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Objective: Data on prognostic tools for indicating mechanical ventilation in older people with COVID-19 are still limited. The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from mechanical ventilation.Design: Longitudinal, multicenter study.Settings and Participants: 502 older people hospitalized for COVID-19 in 10 European hospitals.Methods: MPI was calculated using 8 different domains typical of the CGA. A propensity score, Cox's regression analysis was used for assessing the impact of mechanical ventilation on rehospitalization/mortality for 90 days' follow-up, stratified by MPI = 0.50. The accuracy of MPI in predicting negative outcomes (ie, rehospitalization/mortality) was assessed using the area under the curve (AUC), and the discrimination with several indexes like the Net Reclassification Improvement (NRI) and the Integrated Discrimination Improvement (IDI).Results: Among 502 older people hospitalized for COVID-19 (mean age: 80 years), 152 were treated with mechanical ventilation. In the propensity score analysis, during the 90-day follow-up period, there were 44 rehospitalizations and 95 deaths. Mechanical ventilation in patients with MPI values >= 0.50, indicating frailer participants, was associated with a higher risk of rehospitalization/mortality (hazard ratio 1.56, 95% CI 1.09-2.23), whereas in participants with MPI values < 0.50 this association was not significant. The accuracy of the model including age, sex, respiratory parameters, and MPI was good (AUC = 0.783) as confirmed by an NRI of 0.2756 (P < .001) and an IDI of 0.1858 (P < .001), suggesting a good discrimination of the model in predicting negative outcomes.Conclusions and Implications: MPI could be useful for better individualizing older people hospitalized by COVID-19 who could benefit from mechanical ventilation. (C) 2022 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

The emergent coronavirus-19 disease (COVID-19) pandemic posed and still poses serious issues in the management of the inpatients and in the resource allocation, in particular for those patients requiring Intensive Care Unit (ICU) management. Epidemiological data clearly suggest that multimorbid older patients have the poorest prognosis. However, it is conceivable that age and number of comorbidities alone do not reflect the real condition and the expected prognosis of the patients affected by COVID-19. A different approach based on comprehensive geriatric assessment (CGA) could help to better identify older patients more at risk of dismal outcomes and who, at some point of their clinical course, will need the ICU admission. The Multidimensional Prognostic Index (MPI) is a well-accepted tool derived from a standard CGA which allows to measure prognosis of older patients in different clinical settings including hospital. Therefore, we designed a multicenter, prospective, observational study to evaluate the role of MPI in predicting risk of ICU admission and in-hospital mortality among 500 COVID-19-positive older subjects admitted to geriatric and internal medicine wards. In addition, risk of re-hospitalization, institutionalization and death after 3 months from discharge will be assessed. The MPI yields a straightforward value from 0 to 1 and might be able to adequately stratify complex, vulnerable COVID-19 patients for best possible decision-making and treatment allocation.

Three groups of patients with chronic renal failure (CRF), 16 non-dialyzed, 16 undergoing haemodialysis (HD), 16 undergoing continuous ambulatory peritoneal dialysis (CAPD), and 48 controls were examined. We analyzed the fatty acid composition in membranes from erythrocytes and platelets and the platelet malondialdehyde (MDA) production as an index of thromboxane metabolism. Marked differences in erythrocytes fatty acid composition were observed between patients with CRF and controls and, particularly, among the three groups of patients with CRF. Patients on CAPD were characterized by an increase in oleic acid, while haemodialyzed had a marked increase in arachidonic acid. Platelet fatty acid composition showed similar differences, suggesting a ‘systemic’ membrane abnormality. Platelet MDA was increased in haemodialyzed and positively correlated with the platelet arachidonate content.

Abstract Desaturase enzymes are responsible for the conversion of essential fatty acids to the longer-chain eicosanoid precursors. These enzymes require zinc as an essential cofactor, and the following ratios—C20:4/C18:2, C20:5/C18:3, and C22:6/C20:5—are considered indexes of their activity. We analyzed these parameters in plasma and erythrocyte membranes of 105 essential hypertensive patients, 20 white coat hypertensive patients, and 100 age-matched normotensive control subjects. Dietary analysis excluded significant quantitative and qualitative differences in fatty acid dietary intake between essential hypertensive patients and normotensive control subjects. Zinc levels and C20:4/C18:2, C20:5/C18:3, and C22:6/C20:5 ratios were significantly higher in essential hypertensive patients than control subjects, whereas white coat hypertensive patients showed intermediate values for all these parameters. These data provide evidence for an alteration in fatty acid metabolism of essential hypertensive patients, consistent with increased activity of desaturase enzymes. The consequent greater bioavailability of eicosanoid precursors, and in particular of arachidonic acid, could affect several vascular functions and have a bearing on the pathogenesis or complications of hypertension.

The apparent antagonism between Zinc (Zn) and Copper (Cu) is a well-known phenomenon and has been documented in various chronic diseases. An impairment in Zn and Cu status has been shown in hypertensive animals (1), suggesting a possible relationship with the pathogenesis of hypertension. Zn and Cu are involved in lipid metabolism, and several studies indicated that a major aspect of Zn-Cu interaction may be related to the opposing effects on essential fatty acids (EFA) metabolism or by differential stimulation of the synthesis of prostaglandins (PGs), whose influence on blood pressure (BP) regulation has been widely documented (2). The conversion of C-18 polyunsaturated fatty acids (PUFA) into the longerchain metabolites proceeds through desaturation and elongation steps; desaturation processes are catalyzed by the Δ4-Δ5-Δ6 desaturases, which are the rate-limiting enzymes in the pathway, and whose activities specifically require Zn and Cu (2). Thus, Zn and Cu availability may modulate the balance of PGs precursors. Also, since C-20 and C-22 are the major PUFA found in phospholipids, most of the cellular functions (fluidity, permeability or the ion transport systems activity) are in some way related to their metabolism (3).

Resistance to activated protein C (APC-R) is at present considered the most frequent laboratory abnormality in patients with deep vein thrombosis. An increased risk for venous thrombosis is associated with the use of oral contraceptives (OCs). We recently described a statistically significant association between APC-R status and oral contraceptives use in a healthy group of women. We re-evaluated 50 healthy women taking low-dose combination OCs in order to consider a possible correlation between the APC sensitivity ratio (APC-SR) and different oral contraceptive formulations. Seven women showed an APC ratio < or = 2 (APC-resistant). Only one of the seven women was found to be heterozygous for Leiden factor V mutation. We observed no significant differences between normally sensitive and APC-resistant women in terms of duration of OC use, amount of estrogenic or progestogenic dose, or type of formulation. We conclude that APC-resistance associated with oral contraceptives use seems to occur only in predisposed subjects (in our results, about 12% of the healthy population).

High serum copper (s-Cu) has been reported as an independent risk factor for cardiovascular disease (CVD) in both case-control (1) and large prospective population studies (2, 3). The mechanisms underlying these associations are largely unclear. In vitro Cu is highly efficient in promoting the oxidation of low-density-lipoprotein (4), which is considered an important step in atherogenesis. A synergistic effect between the pro-oxidant action of Cu and low status of selenium (an antioxidant), leading to atherogenesis via an imbalance of defence against free radicals has been suggested in vivo (5). Also, experimental animal studies suggest a role of Cu in lipid metabolism, particularly in cholesterol (6) and fatty acid metabolism (7). Within the framework of a cross-sectional survey aimed to study the status of several trace elements in a sample of healthy adults (8), we examined the relationships between s-Cu and several, well-known, risk factors for CVD, including plasma lipoproteins and fatty acids, and coagulation factors.

1. Iodothyronine 5′-deiodinase, which is mainly responsible for peripheral triiodothyronine (T3) production, has recently been demonstrated to be a selenium-containing enzyme. In the elderly, reduced peripheral conversion of thyroxine (T4) to T3 and overt hypothyroidism are frequently observed. 2. We measured serum selenium and erythrocyte glutathione peroxidase (as indices of selenium status), thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to exclude abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid conditions of undernutrition or malnutrition, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. 3. In order to properly assess the influence of selenium status on iodothyronine 5′-deiodinase type I activity, a double-blind placebo-controlled trial was also carried out on 36 elderly subjects, resident at a privately owned nursing home. 4. In the free-living population, a progressive reduction of the T3/T4 ratio (due to increased T4 levels) and of selenium and erythrocyte glutathione peroxidase activity was observed with advancing age. A highly significant linear correlation between T4, T3/T4 and selenium was observed in the population as a whole (for T4, R = −0.312, P < 0.002; for T3/T4 ratio, R = 0.32, P < 0.01) and in older subjects (for T4, R = −0.40, P < 0.05; for T3/T4 ratio, R = 0.54, P < 0.002). 5. The main result of the double-blind placebo-controlled trial was a significant improvement of selenium indices and a decrease in the T4 level in selenium-treated subjects; serum selenium, erythrocyte glutathione peroxidase activity and thyroid hormones did not change in placebo-treated subjects. 6. We concluded that selenium status influences thyroid hormones in the elderly, mainly modulating T4 levels.

Resistance to activated protein C (APC) is at present considered the most frequent laboratory abnormality in patients with deep-vein thrombosis. An increased risk for venous thrombosis is associated to the use of oral contraceptives (OC). We studied APC sensitivity in 50 healthy women taking OC and in 50 healthy controls, matched for age, smoking habit, educational and social levels, and the main biochemical routinary parameters. Subjects with a personal or familial history of thrombosis and also with chronic or acute diseases were excluded. Protein C, protein S, antithrombin III and lupus anticoagulant activity (LAC) were also evaluated. Increased fibrinogen and protein C levels, decreased protein S. and shortened PT and APTT were also observed in women taking OC. APC sensitivity ratio (APC-SR) was significantly lower in the OC group than in a control group (2.6 +/- 0.38 v 2.81 +/- 0.35, P0.01). Seven of eight women with APC ratioor = 2 (APC resistant) were OC users: the difference of prevalence was statistically significant (chi-squared test, P0.05). Only two out of eight women were found heterozygous for the Leiden factor V mutation. Two APC-resistant women without the Leiden mutation subsequently discontinued OC and both then normalized their APC-SR. We conclude that acquired factors, i.e. oral contraceptives, may play an important role in determining plasma APC resistance.During April-June 1994, at Borgo Roma Polyclinic in Verona, Italy, clinical researchers compared data on 50 healthy women 18-41 who used low-dose combined oral contraceptives (OCs) with data on 50 healthy women matched for age, smoking, education, social class, and biochemical routinary parameters. Almost all the subjects were medical students or medical staff working in the hospital where the study occurred. The researchers aimed to examine the prevalence of resistance to activated protein C (APC) in both groups. They also evaluated protein C, protein S, antithrombin III, and lupus anticoagulant activity. The APC-sensitivity ratio (APC-SR) was much lower in OC users than nonusers (2.6 vs. 2.81; p 0.01). Seven of the eight women with an APC-SR of no greater than 2 (i.e., demonstration of APC resistance) used OCs (p 0.05). Prevalence of APC resistance was higher among OC users than nonusers (14% vs. 2%; p 0.05). Among the eight women with APC resistance, two were heterozygous for the Leiden factor V mutation. One of these women used OCs and the other did not. Two APC resistant women who did not have the Leiden factor V stopped using OCs and their APC-SR subsequently normalized. OC users had higher fibrinogen and protein C levels, a lower protein S level, and shorter prothrombin and activated partial thromboplastin times than nonusers. These findings suggest that OCs may contribute to plasma APC resistance, which in turn increases the risk of venous thrombosis.

Objective : To evaluate the effects of low doses of ω-3 polyunsaturated fatty acids on ambulatory blood pressure monitoring parameters in a group of mild essential hypertensives. Patients : We studied 24 consecutive essential hypertensive patients from our outpatient clinic with mild hypertension (diastolic blood pressure ≤105 mmHg), no previous treatment for 4 weeks at least and no other disease. Methods : After a 3-month run-in period, the patients entered an intervention phase and were given 3g ω-3 polyunsaturated fatty acids (85% eicosapentaenoic and docosahexaenoic acid concentrate) daily for 4 months ; this phase was followed by a 4-month washout period. Ambulatory blood pressure monitoring was performed at the end of each phase ; erythrocyte membrane fatty acids were assessed to check compliance. Results : After 4 months of treatment, erythrocyte ω-3 polyunsaturated fatty acids significantly increased but average systolic and diastolic blood pressure and the heart rate did not significantly change ; no significant variations were recorded in blood pressure or heart rate variability (assessed as blood pressure and heart rate SD) nor in the diurnal blood pressure rhythm. After washout, a significant decrease was observed in erythrocyte ω-3 polyunsaturated fatty acids but the ambulatory blood pressure monitoring parameters were not substantially modified. Conclusions : The present data show that low doses of ω-3 polyunsaturated fatty acids as a single treatment are not effective in lowering blood pressure or the heart rate in mild essential hypertensive patients, despite a significant change in fatty acid cell membrane composition. Nor does this treatment seem likely to affect blood pressure variability or the diurnal rhythm.

1. Selenium status was investigated in patients with chronic renal failure, with special regard to its relations to the dialysis treatments, dietary habits and clinical signs of atherosclerosis. 2. Serum selenium concentration and platelet glutathione peroxidase activity were measured in 45 patients with chronic renal failure subdivided into three groups according to the type of treatment: 15 non-dialysed, 15 on haemodialysis, 15 on continuous ambulatory peritoneal dialysis. A 7-day diet history was carried out in all patients. Seventeen of the patients with chronic renal failure had clinically overt cardiovascular disease. Forty-five age-matched healthy subjects were considered as controls. 3. Both serum selenium concentration and platelet glutathione peroxidase were significantly reduced in all patients with chronic renal failure compared with control subjects; a direct and significant correlation was found between the two parameters. No differences in selenium status were observed among the non-dialysed, haemodialysis and continuous ambulatory peritoneal dialysis groups. No correlation between total calorie or protein intakes and selenium indices were observed. The chronic renal failure patients with cardiovascular complications showed a further significant reduction in both serum selenium concentration and platelet glutathione peroxidase activity as compared with the patients without cardiovascular complications; these two groups were similar with respect to the other well-known cardiovascular risk factors (age, smoking, plasma lipids, hypertension, body mass index). 4. It is concluded that a low selenium concentration is present in chronic renal failure, which is independent of dialysis and is accompanied by biological repercussion in terms of reduced platelet glutathione peroxidase activity. It may represent a previously unrecognized cofactor favouring the ‘accelerated’ atherosclerosis of patients with chronic renal failure.