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  • 1
    In: Liver International, Wiley, Vol. 39, No. 12 ( 2019-12), p. 2301-2308
    Abstract: Recent evidence showed a reduced activity of the lysosomal acid lipase (LAL) in patients with non‐alcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC). However, the relationship between LAL activity and liver fibrosis has never been investigated. Methods Cross‐sectional study including 575 outpatients referred for the management of cardio‐metabolic and liver disease. The absence of liver fibrosis was defined by a FIB‐4  〈  1.30 and NAFLD fibrosis score (NFS) 〈 −1.455. LAL activity was measured with dried blood spot technique. Results Overall, 515 patients had a diagnosis of NAFLD (454 NAFL and 61 biopsy‐proven NASH) and 60 of CC. The value of LAL activity progressively decreased from healthy subjects to NAFL/NASH patients to CC ( P   〈  .001). LAL activity was reduced by 10% in patients with NAFL, by 20% in NASH and by 50% in CC. The prevalence of CC decreased across the tertiles of LAL activity: 22.2% in the lowest, 4.6% in the intermediate and 0.5% in the highest tertile. In NAFLD patients, 69.9% had a FIB4  〈  1.30, and 43.1% a NFS 〈 −1.455. Multivariate logistic regression analysis showed that Log (LAL activity) was associated with FIB‐4  〈  1.30 (Odds ratio [OR] 2.19 95% confidence interval [CI] 1.33‐3.62, P  = .002) and NFS 〈 −1.455 (OR 2.43, 95% CI 1.51‐3.91, P   〈  .001) after adjustment for confounding factors. Conclusions We found a progressive reduction of LAL activity according to liver disease severity. LAL activity was inversely associated with markers of liver fibrosis in patients with NAFLD.
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2124684-1
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  • 2
    In: European Journal of Clinical Investigation, Wiley, Vol. 53, No. 2 ( 2023-02)
    Abstract: Lung hyperinflation and systemic inflammation are currently believed to be the most important causes of right heart alterations in chronic obstructive pulmonary disease (COPD) patients. A multicentre observational study was performed to assess the morphological and functional parameters of right ventricle (RV) in COPD subjects, as well as to evaluate the potential prognostic impact on the development of major cardiovascular adverse events (MACEs). Methods For this retrospective study, from 1 January 2010 to 31 December 2021, we enrolled COPD patients on the basis of their airflow limitation. In particular, we selected subjects spanning across GOLD 1 and 2 functional stages. Clinical, laboratory and functional parameters were collected at baseline. Echocardiography was routinely performed in all COPD patients. RV dysfunction was defined on the basis of tricuspid annular plane systolic excursion (TAPSE) values. MACE occurrence (non‐fatal ischemic stroke, non‐fatal myocardial infarction, cardiac revascularization or coronary bypass surgery and cardiovascular death) was evaluated during a median follow‐up of 55 (36–72) months. Results Among the 749 enrolled patients, 408 subjects had a TAPSE value ≥20 mm, while the remaining 341 had a TAPSE value 〈 20 mm. In patients with TAPSE ≥20 mm the observed MACEs were 1.9 events/100 patient‐year, while in the group with a worse right heart function there were 4.2 events/100 patient‐year ( p   〈  .0001). The multivariate analysis model confirmed the association between RV dysfunction and MACE. Indeed, a 1‐mm increase in TAPSE value and the intake of long‐acting β 2 ‐receptor agonists (LABA)/long‐acting muscarinic antagonist (LAMA) inhaled therapy were protective factors for the onset of MACE, while the presence of diabetes mellitus and high values of both uric acid (UA) and systolic pulmonary arterial pressure (S‐PAP) enhanced the risk of MACE in study participants. Conclusions The results of this study showed that in patients with mild COPD there is an association between right heart dysfunction and the risk of MACE during follow‐up.
    Type of Medium: Online Resource
    ISSN: 0014-2972 , 1365-2362
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2004971-7
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  • 3
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 86, No. 12 ( 2020-12), p. 2455-2463
    Abstract: To investigate the decline of estimated glomerular filtration rate (eGFR) in patients with atrial fibrillation (AF) treated with vitamin K antagonists (VKAs) or non‐VKA oral anticoagulants (NOACs). Methods Multicentre prospective cohort study including 1667 patients with nonvalvular AF. The eGFR was assessed by the CKD‐EPI formula at baseline and during follow‐up. The primary endpoint of the study was the median annual decline of eGFR according to VKA (n = 743) or NOAC (n = 924) use. As secondary endpoints, we analysed the transition to eGFR 〈 50 mL/min/1.73 m 2 and the eGFR class worsening. Results Median age was 73.7 ± 9.1 years and 43.3% were women. VKA‐treated patients showed an eGFR decline of −2.11 (interquartile range [IQR] –5.68/−0.62), which was −0.27 (IQR –9.00/4.54, P 〈 0.001 vs VKAs), −1.21 (IQR –9.98/4.02, P = 0.004 vs VKAs) and −1.32 (IQR –8.70/3.99, P = 0.003 vs VKAs) in patients on dabigatran, rivaroxaban and apixaban, respectively. Transition to eGFR 〈 50 mL/min/1.73 m 2 was lower in dabigatran‐ and apixaban‐treated patients: odds ratio (OR) 0.492, 95% confidence interval (CI) 0.298‐0.813, P = 0.006 and OR 0.449, 95% CI 0.276‐0.728, P = 0.001, respectively. A lower rate of eGFR class worsening was found in all groups of NOACs compared to VKAs. No difference between full and reduced dose of NOAC was found. Subgroup analysis showed that the association between NOAC and eGFR changes was markedly reduced in diabetic patients. Conclusion Patients prescribed NOACs showed a lower decline of renal function compared to those prescribed VKAs. This effect was partially lost in patients with diabetes.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1498142-7
    SSG: 15,3
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  • 4
    Online Resource
    Online Resource
    Wiley ; 2017
    In:  British Journal of Clinical Pharmacology Vol. 83, No. 1 ( 2017-01), p. 88-95
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 83, No. 1 ( 2017-01), p. 88-95
    Abstract: Non‐alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to liver fibrosis and to cirrhosis. NAFLD is considered as the hepatic component of the metabolic syndrome but mechanisms underlying the onset and progression of NAFLD are still under investigation. The traditional ‘two hit hypothesis’ has been developed within a more complex ‘multiple parallel hit hypothesis’ which comprises a wide spectrum of parallel hits. Many therapeutic approaches have been proposed so far and several types of nutraceuticals have been suggested for the treatment of NAFLD and non‐alcoholic steatohepatitis (NASH), the most promising of which are those with antioxidant effects. In particular, vitamin E appears to be effective for the treatment of nondiabetic subjects with more advanced NASH, although the high suggested daily dosages are a matter of concern. Moreover, polyphenols reduce liver fat accumulation, mainly by inhibiting lipogenesis. At present, there are insufficient data to support the use of vitamin C supplements in patients with NAFLD. Data on polyunsaturated fatty acid (PUFA) supplementation are heterogeneous, and no well‐designed randomized controlled studies (RCTs) of adequate size, with histological assessment of steatosis, have been conducted. Based on the available data, silymarin supplementation for the treatment of NAFLD seems to have a favourable effect. The results with anti‐inflammatory agents, such as vitamin D and carnitine are uncertain. In conclusion, there are insufficient data either to support or refute the use of nutraceuticals for subjects with NAFLD. Further RTCs, with histological changes as an outcome measure, are needed.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 1498142-7
    SSG: 15,3
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  • 5
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 85, No. 3 ( 2019-03), p. 508-515
    Abstract: The prevalence and incidence of atrial fibrillation/flutter (AF/AFL) in patients with human immunodeficiency virus type‐1 (HIV‐1) infection have been poorly investigated. We performed a systematic review using PubMed and Cochrane Database of Systematic Reviews, and screening of references, searching for clinical studies reporting on the association between HIV‐1 infection and AF/AFL. We also summarized the main interactions of antiretroviral agents with antithrombotic and antiarrhythmic drugs. We found a prevalence of AF/AFL ranging from 2.0% to 5.13% in patients with HIV‐1, with an incidence rate of 3.6/1000 person‐years. Low CD4+ count ( 〈 200–250 cells ml −1 ) and high viral load were predictors of AF/AFL. Regarding drugs interactions, nucleoside reverse transcriptase inhibitors, integrase inhibitor and maraviroc have the lowest interactions with oral anticoagulants. Among anticoagulants, dabigatran presents the most favourable profile. Most of antiarrhythmic drugs interact with protease inhibitors, with beta blockers and diltiazem having fewer interactions. The few studies available suggest a non‐negligible prevalence of AF/AFL in patients with HIV‐1 infection. Awareness of potential interactions with anticoagulation and antiarrhythmic drugs is needed to offer optimal management in this population.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1498142-7
    SSG: 15,3
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  • 6
    In: British Journal of Haematology, Wiley, Vol. 190, No. 4 ( 2020-08), p. 588-593
    Abstract: Quality of warfarin therapy in patients with a mechanical prosthetic heart valve (MPHV) has been barely investigated. We analysed determinants of low time in the therapeutic range (TiTR 〈 60%) in 2111 patients with MPHVs from the nationwide PLECTRUM study by the Italian Federation of Anticoagulation Clinics. Overall, 48·5% of patients had a TiTR of 〈  60%. At logistic regression analysis, arterial hypertension (odds ratio [OR] 1·502, P   〈  0·001), diabetes (OR 1·732, P   〈  0·001), heart failure (OR 1·484, P  = 0·004), mitral site (vs. aortic) (OR 1·399, P  = 0·006), international normalised ratio (INR) ranges of 2·5–3·5 (OR 2·575, P   〈  0·001) and 3·0–4·0 (OR 8·215, P   〈  0·001) associated with TiTR 〈  60%. TiTR is substantially suboptimal in MPHV patients, particularly in higher INR ranges.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1475751-5
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  • 7
    In: HIV Medicine, Wiley, Vol. 22, No. 6 ( 2021-07), p. 434-444
    Abstract: This study aimed to assess whether gut‐derived lipopolysaccharide (LPS) could affect platelet function in HIV‐1 patients with residual viral load. Methods In 23 HIV‐1 patients on effective antiretroviral treatment, 10 treatment‐naïve HIV‐1 subjects and 20 healthy subjects (HS), LPS, zonulin, markers of platelet activation and oxidative stress were evaluated. In vitro , platelets from HS were exposed to plasma from HIV‐1‐infected treated and untreated patients. Results Compared with HS, LPS was higher in treated and treatment‐naïve subjects with HIV‐1 (7.7 ± 2.9, 80.9 ± 13.7 and 75.3 ± 22.6 pg/mL, P   〈  0.001 vs . HS) as well as serum zonulin (1.3 ± 0.5, 6.1 ± 1.5 and 5.3 ± 1.7 ng/mL, P   〈  0.001 vs . HS). LPS and zonulin were correlated in HIV patients (Spearman correlation coefficient (rS) = 0.73, P   〈  0.0001). Levels of soluble CD40 ligand (sCD40L), soluble P‐selectin (sP‐selectin) and thromboxane B 2 (TxB 2 ) were higher in HIV‐1‐treated and treatment‐naïve subjects compared with HS as well as NADPH oxidase 2 (NOX2) activation and hydrogen peroxide (H 2 O 2 ) production. In vitro , sCD40L, sP‐selectin and TxB 2 production, NOX2 activation and p47 phox phosphorylation were higher in platelets exposed to plasma from HIV‐1 patients with different viral load compared with the exposure to plasma from HS. This effect was blunted in platelets pre‐treated with TLR4 or TLR7 inhibitors. Conclusions Low‐grade endotoxaemia and persistent viraemia increase platelet function with a mechanism mediated by NOX2 in patients with HIV‐1 infection.
    Type of Medium: Online Resource
    ISSN: 1464-2662 , 1468-1293
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2020341-X
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  • 8
    Online Resource
    Online Resource
    Wiley ; 2019
    In:  Liver International Vol. 39, No. 9 ( 2019-09), p. 1787-1787
    In: Liver International, Wiley, Vol. 39, No. 9 ( 2019-09), p. 1787-1787
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2124684-1
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  • 9
    In: International Journal of Cancer, Wiley, Vol. 147, No. 12 ( 2020-12-15), p. 3424-3430
    Abstract: What's new? While patients with atrial fibrillation (AF) are at increased risk of death from cardiovascular events (CVEs), a significant proportion die of cancer. Cancer and CVEs may be related, though little is known about cancer site and cardiovascular complications in AF. In this study involving more 2090 AF patients taking vitamin K anticoagulants, cancer was found to be a common comorbidity, affecting 17.5 percent of patients. In particular, gastrointestinal cancer was associated with increased risk of CVEs, while respiratory tract cancer was associated with an increased risk of thromboembolism. The findings link specific vascular outcomes with cancer site in AF.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 218257-9
    detail.hit.zdb_id: 1474822-8
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  • 10
    In: European Journal of Clinical Investigation, Wiley, Vol. 48, No. 5 ( 2018-05)
    Abstract: Previous studies suggested obstructive sleep apnoea syndrome ( OSAS ) as a major risk factor for incident cardiovascular events. However, the relationship between OSAS severity, the use of continuous positive airway pressure ( CPAP ) treatment and the development of cardiovascular disease is still matter of debate. Study objectives The aim was to test the association between OSAS and cardiovascular events in patients with concomitant cardio‐metabolic diseases and the potential impact of CPAP therapy on cardiovascular outcomes. Methods Prospective observational cohort study of consecutive outpatients with suspected metabolic disorders who had complete clinical and biochemical workup including polysomnography because of heavy snoring and possible OSAS . The primary endpoint was a composite of major adverse cardiovascular and cerebrovascular events ( MACCE ). Results Median follow‐up was 81.3 months, including 434 patients (2701.2 person/years); 83 had a primary snoring, 84 had mild, 93 moderate and 174 severe OSAS , respectively. The incidence of MACCE was 0.8% per year (95% confidence interval [ CI ] 0.2‐2.1) in primary snorers and 2.1% per year (95% CI 1.5‐2.8) for those with OSAS . A positive association was observed between event‐free survival and OSAS severity (log‐rank test; P = .041). A multivariable Cox regression analysis showed obesity ( HR = 8.011, 95% CI 1.071‐59.922, P = .043), moderate OSAS (vs non‐ OSAS HR = 3.853, 95% CI 1.069‐13.879, P = .039) and severe OSAS (vs non‐ OSAS HR = 3.540, 95% CI 1.026‐12.217, P = .045) as predictors of MACCE . No significant association was observed between CPAP treatment and MACCE (log‐rank test; P = .227). Conclusions Our findings support the role of moderate/severe OSAS as a risk factor for incident MACCE . CPAP treatment was not associated with a lower rate of MACCE .
    Type of Medium: Online Resource
    ISSN: 0014-2972 , 1365-2362
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2004971-7
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