Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Blood–brain-barrier organoids for investigating the permeability of CNS therapeutics

In vitro models of the blood–brain barrier (BBB) are critical tools for the study of BBB transport and the development of drugs that can reach the CNS. Brain endothelial cells grown in culture are often used to model the BBB; however, it is challenging to maintain reproducible BBB properties and function. ‘BBB organoids’ are obtained following coculture of endothelial cells, pericytes and astrocytes under low-adhesion conditions. These organoids reproduce many features of the BBB, including the expression of tight junctions, molecular transporters and drug efflux pumps, and hence can be used to model drug transport across the BBB. This protocol provides a comprehensive description of the techniques required to culture and maintain BBB organoids. We also describe two separate detection approaches that can be used to analyze drug penetration into the organoids: confocal fluorescence microscopy and mass spectrometry imaging. Using our protocol, BBB organoids can be established within 2–3 d. An additional day is required to analyze drug permeability. The BBB organoid platform represents an accurate, versatile and cost-effective in vitro tool. It can easily be scaled to a high-throughput format, offering a tool for BBB modeling that could accelerate therapeutic discovery for the treatment of various neuropathologies. Keywords: biological models; blood–brain barrier; cytological techniques; drug screenin

Color vision impairment in type 2 diabetes assessed by the D-15d test and the Cambridge Colour Test

Color vision impairment emerges at early stages of diabetes mellitus type 2 (DM2) and may precede diabetic retinopathy or the appearance of vascular alterations in the retina. The aim of the present study was to compare the evaluation of the color vision with two different tests - the Lanthony desaturated D-15d test (a traditional color arrangement test), and the Cambridge Colour Test (CCT) (a computerized color discrimination test) - in patients diagnosed with DM2 without clinical signs of diabetic retinopathy (DR), and in sex- and age-matched control groups. Both color tests revealed statistically significant differences between the controls and the worst eyes of the DM2 patients. In addition, the degree of color vision impairment diagnosed by both tests correlated with the disease duration. The D-15d outcomes indicated solely tritan losses. In comparison, CCT outcomes revealed diffuse losses in color discrimination: 13.3% for best eyes and 29% for worst eyes. In addition, elevation of tritan thresholds in the DM2 patients, as detected by the Trivector subtest of the CCT, was found to correlate with the level of glycated hemoglobin. Outcomes of both tests confirm that subclinical losses of color vision are present in DM2 patients at an early stage of the disease, prior to signs of retinopathy. Considering the advantages of the CCT test compared to the D-15d test, further studies should attempt to verify and/or improve the efficiency of the CCT test

Improved recovery of captured airborne bacteria and viruses with liquid-coated air filters

The COVID-19 pandemic has revealed the importance of the detection of airborne pathogens. Here, we present composite air filters featuring a bio-inspired liquid coating that facilitates the removal of captured aerosolized bacteria and viruses for further analysis. We tested three types of air filters: commercial polytetrafluoroethylene (PTFE), which is well-known for creating stable liquid coatings, commercial high-efficiency particulate air (HEPA) filters, which are widely used, and in-house manufactured cellulose nanofiber mats (CNFM), which are made from sustainable materials. All filters were coated with omniphobic fluorinated liquid to maximize release. We found that coating both the PTFE and HEPA filters with liquid improved the rate at which Escherichia coli was recovered using a physical removal process compared to uncoated controls. Notably, the coated HEPA filters also increased the total number of recovered cells by 57%. Coating the CNFM filters did not improve either the rate of release or total number of captured cells. The ability of the highest performance materials, the liquid-coated HEPA filters were next evaluated on their ability to facilitate the removal of pathogenic viruses via a chemical removal process. Recovery of infectious JC polyomavirus, a non-enveloped virus which attacks the central nervous system, was increased by 92% over uncoated controls; however, there was no significant difference in the total amount of RNA recovered compared to controls. In contrast, significantly more RNA was recovered for SARS-CoV-2, the airborne, enveloped virus which causes COVID-19, from liquid-coated filters. Although the amount of infectious SARS-CoV-2 recovered was 58% higher, these results were not significantly different from uncoated filters due to high variability. These results suggest that the efficient recovery of airborne pathogens from filters could improve air sampling efforts, enhancing biosurveillance and global pathogen early warning