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

Dynamics of tissue morphogenesis

Form fits function. Tissues and organs obtain their shapes in a complex process involving the integration of internal and external signaling and mechanical and biochemical cues. The mammary gland and other branched organs develop their characteristic tree-like geometries through the process of branching morphogenesis, a process in which the epithelium bifurcates and invades into the surrounding stroma. Controlling the pattern of branching is critical for function of these organs. In vivo, branching of the mammary gland is regulated through epithelial-stromal interactions. Adipocytes are the largest component of the surrounding stroma and yet their role is largely unknown. We used a microlithography-based approach to engineer a three-dimensional culture model that enables the determination of the effect of adipocytes on the branching morphogenesis of mammary epithelial cells. We found that adipocyte-rich stroma induces branching through paracrine signals, including hepatocyte growth factor, but does not affect the sites at which branches initiate. This tissue engineering approach can be expanded to other organs, and should enable piecemeal analysis of the cellular populations that control patterning during normal development. Epithelial cells within three-dimensional tubules have been observed to move in a rotational pattern. To investigate the mechanisms that regulate this movement we simplified the system and examined the emergence of vortical tissue movements in bounded two-dimensional sheets. The observed rotational motion of the epithelial monolayers is dynamic and the direction of rotation switches frequently. The switches in rotational motion correlate with disturbances in the monolayer resulting from cytokinesis. We showed through simulations and experiments that cells within these small tissues behave as Vicsek-Czirók self-propelled particles, and that maintenance of the rotational motion requires neither E-cadherin-mediated cell-cell junctions nor cytoskeletal contractility. As predicted by the simulations, we found a critical role for cell density; increasing density increases correlation and reduces the effect of cytokinesis in disturbing the rotational motion. We also found that as tissue sizes became larger, cell-cell junctions play a greater role in organizing collective motion and producing global rotation. In addition, we mapped the cellular divisions in these tissues and found that the cellular division axes are oriented perpendicular to the radial direction of the tissue and this alignment is regulated by both the cellular motion and the endogenous traction stress profile. Our results suggest that the initial architecture of the tissue in which the cells reside instructs their movements with respect to each other within a collective and orient cellular division axes to guide tissue growth and establish final form

CM: Dynamics of branched tissue assembly

Th e self assembly of cells into tissues and organs is an elegant and intricate process that is vital for development and homeostasis. During organogenesis, the assembly of cells is controlled genetically as well as through cues from cell-cell and cell-matrix interactions Formation of the trachea in D. melanogaster Th e trachea of the fruit fl y is a ductal structure responsible for the delivery of oxygen to tissues. Th is organ forms during embryonic development and involves invagination, division, extension and fusion of select cells of placodes along the lateral ectoderm ( Th e DB consists of approximately six cells and these cells migrate dorsally away from the sac toward the morphogen Branchless (Bnl), which acts as a chemoattrac tant secreted by the surrounding cells Abstract The assembly of cells into tissues is a complex process controlled by numerous signaling pathways to ensure the fi delity of the fi nal structure. Tissue assembly is also very dynamic, as exemplifi ed by the formation of branched organs. Here we present two examples of tissue assembly in branched systems that highlight this dynamic nature: formation of the tracheal network in Drosophila melanogaster and the ducts of the mammary gland in mice. Extension of the branches during tracheal development is a stereotyped process that produces identical organ geometries across individuals, whereas elongation of the ducts of the pubertal mammary gland is a non-stereotyped process that produces unique patterns. By studying these two organs, we can begin to understand the dynamic nature of development of other stereotyped and nonstereotyped branching systems, including the lung, kidney, and salivary gland

Quantitative approaches to uncover physical mechanisms of tissue morphogenesis

Morphogenesis, the creation of tissue and organ architecture, is a series of complex and dynamic processes driven by genetic programs, microenvironmental cues, and intercellular interactions. Elucidating the physical mechanisms that generate tissue form is key to understanding development, disease, and the strategies needed for regenerative therapies. Advancements in imaging technologies, genetic recombination techniques, laser ablation, and microfabricated tissue models have enabled quantitative descriptions of the cellular motions and tissue deformations and stresses with unprecedented temporal and spatial resolution. Using these data synergistically with increasingly more sophisticated physical, mathematical, and computational models will unveil the physical mechanisms that drive morphogenesis