An Amino Acid Mixture to Counteract Skeletal Muscle Atrophy: Impact on Mitochondrial Bioenergetics.

Skeletal muscle atrophy (SMA) is caused by a rise in muscle breakdown and a decline in protein synthesis, with a consequent loss of mass and function. This study characterized the effect of an amino acid mixture (AA) in models of SMA, focusing on mitochondria. C57/Bl6 mice underwent immobilization of one hindlimb (I) or cardiotoxin-induced muscle injury (C) and were compared with controls (CTRL). Mice were then administered AA in drinking water for 10 days and compared to a placebo group. With respect to CTRL, I and C reduced running time and distance, along with grip strength; however, the reduction was prevented by AA. Tibialis anterior (TA) muscles were used for histology and mitochondria isolation. I and C resulted in TA atrophy, characterized by a reduction in both wet weight and TA/body weight ratio and smaller myofibers than those of CTRL. Interestingly, these alterations were lightly observed in mice treated with AA. The mitochondrial yield from the TA of I and C mice was lower than that of CTRL but not in AA-treated mice. AA also preserved mitochondrial bioenergetics in TA muscle from I and C mice. To conclude, this study demonstrates that AA prevents loss of muscle mass and function in SMA by protecting mitochondria.

Eradication of HCV by direct antiviral agents restores mitochondrial function and energy homeostasis in peripheral blood mononuclear cells.

Hepatitis C virus (HCV) adopts several immune evasion mechanisms such as interfering with innate immunity or promoting T-cell exhaustion. However, the recent direct-antiviral agents (DAAs) rapidly eliminate the virus, and the repercussions in terms of immune system balance are unknown. Here we compared the PBMCs transcriptomic profile of patients with HCV chronic infection at baseline (T0) and 12 weeks after the end of the therapy (SVR12) with DAAs. 3862 genes were differently modulated, identifying oxidative phosphorylation as the top canonical pathway differentially activated. Therefore, we dissected PBMCs bioenergetic profile by analyzing mitochondrial respiration and glycolysis at 4 timepoints: T0, 4 weeks of therapy, end of therapy (EoT), and SVR12. Maximal and reserve respiratory capacity considerably increased at EoT, persisting until SVR12. Notably, over time a significant increase was observed in respiratory chain (RC) complexes protein levels and the enzymatic activity of complexes I, II, and IV. Mitochondrial-DNA integrity improved over time, and the expression of mitochondrial biogenesis key regulators such as TFAM, Nrf-1, and PPARGC1A significantly increased at SVR12; hence, RC complexes synthesis and mitochondrial respiration were supported after treatment. HCV clearance with DAAS profoundly changed PBMCs bioenergetic profile, suggesting the immunometabolism study as a new approach to the understanding of viral immune evasion mechanisms and host adaptations during infections and therapies.

Redox Biology and Liver Fibrosis.

Hepatic fibrosis is a complex process that develops in chronic liver diseases. Even though the initiation and progression of fibrosis rely on the underlying etiology, mutual mechanisms can be recognized and targeted for therapeutic purposes. Irrespective of the primary cause of liver disease, persistent damage to parenchymal cells triggers the overproduction of reactive species, with the consequent disruption of redox balance. Reactive species are important mediators for the homeostasis of both hepatocytes and non-parenchymal liver cells. Indeed, other than acting as cytotoxic agents, reactive species are able to modulate specific signaling pathways that may be relevant to hepatic fibrogenesis. After a brief introduction to redox biology and the mechanisms of fibrogenesis, this review aims to summarize the current evidence of the involvement of redox-dependent pathways in liver fibrosis and focuses on possible therapeutic targets.

Redox-Dependent Modulation of Human Liver Progenitor Cell Line Fate.

Redox homeostasis is determinant in the modulation of quiescence/self-renewal/differentiation of stem cell lines. The aim of this study consisted of defining the impact of redox modifications on cell fate in a human hepatic progenitor line. To achieve this, the HepaRG cell line, which shows oval ductular bipotent characteristics, was used. The impact of redox status on the balance between self-renewal and differentiation of HepaRG cells was investigated using different methodological approaches. A bioinformatic analysis initially proved that the trans-differentiation of HepaRG toward bipotent progenitors is associated with changes in redox metabolism. We then exposed confluent HepaRG (intermediate differentiation phase) to oxidized (H2O2) or reduced (N-acetylcysteine) extracellular environments, observing that oxidation promotes the acquisition of a mature HepaRG phenotype, while a reduced culture medium stimulates de-differentiation. These results were finally confirmed through pharmacological modulation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2), a principal modulator of the antioxidant response, in confluent HepaRG. NRF2 inhibition led to intracellular pro-oxidative status and HepaRG differentiation, while its activation was associated with low levels of reactive species and de-differentiation. In conclusion, this study shows that both intra- and extracellular redox balance are crucial in the determination of HepaRG fate. The impact of redox status in the differentiation potential of HepaRG cells is significant on the utilization of this cell line in pre-clinical studies.

CHA2DS2-VASc and R2CHA2DS2-VASc scores predict mortality in high cardiovascular risk population.

BACKGROUND: The CHA2 DS2 -VASc score, widely used to estimate cardioembolic risk in patients with atrial fibrillation (AF), appears to be useful also in predicting vascular adverse events and death in different sets of patients without AF. The R2 CHA2 DS2 -VASc score, which includes renal impairment, allows a better prediction of death and thromboembolism in patients without AF. The aims of our study were to assess, in a large sample of patients at high cardiovascular (CV) risk, (i) the correlation between CHA2 DS2 -VASc and R2 CHA2 DS2 -VASc with all-cause mortality, and (ii) to compare the performances of CHA2 DS2 -VASc and R2 CHA2 DS2 -VASc in predicting all-cause mortality. METHODS: In this single-centre prospective observational study, conducted at the Research Hospital 'Casa Sollievo della Sofferenza' between June 2016 and December 2018, 1017 CV patients at high risk of undergoing coronary angiography were enrolled. RESULTS: CHA2DS2-VASc and R2 CHA2 DS2 -VASc scores significantly associated with all-cause mortality. For each one-point increase in CHA2 DS2 -VASc or R2 CHA2 DS2 -VASc scores, mortality increased by almost 1.5-fold. The R2 CHA2 DS2 -VASc score (C-statistic = 0.71; 95% CI = 0.65-76) outperformed the CHA2 DS2 -VASc score (C-statistic = 0.66; 95% CI = 0.61-0.71) in predicting 4-year mortality (delta C-statistic = 0.05; 95% CI = 0.02-0.07). The better predictive ability of the R-CHA2 DS2 -VASc score was also demonstrated by an IDI = 0.027 (95% CI = 0.021-0.034, p < .00001) and a relative IDI = 62.8% (95% CI = 47.9%-81.3%, p < .00001). The R2 CHA2 DS2 -VASc score correctly reclassified the patients with a NRI = 0.715 (95% = 0.544-0.940, p < .00001). CONCLUSIONS: The CHA2DS2-VASc and R2 CHA2 DS2 -VASc scores are useful predictors of all-cause mortality in subjects at high CV risk, with the R2 CHA2 DS2 -VASc score being the best performer.

Low GFR amplifies the association between coronary three-vessel disease and all-cause mortality.

BACKGROUND AND AIM: Three vessels disease (3VD) has been associated with worse prognosis and higher mortality. Chronic kidney disease (CKD) is an independent risk factor for premature death, mostly due to coronary artery disease (CAD). We aim to examine the prognostic impact of 3VD on all-cause mortality in a cohort of high cardiovascular risk subjects undergoing coronary angiography (CA) and to explore whether low eGFR (<60 ml/min/1.73 m2) modulates the risk of all-cause mortality associated to 3VD. METHODS AND RESULTS: One-thousand-seventeen subjects (759 M, mean age 68.4 ± 11 years) consecutive subjects undergoing CA from 2016 to 2018 were evaluated. Subjects were classified according to the severity of CAD as follows: group "three vessels disease" (3VD), and "no three vessels disease" (No 3VD). Serum creatinine was measured to estimate glomerular filtration rate (eGFR). The whole population was divided into 4 groups (A, B, C, D), according to the presence/absence of low eGFR and/or 3VD. One-hundred-fourteen deaths occurred (median follow-up:44 months). The risk of death in subjects with 3VD was almost 2-time higher than subject without 3VD (adjusted HR = 1.61; 95% CI 1.094-2.373, p = 0.0157). Among 4 subgroups, subjects with low eGFR and 3VD (Group D) had the highest risk of death (adjusted HR = 3.881; 95% CI 2.256-6.676, p < 0.0001). CONCLUSIONS: Low eGFR significantly amplifies the risk of all-cause mortality associated to 3VD. Our results strengthen the role of kidney disease as a risk multiplier for cardiovascular and all-cause mortality and highlight the need to prevent its onset and progression.

Takotsubo Syndrome and Inflammatory Bowel Diseases: Does a Link Exist?

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiac dysfunction in the absence of viral causes or obstructive coronary disease completely reversible within 4-8 weeks. Inflammatory bowel diseases (IBD) are a group of diseases caused by the interaction between immune system, genetic, and environmental factors against intestinal mucosa. Both these syndromes are characterized by complex mechanisms involving endothelial dysfunction and affective disorders. AIM: To assess the possibility of an association between IBD and TTS. METHODS: First, we present a case of TTS in a patient affected by active stenosing Crohn's disease. Articles in English language were collected from PubMed and Google Scholar databases with the search terms "takotsubo," "IBD," "crohn disease," "ulcerative colitis". RESULTS: Both TTS and IBD show multiple common features: preference for female patients, recurrent course of disease, association with endothelial dysfunction, and affective disorders. Patients affected by IBD could show specific triggers for TTS, such as malabsorption, electrolytes disturbances, and affective disorders. CONCLUSIONS: Despite pathophysiological similarities between TTS and IBD in active phase, future studies are needed to confirm this apparently possible association and to assess the presence of a pathophysiological link between these diseases.

Molecular Aspects and Treatment of Iron Deficiency in the Elderly.

Iron deficiency (ID) is the most frequent nutritional deficiency in the whole population worldwide, and the second most common cause of anemia in the elderly. The prevalence of anemia is expecting to rise shortly, because of an ageing population. Even though WHO criteria define anemia as a hemoglobin serum concentration <12 g/dL in women and <13 g/dL in men, several authors propose different and specific cut-off values for the elderly. Anemia in aged subjects impacts health and quality of life, and it is associated with several negative outcomes, such as longer time of hospitalization and a higher risk of disability. Furthermore, it is an independent risk factor of increased morbidity and mortality. Even though iron deficiency anemia is a common disorder in older adults, it should be not considered as a normal ageing consequence, but a sign of underlying dysfunction. Relating to the molecular mechanism in Iron Deficiency Anemia (IDA), hepcidin has a key role in iron homeostasis. It downregulates the iron exporter ferroportin, inhibiting both iron absorption and release. IDA is frequently dependent on blood loss, especially caused by gastrointestinal lesions. Thus, a diagnostic algorithm for IDA should include invasive investigation such as endoscopic procedures. The treatment choice is influenced by the severity of anemia, underlying conditions, comorbidities, and the clinical state of the patient. Correction of anemia and iron supplementation should be associated with the treatment of the causal disease.

Direct-acting antivirals for HCV treatment in older patients: A systematic review and meta-analysis.

The advent of highly effective and well-tolerated direct antiviral antivirals (DAAs) has dramatically changed the landscape of chronic hepatitis C. The effect of DAAs in older adults is difficult to determine since patients aged ≥ 65 years were too few in most clinical trials and data mainly come from observational studies. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of DAAs in patients aged 65 and older. PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, HCV-Trials.com databases were searched for literature published until 1 December 2017. English language articles reporting results of phase 2 or 3 randomized controlled trials (RCTs), single-arm clinical trials (SATs) and observational studies were included in the final analysis. All studies included subgroups of older patients and compared their outcomes with younger individuals. By using a random-effects or fixed-effects model, odds ratio (OR) was calculated for the efficacy and safety. Heterogeneity was tested using I2 statistics. Thirty-seven studies reported data on the DAA efficacy. The OR was 1.66 (95%CI: 1.00-2.75; P = 0.06) in meta-analysis of RCTs, and similar results were found in SATs and observational studies. HCV genotype, stage of fibrosis or HIV co-infection did not affect the rate of SVR in older persons. Prevalence of anaemia (OR 0.26 95%CI: 0.09-0.69; P = 0.007) (OR 0.25 95%CI: 0.09-0.69; P = 0.007) and skin complaints (OR 0.61 95%CI: 0.45-0.83; P = 0.001) was higher in older adults. Finally, geriatric patients affected by chronic HCV infection can be safely treated with DAAs with the same efficacy reported in younger adults.

Diagnostic reliability of the procalcitonin serum marker in septic frail patient.

AIM: Aging is associated with increased inflammation, particularly in frailty. Indeed, such patient presents increased serum inflammatory markers, such as C-reactive protein and interleukin-6. Interleukin-6 is an important stimulating factor for the production of procalcitonin. The aim of this study is to evaluate the diagnostic reliability of serum PCT in the diagnosis of sepsis in frail elderly patients. METHODS: Using Fried's criteria for frailty, 140 older patients hospitalized for any cause were consecutively enrolled and divided in two groups: no-frail (60 patients) and frail (80 patients). Patients were further categorized on the basis of the presence/absence of sepsis. Interleukin-6, procalcitonin and inflammatory indices were sampled at hospital admission. RESULTS: Septic patients from frail and no-frail groups showed higher values of interleukin-6 and procalcitonin. However, focusing on groups without sepsis, a statistically significant difference of interleukin-6 and procalcitonin values among frail and no-frail groups was seen at the post-hoc analysis. In frail group, procalcitonin cut-off of 0.5 ng/ml had a sensibility and specificity, respectively, of 100 and 22%. Through receiver operating characteristic curve (ROC) analysis, we found that procalcitonin serum value of 1.4 ng/ml had better sensibility and specificity (respectively, 93.8 and 84.4%, AUC 0.965). CONCLUSIONS: In our study, we confirm the diagnostic reliability of procalcitonin in frail elderly patients for the diagnosis of sepsis. We found that 1.4 ng/ml was the best cut-off in this population.

Molecular Mechanisms Involved in HCC Recurrence after Direct-Acting Antiviral Therapy.

Chronic hepatitis C is associated with a high risk of developing hepatocellular carcinoma (HCC) because of a direct effect of the Hepatitis C Virus (HCV) proteins and an indirect oncogenic effect of chronic inflammation and impaired immune response. The treatment of chronic hepatitis C markedly reduces all-cause mortality; in fact, interferon-based treatment has shown a reduction of HCC incidence of more than 70%. The recent introduction of the highly effective direct-acting antivirals (DAAs) has completely changed the scenario of chronic hepatitis C (CHC) with rates of HCV cure over 90%. However, an unexpectedly high incidence of HCC recurrence was observed in patients after DAA treatment (27% versus 0.4⁻2% in patients who received interferon treatment). The mechanism that underlies the high rate of tumor relapse is currently unknown and is one of the main issues in hepatology. We reviewed the possible mechanisms involved in HCC recurrence after DAA treatment.

Factors Associated With Recurrence of Advanced Colorectal Adenoma After Endoscopic Resection.

BACKGROUND & AIMS: Studies have identified risk factors for recurrence of advanced colorectal adenoma (ACA) after polypectomy, but the relative importance and interaction of these risk factors, and their potential impact on surveillance recommendations, are unclear. We aimed to develop a model to identify ACA features associated with risk of recurrence after polypectomy. METHODS: In a retrospective study, we collected data from 3360 patients who underwent colonoscopy with polypectomy at University of Foggia from 2004 through 2008 and identified 746 patients with 1017 ACAs. We performed recursive partitioning analysis to identify factors associated with recurrence of ACA within 3 years after polypectomy. RESULTS: Median ACA size was 16 mm (range, 8-34 mm) and median number was 1.5 (range, 1-2). Pedunculated, sessile, and nonpolypoid lesions accounted for 41.3%, 39.4%, and 19.3% of ACAs detected, respectively. Factors independently associated with local recurrence of ACA and metachronous distant polyps within 3 years after polypectomy included size and number of ACAs and grade of dysplasia. The recurrence rate was 4.2% in patients with a single ACA ≤15 mm without high-grade dysplasia (HGD), 21.3% in patients with HGD ≤15 mm, ACA without HGD >15 mm, or multiple ACAs without HGD ≤15 mm, and 57.9% in patients with HGD >15 mm. CONCLUSIONS: In this retrospective analysis of 746 patients with ACA who underwent polypectomy and surveillance colonoscopy within 3 years, the recurrence rate was highest in those with HGD ≥15 mm. These patients might benefit from more intensive surveillance, whereas patients with a single ACA without HGD ≤15 mm are at lower risk for and could be considered for longer follow-up intervals.

Down-regulation of LPCAT expression increases platelet-activating factor level in cirrhotic rat liver: potential antiinflammatory effect of silybin.

Cholestasis is one of the major causes of liver diseases. A chronic accumulation of toxic bile acids in the liver, which occurs in this condition, can induce fibrosis and cirrhosis. Inflammation is a fundamental component of acute and chronic cholestatic liver injury. Platelet-activating factor (PAF) is a proinflammatory lipid which may be generated by two independent pathways called the de novo and remodeling pathway being the last responsible for the synthesis of PAF during inflammation. In recent years a key role in PAF remodeling has been attributed to lysophosphatidylcholine acyltransferase (LPCAT) enzymes. Although the knowledge on their characteristic is growing, the exact mechanism of LPCAT in pathological conditions remains still unknown. Here, we reported that the level of lyso-PAF and PAF significantly increased in the liver of cirrhotic vs. control rats together with a significant decrease in both mRNA abundance and protein level of both LPCAT1 and LPCAT2. Acyltransferase activities of both LPCAT1 and LPCAT2 were parallel decreased in the liver of cirrhotic animals. Interestingly, treatment with silybin strongly decreased the level of both pro-inflammatory lipids and restored the activity and expression of both LPCAT1 and LPCAT2 of cirrhotic liver. Silybin effect was specific for LPCAT1 and LPCAT2 since it did not affect LPCAT3 mRNA abundance of cirrhotic liver.

Depressive-like behavior is paired to monoaminergic alteration in a murine model of Alzheimer's disease.

BACKGROUND: Neuropsychiatric signs are critical in primary caregiving of Alzheimer patients and have not yet been fully investigated in murine models. METHODS: 18-month-old 3×Tg-AD male mice and their wild-type male littermates (non-Tg) were used. The open field test and the elevated plus maze test were used to evaluate anxiety-like behaviors, whereas the Porsolt forced swim test, the tail suspension test, and the sucrose preference test for antidepressant/depression-coping behaviors. Neurochemical study was conducted by microdialysis in freely-moving mice, analyzing the basal and K(+)-stimulated monoamine output in the frontal cortex and ventral hippocampus. Moreover by immunohistochemistry, we analysed the expression of Tyrosin hydroxylase and Tryptophan hydroxylase, which play a key role in the synthesis of monoamines. RESULTS: Aged 3×Tg-AD mice exhibited a higher duration of immobility in the forced swim and tail suspension tests (predictors of depression-like behavior) which was not attenuated by a noradrenaline reuptake inhibitor, desipramine. In the sucrose preference test, 3×Tg-AD mice showed a significantly lower sucrose preference compared to the non-Tg group, without any difference in total fluid intake. In contrast, the motor functions and anxiety-related emotional responses of 3×Tg-AD mice were normal, as detected by the open-field and elevated plus-maze tests. To strengthen these results, we then evaluated the monoaminergic neurotransmissions by in vivo microdialysis and immunohistochemistry. In particular, with the exception of the basal hippocampal dopamine levels, 3×Tg-AD mice exhibited a lower basal extracellular output of amines in the frontal cortex and ventral hippocampus and also a decreased extracellular response to K(+) stimulation. Such alterations occur with obvious local amyloid-ß and tau pathologies and without gross alterations in the expression of Tyrosin and Tryptophan hydroxylase. CONCLUSIONS: These results suggest that 3×Tg-AD mice exhibit changes in depression-related behavior involving aminergic neurotrasmitters and provide an animal model for investigating AD with depression.

Prognostic Nutritional Index and Instant Nutritional Assessement Are Associated with Clinical Outcomes in a Geriatric Cohort of Acutely Inpatients.

BACKGROUND: Among elderly inpatients, malnutrition is one of the most important predictive factors affecting length of stay (LOS), mortality, and risk of re-hospitalization. METHODS: We conducted an observational, retrospective study on a cohort of 2206 acutely inpatients. Serum albumin and lymphocytes were evaluated. Instant Nutritional Assessment (INA) and the Prognostic Nutritional Index (PNI) were calculated to predict in-hospital mortality, LOS, and risk of rehospitalization. RESULTS: An inverse relationship between LOS, serum albumin, and PNI were found. Deceased patients had lower albumin levels, lower PNI values, and third- and fourth-degree INA scores. An accurate predictor of mortality was PNI (AUC = 0.785) after ROC curve analysis; both lower PNI values (HR = 3.56) and third- and fourth-degree INA scores (HR = 3.12) could be independent risk factors for mortality during hospitalization after Cox regression analysis. Moreover, among 309 subjects with a lower PNI value or third- and fourth-class INA, hospitalization was re-hospitalization. CONCLUSIONS: PNI and INA are two simple and quick-to-calculate tools that can help in classifying the condition of hospitalized elderly patients also based on their nutritional status, or in assessing their mortality risk. A poor nutritional status at the time of discharge may represent an important risk factor for rehospitalization in the following thirty days. This study confirms the importance of evaluating nutritional status at the time of hospitalization, especially in older patients. This study also confirms the importance for adequate training of doctors and nurses regarding the importance of maintaining a good nutritional status as an integral part of the therapeutic process of hospitalization in acute departments.

Association between Controlling Nutritional Status (CONUT) Score and Body Composition, Inflammation and Frailty in Hospitalized Elderly Patients.

The Controlling Nutritional Status (CONUT) score has demonstrated its ability to identify patients with poor nutritional status and predict various clinical outcomes. Our objective was to assess the association between the CONUT score, inflammatory status, and body composition, as well as its ability to identify patients at risk of frailty in hospitalized elderly patients. METHODS: a total of 361 patients were retrospectively recruited and divided into three groups based on the CONUT score. RESULTS: patients with a score ≥5 exhibited significantly higher levels of inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Neutrophil/Lymphocytes ratio (NLR), main platelet volume (MPV), and ferritin, compared to those with a lower score. Furthermore, these patients showed unfavorable changes in body composition, including a lower percentage of skeletal muscle mass (MM) and fat-free mass (FFM) and a higher percentage of fatty mass (FM). A positive correlation was found between the CONUT score and inflammatory markers, Geriatric Depression Scale Short Form (GDS-SF), and FM. Conversely, the Mini Nutritional Assessment (MNA), Mini-Mental Status Examination, activity daily living (ADL), instrumental activity daily living (IADL), Barthel index, FFM, and MM showed a negative correlation. Frailty was highly prevalent among patients with a higher CONUT score. The receiver operating characteristic (ROC) curve demonstrated high accuracy in identifying frail patients (sensitivity). CONCLUSIONS: a high CONUT score is associated with a pro-inflammatory status as well as with unfavorable body composition. Additionally, it is a good tool to identify frailty among hospitalized elderly patients.

Association between R2CHA2DS2-VASc score and three-vessel coronary artery disease in a large population at high cardiovascular risk.

Coronary artery disease (CAD), particularly three-vessel coronary disease (3VD), is the main cause of death in industrialized countries. Chronic kidney disease is an independent risk factor for CAD. The CHA2DS2-VASc score shows a good ability to predict CV events in high-risk population independently from atrial fibrillation. The aim of the present study was to evaluate the association between the R2CHA2DS2-VASc score and 3VD in a population of patients at high cardiovascular risk. Monocentric prospective study evaluated 1017 patients undergoing coronary angiography. The R2CHA2DS2-VASc score was obtained by adding 2 points to the CHA2DS2-VASc score in case of eGFR < 60 ml/min/1.73m2. Coronary lesions causing ≥ 50% reduction of a major epicardial vessel diameter were considered significant. Patients were grouped based on R2CHA2DS2-VASc tertiles and according to the severity of CAD: 3VD vs No-3VD. The 3VD group showed significantly higher R2CHA2DS2-VASc score than the No-3VD group (4.20 ± 2.18 vs 3.36 ± 2.06, p < 0.001). The risk of 3VD increased by 21% for every 1-point increase in the score (OR 1.21; 95% CI 1.13-1.28, p < 0.001). The prevalence of 3VD was higher among patients belonging to higher tertiles of R2CHA2DS2-VASc (17.2% vs 26.7% vs 33.6% for first, second, and third tertile respectively, p < 0.001) with a risk more than doubled for the third tertile compared to the first one (OR 2.45; 95% CI 1.71-3.49, p < 0.001). The R2CHA2DS2-VASc score is independently associated with 3VD in patients at high cardiovascular risk. The score could be considered a useful tool for clinicians to identify patients who are at high risk of 3VD.

Endothelial dysfunction associated with mild cognitive impairment in elderly population.

BACKGROUND AND AIMS: According to the original Petersen criteria, we investigated the association between endothelial dysfunction and mild cognitive impairment (MCI) by flow-mediated dilation (FMD). We aimed to verify if endothelial dysfunction occurs in MCI and whether vascular factors are implicated in the MCI pathogenesis. METHODS: This is a cross-sectional study performed on 34 subjects with clinical diagnosis of MCI and 37 controls, older than 60 years. Patients were enrolled from a geriatric outpatient clinic. All the recognized cardiovascular risk factors and an objective state of cognitive impairment were used as exclusion criteria. Cognitive function was evaluated using a scientific-validated neuropsychological battery, whereas MCI was recognized according to the Petersen criteria. Endothelial function was evaluated according to FMD from the brachial artery. The association between FMD and MCI was evaluated both by using a multivariate analysis and a correlation test. Finally, using the ANOVA analysis of variance, we tested the differences in flow-mediated dilation among MCI subgroups. RESULTS: Brachial FMD was significantly associated with MCI (p < 0.01). The multivariate analysis showed that age, years of education and MMSE independently predicted the FMD variation (r (2)  = 0.73; p < 0.0001). In addition, MCI patients with prevalent amnestic multiple domain impairment showed the worst brachial FMD. CONCLUSIONS: This finding suggests that vascular dysfunction may play a role in the pathogenesis of cognitive impairment and underlines the lack of therapeutic strategies targeted to such dysfunctions.

Controlling Nutritional Status (CONUT) Score as a Predictive Marker in Hospitalized Frail Elderly Patients.

The Controlling Nutritional Status (CONUT) score is a simple screening tool able to detect altered nutritional status as well as to predict clinical adverse outcomes in specific populations. No data are available in frail patients. This study aims to investigate the predictive role of the CONUT score on mortality and length of stay (LOS) in frail patients admitted to an Internal Medicine Department. We consecutively enrolled 246 patients aged 65 years or older, divided into two groups based on frailty status. The two groups were further divided according to low (<5) or high (≥5) CONUT score. Length of stay (LOS) was higher in frail patients than not-frail patients, as well as in the frail group with high CONUT scores compared to the frail group with low CONUT scores. Multiple linear regression showed an increase of 2.1 days for each additional point to the CONUT score. In-hospital mortality was higher in frail compared to not-frail patients, but it did not differ between frail patients with high CONUT scores and frail patients with low CONUT scores. An analysis of the survival curve for 30-day mortality showed a higher mortality rate for frail/high-CONUT-score patients as compared to the not-frail/low-CONUT-score group. The CONUT score shows high prognostic value for higher LOS-but not mortality-in the clinical setting of internal medicine departments for old frail patients.