A Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Effect of a Dietary Supplement Containing Dry Artichoke and Bergamot Extracts on Metabolic and Vascular Risk Factors in Individuals with Suboptimal Cholesterol Levels.

The aim of this study was to assess whether dietary supplementation with a nutraceutical blend comprising extracts of bergamot and artichoke-both standardized in their characteristic polyphenolic fractions-could positively affect serum lipid concentration and insulin sensitivity, high-sensitivity C-reactive protein (hs-CRP), and indexes of non-alcoholic fatty liver disease (NAFLD) in 90 healthy individuals with suboptimal cholesterol levels. Participants were randomly allocated to treatment with a pill of either active treatment or placebo. After 6 weeks, the active-treated group experienced significant improvements in levels of triglycerides (TG), apolipoprotein B-100 (Apo B-100), and apolipoprotein AI (Apo AI) versus baseline. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (Non-HDL-C), and hs-CRP also significantly decreased in the active-treated group compared to both baseline and placebo. At the 12-week follow-up, individuals allocated to the combined nutraceutical experienced a significant improvement in TC, LDL-C, Non-HDL-C, TG, Apo B-100, Apo AI, glucose, alanine transaminase (ALT), gamma-glutamyl transferase (gGT), hs-CRP, several indexes of NAFLD, and brachial pulse volume (PV) in comparison with baseline. Improvements in TC, LDL-C, Non-HDL-C, TG, fatty liver index (FLI), hs-CRP, and endothelial reactivity were also detected compared to placebo (p < 0.05 for all). Overall, these findings support the use of the tested dietary supplement containing dry extracts of bergamot and artichoke as a safe and effective approach for the prevention and management of a broad spectrum of cardiometabolic disorders.

Serum uric acid to eGFR ratio correlates with adverse outcomes in elderly hospitalized for acute heart failure.

BACKGROUND: Serum uric acid (SUA) is a known biomarker of severity in acute heart failure (AHF), reflecting the intricate interplay between cardiovascular and metabolic dysfunction. Since SUA can increase in response to worsening kidney function, and subjects with AHF often have cardiorenal syndrome or are on diuretic therapy, we tested whether the ratio of SUA to eGFR might provide prognostic value in elderly hospitalized for AHF. METHODS: The BOTERO-AHF Study (BOlogna study of Therapies, Epidemiology and Radiodiagnostic Outcomes in Acute Heart Failure patients) included 293 patients admitted for AHF who were consecutively enrolled from January 2020 onwards. We compared the baseline characteristics of participants who had a composite outcome (CO) (n = 203) of death or re-hospitalization for AHF within 12 months from discharge to those without CO (n = 90), and we assessed the prognostic impact of SUA/eGFR for 12-months CO. RESULTS: SUA/eGFR was significantly higher in participants who experienced a CO within 12 months from discharge for AHF, compared to those who did not experience any CO (17.8 (16.6) vs. 13.7 (12.1) mg/dl/ml/min*100, p = 0.008). SUA/eGFR, and not SUA alone, was associated with an increase in the rate of CO (unadjusted HR 1.011, CI 95% 1.004-1.019, p = 0.003). This association lost significance in participants under treatment with xanthine oxidase inhibitors but remained significant after adjustment for multiple confounders. CONCLUSION: The SUA/ eGFR ratio provides prognostic value in elderly patients hospitalized for AHF. Future studies may clarify if SUA/eGFR and XOI may represent novel diagnostic and therapeutic approaches for subgroups of patients with AHF.

Effect of dietary supplementation with Diuripres® on blood pressure, vascular health, and metabolic parameters in individuals with high-normal blood pressure or stage I hypertension: The CONDOR randomized clinical study.

Our aim was to evaluate if a nutritional intervention with a dietary supplement (Diuripres®) containing magnesium, standardized extract of orthosiphon, hawthorn, and hibiscus could positively affect blood pressure (BP), vascular health, and metabolic parameters in 60 individuals with high-normal BP or stage I hypertension. Participants followed a low-fat low-sodium Mediterranean diet for 4 weeks before being randomly allocated to 8-week treatment with two pills each day of either Diuripres® or placebo. Diuripres® significantly decreased systolic BP compared to placebo after 4 weeks (3.1 ± 0.8 mmHg; p < 0.05) and more consistently after 8 weeks (3.4 ± 0.9 mmHg; p < 0.05). At 8-week follow-up, after correction for multiple testing, dietary supplementation with Diuripres® was associated with significant improvements in diastolic BP (-3.1 ± 0.6 mmHg; p < 0.05), aortic BP (-4.3 ± 0.4 mmHg; p < 0.05), and high-sensitivity C-reactive protein (hs-CRP; 0.04 ± 0.01 mg/dL; p < 0.05) in comparison with baseline. The reductions in diastolic BP (--3.8 ± 0.7 mmHg; p < 0.05), aortic BP (-5.2 ± 1.0 mmHg; p < 0.05), and hs-CRP (-0.03 ± 0.01 mg/dL; p < 0.05) were also significant compared to placebo. Therefore, our study shows that dietary supplementation with Diuripres® may be useful in individuals with high-normal BP or stage I hypertension.

Noninvasive instrumental evaluation of coenzyme Q10 phytosome on endothelial reactivity in healthy nonsmoking young volunteers: A double-blind, randomized, placebo-controlled crossover clinical trial.

Coenzyme Q10 (CoQ10 ) is a natural antioxidant compound that prevents the vascular damage induced by free radicals and the activation of inflammatory signaling pathways. Supplementation with CoQ10 is safe though its bioavailability is generally low, as far as variable depending on the pharmaceutical form of preparation. Recently, the development of phytosome technology has improved the bioavailability of CoQ10 and definitely facilitated its effective use in clinical practice. The present double-blind, randomized, placebo-controlled, crossover clinical study aimed to investigate the effect on endothelial reactivity and total antioxidant capacity (TAC) of either acute and chronic supplementation with CoQ10 phytosome in a sample of 20 healthy young nonsmoking subjects. CoQ10 phytosome supplementation acutely improved endothelial reactivity in comparison with baseline and placebo (+4.7% ± 0.9% vs. -0.1 %± 0.3% p < 0.05). Middle-term supplementation of the tested pharmaceutical formulation of CoQ10 significantly improved mean arterial pressure (-2.2 ± 1.1 mmHg vs. 0.2 ± 0.7 mmHg, p < 0.05 vs. placebo) and TAC (+29.6% ± 3.2% vs. +1.9% ± 0.8%, p < 0.05 vs. placebo). Endothelial reactivity improved compared with baseline following middle-term dietary supplementation with CoQ10 phytosome (+5.7% ± 1.1%, p < 0.05).

Inequalities in enrollment of women and racial minorities in trials testing uric acid lowering drugs.

AIMS: We investigated sex and racial inequalities in clinical trials testing serum uric acid (SUA) lowering drugs and analyzed the temporal trends of participation among the pre-specified demographic groups. Data were collected from publications of clinical trials testing SUA-lowering drugs. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled in clinical studies. DATA SYNTHESIS: The mean percentage enrollment of women in clinical trials significantly decreased over the time (r = -0.43, P-value = 0.02). Moreover, there was a statistically significant difference in mean percentage enrollment of women among trials testing different SUA-lowering drugs, with the highest representation in rasburicase (71.1%) and the lowest representation of women in dotinurad (0.8%). Over the time, also the mean percentage enrollment of racial minorities decreased, passing from 8.7% to 2.2% in a 10-year period. Women were proportionally underrepresented compared with their share of the population with asymptomatic hyperuricemia, overall (participation-to-prevalence ratio (PPR) = 0.34), in trials testing xanthine oxiase inhibitors (PPR = 0.38) and uricosurics (PPR = 0.29), and in trials with febuxostat, allopurinol, pegloticase, halofenate/arhalofenate, verinurad, lesinurad and dotinurad. Women were proportionally underreppresented also compared with their share of the population with gout, overall (PPR = 0.69) and in trials testing XOIs (PPR = 0.69), uricosurics (PPR = 0.68), and all SUA-lowering drugs excepted for rasburicase, pegloticase and topiroxostat. CONCLUSIONS: Our analysis shows that women and racial and ethnical minorities are underrepresented in controlled clinical trials testing SUA-lowering drugs, with similar pattern across drug classes.

Sudden Fall in the Lipid-Lowering Effect of Evolocumab: The Butler Is Not Always Guilty.

A 78-year-old man came to our attention after undergoing coronary computed tomography angiography documenting multivessel coronary artery disease. He was started on treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab 140 mg subcutaneously every 2 weeks. Treatment-emergent changes in lipids and lipoproteins were long-lasting, and the medication was well tolerated by the patient in the long-term. Unexpectedly, after 2 years of continuous treatment with evolocumab, serum lipids increased, apparently without any reasonable explanation. During the follow-up visit, the patient was found to have habitually injected evolocumab into his right thumb instead of into the appropriate injection sites (i.e., abdomen, thighs or upper arms) after turning the injector upside down.

Stroke/thromboembolism and intracranial hemorrhage in a real-world atrial fibrillation population: the Complications of Atrial Fibrillation in the Bologna Area (CAFBO) study.

BACKGROUND: Ischemic events (IEs) and intracranial hemorrhages (ICHs) are feared complications of atrial fibrillation (AF) and of antithrombotic treatment in patients with these conditions. METHODS: Patients with AF admitted to the EDs of the Bologna, Italy, area with acute IE or ICH were prospectively recorded over 6 months. RESULTS: A total of 178 patients (60 male patients; median age: 85 years) presented with acute IE. Antithrombotic therapy was as follows: (1) vitamin K antagonists (VKAs) in 31 patients (17.4%), with international normalized ratio (INR) at admission of < 2.0 in 16 patients, 2.0 to 3.0 in 13 patients, and > 3.0 in two patients; (2) aspirin (acetylsalicylic acid) (ASA) in 107 patients (60.1%); and (3) no treatment in 40 patients (22.5%), mainly because AF was not diagnosed. Twenty patients (eight male patients; median age: 82 years) presented with acute ICH: 13 (65%) received VKAs (INR, 2.0-3.0 in 11 patients and > 3.0 in two patients), while six (30%) received ASA. Most IEs (88%) and ICHs (95%) occurred in patients aged > 70 years. A modeling analysis of patients aged > 70 years was used to estimate annual incidence in subjects anticoagulated with VKAs in our Network of Anticoagulation Centers (NACs), or those expected to have AF but not included in NACs. The expected incidence of IE was 12.0%/y (95% CI, 10.7-13.3) in non-NACs and 0.57%/y (95% CI, 0.42-0.76) in NACs (absolute risk reduction [ARR], 11.4%/y; relative risk reduction [RRR], 95%; P < .0001). The incidence of ICH was 0.63%/y (95% CI, 0.34-1.04) and 0.30%/y (95% CI, 0.19-0.44), respectively (ARR, 0.33%/y; RRR, 52.4%/y; P = .04). CONCLUSIONS: IEs occurred mainly in elderly patients who received ASA or no treatment. One-half of patients with IEs receiving anticoagulant treatment had subtherapeutic INRs. Therapeutic approaches to elderly subjects with AF require an effective anticoagulant treatment strategy.

QT interval prolongation by acute gastrointestinal bleeding in patients with cirrhosis.

BACKGROUND & AIMS: QT interval prolongation is frequent in cirrhosis, and stressful conditions could further prolong QT. We aimed to test this hypothesis and, if it proved correct, to assess its prognostic meaning. METHODS: We reviewed the clinical records of 70 consecutive cirrhotic and 40 non-cirrhotic patients with acute gastrointestinal bleeding. All patients had been evaluated before bleeding (T0) and were re-evaluated at the time of bleeding (T1) and 6 weeks afterwards (T2). RESULTS: QT corrected by heart rate (QTc) lengthened at T1, returning towards baseline values at T2 (mean ± SEM; from 415.9 ± 4.3 to 453.4 ± 4.3 to 422.2 ± 5.7 ms, P < 0.001) in cirrhotics; contrariwise, QTc did not change in non-cirrhotic patients. The 6-week mortality was 29.6% among cirrhotic patients, while no control patient died. At T1, patients who died had longer QTc (P = 0.001) and higher model of end-stage liver disease (MELD) score (P < 0.001) than survivors. MELD and QTc independently predicted survival. Their areas under the ROC curve were 0.88 (CI 95% 0.78-0.95) and 0.75 (CI 95% 0.63-0.85) respectively; the best cut-off values were MELD ≥20 and QTc ≥ 460 ms. Based on these factors, the 6-week mortality was: 0% for patients without risk factors, 32.1% for those with one risk factor and 70.6% for those with both (P < 0.001). CONCLUSIONS: Acute gastrointestinal bleeding further prolongs QTc in cirrhosis. This abnormality independently predicts bleeding-induced mortality. The combined measurement of QTc interval and MELD can clearly identify three patient strata at increasing risk of bleeding-related mortality, thus improving the decision-making for these patients.

The changing scenario of hepatocellular carcinoma over the last two decades in Italy.

BACKGROUND & AIMS: This study investigates whether the aetiologic changes in liver disease and the improved management of hepatocellular carcinoma (HCC) have modified the clinical scenario of this tumour over the last 20 years in Italy. METHODS: Retrospective study based on the analysis of the ITA.LI.CA (Italian Liver Cancer) database including 3027 HCC patients managed in 11 centres. Patients were divided into 3 groups according to the period of HCC diagnosis: 1987-1996 (year of the "Milano criteria" publication), 1997-2001 (year of release of the EASL guidelines for HCC), and 2002-2008. RESULTS: The significant changes were: (1) progressive patient ageing; (2) increasing prevalence of HCV infection until 2001, with a subsequent decrease, when the alcoholic aetiology increased; (3) liver function improvement, until 2001; (4) increasing "incidental" at the expense of "symptomatic" diagnoses, until 2001; (5) unchanged prevalence of tumours diagnosed during surveillance (around 50%), with an increasing use of the 6-month schedule; (6) favourable HCC "stage migration", until 2001; (7) increasing use of percutaneous ablation; (8) improving survival, until 2001. CONCLUSIONS: Over the last 20 years, several aetiologic and clinical features regarding HCC have changed. The survival improvement observed until 2001 was due to an increasing number of tumours diagnosed in early stages and in a background of compensated cirrhosis, and a growing and better use of locoregional treatments. However, the prevalence of early cancers and survival did not increase further in the last years, a result inciting national policies aimed at implementing surveillance programmes for at risk patients.

Art in the hospital: its impact on the feelings and emotional state of patients admitted to an internal medicine unit.

OBJECTIVE: This descriptive pilot study aimed at assessing the impact of art contemplation on patients' adaptation to hospital confinement and the factors influencing this effect. STUDY DESIGN: Artistic photographs were hung on the walls of the ward. Two hundred and thirty-nine (239) consecutive non-bed-constrained patients who stayed in the ward for at least 3 days (original number enrolled in study were males/females: 148/96, age 19-89 years; 5 patients declined to fill out questionnaires) participated in the study. METHODS: Patients compiled two questionnaires exploring physical, psychologic, and social/family well-being, relative/friend support, and ward functioning. The self-perceived effect of photographs on the hospitalization distress was assessed. Clinical conditions were evaluated with the Eastern Cooperative Oncology Group (ECOG) performance status. RESULTS: Ninety-seven (97) (40.6%) patients belonged to ECOG stage 0, 101 (42.3%) to stage 1, 37 (15.5%) to stage 2, and 4 (1.7%) to stage 3. Two hundred and thirty-nine patients (239) (92%) looked at and 232 (85.5%) repeatedly contemplated the photographs. For most patients (72%), photographs made their stay in the hospital more pleasant. The ECOG performance status and self-perceived anxiety were the only independent modulators of the probability to obtain a restorative effect from the photographs. CONCLUSIONS: Embellishing clinical spaces with photographs has a positive effect on the adaptation to hospitalization in most patients. This effect is influenced by the patients' clinical status and self-perceived anxiety.

Treatments for hepatocellular carcinoma in elderly patients are as effective as in younger patients: a 20-year multicentre experience.

OBJECTIVES: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. We compared the presenting features and outcome of HCC in elderly (>or=70 years) and younger patients (<70 years). DESIGN: Multicentre retrospective cohort study and nested case-control study. Patients 614 elderly and 1104 younger patients from the ITA.LI.CA database, including 1834 HCC cases consecutively diagnosed from January 1987 to December 2004. Both groups were stratified according to treatment: hepatic resection, percutaneous procedures, transarterial chemoembolisation (TACE). Survival was assessed in the whole population and in each treatment subgroup. Age, sex, aetiology, cirrhosis, comorbidities and cancer stage (CLIP score) were tested as predictors of survival. In each subgroup, differences in patient survival were also assessed after adjustment and matching by propensity score. RESULTS: Ageing was associated with a higher prevalence of comorbidities, better liver function and CLIP score. Regardless of age, two-thirds of patients underwent radical treatments or TACE. Elderly patients underwent more ablative procedures and fewer resections or TACE sessions. The survival of elderly and younger patients was comparable in each treatment subset, and was predicted by CLIP score. This result was confirmed by the propensity analysis. CONCLUSIONS: The overall applicability of radical or effective HCC treatments was unaffected by old age. However, treatment distribution differed, elderly individuals being more frequently treated with percutaneous procedures and less frequently with resection or TACE. Survival was unaffected by age and primarily predicted by cancer stage, assessed by the CLIP system, both in the overall population and in treatment subgroups.

Effect of chronic beta-blockade on QT interval in patients with liver cirrhosis.

BACKGROUND/AIMS: QT interval prolongation is frequent in cirrhosis, predicts a poor prognosis and may trigger severe ventricular arrhythmias. Our aim was to evaluate the effect of chronic beta-blockade on QT prolongation. METHODS: Clinical and laboratory evaluation, ECG and hepatic vein pressure gradient (HVPG) measurement were performed in 30 cirrhotic patients before and 1-3 months after prophylactic nadolol. QT was corrected for heart rate by the cirrhosis-specific formula and other formulas. RESULTS: QT(cirrhosis) was prolonged in 10 patients (33%); HVPG was increased in all cases. QT(cirrhosis) was correlated with the Child-Pugh score (r=0.40; p=0.027). Nadolol shortened QT interval only with the Bazett formula (p=0.01), remaining unchanged with the other formulas. The QT interval shortened only if prolonged at baseline (from 473.3+/-5.5 to 458.4+/-6.5 ms; p=0.007), while it lengthened when normal (from 429.8+/-3.1 to 439.3+/-2.9 ms; p=0.01). QTc changes were directly related to the baseline value (p<0.001). HVPG decreased from 19.4+/-0.8 to 15.6+/-1.3 mmHg (p=0.004). The HVPG changes did not correlate with QTc changes. CONCLUSIONS: Chronic beta-blockade shortens the QT interval only in patients with prolonged baseline values, and this is likely due to a direct cardiac effect.

Daily profile of circulating C-type natriuretic peptide in pre-ascitic cirrhosis and in normal subjects: relationship with renal function.

OBJECTIVE: To investigate whether the C-type natriuretic peptide (CNP) has a role in the regulation of fluid and sodium homeostasis in normal subjects and in pre-ascitic cirrhotic patients. MATERIAL AND METHODS: The daily profile of CNP plasma levels was assessed by serial measurements (0700 h, 0900 h, 1800 h, 2300 h) in 10 pre-ascitic cirrhotic outpatients (age 56+/-4 years) and in 10 age-matched healthy controls (54+/-2 years) on a normal sodium diet (150 mmol/day) while carrying on their usual activities (mobile from 0700 h to 2200 h), after an equilibration period of 5 days. Daily diuresis and natriuresis were also monitored. RESULTS: Mean daily CNP was comparable in cirrhotic and healthy subjects (3.64+/-0.32 versus 3.20+/-0.20 pg/ml; p=0.139); CNP concentration showed a tendency towards a circadian fluctuation in healthy subjects (p=0.053) but not in patients (p=0.171). Mean daily CNP concentration significantly correlated with 24-h natriuresis (r=0.709; p=0.022) and urine volume (r=0.745; p=0.013) in patients but not in healthy subjects. CONCLUSIONS: CNP plasma levels appear to play a role in the water-sodium balance regulation in patients with pre-ascitic cirrhosis.

QT interval correction in patients with cirrhosis.

INTRODUCTION: QT interval prolongation is a common electrophysiological abnormality in patients with cirrhosis. As QT interval varies with the heart rate, many QT correction formulas have been proposed, the Bazett's one being the most criticized because it over-corrects the QT interval and may be misleading. This study focused on the QT-RR relationship in patients with cirrhosis to derive a population-specific QT correction formula. METHODS: One hundred cirrhotic patients of different etiology and severity and 53 healthy controls comparable for age and sex were enrolled. The QT-RR relationship was analyzed in patients by five regression analysis models to derive the population-specific QT-RR equation. The QTc was calculated and compared with those calculated by four common QT correction formulas (Bazett, Fridericia, Framingham, and Hodges). The correlation coefficient QTc-RR was calculated as a measure of the independence of QTc from the original RR interval. RESULTS: In patients the QT-RR relationship was best described by the power equation "QT = 453.65 x RR1/3.02" (R2 = 0.41), similar to the Fridericia's formula. Bazett's formula led to the longest QTc (P < 0.0001), which was still significantly influenced by the RR interval (R = -0.39; P < 0.0001), while the estimated equation led to a QTc value not influenced by RR (R = -0.014). CONCLUSION: Bazett's correction should be avoided in patients with cirrhosis because it still provides a rate-dependent QTc value and might be misleading, particularly when assessing the overall preoperative cardiac risk and the effect of drugs affecting the QT interval. In its place, our formula or that of Fridericia can be confidently employed.