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Context .—The rate of surgical pathology report defects is an indicator of quality and it affects clinician satisfaction. Objective .—To establish benchmarks for defect rates and defect fractions through a large, multi-institutional prospective application of standard taxonomy. Design .—Participants in a 2011 Q-Probes study of the College of American Pathologists prospectively reviewed all surgical pathology reports that underwent changes to correct defects and reported details regarding the defects. Results .—Seventy-three institutions reported 1688 report defects discovered in 360 218 accessioned cases, for an aggregate defect rate of 4.7 per 1000 cases. Median institutional defect rate was 5.7 per 1000 (10th to 90th percentile range, 13.5–0.9). Defect rates were higher in institutions with a pathology training program (8.5 versus 5.0 per 1000, P = .01) and when a set percentage of cases were reviewed after sign-out (median, 6.7 versus 3.8 per 1000, P = .10). Defect types were as follows: 14.6% misinterpretations, 13.3% misidentifications, 13.7% specimen defects, and 58.4% other report defects. Overall, defects were most often detected by pathologists (47.4%), followed by clinicians (22.0%). Misinterpretations and specimen defects were most often detected by pathologists (73.5% and 82.7% respectively, P < .001), while misidentifications were most often discovered by clinicians (44.6%, P < .001). Misidentification rates were lower when all malignancies were reviewed by a second pathologist before sign-out (0.0 versus 0.6 per 1000, P < .001), and specimen defect rates were lower when intradepartmental review of difficult cases was conducted after sign-out (0.0 versus 0.4 per 1000, P = .02). Conclusion .—This study provides benchmarking data on report defects and defect fractions using standardized taxonomy.

For influenza hemagglutination inhibition (HAI) assays, species selection of red blood cells (RBCs) is critical to determine antibody titers to influenza viruses reliably. We compared pandemic influenza virus A/H1N1 (pdH1N1) HAI titers using turkey or guinea pig RBCs. Turkey RBCs appear to be the more appropriate species choice for influenza A/pH1N1 HAI assays.

ABSTRACT Antibodies are biological molecules generated by the host immune system in response to the invasion of foreign bodies or antigens. Therefore, antibodies must possess high specificity toward target antigens in order for the antigen to be recognized and subsequently destroyed. Because of this specificity, antibodies or antibody fragments that maintain binding specificity are heavily used in diagnostic assays and are becoming increasingly important in many therapeutic applications. Classical immunoassays such as radioimmunoassay and enzyme-linked immunosorbent assay are effective analytical techniques that have been widely used to screen and determine antibody specificity. Because of increased demands for antibodies with well-defined specificities, other techniques have been developed that facilitate generation and characterization of antibody-binding specificities under different conditions, such as when the protein is expressed on a cell surface or the target antigen is hard to isolate. Here, we describe three alternate techniques that provide unique abilities to characterize antibody-antigen binding events: (i) surface plasmon resonance, (ii) fluorescence activated cell sorting, and (iii) atomic force microscopy. These different techniques take advantage of various changes in physical and/or chemical properties of the analytes that occur upon binding, such as refractive index, surface charge, and changes in structure. These techniques provide unique powerful advantages over traditional immunoassays including real-time and label-free detection, low sample volume and concentration requirements, and molecular-level detection sensitivity. This article provides an overview of how these alternate approaches to studying antibody-antigen interactions can be used to facilitate rapid development of new antibody-based reagents for diagnostic and therapeutic applications.

ObjectivesOur objective was to determine if technical changes combined with radiation safety initiatives reduced the radiation dose delivered to patients during congenital catheterization.BackgroundUse of ionizing radiation is necessary during cardiac catheterization. Minimizing radiation dose, while maintaining clinically useful image quality, is an important safety issue. In our congenital heart center intentional practice changes, including technical changes and provider awareness initiatives, were implemented to decrease radiation dose.MethodsData were retrospectively collected for all procedures involving children and adults with congenital heart disease (CHD) undergoing catheterization over 45 months. Cases were divided into three categories including: noninterventional (NI), simple intervention (SI), and complex intervention (CI). The change in dose was modeled as log of cumulative air kerma (Ka,r). The change in Ka,r was evaluated for each procedural category as well as changes occurring as a function of age and weight.ResultsConsidering all procedures (n = 1,082), Ka,r decreased by 61%. In the NI group (n = 481), Ka,r decreased by 71%. In the SI group (n = 424), Ka,r decreased by 74%. The Ka,r for the 10–17 year old group (n = 125) and those ≥18 years (n = 709) decreased 74 and 67%, respectively. The Ka,r decreased 72 and 66% for those 20–60 kg and ≥60 kg, respectively. Groups not showing significant change in Ka,r included CI, age ≤9 years, and weight ≤20 kg.ConclusionsThrough technical changes and provider awareness initiatives, our institution dramatically reduced the radiation dose in the majority of pediatric and adult CHD patients undergoing cardiac catheterization. © 2014 Wiley Periodicals, Inc.

SummaryTestosterone (T) impacts luteinizing hormone (LH) secretion through negative feedback via the androgen receptor (AR) in the hypothalamo‐pituitary system. An untested postulate is that increasing body mass index (BMI), abdominal visceral fat (AVF) or total abdominal fat (TAF) with ageing decreases LH secretion by heightening T negative feedback via AR. This hypothesis was tested in a prospective, randomized double‐blind cross‐over study of 19 healthy men comparing the effects of flutamide, a selective non‐steroidal AR antagonist and placebo administration on basal and pulsatile LH secretion as a function of age and obesity measures. To this end, serum levels of 2‐hydroxyflutamide (2‐OHF), a major active flutamide metabolite, were measured by mass spectrometry, and AVF/TAF quantified by abdominal computerized tomography. Statistical analysis showed that antiandrogen administration elevated 6‐h mean LH concentrations to 5.4 ± 1.3 IU/L compared with 3.3 ± 1.2 IU/L for placebo (p < 10−3), and total T by 35% (p < 10−4). The LH‐T concentration product doubled (p < 10−8). According to deconvolution analysis, flutamide exposure increased total LH secretion (p < 10−3) and pulsatile LH secretion (p = 0.0077), along with LH pulse frequency (p = 0.019). Despite feedback inhibition, the LH‐T product declined as a linear function of AVF (p = 0.021) and TAF (p = 0.017). This was explained by the fact that higher BMI was associated with lower 2‐OHF concentrations (R = −0.562, p = 0.012). In contrast, age was associated with less pulsatile LH secretion (R = −0.567, p = 0.011) even when LH responses were normalized to antiantrogen levels. In conclusion, increased AVF, TAF and BMI predict decreased LH and flutamide blood levels, whereas older age is marked by impaired stimulation of pulsatile LH secretion even when normalized for antiandrogen levels, suggesting different mechanisms of regulation by adiposity and age.

SummaryBackgroundChronic ulcerative colitis (CUC) and colonic Crohn's disease (CD) increase colorectal neoplasia (CRN) risk. While sessile serrated polyp (SSP) is a known cancer precursor, serrated epithelial changes (SEC) are of uncertain prevalence and neoplastic risk.AimTo assess the serrated lesion detection rates in CUC and CD and documented incidence of subsequent CRN in a retrospective, single‐centre cohort study.MethodsPatients were identified by a central diagnostic index and pathology review confirmed SEC, SSP, CUC and CD diagnoses from 2006–12. Matched controls were identified from among all CUC and CD patients having colonoscopy during the second half of the time period. All were followed for incident CRN, estimated by the Kaplan–Meier method.ResultsBetween 2006 and 2012, 79 SEC and 10 SSP cases were identified. Detection rates were estimated to be 10/1000 and 2/1000 patients, for SEC and SSP respectively, among 4208 unique CUC or CD patients having colonoscopy from 2010–12. With only 10 cases, SSP patients were not further analysed. Cumulative incidence of subsequent CRN at 1 and 3 years was 12% (95% CI, 0–30%) and 30% (3–57%), respectively, in SEC patients compared to 4% (0–12%) and 9% (0–23%), respectively, in CUC or CD controls (P = 0.047, log‐rank). However, this statistical difference was not significant after patients were stratified for history of prior or synchronous dysplasia (P = 0.09).ConclusionsSerrated epithelial changes and sessile serrated polyps are uncommonly detected by colonoscopy in chronic ulcerative colitis and Crohn's disease patients. Histology with changes of serrated epithelium may be associated with risk of subsequent colorectal neoplasia, however further studies are needed to explore this relationship.