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Background The risk for symptomatic COVID-19 requiring hospitalization is higher in the older population. The course of the disease in hospitalised older patients may show significant variation, from mild to severe illness, ultimately leading to death in the most critical cases. The analysis of circulating biomolecules involved in mechanisms of inflammation, cell damage and innate immunity could lead to identify new biomarkers of COVID-19 severity, aimed to improve the clinical management of subjects at higher risk of severe outcomes. In a cohort of COVID-19 geriatric patients ( n = 156) who required hospitalization we analysed, on-admission, a series of circulating biomarkers related to neutrophil activation (neutrophil elastase, LL-37), macrophage activation (sCD163) and cell damage (nuclear cfDNA, mithocondrial cfDNA and nuclear cfDNA integrity). The above reported biomarkers were tested for their association with in-hospital mortality and with clinical, inflammatory and routine hematological parameters. Aim of the study was to unravel prognostic parameters for risk stratification of COVID-19 patients. Results Lower n-cfDNA integrity, higher neutrophil elastase and higher sCD163 levels were significantly associated with an increased risk of in-hospital decease. Median (IQR) values observed in discharged vs. deceased patients were: 0.50 (0.30-0.72) vs. 0.33 (0.22-0.62) for n-cfDNA integrity; 94.0 (47.7-154.0) ng/ml vs. 115.7 (84.2-212.7) ng/ml for neutrophil elastase; 614.0 (370.0-821.0) ng/ml vs. 787.0 (560.0-1304.0) ng/ml for sCD163. The analysis of survival curves in patients stratified for tertiles of each biomarker showed that patients with n-cfDNA integrity < 0.32 or sCD163 in the range 492-811 ng/ml had higher risk of in-hospital decease than, respectively, patients with higher n-cfDNA integrity or lower sCD163. These associations were further confirmed in multivariate models adjusted for age, sex and outcome-related clinical variables. In these models also high levels of neutrophil elastase (>150 ng/ml) appeared to be independent predictor of in-hospital death. An additional analysis of neutrophil elastase in patients stratified for n-cfDNA integrity levels was conducted to better describe the association of the studied parameters with the outcome. Conclusions On the whole, biomarkers of cell-free DNA integrity, neutrophil and macrophage activation might provide a valuable contribution to identify geriatric patients with high risk of COVID-19 in-hospital mortality.

We investigated whether incubation of cultured human aortic endothelial cells (HAEC) with crystalline silica at the concentration 1 cm2/ml (chosen on the basis of a pilot experiment) leads to alterations typical of apoptosis. The binding of annexin V as early, and DNA fragmentation as late events of apoptosis were measured besides the number of cells with depolarized mitochondria. The generation of reactive oxygen species (ROS) by HAEC in presence of silica was determined as well as silica ability to in vitro generate hydroxyl radicals was investigated. After 18 h of silica incubation, about 30% of viable cells bound annexin V. After 24 h of silica treatment, the percentage of cells with fragmented DNA (Tunel positive) was 27% and it increased up to 50% after 48 h, whereas in untreated cells this percentage was 7% and 11% after 24 and 48 h, respectively. The presence of fragmented DNA in cells treated with silica was confirmed by agarose gel electrophoresis. In agreement with these results showing an induction of HAEC apoptosis by silica incubation, the number of cells with depolarized mitochondria was significantly higher after silica treatment as compared to the control. Apoptosis was also obtained with silica added to aliquots of anti-C5a-absorbed-medium. In the cells exposed to silica there was a significant increasing of ROS generation in comparison to the untreated cells. Apoptosis might be due to peroxidative stress since silica can generate hydroxyl radicals.

Neutrophils are the first barrier against infections. Aged neutrophils display impaired oxidative burst and phagocytosis with subsequent less capability to destroy bacteria. In successful ageing (nonagenarians), neutrophil efficiency (phagocytosis) increases. After ingested microbes, aged neutrophils are less prone to undergo apoptosis favouring chronic inflammation. Moreover, the superoxide dismutase (SOD) activity, which is necessary in avoiding ROS produced by oxidative burst, is limited in ageing. The mechanisms of age-related changes in neutrophil function are not fully understood, taking also into account that nonagenarians escape infections in comparison with elderly. Zinc pool may be involved because it is pivotal for neutrophil efficiency and SOD activity. Since zinc also controls the inflammation, via IL-6 and soluble factor of gp130 (sgp130), we have assessed the possible interrelationship among oxidative burst, apoptosis, inflammation, SOD, adhesion molecule Mac-1 and zinc pool in elderly and in nonagenarians. The oxidative burst and the capacity to increase Mac-1 after PMA stimulation decrease both in elderly and nonagenarians, but the latter display a slight increased neutrophil induced apoptosis, decreased sgp130, increased SOD, and more neutrophil zinc content, as it occurs in young-adults. Significant correlation exists between sgp130 and zinc pool in very old age. These findings suggest lower chronic inflammation in nonagenarians, via more zinc available, with subsequent long-life survival. Therefore, a more correct interrelationship among neutrophil efficiency, inflammation, antioxidant activity and zinc pool exists in successful ageing with subsequent more effectiveness to control the inflammatory response to pathogens.

Pineal graft from young to old rats was performed and red blood cell hemolysis, induced by the water-soluble radical initiator 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH), was evaluated 6 months after graft. Pineal graft modified the hemolysis curve kinetic profile in grafted rats versus age-matched controls, the 50% hemolysis time as well as the lag time were longer, whereas the maximal amount of hemolysis was lower, and it occurred over a longer period of time. Thiobarbituric acid reactive substances production was lower in pineal-grafted rats than in controls and the age-related decrease of erythrocyte membrane fluidity was prevented by pineal graft. The present findings support an important physiological role of pineal gland in preventing age-related alterations of erythrocyte membranes and suggest a possible antioxidant action of melatonin.

Worldwide lockdown reduced air pollution during the first phase of the COVID-19 pandemic. The relationship between exposure to ambient air pollution, digital display device use and dry eye symptoms amongst patients with severe ocular surface disease (OSD) were considered. Symptoms and air pollutant concentrations for three different time periods (pre, during and post COVID-19 lockdown) were analysed in 35 OSD patients who achieved an immunosuppression risk-stratification score > 3 fulfilling the UK Government criteria for 12-week shielding. OSDI symptoms questionnaire, residential postcode air pollution data obtained from the Defra Automated Urban and Rural monitoring network for concentrations of nitrogen dioxide (NO 2 ), nitrogen oxides (NOx), particulate matter (PM) with diameters below 10 µm and 2.5 µm, and English Indices of Deprivation were analysed. Significant reductions in NO 2 and NOx concentrations were observed between pre- and during-lockdown periods, followed by a reversal in the post-lockdown period. Changes were linked to the Living Environment outdoor decile. A 12% increase ( p  = 0.381) in symptomatology during-lockdown was observed that reversed post-lockdown by 19% ( p  = 0.144). OSDI scores were significantly correlated with hours spent on digital devices ( r 2  = 0.243) but not with air pollutant concentrations. Lockdown measures reduced ambient air pollutants whilst OSD symptomatology persisted. Environmental factors such as increased time indoors and use of bluescreen digital devices may have partly played a role.

This paper proposes a new approach to the regionalization of national input–output tables where suitable regional data are scarce and analysts are considering using location quotients (LQs). We focus on the FLQ formula, which frequently yields the best results of the pure LQ-based methods, and develop an enhanced way of implementing this approach. We use a modified cross-entropy (MCE) method, along with a regression model, to estimate values of the unknown parameter δ in the FLQ formula, specific to both region and country. An analysis of survey-based data for 16 South Korean regions reveals that the proposed FLQ+ approach yields more accurate estimates of both input coefficients and sectoral output multipliers than those from simpler LQ-based methods or the MCE approach alone. Sectoral outputs (or employment) are the only regional data required. The MCE method also clearly outperforms GRAS.

Microbial keratitis (MK) is the most common non-surgical ophthalmic emergency, and can rapidly progress, causing irreversible sight-loss. This study explored whether the COVID-19 (C19) national lockdown impacted upon the clinical presentation and outcomes of MK at a UK tertiary-care centre. Medical records were retrospectively reviewed for all patients with presumed MK requiring corneal scrapes, presenting between 23rd March and 30th June in 2020 (Y2020), and the equivalent time windows in 2017, 2018 and 2019 (pre-C19). In total, 181 and 49 patients presented during the pre-C19 and Y2020 periods, respectively. In Y2020, concurrent ocular trauma (16.3% vs. 5.5%, p = 0.030) and immunosuppression use (12.2% vs 1.7%, p = 0.004) were more prevalent. Despite proportionately fewer ward admissions during the pandemic (8.2% vs 32.6%, p<0.001), no differences were observed in baseline demographics; presenting visual acuity (VA; median 0.6 vs 0.6 LogMAR, p = 0.785); ulcer area (4.0 vs 3.0mm2, p = 0.520); or final VA (0.30 vs 0.30 LogMAR, p = 0.990). Whilst the overall rates of culture positivity were similar in Y2020 and pre-C19 (49.0% vs. 54.7%, p = 0.520), there were differences in the cultures isolated, with a lower rate of poly-microbial cultures in Y2020 (8.3% vs. 31.3%, p = 0.022). Patient characteristics, MK severity and final visual outcomes did not appear to be affected in the first UK lockdown, despite fewer patients being admitted for care. Concurrent trauma and systemic immunosuppression use were greater than in previous years. The difference in spectra of isolated organisms may relate to behavioural changes, such as increased hand hygiene.

BackgroundSecondary conditions may reduce function and participation in individuals with chronic Spinal Cord Injury (SCI). The knowledge of reasons for readmission to the hospital may be enlightening to prevent them and remodel the health services.Study designMulticenter prospective observational study of all consecutive readmissions of persons with SCI after rehabilitation completion.ObjectivesTo explore the characteristics of individuals with SCI readmitted to the hospital, the reasons for readmissions and the burden on hospitalization in terms of length of stay (LoS) for different conditions.Setting31 Italian specialized SCI centers.MethodsData on people with traumatic SCI readmitted to SCI centers were recorded about: age, sex, SCI level and severity group, geographical origin, readmission causes, clinical interventions during hospitalization, LoS and discharge destination. Linear and multiple logistic regression analyses were performed considering LoS (days) as dependent variable for correlations with independent variables. All tests were two-sided.ResultsAmong 1039 persons with traumatic SCI enrolled (mean age 46, males 85%, tetraplegia 43%), 59.09% of the readmissions were caused by urological problems, 39.74% by pressure injury and 35.41% by spasticity (68% readmitted for ≥2 causes, associated with longer LoS). The mean LoS was 48 days: pressure injury, rehabilitative needs, sexual, bowel, and pain problems were associated with longer and urological problems with shorter LoS. People from the South of the country were frequently (68%) readmitted to the northern centers.ConclusionsUrological problems, pressure injury and spasticity were the most frequent causes of re-hospitalization in individuals with traumatic SCI. The migration trend seeking SCI-specific treatments suggests geographic areas to which health care organizations need to pay more attention.

Study design: Observational prospective population-based incidence study. Objectives: The main objective of this study was to assess the incidence of traumatic spinal cord injuries (TSCIs) and incidence rates, in order to provide estimates by age, gender, characteristics and cause. Setting: This study was conducted at acute-care spinal cord injury (SCI) hospitals and SCI centers from 11 Italian regions, between 1 October 2013 and 30 September 2014. Methods: Data of all consecutive patients with acute TSCI who met the inclusion criteria were obtained through case reporting by clinicians. The data were collected into a web database. Incidence rates and incidence rate ratios were calculated and stratified by age, gender, cause, level and completeness. Results: From 50% of the entire population of Italy, 445 new cases of TSCI were included. The crude incidence rate of TSCI was 14.7 cases per million per year (95% CI: 13.4–16.4); the overall male to female ratio was 4:1 and the mean age was 54. Complete information was available in 85% of the sample and revealed tetraplegia in 58% and incomplete lesion in 67% of cases. The leading cause of TSCI was falls (40.9%) followed by road traffic accidents (33.5%). The leading cause was falls for patients over 55 and road traffic accidents for patients under 55. Conclusion: The changing trend of TSCI epidemiology concerns the increase in the average age of TSCI people and the increase of both cervical and incomplete lesions. The etiology shows the primacy of falls over road traffic accidents and suggests the need for a change in prevention policies.