State Aid Policies in Response to the COVID-19 Shock: Observations and Guiding Principles.

As a general principle, state aid to firms and sector-specific support schemes should be used only when there are market failures; that is, when there are good reasons to believe that the market would not deliver efficient and/or equitable outcomes.

Lipoprotein(a) in patients with hepatocellular carcinoma and portal vein thrombosis.

BACKGROUND: The mechanism for hypercoagulability in malignancy is not entirely understood. Although several studies report contrasting finding about the link between elevated plasma levels of the lipoprotein(a) [Lp(a)] and the possible recurrence of venous thromboembolism, we perform a study to evaluate the impact of the Lp(a) in the development of portal vein thromboembolism (PVT) in patients with HCC. METHODS: We compared 44 PVT patients with 50 healthy subjects and 50 HCC patients. RESULTS: The comparison between PVT patients and HCC showed in the former the mean value of serum lipoprotein levels was higher than 37.3 mg/dl (p = 0.000). The comparison between PVT versus healthy controls showed that in the former, mean value of serum lipoprotein levels was higher than 75 mg/dl (p = 0.000). The predictive value test of serum lipoprotein(a) on PVT was 0.72 and on HCC was 0.83. The odds ratio of lipoprotein(a) was 9.21 on PVT and 6.33 on HCC. CONCLUSION: Patients with PVT and HCC showed a statistical significant serum lipoprotein(a) level higher than the subjects with HCC and no PVT or the healthy subject. So we assume a role of lipoprotein(a) as predictor of venous thromboembolism in neoplastic patients.

Silybin supplementation during HCV therapy with pegylated interferon-α plus ribavirin reduces depression and anxiety and increases work ability.

BACKGROUND: Hepatitis C virus infection and interferon treatment are often associated with anxiety, depressive symptoms and poor health-related quality of life. To evaluate the Silybin-vitamin E-phospholipids complex effect on work ability and whether health related factors (anxiety and depression) were associated with work ability in subjects with chronic hepatitis C treated with Pegylated-Interferon-α2b (Peg-IFN) and Ribavirin (RBV). METHODS: Thirty-one patients (Group A) with chronic hepatitis and other 31 subjects in Group B were recruited in a randomized, prospective, placebo controlled, double blind clinical trial. Group A received 1.5 mg/kg per week of Peg-IFN plus RBV and placebo, while Group B received the same dosage of Peg-IFN plus RBV plus association of Silybin 94 mg + vitamin E 30 mg + phospholipids 194 mg in pills for 12 months. All subjects underwent to laboratory exams and questionnaires to evaluate depression (Beck Depression Inventory - BDI), anxiety (State-trait anxiety inventory - STAI) and work ability (Work ability Index - WAI). RESULTS: The comparison between group A and group B showed significant differences after 6 months in ALT (P < 0.001), and viremia (P < 0.05), after 12 months in ALT (P < 0.001), and AST (P < 0.001), at follow up in AST (P < 0.05), and ALT (P < 0.001). Significant difference were observed after 1 month in WAI (p < 0.001) and BDI (P < 0.05), after 6 months in WAI (P < 0.05) and STAI (P < 0.05), after 12 months and at follow up in WAI, STAI and BDI (p < 0.01). CONCLUSIONS: The supplementation with Silybin-vitamin E -phospholipids complex increased work ability and reduced depression and anxiety in patients treated with Peg-IFN and RBV. TRIAL REGISTRATION: NCT01957319 , First received: September 25, 2013. Last updated: September 30, 2013 (retrospectively registered).

Assessing Humoral Immuno-Inflammatory Pathways Associated with Respiratory Failure in COVID-19 Patients.

All severe cases of SARS-CoV-2 infections are characterized by a high risk of disease progression towards ARDS, leading to a bad outcome. Respiratory symptoms in COVID-19 patients often do not correspond to disease's worsening. In our sample, median age was 74 years (72-75) and 54% were men. The median period of hospitalization was 9 days. Firstly, we observed a significant asynchronous trend of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in 764 selected among 963 patients, who were consecutively recruited in two hospitals (Cannizzaro, S. Marco) in Catania, Italy. NLR values in deceased patients showed an increase from baseline over time. By contrast, CRP tended to fall from baseline to median day of hospitalization in all three subgroups, but steeply increased at the end of hospitalization only in ICU-admitted patients. Then, we evaluated the relationships between NLR and CRP as continuous variables with PaO2/FiO2 ratio (P/F). NLR was an independent predictor of mortality (HR: 1.77, p < 0.0001), while ICU admission was more significantly associated with CRP (HR: 1.70, p < 0.0001). Finally, age, neutrophils, CRP, and lymphocytes are significantly and directly linked to P/F, while the influence of inflammation on P/F, reflected by CRP, was also mediated by neutrophils.

Cytokine serum profile in a group of Sicilian nonagenarians.

The aim of our study was to evaluate the possibility of using multiplex analysis of the cytokine profile as a marker for successful aging by comparing cytokine plasmatic levels of a group of Sicilian nonagenarians with those of young controls. We analyzed a panel of 17 cytokines, comprehensive of haematopoietic factors T helper 1 (Th1), Th2, inflammation regulatory cytokines, and chemokines. The assay was carried out using the Luminex system. Interleukin (IL)-6 levels (p = 0.01) were increased in nonagenarians, whereas no modifications of other proinflammatory cytokines and chemokines were observed. Interferon-gamma (IFN-γ) and IL-2 levels are unmodified, suggesting a substantial maintenance of relevant T cell functions. In addition, a significant increase of IL-12 serum levels in nonagenarians versus young controls that might be related to the increase of natural killer (NK) cell functions characterizing aging processes was observed. The analysis of Th2 cytokines show an increase of IL-13 and a reduction of IL-4 levels mirroring the maintenance of some effector's mechanisms of the immunoresponse in advanced ages. Our results suggest that the multiplex analysis of cytokine levels might be useful in defining a successful aging profile.

Centenarians and supercentenarians: a black swan. Emerging social, medical and surgical problems.

The Black Swan Theory was described by Nassim Nicholas Taleb in his book "The Black Swan". This theory refers to "high-impact, hard-to-predict, and rare events beyond the realm of normal expectations". According to Taleb's criteria, a Black Swan Event is a surprise, it has a major impact and after the fact, the event is rationalized by hindsight, as if it had been expected. For most of human history centenarians were a rare and unpredictable phenomenon. The improvements of the social-environmental conditions, of medical care, and the quality of life caused a general improvement of the health status of the population and a consequent reduction of the overall morbidity and mortality, resulting in an overall increase of life expectancy. The study of centenarians and supercentenarians had the objective to consider this black swan and to evaluate the health, welfare, social and economic consequences of this phenomenon.

Neutrophil-to-Lymphocyte Ratio (NLR) Is a Promising Predictor of Mortality and Admission to Intensive Care Unit of COVID-19 Patients.

The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker predicting the prognosis of several diseases. We aimed to assess its role as a predictor of mortality or admission to the intensive care unit in COVID-19 patients. We retrospectively evaluated a cohort of 411 patients with COVID-19 infection. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) of patients with COVID-19 were compared. The median age of our sample was 72 years (interquartile range: 70−75); 237 were males. Hypertension, diabetes and ischemic heart disease were the most common comorbidities. The study population was subdivided into three groups according to NLR tertiles. Third-tertile patients were older, showing significantly higher levels of inflammatory markers; 133 patients (32%) died during hospitalization, 81 of whom belonged to the third tertile; 79 patients (19%) were admitted to ICU. NLR showed the largest area under the curve (0.772), with the highest specificity (71.9%) and sensitivity (72.9%), whereas CRP showed lower sensitivity (60.2%) but slightly higher specificity (72.3%). Comparisons between NLR and CRP ROC curves were significantly different (p = 0.0173). Cox regression models showed that the association between NLR and death was not weakened after adjustment for confounders. Comparisons of ROC curves showed no significant differences between NLR, PLR, and CRP. Cox regression analysis showed that NLR predicted the risk of admission to ICU independently of demographic characteristics and comorbidities (HR: 3.9597, p < 0.0001). These findings provide evidence that NLR is an independent predictor of mortality and a worse outcome in COVID-19 patients and may help identify high-risk individuals with COVID-19 infection at admission.

Acetyl-L-carnitine reduces depression and improves quality of life in patients with minimal hepatic encephalopathy.

BACKGROUND: Minimal hepatic encephalopathy (MHE) represents a common complication present in well-compensated cirrhotic patients that impairs patients' daily functioning and health-related quality of life (HRQL). Acetyl-L-carnitine (ALC) has been shown to be useful in improving blood ammonia and cognitive functions in cirrhotic patients with MHE. OBJECTIVE: This study evaluated the effects of ALC treatment on HRQL and depression in patients with MHE. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study. Sixty-seven patients with MHE were recruited to the study. They were randomly assigned to two groups and received either 2 g acetyl-L-carnitine twice a day (n = 33) or placebo (n = 34) for 90 days. The primary efficacy measures were changes in aspartate aminotransferase, alanine aminotransferase, γ-glutamyl-transpeptidase, albumin, alkaline phosphatase, prothrombin time, and ammonia. Clinical and laboratory assessments, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients. RESULTS: At the end of the study period, between the two groups, we observed a significant difference in physical function (p < 0.001), role physical (p < 0.001), general health (p < 0.001), social function (p < 0.05), role emotional (p < 0.05), mental health (p < 0.05), Beck Depression Inventory (p < 0.001), TMT-B s (p < 0.001), State Trait Inventory (p < 0.001), urea (p < 0.05), NH(4)(+) (p < 0.001), and bilirubin (p < 0.001). CONCLUSIONS: This study shows that ALC treatment is associated with significant improvement in patient energy levels, general functioning and well-being. The improvement of quality of life is associated with reduction of anxiety and depression.

Acetyl-L-carnitine improves cognitive functions in severe hepatic encephalopathy: a randomized and controlled clinical trial.

The aim of this study was to investigate the effects of ALC treatment on cognitive functions in patients with severe hepatic encephalopathy. This was a randomized, double-blind, placebo-controlled study. 61 patients with severe hepatic encephalopathy were recruited to the study. The 2 groups received either 2 g ALC twice a day (n = 30) or placebo (n = 30) for 90 days. Clinical and laboratory assessment, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients. At the end of the study period, between the 2 groups we observed a significant difference in Everyday Memory Questionnaire -23.9 vs 4.4 (p < 0.001), Logical Memory (Paragraph recall) test 22.3 vs 0.7 (p < 0.001), Trail Making Test A -7.5 vs -2.6 (p < 0.001), Trail Making Test B -10.5 vs -3.1 (p < 0.001), Controlled Oral Word Association Test 4.2 vs 0.5 (p < 0.001), Hooper test 2.6 vs 0.1 (p < 0.05), Judgement of line orientation 2.8 vs 0.3 (p < 0.001), Digit Cancellation time -24.5 vs -2.4 (p < 0.001), NH4⁺ 30.5 vs 13.5 (p < 0.001), prothrombin time 2 vs 2.4 (p < 0.05), alanine transaminase -10.7 vs -13.6 (p < 0.001). 88% of patients treated with ALC vs 72% of patients treated with placebo showed a significant improvement in EEG. The improvement of cognitive deficits, the reduction of ammonia, and the modification of EEG in patients treated with ALC suggest that ALC could represent a new tool in the treatment of severe hepatic encephalopathy.

A review on the actual trends of insulin treatment in elderly with diabetes.

The diabetes of the elderly subjects has two forms: diabetes of long duration, manifesting itself in younger or medium ages, and senile diabetes, appearing above the age of 65 years. The diabetes of the elderly has usually only modest symptoms: it is not ketosic, but in spite of this, in order to avoid the chronic-degenerative complications, it is important to maintain a good, even if not an optimal compensation. The therapeutic intervention cannot neglect a correct alimentary regime and a programmed physical activity in correlation with the clinical conditions of the patient. If the compensation is not achieved only with these tools, one can add oral antidiabetic treatments. In the elderly patients we usually observe primary or secondary failure of the oral antidiabetic treatments, and in such context we have to apply insulin treatment, even in cases of moderate glycometabolic decompensations. While we are waiting for the gene-therapy or the inhalatory insulin preparations, actually there are at disposal only the insulin analogs in rapid, slow and mixed forms. We propose two treatment schemes: (i) The first one consists of three administrations of rapid insulin with the meals, and on dose of slow insulin 2h after the last meal in the evening. (ii) The second scheme consists of one administration of rapid insulin at lunch, one administration of mixed insulin at dinner, with the addition of oral antidiabetics of peripheric action, in the morning and the evening. A better compliance can be obtained, being a fundamental aspect in the elderly diabetics, and a reduction of the number and severity of the hypoglycemia, which are the most important aspects in the elderly diabetes.

Insulin-resistance (IR) in older age.

A study pool of 1549 normoglycemic elderly in the age range of 65-84 years, taken from the epidemiological Italian Longitudinal Study on Aging (ILSA), was constructed. The values of IR, %B and %S were analyzed using the homeostasis assessment model-2 (HOMA-2). In the subjects displaying normal values of several studied parameters such as the arterial blood pressure, total cholesterol (T-CH), high-density lipoproteins (HDL), and triglycerides (TG), the values of IR, %B and %S remained in the normal ranges (in average 1.66+/-1.11, 133.64+/-63.56 and 91.12+/-79.75, respectively). These latter values increase in the subjects who had altered values of the studied basic parameters listed above, and the increases were higher with the higher frequency of the altered parameters. The results seem to confirm the possibility that the normoglycemic elderly subjects having a compensatory insulin hypersecretion against the IR, may develop a type 2 diabetes or a metabolic syndrome.

Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue.

Fatigue is one of the conditions most frequently complained by the elderly. There are few effective treatment options for patients with chronic fatigue syndrome. To determine the efficacy, tolerability and impact on the fatigue, as well as on cognitive and functional status of elderly subjects with acetyl L-carnitine (ALC), 96 aged subjects (>70 years, range 71-88) were investigated (50 females and 46 males; mean age 76.2+/-7.6 and 78.4+/-6.4 years, respectively). They met four or more of the Holmes major criteria or at least six of Fukuda minor criteria. Fatigue was measured with the Wessely and Powell [Wessely, S., Powell, R., 1989. Fatigue syndromes: a comparison of chronic postviral fatigue with neuromuscular and affective disorders. J. Neurol. Neurosurg. Psychiatry 52, 940-948] scores, with the fatigue severity scale. At the end of the treatment, we observed a decrease of physical fatigue: 6.2 (p<0.001), of mental fatigue: 2.8 (p<0.001), of severity fatigue: 21.0 (p<0.001) and improvements in functional status: 16.1 (p<0.001) and cognitive functions: 2.7 (p<0.001). By the end of the treatment, significant differences between the two groups were found for the following parameters: muscle pain -27% versus -3% (p<0.05); prolonged fatigue after exercise: 51% versus -4% (p<0.0001); sleep disorders: 28% versus 4% (p<0.05); physical fatigue: 7 versus -0.5 (p<0.0001); mental fatigue: -3.3 versus 0.6 (p<0.0001); fatigue severity scale: -22.5 versus 1.2 (p<0.0001); functional status 17.1 versus 0.6 (p<0.0001); mini mental state examination (MMSE) improvements: 3.4 versus 0.5 (p<0.0001). Our data show that administering ALC may reduce both physical and mental fatigue in elderly and improves both the cognitive status and physical functions.

Resveratrol in Patients with Minimal Hepatic Encephalopathy.

BACKGROUND: Minimal Hepatic Encephalopathy (MHE) is characterized by an impairment of social interaction, emotional behavior, sleep disorders, physical and mental symptoms, and diminished Quality of Life (QoL). The aim of our study is evaluating the potential liver health promoting a perspective of Resveratrol (RV) activities and evaluate whether RV treatment may improve health related quality of life (HRQL) and reduce depression and anxiety in patients with MHE. METHODS: We evaluated depression using the Beck Depression Inventory test, anxiety with State-trait anxiety inventory test, quality of life through SF-36 test, and ammonia serum levels in 70 MHE patients that were randomized into two groups. RESULTS: In the comparison between RV group and placebo group we observed a decrease in Back Depression Inventory (BDI) (p < 0.001), in State-trait anxiety inventory (STAI) (p < 0.001), and improve in physical function (p < 0.001), in role physical (p < 0.05), in body pain (p < 0.05), in general health (p < 0.001), in vitality (p < 0.05), and in social function (p < 0.001). CONCLUSIONS: Resveratrol showed efficacy in the treatment of depression, anxiety, and ammonia serum levels, and improved the quality of life Of MHE patients.

L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial.

BACKGROUND: Centenarians are characterized by weakness, decreasing mental health, impaired mobility, and poor endurance. L-Carnitine is an important contributor to cellular energy metabolism. OBJECTIVE: This study evaluated the efficacy of L-carnitine on physical and mental fatigue and on cognitive functions of centenarians. DESIGN: This was a placebo-controlled, randomized, double-blind, 2-phase study. Sixty-six centenarians with onset of fatigue after even slight physical activity were recruited to the study. The 2 groups received either 2 g levocarnitine once daily (n = 32) or placebo (n = 34). Efficacy measures included changes in total fat mass, total muscle mass, serum triacylglycerol, total cholesterol, HDL cholesterol, LDL cholesterol, Mini-Mental State Examination (MMSE), Activities of Daily Living, and a 6-min walking corridor test. RESULTS: At the end of the study period, the levocarnitine-treated centenarians, compared with the placebo group, showed significant improvements in the following markers: total fat mass (-1.80 compared with 0.6 kg; P < 0.01), total muscle mass (3.80 compared with 0.8 kg; P < 0.01), plasma concentrations of total carnitine (12.60 compared with -1.70 mumol; P < 0.05), plasma long-chain acylcarnitine (1.50 compared with -0.1 micromol; P < 0.001), and plasma short-chain acylcarnitine (6.0 compared with -1.50 micromol; P < 0.001). Significant differences were also found in physical fatigue (-4.10 compared with -1.10; P < 0.01), mental fatigue (-2.70 compared with 0.30; P < 0.001), fatigue severity (-23.60 compared with 1.90; P < 0.001), and MMSE (4.1 compared with 0.6; P < 0.001). CONCLUSIONS: Our study indicates that oral administration of levocarnitine produces a reduction of total fat mass, increases total muscular mass, and facilitates an increased capacity for physical and cognitive activity by reducing fatigue and improving cognitive functions.

Value and significance of new diagnostic criteria of diabetes mellitus in older people.

In 1998, the World Health Organization (WHO) accepted the diagnostic criteria proposed in 1997 by the American Diabetes Association (ADA) and confirmed that, independent of age, the fasting plasma glucose (FPG) level from and above 126mg/dl in the morning should be considered as diabetic, while subjects with FPG 110-125mg/dl have an impaired fasting glucose (IFG), compared with the normal fasting glucose (NFG) level (up to 110mg/dl). In a pool of 4492 elderly people (65-84 years), we assessed the significance and meaning of these new diagnostic criteria of diabetes. A 5-year follow-up was carried out, during which out of 4492 elderly subjects, 2750 were re-examined. As regards the diagnosis, we applied both the criteria of WHO (1985, 1998). At our first observation (1992), 13.1% were diabetic in the elderly group, if applying the WHO (1985) criteria, and 15.1% applying the ADA-WHO definitions. When re-analyzing the subjects with FPG of 126-139mg/dl after 5 years, it became evident that the diagnosis of diabetes is not stable in this group, because 50.7% of them displayed FPG<126mg/dl (14.5% IFG; 36.2% even NFG). It means that the significance of FPG and the conditions of diabetes are different in the elderly, as compared with the younger adults. Furthermore, the oral glucose tolerance test (OGTT) of 60 elderly subjects in the age range of 71-80 years, admitted in our day hospital, were considered. Among the subjects with an FPG 126-140mg/dl, the OGTT was of diabetic type in 90%, while among IFG and NFG subjects, it was in 50 and 10%, respectively. In conclusion, in elderly subjects with FPG of 126-140mg/dl, the diagnosis of diabetes is not stable and requires further confirmation.

Cardio-cerebrovascular complications in elderly with diabetes.

Authors have considered the prevalence of hypertension (HT), myocardial infarction (MI) and stroke (S), in elderly subjects with diabetes, impaired fasting glucose (IFG) and normal fasting glucose (NFG), respectively. A high occurrence of diabetes in elderly subjects has been found. MI and S were more frequent in diabetic group than in IFG and NFG ones. HT proved to be elevated in the total pool, especially in older olds, and with a higher prevalence among those with diabetes. A 5-year follow-up has been carried out. The index of survival for MI and S was lower in subjects with diabetes. The subjects affected by both MI and S displayed the worst index of survival in all the three categories considered, therefore, it can be stated that such an association is a determinant factor of mortality.

The chromogranin-A (CgA) in prostate cancer.

Prostate cancer is one of the most frequent tumors in men. The neuroendocrine differentiation in prostate cancer has become more widely recognized and has attracted considerable attention as a potentially new finding with major diagnostic, prognostic and therapeutic implications. We investigated the role of the serum concentrations of CgA in a group of 57 patients with prostate cancer and in 61 elderly subjects with benign prostate hyperplasia (BPH). Neuron-specific enolase (NSE) is the most frequently employed marker to detect neuroendocrine features. Serum prostate-specific antigen (PSA), CgA and NSE levels were determined. Comparing prostate cancer group versus BPH group, the CgA level difference was 63.00 ng/ml (p<0.0001) and the PSA level difference was 50.86 mcg/ml (p<0.0001). Between prostate cancer group and control group the CgA level difference was 94.3 ng/ml (p<0.0001), the PSA level difference was 52.91 mcg/ml (p<0.0001), and the NSE level difference was 1.34 microg/l (p<0.0001). Patients with higher CgA levels had poorer prognosis and survival, compared to those with lower CgA levels. These results support the concept that serum CgA level determination before treatment is a potential prognostic factor for prostate cancer.

Endozepine-4 levels are increased in hepatic coma.

AIM: To evaluate the serum levels of endozepine-4, their relation with ammonia serum levels, the grading of coma and the severity of cirrhosis, in patients with hepatic coma. METHODS: In this study we included 20 subjects with Hepatic coma, 20 subjects with minimal hepatic encephalopathy (MHE) and 20 subjects control. All subjects underwent blood analysis, Child Pugh and Model for End - stage liver disease (MELD) assessment, endozepine-4 analysis. RESULTS: Subjects with hepatic coma showed significant difference in endozepine-4 (P < 0.001) and NH3 levels (P < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation (P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD (P = 0.017; Pearson correlation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma, with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia (P < 0.001). In patients with grade IV hepatic coma, endozepine levels were significantly higher compared to other groups. CONCLUSION: This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion, data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.