The Barts Health NHS Trust COVID-19 cohort: characteristics, outcomes and risk scoring of patients in East London.

BACKGROUND: Barts Health National Health Service Trust (BHNHST) serves a diverse population of 2.5 million people in London, UK. We undertook a health services assessment of factors used to evaluate the risk of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection.METHODS: Patients with confirmed polymerase chain reaction (PCR) test results admitted between 1 March and 1 August 2020 were included, alongwith clinician-diagnosed suspected cases. Prognostic factors from the 4C Mortality score and 4C Deterioration scores were extracted from electronic health records and logistic regression was used to quantify the strength of association with 28-day mortality and clinical deterioration using national death registry linkage.RESULTS: Of 2783 patients, 1621 had a confirmed diagnosis, of whom 61% were male and 54% were from Black and Minority Ethnic groups; 26% died within 28 days of admission. Mortality was strongly associated with older age. The 4C mortality score had good stratification of risk with a calibration slope of 1.14 (95% CI 1.01-1.27). It may have under-estimated mortality risk in those with a high respiratory rate or requiring oxygen.CONCLUSION: Patients in this diverse patient cohort had similar mortality associated with prognostic factors to the 4C score derivation sample, but survival might be poorer in those with respiratory failure.

Endothelial implants provide long-term control of vascular repair in a porcine model of arterial injury.

Cell culture and animal data support the role of endothelial cells and endothelial-based compounds in regulating vascular repair after injury. We describe a long-term study in pigs in which the biological and immunological responses to endothelial cell implants were investigated 3 months after angioplasty, approximately 2 months after the implants have degraded. Confluent porcine or bovine endothelial cells grown in polymer matrices were implanted adjacent to 28 injured porcine carotid arteries. Porcine and bovine endothelial cell implants significantly reduced experimental restenosis compared to control by 56 and 31%, respectively. Host humoral responses were investigated by detection of an increase in serum antibodies that bind to the bovine or porcine cell strains used for implantation. A significant increase in titer of circulating antibodies to the bovine cells was observed after 4 days in all animals implanted with xenogeneic cells. Detected antibodies returned to presurgery levels after Day 40. No significant increase in titer of antibodies to the porcine cells was observed during the time course of the experiment in animals implanted with porcine endothelial cells. No implanted cells, Gelfoam, or focal inflammatory reaction could be detected histologically at any of the implant sites at 90 days. These data suggest that tissue-engineered endothelial cell implants may provide long-term control of vascular repair after injury, rather than simply delaying lesion formation and that allogeneic implants are able to provide a greater benefit than xenogeneic implants.

Perlecan is required to inhibit thrombosis after deep vascular injury and contributes to endothelial cell-mediated inhibition of intimal hyperplasia.

Perlecan, a heparan sulfate proteoglycan, has been suggested to be critical for regulation of vascular repair. We generated clones of endothelial cells expressing an antisense vector targeting domain III of perlecan. Transfected cells produced significantly less perlecan than parent cells and showed a reduced ability to inhibit the binding and mitogenic activity of fibroblast growth factor-2 in vascular smooth muscle cells. Endothelial cells were seeded onto three-dimensional polymeric matrices and implanted adjacent to porcine carotid arteries subjected to deep injury. Although the parent endothelial cells prevented occlusive thrombosis, perlecan-deficient cells were completely ineffective. The ability of endothelial cells to inhibit intimal hyperplasia, however, was abrogated only in part by perlecan suppression. The differential regulation by perlecan of these different aspects of vascular repair may explain why control of clinical clot formation does not lead to full control of intimal hyperplasia. Thus the use of genetically modified tissue-engineered cells provides a new approach for dissecting the role of specific factors within the complex environment of the blood vessel wall.

Biological surface engineering: a simple system for cell pattern formation.

Biological surface engineering using synthetic biological materials has a great potential for advances in our understanding of complex biological phenomena. We developed a simple system to engineer biologically relevant surfaces using a combination of self-assembling oligopeptide monolayers and microcontact printing (muCP). We designed and synthesized two oligopeptides containing a cell adhesion motif (RADS)n (n = 2 and 3) at the N-terminus, followed by an oligo(alanine) linker and a cysteine residue at the C-terminus. The thiol group of cysteine allows the oligopeptides to attach covalently onto a gold-coated surface to form monolayers. We then microfabricated a variety of surface patterns using the cell adhesion peptides in combination with hexa-ethylene glycol thiolate which resist non-specific adsorption of proteins and cells. The resulting patterns consist of areas either supporting or inhibiting cell adhesion, thus they are capable of aligning cells in a well-defined manner, leading to specific cell array and pattern formations.

Endothelial implants inhibit intimal hyperplasia after porcine angioplasty.

The perivascular implantation of tissue-engineered endothelial cells around injured arteries offers an opportunity to study fundamental vascular physiology as well as restore and improve tissue function. Cell source is an important issue because the ability to implant either xenogeneic or allogeneic cells would greatly enhance the clinical applications of tissue-engineered grafts. We investigated the biological and immunological responses to endothelial cell xenografts and allografts in pigs 4 weeks after angioplasty of the carotid arteries. Porcine or bovine aortic endothelial cells were cultured within Gelfoam matrices and implanted in the perivascular space of 42 injured arteries. Both porcine and bovine endothelial cell grafts reduced the restenosis index compared with control by 54% and 46%, respectively. Perivascular heparin release devices, formulated to release heparin at twice the rate of release of heparan sulfate proteoglycan from endothelial cell implants, produced no significant reduction in the restenosis index. Endothelial cell implants also reduced occlusive thrombosis compared with control and heparin release devices. Host immune responses to endothelial implants were investigated by immunohistochemical examination of explanted devices and by immunocytochemistry of serum samples. The bovine cell grafts displayed infiltration of leukocytes, consisting primarily of lymphocytes, and caused an increase in antibodies detected in serum samples. Reduced cellular infiltration and no humoral response were detected in animals that received allografts. Despite the difference in immune response, the biological effects of xenografts or allografts did not differ significantly.

Peru: children as health and nutrition promoters.

PIP: EDAPROSPO, a Peruvian nongovernmental organization, in 1985-87, developed a health training program for students of 13 grammar schools in Huaycan, San Martin de Porres, and Comas. The principle aim of the program is to encourage and prepare children to be responsible for their health and environment, and to strengthen school health delegates and health teams. School health delegates are children selected by their classmates to work with teacher volunteers to form health teams. It is hoped that participants will spread the message to their families, friends, and neighbors. The project is being extended to other 10-14 year old students and community groups in the area. and with the support of the Ministry of Education, should reach 57 schools, 312 student delegates, and 3300 students. Activities will be expanded to include an evaluation of the main health problems in the community, the identification of vulnerable groups, and community leaders who are interested in supporting children in project activities. EDAPROSPO is also collaborating with ALTERNATIVA, a group working with children aged 3-6 years. Both groups are funded by Radda Barnen, a Swedish development agency.^ieng

Family histories of depressed and severely anxious children.

Of 127 relatives of 12 anxious and 11 depressed children, 72% received Family History RDC diagnoses, most commonly depression and alcoholism. The family histories of the two groups were similar, suggesting that childhood depressive and anxiety disorders may be familially related.