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Background: The CHA 2 DS 2 -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 R 2 CHA 2 DS 2 -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 CHA 2 DS 2 -VASc and R 2 CHA 2 DS 2 -VASc with all-cause mortality, and (ii) to compare the performances of CHA 2 DS 2 -VASc and R 2 CHA 2 DS 2 -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 R 2 CHA 2 DS 2 -VASc scores significantly associated with all-cause mortality. For each one-point increase in CHA 2 DS 2 -VASc or R 2 CHA 2 DS 2 -VASc scores, mortality increased by almost 1.5-fold. The R 2 CHA 2 DS 2 -VASc score (C-statistic = 0.71; 95% CI = 0.65-76) outperformed the CHA 2 DS 2 -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-CHA 2 DS 2 -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 R 2 CHA 2 DS 2 -VASc score correctly reclassified the patients with a NRI = 0.715 (95% = 0.544-0.940, p < .00001)., Conclusions: The CHA₂DS₂-VASc and R 2 CHA 2 DS 2 -VASc scores are useful predictors of all-cause mortality in subjects at high CV risk, with the R 2 CHA 2 DS 2 -VASc score being the best performer., (© 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Purpose: The aim of this study was to investigate the clinical applicability of transthoracic ultrasound (TUS) in the diagnosis and follow-up of community acquired pneumonia (CAP)., Methods: We designed a pilot study in 15 patients and subsequently investigated 342 patients (206 men and 136 women) consecutively admitted to our Department from September 2005 to November 2009 because of radiographically diagnosed CAP. All patients underwent standard chest radiography, and consequently TUS. Follow-up TUS were performed at 4th and 8-10th day, in most patients., Results: Concerning the reproducibility of TUS method, no reader's bias was present (P=0·18), overall variability and between-subject variability (inter-reader agreement) did not show any difference between readers (P = 0·62 and P = 0·32 respectively), and estimated within-subject variabilities (intra-reader agreement) suggested a very high repeatability of the method (P ∼ 1). Of 342 patients with Rx diagnosis of CAP, in 314 patients (92% of cases) a pulmonary consolidation was also detected using TUS, whose ultrasonographic patterns were studied. Pleural effusion was detected in 120/342 (35%) patients using ultrasound and in 111/342 (32%) patients using chest radiography. Overall dimensional changes of the lung consolidated areas assessed with TUS method showed highly significant results. (1st day mean ± SD: 66·34 ± 19·25; 4th day: 39·92 ± 14·61; 8-10th day: 7·41 ± 1·50; P < 0·0001)., Conclusions: TUS is easily reproducible and we proved it to be a useful complementary diagnostic tool for the diagnosis and the follow-up of CAP., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Mitochondrial dysfunction is considered a key player in non-alcoholic steatohepatitis (NASH) but no data are available on the mitochondrial function and ATP homeostasis in the liver during NASH progression. In the present paper we evaluated the hepatic mitochondrial respiratory chain activity and ATP synthesis in a rodent model of NASH development., Materials and Methods: Male Wistar rats fed a High Fat/Methionine-Choline Deficient (MCD) diet to induce NASH or a control diet (SHAM), and sacrificed after 3, 7 and 11 weeks. The oxidative phosphorylation, the F(0)F(1)ATPase (ATP synthase) and the ATP content were assessed in liver mitochondria., Results: NASH mitochondria exhibited an increased rate of substrate oxidation at 3 weeks, which returned to below the normal level at 7 and 11 weeks, concomitantly with the coupling between the phosphorylation activity and the mitochondrial respiration (ADP/O). Uncoupling of NASH liver mitochondria did not allow the recovery of the maximal respiration rate at 7 and 11 weeks. The ATPase (ATP synthase) activity was similar in NASH and SHAM rats, but the mitochondrial ATP content was significantly lower in NASH livers., Conclusions: The loss of hepatic ATP stores is not dependent on the F(0)F(1)-ATPase but resides in the respiratory chain. Dysfunction of both Complex I and II of the mitochondrial respiratory chain during NASH development implies a mitochondrial adaptive mechanism occurring in the early stages of NASH.

Background: Erythrocyte membrane modifications in patients with cholestasis are supposed to reflect those of hepatocytes., Methods: Erythrocyte membrane composition (cholesterol, phospholipids, fatty acids, protein sulphydrils and carbonyls) was assessed and related to the stage of liver disease in patients with primary biliary cirrhosis before and after 1 year of ursodeoxycholate treatment., Results: Compared with controls, patients showed lower levels of protein sulphydrils (28.9 +/- 7.1 vs. 65.6 +/- 1.8 nmol mg(-1) prot) and accumulation of carbonyls (4.7 +/- 1.7 vs. 1.4 +/- 0.1 nmol mg(-1) prot). Phosphatidylethanolamine level was lower in stage III-IV cirrhosis while phosphatidylcholine and cholesterol levels were higher; as a consequence the phosphatidylcholine/sphingomyelin ratio was higher than in controls (4.25 +/- 0.55 in the I-II stage and 2.89 +/- 0.44 in the stage III-IV vs. 1.61 +/- 0.30). These changes were particularly evident in patients with more advanced stages of liver disease. Protein sulphydrils and carbonyls, phosphatidylethanolamine and cholesterol levels correlated (P<0.05) with the histological stage of the liver disease, serum and membrane cholesterol levels were significantly related (r=0.66, P<0.05). One year of ursodeoxycholate administration was accompanied by major changes of the membrane lipid composition, partial reversal of protein oxidation, and improvement of serum parameters., Conclusions: This study indicates that major alterations in protein status and lipid composition occur in erythrocyte membrane of patients with primary biliary cirrhosis. These changes were more pronounced in patients with advanced liver disease. Ursodeoxycholate was able to revert in part serum and erythrocyte alterations, especially in patients with early stages of liver disease.

Background: The reason why some hepatitis C virus carriers with normal aminotransferase activity present, during time, an activation of the disease, is unknown. The aim of this study was to assess the oxidative balance in such patients and to evaluate its possible role on the severity of disease., Materials and Methods: Histology, glutathione and malondialdehyde were determined in the liver of 30 HCV-RNA positive patients with persistently normal aminotransferase. Patients were followed-up for 18 months with plasmatic determinations of aminotransferase, ferritin, glutathione, malondialdehyde, carbonyl and sulphydryl protein levels (every 2 months) and serum HCV-RNA (every 3 months)., Results: Four subjects had normal histology, whereas the remaining 26 showed mild/moderate chronic hepatitis. Hepatic glutathione and malondialdehyde concentrations were normal in 16 patients and clearly altered in the other 14. The hepatic redox state did not correlate with histology whereas it correlated with plasmatic oxidative markers. During the study, aminotransferase flared up in 11 patients, 9 of these (82%) having at enrollment an altered hepatic oxidative balance. Patients with aminotransferase elevation showed increased blood indices of oxidative stress, which occurred earlier than aminotransferase flare-ups. No oxidative stress was observed in the remaining subjects., Discussion: This study suggests that symptom-free HCV carriers with impaired redox state have a higher risk of aminotransferase flare-up; therefore the impaired oxidative balance may have a prognostic significance on disease activity.

Background: Little is known about gallbladder motility in patients with black pigment stones when compared to cholesterol gallstone patients, or about their relationship to biliary composition, crystallization and stone characteristics., Design: Fasting and postprandial gallbladder volumes were studied by ultrasonography in 49 gallstone patients with pigment (n = 14) or cholesterol (n = 35) stones and 30 healthy controls. After cholecystectomy stone composition, gallbladder wall inflammation, cholesterol saturation index and appearance of platelike cholesterol crystals in bile were evaluated in gallstone patients., Results: Fasting gallbladder volume was significantly (P < 0.05) increased in cholesterol stone patients (31.7 +/- 1.9 mL) but not in pigment stone patients (21.9 +/- 3.1 mL), compared to controls (21.0 +/- 1.5 mL). Postprandial emptying was delayed in patients (half-emptying time: 31 +/- 2 min, 35 +/- 3 min, 24 +/- 2 min in cholesterol stone patients, pigment stone patients and controls, respectively, P < 0.05) and incomplete (residual volume: 43.2 +/- 2.7%, 40.0 +/- 4.3%, 15.8 +/- 1.6% min in cholesterol stone patients, pigment stone patients and controls, respectively, P < 0.05). The inflammation of the gallbladder wall was mild or absent in all cases. Biliary cholesterol saturation index was 152.3 +/- 8.5% and 92.9 +/- 4.8% in patients with cholesterol and pigment stones, respectively (P < 0.01). Whereas cholesterol crystals never appeared during 21 days in biles from patients with pigment stones, crystal observation time in patients with cholesterol gallstone was 5 days (median) and was significantly shorter in patients with multiple (4 days) than in patients with solitary (12 days) cholesterol stones (P = 0.0019)., Conclusions: Patients with black pigment stones who do not have excess cholesterol and do not grow cholesterol crystals in bile have decreased gallbladder emptying, although to a lesser extent than patients with cholesterol stones. Thus, gallbladder stasis is likely to put a subset of subjects at risk for the formation of pigment gallstones, and pathogenic mechanisms need to be further investigated.