IMPORTANCECerebrospinal fluid phosphorylated tau (p-tau) 181, p-tau217, and p-tau231 are associated with neuropathological outcomes, but a comparison of these p-tau isoforms in blood samples is needed. OBJECTIVE To conduct a head-to-head comparison of plasma p-tau181 and p-tau231 measured on the single-molecule array (Simoa) platform and p-tau181 and p-tau217 measured on the Meso Scale Discovery (MSD) platform on amyloid and tau positron emission tomography (PET) measures, neurodegeneration, vascular pathology, and cognitive outcomes.

No abstract

Purpose To re-evaluate the population-based incidence of idiopathic intracranial hypertension (IIH) and determine if it mirrors the rise in obesity. Design Retrospective, population-based cohort. Participants All residents of Olmsted County, Minnesota, USA, diagnosed with idiopathic intracranial hypertension between January 1, 1990, and December 31, 2014. Methods All cases of IIH were identified using the Rochester Epidemiology Project, which is a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota residents. All medical records were reviewed to confirm a diagnosis of idiopathic intracranial hypertension. The incidence rates of IIH were compared against the incidence of obesity in Minnesota over the same time period. Main Outcome Measures Incidence of IIH, lumbar puncture opening pressures, body mass index. Results There were 63 new cases of IIH, yielding an overall age- and sex-adjusted annual incidence of 1.8/100,000 (95% CI: 1.3–2.2) between 1990 and 2014. It increased from 1.0/100,000 (1990–2001) to 2.4/100,000 (2002–2014) (p=0.007). The incidence of IIH was 3.3/100,000 in women and 0.3/100,000 in men (p=<0.001). In obese women aged 15 to 44 years, the incidence was 22.0/100,000 compared to 6.8/100,000 among all female patients in the same age group. A strong correlation was observed between IIH incidence rates and obesity rates in Minnesota (R2=0.70, p=0.008). Conclusion The incidence of IIH has increased since 1990, which is highly correlated with the rise in obesity during the same time period.

No abstract

Purpose Optimal early detection and prevention for breast cancer depend on accurate identification of women at increased risk. We present a risk prediction model that incorporates histologic features of biopsy tissues from women with benign breast disease (BBD) and compare its performance to the Breast Cancer Risk Assessment Tool (BCRAT). Methods We estimated the age-specific incidence of breast cancer and death from the Mayo BBD cohort and then combined these estimates with a relative risk model derived from 377 patient cases with breast cancer and 734 matched controls sampled from the Mayo BBD cohort to develop the BBD–to–breast cancer (BBD-BC) risk assessment tool. We validated the model using an independent set of 378 patient cases with breast cancer and 728 matched controls from the Mayo BBD cohort and compared the risk predictions from our model with those from the BCRAT. Results The BBD-BC model predicts the probability of breast cancer in women with BBD using tissue-based and other risk factors. The concordance statistic from the BBD-BC model was 0.665 in the model development series and 0.629 in the validation series; these values were higher than those from the BCRAT (0.567 and 0.472, respectively). The BCRAT significantly underpredicted breast cancer risk after benign biopsy (P = .004), whereas the BBD-BC predictions were appropriately calibrated to observed cancers (P = .247). Conclusion We developed a model using both demographic and histologic features to predict breast cancer risk in women with BBD. Our model more accurately classifies a woman's breast cancer risk after a benign biopsy than the BCRAT.

Over one million American women have a benign breast biopsy annually. Sclerosing adenosis (SA) is a common, but poorly understood benign breast lesion demonstrating increased numbers of distorted lobules accompanied by stromal fibrosis. Few studies of its association with breast cancer have been conducted, with contradictory results. We studied SA in the Mayo Benign Breast Disease (BBD) Cohort, which includes women who had benign biopsies at Mayo-Rochester 1967–2001. Breast cancer risk in defined subsets was assessed using standardized incidence ratios (SIRs), relative to the Iowa Surveillance, Epidemiology, and End Results registry. This BBD cohort of 13,434 women was followed for a median of 15.7 years. SA was present in 3,733 women (27.8 %) who demonstrated an SIR for breast cancer of 2.10 (95 % CI 1.91–2.30) versus an SIR of 1.52 (95 % CI 1.42–1.63) for the 9,701 women without SA. SA was present in 62.4 % of biopsies with proliferative disease without atypia and 55.1 % of biopsies with atypical hyperplasia. The presence of SA stratified risk in subsets of women defined by age, involution status, and family history. However, SA does not further stratify risk in women diagnosed with other forms of proliferative breast disease, either with or without atypia. SA is a common proliferative lesion of the breast which, as a single feature, conveys an approximate doubling of breast cancer risk. Its role in breast carcinogenesis remains undefined; its presence may aid in risk prediction for women after a breast biopsy.

Objective Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome (ARDS) are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to ARDS by reducing lung inflammation and enhancing alveolar fluid clearance. Design Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the fraction of inspired oxygen (S/F) through day 5. We also analyzed categorical change in S/F by > 20%. Other outcomes included need for mechanical ventilation and development of ARDS. Setting Five academic centers in the United States. Patients Adult patients admitted through the emergency department at risk for ARDS. Interventions Aerosolized budesonide/formoterol vs. placebo twice daily for up to 5 days. Measurements and Main Results Sixty-one patients were enrolled from September 3, 2013 to June 9, 2015. Median time from presentation to first study drug was < 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p=0.02) and independent of shock (p=0.04). Categorical change in S/F improved (p=0.01) but not after adjustment for shock (p=0.15). More patients in the placebo group developed ARDS (7 versus 0) and required mechanical ventilation (53% versus 21%). Conclusions Early treatment with inhaled budesonide/formoterol in patients at-risk for ARDS is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of ARDS.

IMPORTANCE Anemia is common and has been associated with poor outcomes in the critically ill population, yet the timing and extent of hemoglobin recovery remains incompletely described, which may have important implications for clinical outcomes following discharge from intensive care. OBJECTIVES To describe longitudinal changes in anemia status during and after critical illness and assess the associations between hemoglobin concentrations and postdischarge mortality.