New take on the post-take ward round: a quality improvement project undertaken in a district general hospital.

A patient's first encounter with a consultant clinician, known as the post-take ward round (PTWR), is a pivotal encounter at the start of their hospital journey. It is a chance for a review of history, examination and investigations, formulation of preliminary diagnosis and management plan. High-quality patient care is reliant on effective communication of clinical information between teams, and the PTWR record is an integral part of this handover of information across different clinicians, medical teams and wards.Consensus of consultant opinion allowed for the formation of a standard against which the quality of PTWR documentation could be measured. This project aimed to assess and improve compliance with the devised standard.Following a survey of referrals made to the medical team after the move to electronic record keeping, it was found that important information was being missed from PTWR records. For example, of the 446 records analysed, only 34% had a documented potential discharge date (PDD) and 20% had a documented escalation plan. Analysis showed overall compliance to core criteria was 63%.Several changes within the department of acute medicine were trialled, including the introduction of a checklist, prompt cards for clinical staff to carry and finally the implementation of an electronic form for PTWR records.Over the course of several cycles of data collection, compliance with core criteria improved from 63% to 86%. Most notably, improvement was seen in documentation of social history (42%-87%), frailty score (0%-63%), PDD (41%-81%) and escalation plan (21%-66%).This work demonstrates the value of development of a standard for PTWR documentation, and of a proforma. The actions taken in this hospital may be of benefit to other medical departments.

Interpretable multimodal deep learning for real-time pan-tissue pan-disease pathology search on social media.

Pathologists are responsible for rapidly providing a diagnosis on critical health issues. Challenging cases benefit from additional opinions of pathologist colleagues. In addition to on-site colleagues, there is an active worldwide community of pathologists on social media for complementary opinions. Such access to pathologists worldwide has the capacity to improve diagnostic accuracy and generate broader consensus on next steps in patient care. From Twitter we curate 13,626 images from 6,351 tweets from 25 pathologists from 13 countries. We supplement the Twitter data with 113,161 images from 1,074,484 PubMed articles. We develop machine learning and deep learning models to (i) accurately identify histopathology stains, (ii) discriminate between tissues, and (iii) differentiate disease states. Area Under Receiver Operating Characteristic (AUROC) is 0.805-0.996 for these tasks. We repurpose the disease classifier to search for similar disease states given an image and clinical covariates. We report precision@k = 1 = 0.7618 ± 0.0018 (chance 0.397 ± 0.004, mean ±stdev ). The classifiers find that texture and tissue are important clinico-visual features of disease. Deep features trained only on natural images (e.g., cats and dogs) substantially improved search performance, while pathology-specific deep features and cell nuclei features further improved search to a lesser extent. We implement a social media bot (@pathobot on Twitter) to use the trained classifiers to aid pathologists in obtaining real-time feedback on challenging cases. If a social media post containing pathology text and images mentions the bot, the bot generates quantitative predictions of disease state (normal/artifact/infection/injury/nontumor, preneoplastic/benign/low-grade-malignant-potential, or malignant) and lists similar cases across social media and PubMed. Our project has become a globally distributed expert system that facilitates pathological diagnosis and brings expertise to underserved regions or hospitals with less expertise in a particular disease. This is the first pan-tissue pan-disease (i.e., from infection to malignancy) method for prediction and search on social media, and the first pathology study prospectively tested in public on social media. We will share data through http://pathobotology.org . We expect our project to cultivate a more connected world of physicians and improve patient care worldwide.

Bioengineering the liver: scale-up and cool chain delivery of the liver cell biomass for clinical targeting in a bioartificial liver support system.

Acute liver failure has a high mortality unless patients receive a liver transplant; however, there are insufficient donor organs to meet the clinical need. The liver may rapidly recover from acute injury by hepatic cell regeneration given time. A bioartificial liver machine can provide temporary liver support to enable such regeneration to occur. We developed a bioartificial liver machine using human-derived liver cells encapsulated in alginate, cultured in a fluidized bed bioreactor to a level of function suitable for clinical use (performance competence). HepG2 cells were encapsulated in alginate using a JetCutter to produce ∼500 µm spherical beads containing cells at ∼1.75 million cells/mL beads. Within the beads, encapsulated cells proliferated to form compact cell spheroids (AELS) with good cell-to-cell contact and cell function, that were analyzed functionally and by gene expression at mRNA and protein levels. We established a methodology to enable a ∼34-fold increase in cell density within the AELS over 11-13 days, maintaining cell viability. Optimized nutrient and oxygen provision were numerically modeled and tested experimentally, achieving a cell density at harvest of >45 million cells/mL beads; >5×10(10) cells were produced in 1100 mL of beads. This process is scalable to human size ([0.7-1]×10(11)). A short-term storage protocol at ambient temperature was established, enabling transport from laboratory to bedside over 48 h, appropriate for clinical translation of a manufactured bioartificial liver machine.

The role of the Bcl-3 proto-oncogene in thyroid hormone-induced liver cell proliferation.

The aim of the study was to determine if thyroid hormone-induced liver cell proliferation occurs through the Bcl-3 proto-oncogene. Rodents (including Bcl-3 knockout mice and the wild-type strain) were injected with a single dose of tri-iodothyronine (T(3)) and sacrificed at various time points. Hepatic mRNA (real-time polymerase chain reaction ) and protein expression (Western analysis) of Bcl-3 was quantified in rats stimulated with T(3). Cell proliferation was induced in a variety of cell types after T(3) injection at 24 h including hepatocytes (7 +/- 1.1% vs. 0.45 +/- 0.025%; P < 0.01), hepatic nonparenchymal cells (3.8 +/- 1.2% vs. 0.3 +/- 0.01%; P < 0.01), renal tubular cells (8.1 +/- 1.6% vs. 0.2 +/- 0.035%; P < 0.01), and splenic lymphocytes (4.8 +/- 1.2% vs. 0.35 +/- 0.02%; P < 0.01). We showed a twofold increase in hepatic Bcl-3 mRNA (P < 0.01) and protein expression (P < 0.01) at 24 h in rats stimulated with T(3). However, there were no differences in the rate of liver cell proliferation between Bcl-3 knockout mice and the wild-type strain (0.4 +/- 0.15% vs. 0.3 +/- 0.1%), indicating that Bcl-3 was not functionally involved in thyroid hormone-induced liver cell proliferation. A single gene is unlikely to initiate the process of thyroid hormone-induced cell proliferation. A complex interaction between the genomic and nongenomic effects of thyroid hormone is likely to regulate the mitogenic effects.

Increased expression of uncoupling protein 2 in HepG2 cells attenuates oxidative damage and apoptosis.

INTRODUCTION: Oxidative damage plays a major part in the pathogenesis of liver disease. Uncoupling proteins (UCPs) may be able to limit the generation of reactive oxygen species (ROS) and be cytoprotective. METHODS: We investigated the effect of up-regulation of UCP2 in a hepatoblastoma cell line exposed to menadione or hypoxia/re-oxygenation. RESULTS: Lipid and protein oxidation was increased in HepG2 cells exposed to ROS but this increase was significantly lower in cells over-expressing UCP2 under identical conditions. LDH release increased 2.5-fold in response to hypoxia/re-oxygenation in control HepG2 cells with no significant increase in UCP2 transfected cells. Hypoxia/re-oxygenation resulted in a reduction in liver-specific protein secretion that was attenuated in transfected cells and UCP2 over-expression also resulted in a 66% reduction in apoptosis compared with non-transfected controls. CONCLUSIONS: These data suggest that UCP2 can limit oxidative damage in HepG2 cells in response to oxidative stress resulting in improved cell function and resistance to apoptosis.

Altered mitochondrial function and cholesterol synthesis influences protein synthesis in extended HepG2 spheroid cultures.

Cultures of hepatocytes and HepG2 cells provide useful in vitro models of liver specific function. In this study, we investigated metabolic and biosynthetic function in 3-D HepG2 spheroid cultures, in particular to characterise changes on prolonged culture. We show that HepG2 cells cultured in spheroids demonstrate a reduction in mitochondrial membrane potential and respiration following 10 days of culture. This coincides with a modest reduction in glycolysis but an increase in glucose uptake where increased glycogen synthesis occurs at the expense of the intracellular ATP pool. Lowered biosynthesis coincides with and is linked to mitochondrial functional decline since low glucose-adapted spheroids, which exhibit extended mitochondrial function, have stable biosynthetic activity during extended culture although biosynthetic function is lower. This indicates that glucose is required for biosynthetic output but sustained mitochondrial function is required for the maintenance of biosynthetic function. Furthermore, we show that cholesterol synthesis is markedly increased in spheroids cf. monolayer culture and that inhibition of cholesterol synthesis by lovastatin extends mitochondrial and biosynthetic function. Therefore, increased cholesterol synthesis and/or its derivatives contributes to mitochondrial functional decline in extended HepG2 spheroid cultures.