Citations

AbstractPurposeThe purpose of this study is to determine the effect of bioabsorbable interference screw (BIS) tibial fixation with the Delta screw (antegrade) and RetroScrew (retrograde) on initial (time zero) intra‐articular graft tension in soft tissue anterior cruciate ligament (ACL) reconstruction in a cadaveric model.MethodsTen matched pairs of cadaveric tibias received one of two tibial fixation constructs using quadrupled hamstring grafts, Delta screw (antegrade) or the RetroScrew (retrograde). Each specimen was mounted to the materials testing device with the displacement force vector in line with the tibial tunnel. The construct was pre‐tensioned (10–30 N, 0.1 Hz, 10 cycles), a baseline tension of 25 N was introduced, and the change in intra‐articular graft tension before and after screw insertion was recorded.ResultsSegmental (proximal, middle, distal) BMD was utilized to assess BMD using quantitative computed tomography (qCT). The Delta screw had a higher maximum insertion torque (P = 0.03) and exhibited a larger increase in intra‐articular graft tension as compared to the RetroScrew (38.3 ± 17.9 N, 7.6 N ± 14.4, P = 0.004), respectively. There were no significant correlations between intra‐articular graft tension increase to maximum insertion torque (P = NS) or corresponding segmental BMD (P = NS).ConclusionsDelta screw tibial fixation (antegrade) in soft tissue ACL reconstruction significantly increases the initial intra‐articular graft tension as compared to RetroScrew screw fixation (retrograde) in this cadaveric model. Delta screw (antegrade) tibial fixation may increase initial quadrupled hamstring graft intra‐articular tension with currently accepted insertion techniques.

This article focuses on the effects of operational differences in case ascertainment on estimates of prevalence and incidence of cognitive impairment and/or dementia of the Alzheimer type. Experience and insights are discussed by investigators from the Framingham Heart Study, the East Boston Senior Health Project, the Chicago Health and Aging Project, the Mayo Clinic Study of Aging, the Baltimore Longitudinal Study of Aging, and the Aging, Demographics, and Memory Study. There is a general consensus that the single most important factor determining prevalence estimates of Alzheimer's disease (AD) is the severity of cognitive impairment used as a threshold to define cases. Studies that require a level of cognitive impairment in which persons are unable to provide self‐care will have much lower estimates than the studies aimed at identifying persons in the earliest stages of AD. There are limited autopsy data from the aforementioned epidemiological studies to address accuracy in the diagnosis of etiological subtype, namely the specification of AD alone or in combination with other types of pathology. However, other community‐based cohort studies show that many persons with mild cognitive impairment and also some persons without dementia or mild cognitive impairment meet pathological criteria for AD, thereby suggesting that the number of persons who would benefit from an effective secondary prevention intervention is probably higher than the published prevalence estimates. Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiological studies.

Declines in heart disease and stroke mortality rates are conventionally attributed to reductions in cigarette smoking, recognition and treatment of hypertension and diabetes, effective medications to improve serum lipid levels and to reduce clot formation, and general lifestyle improvements. Recent evidence implicates these and other cerebrovascular factors in the development of a substantial proportion of dementia cases. Analyses were undertaken to determine whether corresponding declines in age‐specific prevalence and incidence rates for dementia and cognitive impairment have occurred in recent years. Data spanning 1 or 2 decades were examined from community‐based epidemiological studies in Minnesota, Illinois, and Indiana, and from the Health and Retirement Study, which is a national survey. Although some decline was observed in the Minnesota cohort, no statistically significant trends were apparent in the community studies. A significant reduction in cognitive impairment measured by neuropsychological testing was identified in the national survey. Cautious optimism appears justified.

Passive surveillance for disease is a public health approach that relies on documentation available within existing health records for the region or community being studied. Its two primary advantages over active case‐finding are the lower cost of research and the lower burden on the population under study. The effectiveness of passive case‐finding depends on the comprehensiveness of the healthcare coverage in a given community and the adequacy of the available medical records. The Rochester Epidemiology Project has permitted dementia case detection for Olmsted County, Minnesota, using a medical records‐linkage system. These data were compared with case ascertainment using direct assessment of individuals in an epidemiological study of the same community. At the Group Health Research Institute, investigators compared dementia and Alzheimer's disease cases detected using an electronic medical record database search with those identified by a parallel active case‐finding study. In this article, the advantages and disadvantages of passive case‐finding were discussed, and the following conclusion was drawn: the purpose of the study being conducted should determine the case‐finding approach that is to be used.

Purpose Findings from the human epidermal growth factor receptor 2 (HER2) –positive National Surgical Adjuvant Breast and Bowel Project (NSABP) B31 trial suggested that MYC/HER2 coamplification (> 5.0 copies/nucleus) was associated with additional benefit from adjuvant trastuzumab in patients with early-stage breast cancer. To further explore this relationship, we investigated associations between MYC amplification and disease-free survival (DFS) in a similar adjuvant trastuzumab HER2-positive breast cancer trial—North Central Cancer Treatment Group (NCCTG) N9831. Patients and Methods This analysis included 799 patients randomly assigned to receive chemotherapy alone or with concurrent trastuzumab on N9831. Fluorescence in situ hybridization (FISH) was performed by using a dual-probe mixture for MYC and centromere 8 (MYC:CEP8) on tissue microarrays. MYC amplification was prespecified as MYC:CEP8 ratio > 2.2 or average MYC copies/nucleus > 5.0. Exploratory variables included polysomy 8. Results In comparing DFS (median follow-up, 4.0 years) between treatments, patients with MYC:CEP8 ratio ≤ 2.2 (n = 618; 77%) and > 2.2 (n = 181; 23%) had hazard ratios (HRs) of 0.46 (P < .001) and 0.67 (P = .33), respectively (interaction P = .38). Patients with MYC copies/nucleus ≤ 5.0 (n = 534; 67%) and > 5.0 (n = 265; 33%) had HRs of 0.52 (P = .002) and 0.48 (P = .02), respectively (interaction P = .94). Patients with MYC:CEP8 ratio < 1.3 with normal chromosome 8 copy number (n = 141; 18%) and ≥ 1.3 or < 1.3 with polysomy 8 (n = 658; 82%) had HRs of 0.66 (P = .28) and 0.44 (P < .001), respectively (interaction P = .23). Patients with MYC copies/nucleus < 2.5 (n = 130; 16%) and ≥ 2.5 (n = 669; 84%) had HRs of 1.07 (P = .87) and 0.42 (P < .001), respectively (interaction P = .05). Conclusion We did not confirm the B31 association between MYC amplification and additional trastuzumab benefit. Exploratory analyses revealed potential associations between alternative MYC/chromosome 8 copy number alterations and differential benefit of adjuvant trastuzumab.

BACKGROUND The limits of chromatographic speed and mechanical frontend capabilities have been reached for many high-volume liquid chromatography–tandem mass spectrometry (LC-MS/MS) tests, curtailing the maximal achievable sample throughput. To overcome these boundaries, we developed and validated a derivatization-based sample-multiplex LC-MS/MS assay for detection of 25-hydroxyvitamins D2 and D3 [25(OH)D2 and 25(OH)D3], which increased sample throughput 5-fold. METHODS After separate derivatization with 1 of 5 different triazoline-diones (TADs), 5 calibrators, controls, or patient specimens were combined and injected together into an LC-MS/MS. On the basis of mass differences between TADs, the MS/MS quantified analyte and stable isotope internal standards for 25(OH)D2 and 25(OH)D3 for each respective multiplexed sample within the injection. Limits of detection and quantification, spiked recovery, linearity, imprecision, and patient results were determined and compared against our standard LC-MS/MS assay. RESULTS TAD multiplexing increased throughput on an LC-quadruplexed LC-MS/MS system from 60 samples/h to 300 samples/h. Limits of detection and quantification were 4.9 nmol/L [2 μg/L, 25(OH)D2], 2.2 nmol/L [0.9 μg/L, 25(OH)D3], and 10 nmol/L [4 μg/L, 25(OH)D2], 5 nmol/L [2 μg/L, 25(OH)D3], respectively. The assay was linear to 250 nmol/L (100 μg/L). Interassay CVs across the reportable range were 3.7%–15.2%. Spiked recoveries were 94%–119%. The method comparison with the standard LC-MS/MS method showed slopes of 0.96 and 0.97 (Deming regression) for 25(OH)D2 (n = 1733) and 25(OH)D3 (n = 7614) (R2=0.96 and 0.97), respectively. CONCLUSIONS Multiplexing samples by differential mass tagging in LC-MS/MS measurement of 25(OH)D2 and 25(OH)D3 allows for reliable quantification, with throughput increased over standard methods by the multiplexing factor.