79 years, 2,431,911 (4.9%, 95% CI = 4.3% to 5.4%) would have a positive benefit/risk index for tamoxifen chemoprevention. Of the 7,481,779 black U.S. women aged 35-79 years, only 42,768 (0.6%, 95% CI = 0.2% to 1.3%) would have a positive benefit/risk index. Among white women, 28,492 (95% CI = 24,693 to 32,292) breast cancers would be prevented or deferred if those women who have a positive net benefit index took tamoxifen over the next 5 years. CONCLUSION: A substantial percentage of U.S. women would be eligible for tamoxifen chemoprevention according to FDA criteria, but a much smaller percentage would have an estimated net benefit. Nevertheless, this latter percentage corresponds to more than two million women.

Adult↗