Cancer diagnostics and surgery have been disrupted by the response of health care services to the coronavirus disease 2019 (COVID-19) pandemic. Progression of cancers during delay will impact on ...patients' long-term survival.
We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013–2017. We modelled per-patient delay of 3 and 6 months and periods of disruption of 1 and 2 years. Using health care resource costing, we contextualise attributable lives saved and life-years gained (LYGs) from cancer surgery to equivalent volumes of COVID-19 hospitalisations.
Per year, 94 912 resections for major cancers result in 80 406 long-term survivors and 1 717 051 LYGs. Per-patient delay of 3/6 months would cause attributable death of 4755/10 760 of these individuals with loss of 92 214/208 275 life-years, respectively. For cancer surgery, average LYGs per patient are 18.1 under standard conditions and 17.1/15.9 with a delay of 3/6 months (an average loss of 0.97/2.19 LYGs per patient), respectively. Taking into account health care resource units (HCRUs), surgery results on average per patient in 2.25 resource-adjusted life-years gained (RALYGs) under standard conditions and 2.12/1.97 RALYGs following delay of 3/6 months. For 94 912 hospital COVID-19 admissions, there are 482 022 LYGs requiring 1 052 949 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.08 LYG and 0.46 RALYGs.
Modest delays in surgery for cancer incur significant impact on survival. Delay of 3/6 months in surgery for incident cancers would mitigate 19%/43% of LYGs, respectively, by hospitalisation of an equivalent volume of admissions for community-acquired COVID-19. This rises to 26%/59%, respectively, when considering RALYGs. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued.
•Lockdown and re-deployment due to the COVID-19 pandemic have caused significant disruption to cancer diagnosis and management.•A 3-month delay to surgery across all stage 1–3 cancers is estimated to cause >4700 attributable deaths per year in England.•The impact on life-years lost of 3–6-month delay to surgery for stage 1–3 disease varies widely between tumour types.•Strategic prioritisation of patients for diagnostics and surgery has potential to mitigate deaths attributable to delays.•The resource-adjusted benefit in avoiding delay in cancer management compares favourably with admission for COVID-19 infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic ...drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Measurement of interaction forces distributed across the attachment interface in wearable devices is critical for understanding ergonomic physical human-robot interaction (pHRI). The main challenges ...in sensorization of pHRI interfaces are (i) capturing the fine nature of force transmission from compliant human tissue onto rigid surfaces in the wearable device and (ii) utilizing a low-cost and easily implementable design that can be adapted for a variety of human interfaces. This paper addresses both challenges and presents a modular sensing panel that uses force-sensing resistors (FSRs) combined with robust electrical and mechanical integration principles that result in a reliable solution for distributed load measurement. The design is demonstrated through an upper-arm cuff, which uses 24 sensing panels, in conjunction with the Harmony exoskeleton. Validation of the design with controlled loading of the sensorized cuff proves the viability of FSRs in an interface sensing solution. Preliminary experiments with a human subject highlight the value of distributed interface force measurement in recognizing the factors that influence ergonomic pHRI and elucidating their effects. The modular design and low cost of the sensing panel lend themselves to extension of this approach for studying ergonomics in a variety of wearable applications with the goal of achieving safe, comfortable, and effective human-robot interaction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Proper cell–cell communication through physical contact is crucial for a range of fundamental biological processes including, cell proliferation, migration, differentiation, and apoptosis and for the ...correct function of organs and other multicellular tissues. The spatial and temporal arrangements of these cellular interactions in vivo are dynamic and lead to higher-order function that is extremely difficult to recapitulate in vitro. The development of three-dimensional (3D), in vitro model systems to investigate these complex, in vivo interconnectivities would generate novel methods to study the biochemical signaling of these processes, as well as provide platforms for tissue engineering technologies. Herein, we develop and employ a strategy to induce specific and stable cell–cell contacts in 3D through chemoselective cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. This strategy uses liposome fusion for the delivery of ketone or oxyamine groups to different populations of cells for subsequent cell assembly via oxime ligation. We demonstrate how this method can be used for several applications including, the delivery of reagents to cells for fluorescent labeling and cell-surface engineering, the formation of small, 3D spheroid cell assemblies, and the generation of large and dense, 3D multilayered tissue-like structures for tissue engineering applications.
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IJS, KILJ, NUK, PNG, UL, UM
In this report, we develop smart surfaces for the spatial and temporal control of mammalian cell behavior. We integrate a bioactive surface strategy with a photo-electroactive surface strategy to ...generate dynamic ligand surface gradients for controlling cell adhesion, tissue shape morphing, and cell tissue migration.
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IJS, KILJ, NUK, PNG, UL, UM
We report a molecularly controlled interfacial chemoselective methodology to immobilize ligands and cells in patterns and gradients to self-assembled monolayers on gold. This strategy is based on ...reacting soluble ketone or aldehyde tethered ligands to surface-bound oxyamine alkeanethiols to generate a covalent oxime linkage to the surface. We characterize the kinetic behavior of the reaction on the surface with ferrocenecarboxaldehyde (FcCHO) as a model ligand. The precise extent of immobilization and therefore surface density of FcCHO on the SAM is monitored and determined by cyclic voltammetry, which shows a peudo-first-order rate constant of 0.13 min−1. In order to generate complex surface patterns and gradients of ligands on the surface, we photoprotected the oxyamine group with nitroveratryloxycarbonyl (NVOC). We show that ultraviolet light irradiation through a patterned microfiche film reveals the oxyamine group and we characterize the rate of deprotection by immobilization of ketone containing redox active groups. Finally, we extend this strategy to show biospecific cell attachement of fibroblast cells by immobilizing ketone-GRGDS peptides in patterns. The interfacial oxime reaction is chemoselective and stable at physiological conditions (pH 7.0, 37 °C) and may potentially be used to install ligands on the surface in the presence of attached cells to modulate the cell microenvironment to generate dynamic surfaces for monitoring changes in cell behavior in real time.
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IJS, KILJ, NUK, PNG, UL, UM
This report describes the development of an electroactive mask that permits the patterning of two different cell populations to a single substrate. This mask is based on a self-assembled monolayer of ...alkanethiolates on gold that could be switched from a state that prevents the attachment of cells to a state that promotes the integrin-mediated attachment of cells. Monolayers were patterned into regions having this electroactive monolayer and a second set of regions that were adhesive. After Swiss 3T3 fibroblasts had attached to the adhesive regions of this substrate, the second set of regions was activated electrically to permit the attachment of a second population of fibroblast cells. This method provides a general strategy for patterning the attachment of multiple cell types and will be important for studying heterotypic cell-cell interactions.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Proper cell–cell contact and communication are essential for the correct development and survival of higher order organisms. In order to study complex cell interactions that occur in vivo, model ...systems that are able to recapitulate 3D cell–cell interactions in vitro are key to advancing new biotechnologies, therapeutics, and tissue engineering applications. Herein, we show a new strategy to rapidly and efficiently generate complex multiple cell line containing spheroids and tissues in microfluidic flow without the use of scaffolds, molecular biology, or metabolic biosynthesis. The method relies on the integration of microfluidics, liposome fusion, bio-orthogonal chemistry, and cell surface engineering to rapidly click coculture cell assemblies in flow. We demonstrate this strategy by assembling various combinations of cell types with an interfacial cell to cell click chemistry in microfluidic flow to generate a range of spheroid types and oriented tissue multilayers.
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IJS, KILJ, NUK, PNG, UL, UM
Synthetic polyesters have deeply impacted various biomedical and engineering fields, such as tissue scaffolding and therapeutic delivery. Currently, many applications involving polyesters are being ...explored with polymers derived from monomers that are endogenous to the human metabolism. Examples of these monomers include glycerol, xylitol, sorbitol, and lactic, sebacic, citric, succinic, alpha-ketoglutaric, and fumaric acids. In terms of mechanical versatility, crystallinity, hydrophobicity, and biocompatibility, polyesters synthesized partially or completely from these monomers can display a wide range of properties. The flexibility in these macromolecular properties allows for materials to be tailored according to the needs of a particular application. Along with the presence of natural monomers that allows for a high probability of biocompatibility, there is also an added benefit that this class of polyesters is more environmentally friendly than many other materials used in biomedical engineering. While the selection of monomers may be limited by nature, these polymers have produced or have the potential to produce an enormous number of successes in vitro and in vivo.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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