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Context Although Pseudomonas aeruginosa is the most common virulent respiratory pathogen in cystic fibrosis (CF), the longitudinal development of P aeruginosa infection and its effect on antibody responses and lung disease progression in children with CF remain unclear.Objective To prospectively examine the epidemiology of P aeruginosa infection and its impact on CF pulmonary morbidity. Design, Setting, and PatientsWe prospectively evaluated 56 CF patients at 2 CF centers in Madison and Milwaukee, Wis, from birth up to age 16 years between April 15, 1985, and April 15, 2004, with diagnoses made through the Wisconsin CF Neonatal Screening Project.Main Outcome Measures Timing of nonmucoid P aeruginosa and mucoid P aeruginosa acquisition was assessed by first positive result. Longitudinal development from no P aeruginosa to nonmucoid P aeruginosa and from nonmucoid P aeruginosa to mucoid P aeruginosa was examined. Outcome measurements included antibody titers, respiratory symptoms, quantitative chest radiography, and pulmonary function tests. ResultsSixteen patients (29%) acquired nonmucoid P aeruginosa in the first 6 months of life. The age-specific prevalence of mucoid P aeruginosa increased markedly from age 4 to 16 years. Nonmucoid and mucoid P aeruginosa were acquired at median ages of 1.0 and 13.0 years, respectively. In contrast with the short transition time from no P aeruginosa to nonmucoid P aeruginosa, the transition time from nonmucoid to mucoid P aeruginosa was relatively long (median, 10.9 years) and could be slightly extended by brief/low anti-P aeruginosa antibiotic treatment. Antibody titers increased with both transitions, but the deterioration in cough scores, chest radiograph scores, and pulmonary function correlated best with transition from nonmucoid to mucoid P aeruginosa.Conclusions Early prevention and detection of nonmucoid and mucoid P aeruginosa are critical because of early acquisition and prevalence. There is a window of opportunity for suppression and possible eradication (by aggressive anti-P aeruginosa treatment) of initial nonmucoid P aeruginosa. Mucoid P aeruginosa plays a much greater role in CF lung disease progression than nonmucoid P aeruginosa. Antibody titers, cough scores, and chest radiographs are early signs of nonmucoid P aeruginosa and especially mucoid P aeruginosa stages.

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Daycare attendance and siblings are associated with viral-induced wheezing in children. Preexisting immunologic factors may influence the expression of viral infections in infancy, and in turn, recurrent infections may influence the development of immune responses. A total of 285 children were enrolled in the Childhood Origins of Asthma Project at birth and followed for at least 1 year. Cord blood and 1-year mononuclear cells were stimulated with phytohemagglutinin, and cytokine-response profiles were measured by enzyme-linked immunosorbent assay. Nasal lavage was performed for moderate to severe respiratory illnesses. Daycare attendance and/or siblings significantly increased the likelihood of contracting respiratory syncytial virus (1.5-1.6-fold increase) and rhinovirus (1.8-2.1-fold increase), and increased the risk of rhinovirus-induced wheezing (14-18% vs. 2%, p = 0.011). Cord blood IFN-gamma responses were inversely related to the frequency of viral respiratory infections (r(s) = -0.11, p = 0.05), and more significant for subjects with high exposure to other children (r(s) = -0.27, p = 0.028). The interval change in infantile IFN-gamma responses correlated positively with the frequency of viral infections in infancy (r(s) = 0.12, p = 0.047). These data suggest that neonatal IFN-gamma responses may influence antiviral activity, or may represent a marker of antiviral immunity maturation. Conversely, the frequency of viral infections in infancy can influence IFN-gamma responses.

Background Achieving negative surgical margins is critical to minimizing the risk of tumor recurrence in patients undergoing breast conservation surgery (BCS) for a breast malignancy. Our objective was to perform a systematic review comparing reexcision rates, sensitivity and specificity of the intraoperative use of the margin assessment techniques of imprint cytology (IC) and frozen section analysis (FSA), against permanent histopathologic section (PS). Methods The databases PubMed, Web of Knowledge, Cochrane Library and CINAHL Plus were searched for literature published from 1997 to 2011. Original investigations of patients who underwent BCS for breast cancer that evaluated margin assessment with PS and/or IC or FSA were included. Of 182 titles identified, 41 patient cohorts from 37 articles met inclusion criteria: PS (n = 19), IC (n = 7) and FSA (n = 15). Studies were summarized qualitatively using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies and the Strength of Recommendation Taxonomy (SORT) numerical scale for diagnostic studies. Results The final reexcision rates after primary BCS were 35 % for PS, 11 % for IC (p = 0.001 vs. PS) and 10 % for FSA (p < 0.0001 vs. PS). For IC, reexcision rates decreased from 26 to 4 % (p = 0.18) and for FSA, reexcision rates decreased from 27 to 6 % (p < 0.0001). The pooled sensitivity of IC and FSA were 72 and 83 %. The pooled specificity of IC and FSA were 97 and 95 %. The average length of each technique was 13 min for IC and 27 min for FSA. Conclusions Patients who underwent BCS with intraop-erative IC or FSA to assess negative surgical margins had significantly fewer secondary surgical procedures for excision of their breast malignancies.