Patient-derived tumor organoids (PDOs) are a highly promising preclinical model that recapitulates the histology, gene expression, and drug response of the donor patient tumor. Currently, PDO culture relies on basement-membrane extract (BME), which suffers from batch-to-batch variability, the presence of xenogeneic compounds and residual growth factors, and poor control of mechanical properties. Additionally, for the development of new organoid lines from patient-derived xenografts, contamination of murine host cells poses a problem. We propose a nanofibrillar hydrogel (EKGel) for the initiation and growth of breast cancer PDOs. PDOs grown in EKGel have histopathologic features, gene expression, and drug response that are similar to those of their parental tumors and PDOs in BME. In addition, EKGel offers reduced batch-to-batch variability, a range of mechanical properties, and suppressed contamination from murine cells. These results show that EKGel is an improved alternative to BME matrices for the initiation, growth, and maintenance of breast cancer PDOs.
BackgroundResearch suggests that 90% of patients labeled beta-lactam allergic are able to tolerate penicillins following further assessment. This study aims to define and describe the frequency of true beta-lactam allergy following allergy patient evaluation in a predominantly pediatric population.Methods306 primary care patients referred between January 2010 and June 2015 were assessed for a suspected beta-lactam allergy. Patient demographics, history and test results were extracted from electronic medical records. Testing performed was based on specialist recommendation following review of patient history.Results34% of the study participants had intradermal testing. Oral challenge was given to 96.7% of the sample. 96% of patients with a prior history of beta-lactam allergy were advised that they could re-introduce beta-lactam antibiotics following evaluation.ConclusionsAmong patients with a documented beta-lactam allergy or a recent history of a reaction there is a low rate of ‘true’ beta-lactam allergy. Consistent evaluation of beta-lactam antibiotic allergies can reduce rates of broad spectrum antibiotic prescribing, among other harmful consequences.
The present paper represents an extension of the work outlined in number VII of this series, "Factors causing acidosis in nephritis" (1), with an attempt to explain in part the disturbances of the total acidbase equilibrium of the serum which were there described. The acidosis, a term applied to conditions in which the concentration of bicarbonate of serum is low, appeared to be due to several different types of electrolyte disturbances of which the chief were reduction of total base and increase of undetermined acid (i.e., acids other than bicarbonate, chloride, phosphate and protein). Phosphate increases seemed to play a less important r6le. Variable changes in the level of Cl, usually reductions in its concentration, were observed with great frequency.To the data then presented many observations have been added, and collateral studies, bearing especially on chloride metabolism, have been made.
EXPERIMENTAL METHODSSince the appearance of the first paper of this series (2) certain changes in the technique -and calculations used in the determination of the total acid-base equilibrium of the serum have ben adopted to increase accuracy. Although these changes in no way alter the conclusions reached in previous articles, they have necessitated a redetermination and restatement of normal values and recalculations of earlier data.
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