The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

Fasting times showed little association with lipid subclass levels in a community-based population, which suggests that fasting for routine lipid levels is largely unnecessary.

Subclassification of endometrial carcinoma according to histological type shows variable interobserver agreement. The aim of this study was to assess specifically the interobserver agreement of histological type in high-grade endometrial carcinomas, recorded by gynecological pathologists from five academic centers across Canada. In a secondary aim, the agreement of consensus diagnosis with immunohistochemical marker combinations was assessed including six routine (TP53, CDKN2A (p16), ER, PGR, Ki67, and VIM) and six experimental immunohistochemical markers (PTEN, ARID1A, CTNNB1, IGF2BP3, HNF1B, and TFF3). The paired interobserver agreement ranged from j 0.50 to 0.63 (median 0.58) and the intraobserver agreement from j 0.49 to 0.67 (median 0.61). Consensus about histological type based on morphological assessment was reached in 72% of high-grade endometrial carcinomas. A seven-marker immunohistochemical panel differentiated FIGO grade 3 endometrioid from serous carcinoma with a 100% concordance rate compared with the consensus diagnosis. More practically, a three-marker panel including TP53, ER, and CDKN2A (p16) can aid in the differential diagnosis of FIGO grade 3 endometrioid from endometrial serous carcinoma. Our study demonstrates that the inter-and intraobserver reproducibility of histological type based on morphology alone are mostly moderate. Ancillary techniques such as immunohistochemical marker panels are likely needed to improve diagnostic reproducibility of histological types within high-grade endometrial carcinomas.

This review discusses the factors that affect the concentrations of methoxypyrazines (MPs) and the techniques used to analyze MPs in grapes, musts, and wines. MPs are commonly studied pyrazines in food science due to their contribution of aroma and flavor to numerous vegetables such as peas and asparagus. They are described as highly odorous compounds with a very low olfactory threshold. The grape varietals that exhibit green or herbaceous aromas that are characteristic of MPs are predominantly Vitis vinifera cv. Cabernet Sauvignon and Sauvignon Blanc, but include others. The most extensively studied MPs include 3-isobutyl-2-methoxypyrazine, 3-isopropyl-2-methoxypyrazine, and 3-sec-butyl-2-methoxypyrazine. It outlines the significance of methoxypyrazines in grapes, musts, and wines in terms of the concentrations that are capable of contributing their sensory characteristics to wines. This review discusses methods for analyzing MPs including gas chromatography-mass spectroscopy (one or two dimension) and high-performance liquid chromatography, the appropriate extraction techniques, and the efficacy of these methods. Additionally, this review explores factors that affect pyrazine content of grapes, must, and wines, such as the effects of different viticultural practices, effects of light exposure and grape maturation, climate, soil, the multi-colored Asian lady beetle and the effects of different vinification processes.