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Article ; Online: Associations of pro-protein convertase subtilisin-like kexin type 9, soluble low-density lipoprotein receptor and coronary artery disease.

Scicali, Roberto

2022 Volume 353, Page(s) 118

MeSH term(s)	Coronary Artery Disease ; Humans ; Lipoproteins, LDL ; Subtilisin
Chemical Substances	Lipoproteins, LDL ; Subtilisin (EC 3.4.21.62)
Language	English
Publishing date	2022-02-02
Publishing country	Netherlands
Document type	Editorial ; Comment
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2022.01.058
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Article ; Online: Emerging Circulating Biomarkers in Atherosclerosis: From Molecular Mechanisms to Therapeutic Strategies.

Mandraffino, Giuseppe / Mattina, Alessandro / Scicali, Roberto

Biomolecules

2022 Volume 12, Issue 6

Abstract: Atherosclerosis is a long-term damaging process, and its progression leads to cardiovascular system injury [ ... ]. ...

Abstract	Atherosclerosis is a long-term damaging process, and its progression leads to cardiovascular system injury [...].
MeSH term(s)	Atherosclerosis ; Biomarkers ; Cardiovascular Diseases ; Humans ; Risk Factors
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-06-09
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12060809
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Article: Author's reply to: Arterial stiffness improvement after adding on PCSK9 inhibitors in patients with familial hypercholesterolemia, a letter from Papaioannou and colleagues.

Mandraffino, Giuseppe / Scicali, Roberto / Squadrito, Giovanni

Journal of clinical lipidology

2020 Volume 14, Issue 4, Page(s) 543

MeSH term(s)	Anticholesteremic Agents/therapeutic use ; Ezetimibe ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hyperlipoproteinemia Type II/drug therapy ; Lipids ; Proprotein Convertase 9 ; Vascular Stiffness
Chemical Substances	Anticholesteremic Agents ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipids ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) ; Ezetimibe (EOR26LQQ24)
Language	English
Publishing date	2020-05-06
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2365061-8
ISSN	1876-4789 ; 1933-2874
ISSN (online)	1876-4789
ISSN	1933-2874
DOI	10.1016/j.jacl.2020.04.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Is the relationship between erythropoiesis and renal function one of the secrets of extreme longevity?

Basile, Giorgio / Bellone, Federica / Catalano, Antonino / Maltese, Giuseppe / Corica, Francesco / Squadrito, Giovanni / Scicali, Roberto / Mandraffino, Giuseppe

Nutrition, metabolism, and cardiovascular diseases : NMCD

2023 Volume 33, Issue 4, Page(s) 868–872

Abstract: Background and aims: Renal function and erythropoiesis could be impaired with advancing age. Neutrophil gelatinase-associated lipocalin (NGAL) as well as erythropoietin (EPO) levels are two useful biomarkers of the renal status. In advanced age, the ... ...

Abstract	Background and aims: Renal function and erythropoiesis could be impaired with advancing age. Neutrophil gelatinase-associated lipocalin (NGAL) as well as erythropoietin (EPO) levels are two useful biomarkers of the renal status. In advanced age, the relationships between NGAL, EPO and hemoglobin (Hb) levels remains unknown. The aim of the present study is to evaluate the relationship between renal function and erythropoiesis in a small cohort of centenarians. Methods and results: We observed thirty-one healthy centenarians with normal hemoglobin levels, a mild reduction in eGFR and no need of erythropoiesis support. We found a significant inverse association between NGAL and GFR, hemoglobin levels and EPO, confirming the key role of the renal function on erythropoiesis also in extreme longevity. A gender difference emerged, showing female participants with lower eGFR and Hb values more than males. Conclusions: Our findings suggested a new link between renal function, erythropoiesis and longevity in centenarians and these could have relevant implications in clinical practice. These findings could explain why very old subjects presenting a slight GFR reduction seemed not to be exposed to a significant risk of mortality.
MeSH term(s)	Male ; Aged, 80 and over ; Humans ; Female ; Lipocalin-2 ; Erythropoiesis ; Longevity ; Kidney/physiology ; Biomarkers ; Hemoglobins
Chemical Substances	Lipocalin-2 ; Biomarkers ; Hemoglobins
Language	English
Publishing date	2023-01-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1067704-5
ISSN	1590-3729 ; 0939-4753
ISSN (online)	1590-3729
ISSN	0939-4753
DOI	10.1016/j.numecd.2023.01.019
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Article: Management of Statin Intolerant Patients in the Era of Novel Lipid Lowering Therapies: A Critical Approach in Clinical Practice.

Bosco, Giosiana / Di Giacomo Barbagallo, Francesco / Spampinato, Salvatore / Lanzafame, Lorena / Di Pino, Antonino / Piro, Salvatore / Purrello, Francesco / Scicali, Roberto

Journal of clinical medicine

2023 Volume 12, Issue 6

Abstract: Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle ... ...

Abstract	Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice.
Language	English
Publishing date	2023-03-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12062444
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Article ; Online: The Lipoprotein Profile Evaluated by 1H-NMR Improves the Performance of Genetic Testing in Familial Hypercholesterolemia.

Ibarretxe, Daiana / Llop, Dídac / Rodríguez-Borjabad, Cèlia / Andreychuk, Natalia / Plana, Núria / Scicali, Roberto / González-Lleó, Ana / Amigó, Núria / Girona, Josefa / Masana, Lluís

The Journal of clinical endocrinology and metabolism

2024

Abstract: Background: The familial hypercholesterolemia (FH) diagnosis is based on clinical and genetic criteria. A relevant proportion of FH patients fulfilling the criteria for definite FH have negative genetic testing. Increasing the identification of true ... ...

Abstract	Background: The familial hypercholesterolemia (FH) diagnosis is based on clinical and genetic criteria. A relevant proportion of FH patients fulfilling the criteria for definite FH have negative genetic testing. Increasing the identification of true genetic-based FH is a clinical challenge. Deepening the analysis of lipoprotein alterations could help increase the yield of genetic testing. We evaluated whether the number, size, and composition of lipoproteins assessed by 1H-NMR could increase the identification of FH patients with pathogenic gene variants. Methods: We studied 294 clinically definite FH patients, 222 (75.5%) with positive genetic testing, as the discovery cohort. As an external validation cohort, we studied 88 children with FH, 72 (81%) with positive genetic testing. The advanced lipoprotein test based on 1H-NMR (Liposcale®) was performed at baseline after a lipid-lowering drug wash-out of at least 6 weeks. The association of variables with genetic variants was evaluated by random forest and logistic regression. Areas under the curve (AUCs) were calculated. A predictive formula was developed and applied to the validation cohort. Results: A formula derived from NMR lipoprotein analyses improved the identification of genetically positive FH patients beyond LDL-C levels (AUC=0.87). The parameters contributing the most to the identification formula were LDL particle number, HDL size and remnant cholesterol. The formula also increases the classification of FH children with a pathogenic genetic variation. Conclusions: NMR lipoprotein profile analysis identifies differences beyond standard lipid parameters that help identify FH with a positive pathogenic gene variant, increasing the yield of genetic testing in FH patients.
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae037
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Article ; Online: Effect of PCSK9 inhibitors on pulse wave velocity and monocyte-to-HDL-cholesterol ratio in familial hypercholesterolemia subjects: results from a single-lipid-unit real-life setting.

Scicali, Roberto / Di Pino, Antonino / Ferrara, Viviana / Rabuazzo, Agata Maria / Purrello, Francesco / Piro, Salvatore

Acta diabetologica

2021 Volume 58, Issue 7, Page(s) 949–957

Abstract: Aims: Subjects with familial hypercholesterolemia (FH) are characterized by an increased amount of low-density lipoprotein cholesterol (LDL-C) that promotes a continuous inflammatory stimulus. Our aim was to evaluate the effect of PCSK9-i on ... ...

Abstract	Aims: Subjects with familial hypercholesterolemia (FH) are characterized by an increased amount of low-density lipoprotein cholesterol (LDL-C) that promotes a continuous inflammatory stimulus. Our aim was to evaluate the effect of PCSK9-i on inflammatory biomarkers, neutrophil-to-lymphocyte ratio, monocyte-to-high-density lipoprotein ratio (MHR), and on early atherosclerosis damage analyzed by pulse wave velocity (PWV) in a cohort of FH subjects. Methods: In this prospective observational study, we evaluated 56 FH subjects on high-intensity statins plus ezetimibe and with an off-target LDL-C. All subjects were placed on PCSK9-i therapy and obtained biochemical analysis as well as PWV evaluation at baseline and after six months of PCSK9-i therapy. Results: After six months of add-on PCSK9-i therapy, only 42.9% of FH subjects attained LDL-C targets. As expected, a significant reduction of LDL-C (- 49.61%, p < 0.001) was observed after PCSK9-i therapy. Neutrophil count (NC) and MHR were reduced by PCSK9-i (-13.82% and -10.47%, respectively, p value for both < 0.05) and PWV significantly decreased after PCSK9-i therapy (- 20.4%, p < 0.05). Finally, simple regression analyses showed that ∆ PWV was significantly associated with ∆ LDL-C (p < 0.01), ∆ NC and ∆ MHR (p value for both < 0.05). Conclusions: In conclusion, PCSK9-i therapy significantly improved lipid and inflammatory profiles and PWV values in FH subjects; our results support the positive effect of PCSK9-i in clinical practice.
MeSH term(s)	Aged ; Anticholesteremic Agents/administration & dosage ; Anticholesteremic Agents/adverse effects ; Anticholesteremic Agents/pharmacology ; Blood Flow Velocity/drug effects ; Cholesterol, HDL/blood ; Cohort Studies ; Drug Therapy, Combination ; Ezetimibe/administration & dosage ; Ezetimibe/adverse effects ; Ezetimibe/pharmacology ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Hyperlipoproteinemia Type II/blood ; Hyperlipoproteinemia Type II/drug therapy ; Hyperlipoproteinemia Type II/physiopathology ; Italy ; Leukocyte Count ; Lipid Metabolism/drug effects ; Male ; Middle Aged ; Monocytes/drug effects ; Monocytes/pathology ; PCSK9 Inhibitors ; Prospective Studies ; Pulse Wave Analysis
Chemical Substances	Anticholesteremic Agents ; Cholesterol, HDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; PCSK9 Inhibitors ; PCSK9 protein, human (EC 3.4.21.-) ; Ezetimibe (EOR26LQQ24)
Language	English
Publishing date	2021-03-21
Publishing country	Germany
Document type	Journal Article ; Observational Study
ZDB-ID	1097676-0
ISSN	1432-5233 ; 0940-5429
ISSN (online)	1432-5233
ISSN	0940-5429
DOI	10.1007/s00592-021-01703-z
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Article ; Online: Management of Statin Intolerant Patients in the Era of Novel Lipid Lowering Therapies

Giosiana Bosco / Francesco Di Giacomo Barbagallo / Salvatore Spampinato / Lorena Lanzafame / Antonino Di Pino / Salvatore Piro / Francesco Purrello / Roberto Scicali

Journal of Clinical Medicine, Vol 12, Iss 2444, p

A Critical Approach in Clinical Practice

2023 Volume 2444

Abstract	Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice.
Keywords	statin intolerance ; non-statin lipid lowering therapy ; LDL-C target ; therapeutic adherence ; cardiovascular risk reduction ; Medicine ; R
Subject code	616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Is the relationship between erythropoiesis and renal function one of the secrets of extreme longevity?

Basile, Giorgio / Bellone, Federica / Catalano, Antonino / Maltese, Giuseppe / Corica, Francesco / Squadrito, Giovanni / Scicali, Roberto / Mandraffino, Giuseppe

The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University Nutrition, Metabolism and Cardiovascular Diseases. 2023 Apr., v. 33, no. 4 p.868-872

2023

Abstract: Renal function and erythropoiesis could be impaired with advancing age. Neutrophil gelatinase-associated lipocalin (NGAL) as well as erythropoietin (EPO) levels are two useful biomarkers of the renal status. In advanced age, the relationships between ... ...

Abstract	Renal function and erythropoiesis could be impaired with advancing age. Neutrophil gelatinase-associated lipocalin (NGAL) as well as erythropoietin (EPO) levels are two useful biomarkers of the renal status. In advanced age, the relationships between NGAL, EPO and hemoglobin (Hb) levels remains unknown. The aim of the present study is to evaluate the relationship between renal function and erythropoiesis in a small cohort of centenarians. We observed thirty-one healthy centenarians with normal hemoglobin levels, a mild reduction in eGFR and no need of erythropoiesis support. We found a significant inverse association between NGAL and GFR, hemoglobin levels and EPO, confirming the key role of the renal function on erythropoiesis also in extreme longevity. A gender difference emerged, showing female participants with lower eGFR and Hb values more than males. Our findings suggested a new link between renal function, erythropoiesis and longevity in centenarians and these could have relevant implications in clinical practice. These findings could explain why very old subjects presenting a slight GFR reduction seemed not to be exposed to a significant risk of mortality.
Keywords	biomarkers ; elderly ; erythropoiesis ; erythropoietin ; females ; gender differences ; hemoglobin ; longevity ; metabolism ; mortality ; neutrophils ; nutrition ; renal function ; risk ; Centenarians ; NGAL ; CKD-EPI ; BIS1 ; MDRD ; eGFR
Language	English
Dates of publication	2023-04
Size	p. 868-872.
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	1067704-5
ISSN	0939-4753
ISSN	0939-4753
DOI	10.1016/j.numecd.2023.01.019
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The impact of obesity and dyslipidemia on Remdesivir effectiveness in hospitalized patients with SARS-CoV-2-related pneumonia: An observational study.

Tumminia, Andrea / Romano, Raffaella / Brugaletta, Giuseppe / Scicali, Roberto / Biondi, Giuseppina / Oliveri, Rosario / Romano, Marcello / San Lio, Paola Magnano

Nutrition, metabolism, and cardiovascular diseases : NMCD

2022 Volume 32, Issue 7, Page(s) 1635–1641

Abstract: Background and aims: Remdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase was early identified as a promising therapeutic candidate against COVID-19. Our aim was to evaluate the impact of several metabolic parameters on ... ...

Abstract	Background and aims: Remdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase was early identified as a promising therapeutic candidate against COVID-19. Our aim was to evaluate the impact of several metabolic parameters on Remdesivir effectiveness among hospitalized COVID-19 patients. Methods and results: We conducted an observational study on patients with SARS-CoV-2-related pneumonia admitted between May 2020 and September 2021 to the COVID-19 Units of Internal Medicine, Pneumology and Intensive Care of Garibaldi Hospital, Catania, Italy, and treated with Remdesivir. The "Ordinal Scale For Clinical Improvement" was used to assess patients' clinical improvement within 28 days of hospitalization. Short-term mortality rate was also evaluated. A total of 142 patients with SARS-CoV-2-related pneumonia were studied. The prevalence of obesity (20.7% vs. 41.9%, p = 0.03), the average BMI (27.1 ± 4.4 vs. 31.1 ± 6.1, p < 0.01) and the mean LDL-C levels (78 ± 19 mg/dl vs. 103 ± 18 mg/dl, p = 0.03) were significantly lower in early-improved (EI) compared to not-improved (NI) individuals. Obesity was negatively associated to clinical improvement after Remdesivir (OR 0.48, 95%CI 0.17-0.97, p = 0.04). Both obesity (OR 2.82, 95% CI 1.05-7.71, p = 0.04) and dyslipidemia (OR 2.78, 95%CI 1.17-7.16, p = 0.03) were significantly related to patients' mortality. Dyslipidemic subjects experienced a slower clinical improvement than non-dyslipidemic ones (Long-Rank p = 0.04). Conclusion: Our study showed that unfavorable metabolic conditions such as obesity and dyslipidemia could predict a worse clinical response to Remdesivir as well as the mortality in hospitalized COVID-19 patients. Further prospective and larger-scale studies are needed to confirm these preliminary findings.
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; Antiviral Agents/adverse effects ; COVID-19/drug therapy ; Dyslipidemias/diagnosis ; Dyslipidemias/drug therapy ; Dyslipidemias/epidemiology ; Humans ; Obesity/diagnosis ; Obesity/drug therapy ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2022-04-10
Publishing country	Netherlands
Document type	Journal Article ; Observational Study
ZDB-ID	1067704-5
ISSN	1590-3729 ; 0939-4753
ISSN (online)	1590-3729
ISSN	0939-4753
DOI	10.1016/j.numecd.2022.04.005
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