Publications by authors named "Carmine Vecchione"

122 Publications

Clinical conditions and echocardiographic parameters associated with mortality in COVID-19.

Eur J Clin Invest 2021 Jul 20:e13638. Epub 2021 Jul 20.

Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy.

Background: Coronavirus disease 2019 (COVID-19) is a recently recognized viral infective disease which can be complicated by acute respiratory stress syndrome (ARDS) and cardiovascular complications including severe arrhythmias, acute coronary syndromes, myocarditis and pulmonary embolism. The aim of the present study was to identify the clinical conditions and echocardiographic parameters associated with in-hospital mortality in COVID-19.

Methods: This is a multicentre retrospective observational study including seven Italian centres. Patients hospitalized with COVID-19 from 1 March to 22 April 2020 were included into study population. The association between baseline variables and risk of in-hospital mortality was assessed through multivariable logistic regression and competing risk analyses.

Results: Out of 1401 patients admitted at the participating centres with confirmed diagnosis of COVID-19, 226 (16.1%) underwent transthoracic echocardiography (TTE) and were included in the present analysis. In-hospital death occurred in 68 patients (30.1%). At multivariable analysis, left ventricular ejection fraction (LVEF, P < .001), tricuspid annular plane systolic excursion (TAPSE, P < .001) and ARDS (P < .001) were independently associated with in-hospital mortality. At competing risk analysis, we found a significantly higher risk of mortality in patients with ARDS vs those without ARDS (HR: 7.66; CI: 3.95-14.8), in patients with TAPSE ≤17 mm vs those with TAPSE >17 mm (HR: 5.08; CI: 3.15-8.19) and in patients with LVEF ≤50% vs those with LVEF >50% (HR: 4.06; CI: 2.50-6.59).

Conclusions: TTE might be a useful tool in risk stratification of patients with COVID-19. In particular, reduced LVEF and reduced TAPSE may help to identify patients at higher risk of death during hospitalization.
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http://dx.doi.org/10.1111/eci.13638DOI Listing
July 2021

PD-L1 Dysregulation in COVID-19 Patients.

Front Immunol 2021 7;12:695242. Epub 2021 Jun 7.

Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Baronissi (SA), Italy.

The COVID-19 pandemic has reached direct and indirect medical and social consequences with a subset of patients who rapidly worsen and die from severe-critical manifestations. As a result, there is still an urgent need to identify prognostic biomarkers and effective therapeutic approaches. Severe-critical manifestations of COVID-19 are caused by a dysregulated immune response. Immune checkpoint molecules such as Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) play an important role in regulating the host immune response and several lines of evidence underly the role of PD-1 modulation in COVID-19. Here, by analyzing blood sample collection from both hospitalized COVID-19 patients and healthy donors, as well as levels of PD-L1 RNA expression in a variety of model systems of SARS-CoV-2, including tissue cultures, ex-vivo infections of primary epithelial cells and biological samples obtained from tissue biopsies and blood sample collection of COVID-19 and healthy individuals, we demonstrate that serum levels of PD-L1 have a prognostic role in COVID-19 patients and that PD-L1 dysregulation is associated to COVID-19 pathogenesis. Specifically, PD-L1 upregulation is induced by SARS-CoV-2 in infected epithelial cells and is dysregulated in several types of immune cells of COVID-19 patients including monocytes, neutrophils, gamma delta T cells and CD4+ T cells. These results have clinical significance since highlighted the potential role of PD-1/PD-L1 axis in COVID-19, suggest a prognostic role of PD-L1 and provide a further rationale to implement novel clinical studies in COVID-19 patients with PD-1/PD-L1 inhibitors.
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http://dx.doi.org/10.3389/fimmu.2021.695242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215357PMC
July 2021

A case report of takotsubo syndrome complicated by ischaemic stroke: the clinical dilemma of anticoagulation.

Eur Heart J Case Rep 2021 Mar 15;5(3):ytab051. Epub 2021 Mar 15.

Cardiothoracic and Vascular Department, Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Heart Tower-Room 807, Largo Città d'Ippocrate, 84131 Salerno, Italy.

Background: Takotsubo syndrome (TTS) is an acute and transient heart failure syndrome due to reversible myocardial dysfunction characterized by a wide spectrum of possible clinical scenarios. About one-fifth of TTS patients experience adverse in-hospital events. Thromboembolic complications, especially stroke, have been reported, albeit in a minority of patients.

Case Summary: A 69-year-old woman presented to our emergency department for dyspnoea after a family quarrel. Electrocardiogram revealed ST-segment elevation in anterolateral leads and laboratory exams showed a slight elevation of high-sensitivity cardiac troponin. The patient was treated according to current guidelines on ST-elevation myocardial infarction and referred to the cath lab. Urgent coronary angiography revealed normal coronary arteries. Based on the patient profile and instrumental findings, a diagnosis of TTS was hypothesized. After 6 days, the patient developed dysarthria and right hemiparesis under therapy with aspirin, whilst low molecular weight heparin had been previously withdrawn. Transthoracic echocardiography (TTE) revealed persisting apical akinesia and a subtle intraventricular thrombus. Head computed tomography and magnetic resonance imaging detected focal areas of ischaemic necrosis resembling diffuse cardioembolic lesions. Anticoagulation therapy was started and regular TTE showed complete recovery of myocardial systolic function and absence of ventricular thrombi at 1-month follow-up. The patient fully recovered speech after 5 months.

Discussion: This challenging case reinforces current recommendations to administer antithrombotic therapy in TTS patients with extensive apical dysfunction up to complete or near-complete recovery of myocardial contractility, regardless of the presence of atrial fibrillation, and highlights the importance of close TTE monitoring during the acute phase.
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http://dx.doi.org/10.1093/ehjcr/ytab051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186932PMC
March 2021

Predictors of complications in initially haemodynamically stable patients admitted in a modern coronary care unit.

J Cardiovasc Med (Hagerstown) 2021 Jul;22(7):553-559

Department of Cardiology, Intensive Cardiac Care Unit, Ruggi D' Aragona Hospital.

Aims: Resource optimization in the intensive cardiac care unit (ICCU) is, nowadays, of great importance because of the increasing number of acute cardiovascular patients requiring high-intensity level-of-care. Because of natural limits in ICCU bed availability, understanding, which patients will really benefit from in a such a critical care setting, is of paramount importance. In our study, we analysed a heterogeneous ICCU population with initially stable haemodynamic conditions, in order to find potential predictors of severe complications.

Methods: Nine hundred and fifty patients admitted to our ICCU during the year 2019 were screened in order to detect those with a stable haemodynamic condition at admission. Data were extrapolated from an internal database. Comorbidity burden was expressed by the Charlson Comorbidity Index (CCI). Our primary end point was defined by a combination of severe complications requiring critical care, and in-hospital death.

Results: Ninety-eight patients (14.1% of 695 stable patients identified) developed severe complications. After a multivariable logistic regression analysis, four predictors were identified: signs of congestive heart failure [OR: 9.25, 95% confidence interval (CI): 5.61-15.25; P < 0.001], SBP 120 mmHg or less (OR: 2.10, 95% CI: 1.27-3.47; P = 0.004), haemoglobin level 13 g/dl or less (OR: 1.75, 95% CI: 1.03-2.95; P = 0.037), and the CCI above 3 (OR: 2.27, 95% CI: 1.13-4.56; P = 0.022).

Conclusion: In our study, 73% of patients showed a stable haemodynamic condition on admission. Severe complications occurred in 14.1% of these patients, and signs of heart failure were the main determinants of the outcome. SBP, haemoglobin level, and the CCI concurred in the prediction of severe complications during the hospital stay.
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http://dx.doi.org/10.2459/JCM.0000000000001173DOI Listing
July 2021

Vitamin D: Not Just Bone Metabolism but a Key Player in Cardiovascular Diseases.

Life (Basel) 2021 May 18;11(5). Epub 2021 May 18.

IRCCS Neuromed, 86077 Pozzilli, Italy.

Vitamin D is the first item of drug expenditure for the treatment of osteoporosis. Its deficiency is a condition that affects not only older individuals but also young people. Recently, the scientific community has focused its attention on the possible role of vitamin D in the development of several chronic diseases such as cardiovascular and metabolic diseases. This review aims to highlight the possible role of vitamin D in cardiovascular and metabolic diseases. In particular, here we examine (1) the role of vitamin D in diabetes mellitus, metabolic syndrome, and obesity, and its influence on insulin secretion; (2) its role in atherosclerosis, in which chronic vitamin D deficiency, lower than 20 ng/mL (50 nmol/L), has emerged among the new risk factors; (3) the role of vitamin D in essential hypertension, in which low plasma levels of vitamin D have been associated with both an increase in the prevalence of hypertension and diastolic hypertension; (4) the role of vitamin D in peripheral arteriopathies and aneurysmal pathology, reporting that patients with peripheral artery diseases had lower vitamin D values than non-suffering PAD controls; (5) the genetic and epigenetic role of vitamin D, highlighting its transcriptional regulation capacity; and (6) the role of vitamin D in cardiac remodeling and disease. Despite the many observational studies and meta-analyses supporting the critical role of vitamin D in cardiovascular physiopathology, clinical trials designed to evaluate the specific role of vitamin D in cardiovascular disease are scarce. The characterization of the importance of vitamin D as a marker of pathology should represent a future research challenge.
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http://dx.doi.org/10.3390/life11050452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158519PMC
May 2021

"One Health" Approach for Health Innovation and Active Aging in Campania (Italy).

Front Public Health 2021 11;9:658959. Epub 2021 May 11.

Dipartimento di Sanità Pubblica, Università degli Studi di Napoli "Federico II, " Naples, Italy.

This article describes how innovations are exploited in Campania (Italy) to improve health outcomes, quality of life, and sustainability of social and healthcare services. Campania's strategy for digitalization of health and care and for healthy aging is based on a person-centered, life-course, "One Health" approach, where demographic change is considered capable of stimulating a growth dynamic linked to the opportunities of combining the "Silver Economy" with local assets and the specific health needs of the population. The end-users (citizens, patients, and professionals) contribute to the co-creation of products and services, being involved in the identification of unmet needs and test-bed activity. The Campania Reference Site of the European Innovation Partnership on Active and Healthy Aging is a flexible regional ecosystem to address the challenge of an aging population with a life-course approach. The good practices, developed in the context of research and innovation projects and innovative procurements by local stakeholders and collaborations with international networks, have been allowing the transfer of innovative solutions, knowledge, and skills to the stakeholders of such a multi-sectoral ecosystem for health.
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http://dx.doi.org/10.3389/fpubh.2021.658959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144456PMC
June 2021

Characterization of phase I and phase II metabolites of hop (Humulus lupulus L.) bitter acids: In vitro and in vivo metabolic profiling by UHPLC-Q-Orbitrap.

J Pharm Biomed Anal 2021 Jul 30;201:114107. Epub 2021 Apr 30.

Department of Pharmacy, University of Salerno, Fisciano, SA, Italy; European Biomedical Research Institute of Salerno, Via De Renzi 50, I-84125, Salerno, Italy. Electronic address:

Bitter acids are a class of prenylated phloroglucinol derivatives present in Humulus lupulus L., known for their multiple healthy properties, nevertheless, research regarding their metabolism and stability is lacking. This study was aimed to elucidate the metabolic stability of hop α- and β-acids and characterize I and II phase metabolites in vitro and in vivo. For this purpose, an ultra high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) method was developed and validated. Mice liver microsomes were used to assess metabolic stability; in vitro t and clearance values were calculated, showing a moderate metabolism for α-acids (t: 120.01 min, CL 11.96 μL/min/mg), while β-acids were metabolized faster (t: 103.01 min, CL: 13.83 μL/min/mg). I and II phase metabolites were characterized both in in vitro, and in vivo, in mouse plasma and urine after oral administration. A combined full scan/data dependent/precursor ion list-triggered neutral loss (FS/dd-MS/PIL-tNL) strategy was used to detect unknown and expected metabolites. As a result, 33 compounds were detected, including novel metabolites, such as 9 potential oxidized metabolites of humulones (M6-M14), and 10 glucuronide conjugates of α-acids, comprising 7 glucuronide derivatives of oxidized phase I metabolites (M26-M32). The proposed method extends the current knowledge regarding metabolization of hop α- and β-acids and could be applied for the comprehension of the metabolic fate of this class of compounds in different species, as well as for in vivo pharmacokinetic studies.
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http://dx.doi.org/10.1016/j.jpba.2021.114107DOI Listing
July 2021

Clinical outcome of patients with ST-elevation myocardial infarction and angiographic evidence of coronary artery ectasia.

Catheter Cardiovasc Interv 2021 May 5. Epub 2021 May 5.

Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi (Salerno), Italy.

Objectives: The aim of this study was to describe the prevalence of coronary artery ectasia (CAE) in patients with ST-elevation myocardial infarction (STEMI) and to compare the long-term outcome of subjects with and without CAE undergoing emergent coronary angiography.

Background: The prognostic impact of CAE in STEMI patients has been poorly investigated.

Methods: This retrospective, single-center, study included consecutive patients with STEMI undergoing emergent coronary angiography from January 2012 to December 2017. The primary endpoint was the assessment of recurrent myocardial infarction (MI) in patients with versus those without CAE at the longest available follow-up. The propensity score weighting technique was employed to account for potential selection bias between groups.

Results: From 1,674 patients with STEMI, 154 (9.2%) had an angiographic evidence of CAE; 380 patients were included in the no CAE group. CAE patients were more often males and smokers, and showed a lower prevalence of diabetes than no CAE patients. After percutaneous coronary intervention, the corrected thrombolysis in MI frame count (p < .001) and the myocardial blush grade (p < .001) were significantly lower in CAE than in no CAE patients. The mean follow-up was 1,218.3 ± 574.8 days. The adjusted risk for the primary outcome resulted significantly higher in patients with CAE compared to those without (adjusted HR: 1.84; p = .017). No differences in terms of all-cause and cardiac death were found between groups.

Conclusions: In this study, STEMI patients with CAE had a distinct clinical and angiographic profile, and showed a significantly higher risk of recurrent MI than those without CAE.
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http://dx.doi.org/10.1002/ccd.29738DOI Listing
May 2021

A Novel Vasoactive Peptide "PG1" from Buffalo Ice-Cream Protects from Angiotensin-Evoked High Blood Pressure.

Antioxidants (Basel) 2021 Mar 12;10(3). Epub 2021 Mar 12.

Department of Medicine and Surgery, University of Salerno, 84081 Baronissi, SA, Italy.

Background: Arterial hypertension is the most important risk factor for cardiovascular diseases, myocardial infarction, heart failure, renal failure and peripheral vascular disease. In the last decade, milk-derived bioactive peptides have attracted attention for their beneficial cardiovascular properties.

Methods: Here, we combined in vitro chemical assay such as LC-MS/MS analysis of buffalo ice cream, ex vivo vascular studies evaluating endothelial and smooth muscle responses using pressure myograph, and translational assay testing in vivo the vascular actions of PG1 administration in murine models.

Results: We demonstrate that a novel buffalo ice-cream-derived pentapeptide "QKEPM", namely PG1, is a stable peptide that can be obtained at higher concentration after gastro-intestinal digestions (GID) of buffalo ice-cream (BIC). It owns potent vascular effect in counteract the effects of angiotensin II-evoked vasoconstriction and high blood pressure levels. Its effects are mediated by the inhibitory effect on AT1 receptor leading to a downregulation of p-ERK½/Rac1-GTP and consequent reduction of oxidative stress.

Conclusions: These results strongly candidate PG1, as a novel bioactive peptide for the prevention and management of hypertension, thus expanding the armamentarium of preventive strategies aimed at reducing the incidence and progression of hypertension and its related cardiovascular complications.
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http://dx.doi.org/10.3390/antiox10030441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002072PMC
March 2021

Exercise Training and Cardiac Rehabilitation in COVID-19 Patients with Cardiovascular Complications: State of Art.

Life (Basel) 2021 Mar 21;11(3). Epub 2021 Mar 21.

Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende 43, 84081 Baronissi, Italy.

Recent scientific literature has investigated the cardiovascular implications of COVID-19. The mechanisms of cardiovascular damage seem to involve the protein angiotensin-converting enzyme 2 (ACE2), to which severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) binds to penetrate cells and other mechanisms, most of which are still under study. Cardiovascular sequelae of COVID-19 include heart failure, cardiomyopathy, acute coronary syndrome, arrhythmias, and venous thromboembolism. This article aims to collect scientific evidence by exploiting PubMed, Scopus, and Pedro databases to highlight the cardiovascular complications of COVID-19 and to define the physiotherapy treatment recommended for these patients. Exercise training (ET), an important part of cardiac rehabilitation, is a powerful tool in physiotherapy, capable of inducing significant changes in the cardiovascular system and functional in the recovery of endothelial dysfunction and for the containment of thromboembolic complications. In conclusion, due to the wide variety of possible exercise programs that can be obtained by combining intensity, duration, and speed in various ways, and by adjusting the program based on continuous patient monitoring, exercise training is well suited to the treatment of post-COVID patients with an impaired cardiovascular system of various degrees.
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http://dx.doi.org/10.3390/life11030259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004041PMC
March 2021

Prognostic impact of acute pulmonary triggers in patients with takotsubo syndrome: new insights from the International Takotsubo Registry.

ESC Heart Fail 2021 06 13;8(3):1924-1932. Epub 2021 Mar 13.

Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany.

Aims: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes.

Methods And Results: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002).

Conclusions: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.
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http://dx.doi.org/10.1002/ehf2.13165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120351PMC
June 2021

Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients.

Life (Basel) 2021 Jan 30;11(2). Epub 2021 Jan 30.

Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, 84081 Baronissi, Italy.

Reactive oxygen species (ROS) are molecules involved in signal transduction pathways with both beneficial and detrimental effects on human cells. ROS are generated by many cellular processes including mitochondrial respiration, metabolism and enzymatic activities. In physiological conditions, ROS levels are well-balanced by antioxidative detoxification systems. In contrast, in pathological conditions such as cardiovascular, neurological and cancer diseases, ROS production exceeds the antioxidative detoxification capacity of cells, leading to cellular damages and death. In this review, we will first describe the biology and mechanisms of ROS mediated oxidative stress in cardiovascular disease. Second, we will review the role of oxidative stress mediated by oncological treatments in inducing cardiovascular disease. Lastly, we will discuss the strategies that potentially counteract the oxidative stress in order to fight the onset and progression of cardiovascular disease, including that induced by oncological treatments.
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http://dx.doi.org/10.3390/life11020105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911715PMC
January 2021

The Role of Oxidative Stress in Cardiovascular Aging and Cardiovascular Diseases.

Life (Basel) 2021 Jan 15;11(1). Epub 2021 Jan 15.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, 84081 Salerno, Italy.

Aging can be seen as process characterized by accumulation of oxidative stress induced damage. Oxidative stress derives from different endogenous and exogenous processes, all of which ultimately lead to progressive loss in tissue and organ structure and functions. The oxidative stress theory of aging expresses itself in age-related diseases. Aging is in fact a primary risk factor for many diseases and in particular for cardiovascular diseases and its derived morbidity and mortality. Here we highlight the role of oxidative stress in age-related cardiovascular aging and diseases. We take into consideration the molecular mechanisms, the structural and functional alterations, and the diseases accompanied to the cardiovascular aging process.
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http://dx.doi.org/10.3390/life11010060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829951PMC
January 2021

Cardiovascular risk factors and mortality in hospitalized patients with COVID-19: systematic review and meta-analysis of 45 studies and 18,300 patients.

BMC Cardiovasc Disord 2021 01 7;21(1):23. Epub 2021 Jan 7.

Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Salerno, Italy.

Background: A high prevalence of cardiovascular risk factors including age, male sex, hypertension, diabetes, and tobacco use, has been reported in patients with Coronavirus disease 2019 (COVID-19) who experienced adverse outcome. The aim of this study was to investigate the relationship between cardiovascular risk factors and in-hospital mortality in patients with COVID-19.

Methods: MEDLINE, Cochrane, Web of Sciences, and SCOPUS were searched for retrospective or prospective observational studies reporting data on cardiovascular risk factors and in-hospital mortality in patients with COVID-19. Univariable and multivariable age-adjusted analyses were conducted to evaluate the association between cardiovascular risk factors and the occurrence of in-hospital death.

Results: The analysis included 45 studies enrolling 18,300 patients. The pooled estimate of in-hospital mortality was 12% (95% CI 9-15%). The univariable meta-regression analysis showed a significant association between age (coefficient: 1.06; 95% CI 1.04-1.09; p < 0.001), diabetes (coefficient: 1.04; 95% CI 1.02-1.07; p < 0.001) and hypertension (coefficient: 1.01; 95% CI 1.01-1.03; p = 0.013) with in-hospital death. Male sex and smoking did not significantly affect mortality. At multivariable age-adjusted meta-regression analysis, diabetes was significantly associated with in-hospital mortality (coefficient: 1.02; 95% CI 1.01-1.05; p = 0.043); conversely, hypertension was no longer significant after adjustment for age (coefficient: 1.00; 95% CI 0.99-1.01; p = 0.820). A significant association between age and in-hospital mortality was confirmed in all multivariable models.

Conclusions: This meta-analysis suggests that older age and diabetes are associated with higher risk of in-hospital mortality in patients infected by SARS-CoV-2. Conversely, male sex, hypertension, and smoking did not independently correlate with fatal outcome.
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http://dx.doi.org/10.1186/s12872-020-01816-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789083PMC
January 2021

Analysis of the metabolic switch induced by the spirulina peptide SP6 in high fat diet ApoE mice model: A direct infusion FT-ICR-MS based approach.

J Pharm Biomed Anal 2021 Feb 24;195:113865. Epub 2020 Dec 24.

Department of Pharmacy, University of Salerno, Fisciano, SA, Italy; European Biomedical Research Institute of Salerno, Via De Renzi 50, I-84125 Salerno, Italy.

Atherosclerosis, dyslipidemia and hypertension are comorbid diseases often found in combination. Among different pharmacological approaches the employment of natural multifunctional peptides is an attractive option as side therapy. Mass spectrometry-based metabolomics provide valuable information on metabolic changes and can be useful to elucidate peptide pharmacodynamics. In this this work we performed a preliminary investigation on the potential effect of a recently characterized Spirulina platensis peptide named SP6 (GIVAGDVTPI) on the modulation of metabolism in a high fat diet ApoE mice atherosclerotic model. A direct infusion Fourier transform ion cyclotron resonance mass spectrometry (DI-FT-ICR-MS) approach was used to elucidate polar and non-polar metabolites extracted by mice plasma following four weeks SP6 treatment. The method delivered fast analysis time, repeatability, high mass accuracy and resolution for unambiguous molecular formula assignment. Multivariate statistical analysis (PLS-DA) highlighted a clear class separation, revealing the alteration of numerous metabolites levels belonging to different classes. In particular sphingolipids, glycerophospholipids, TCA cycle intermediates, and amino acids, which are key players in the atherosclerotic process and progression, were upregulated in saline alone HFD ApoE group, while were sensibly decreased after treatment with SP6 peptide. These results could open the way to further, large-scale, investigation of SP6 peptide effects in the regulation of atherosclerotic disease development and progression, and show the potential of DI-FT-ICR as fast analytical tool to take snaphshots of metabolic changes before moving to targeted MS-based approaches.
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http://dx.doi.org/10.1016/j.jpba.2020.113865DOI Listing
February 2021

Artificial Intelligence as a Business Partner in Cardiovascular Precision Medicine: an Emerging Approach for Disease Detection and Treatment Optimization.

Curr Med Chem 2020 12 18. Epub 2020 Dec 18.

Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi. Italy.

Background: In the real world, medical practice is changing hand in hand with the development of new Artificial Intelligence (AI) systems and problems from different areas have been successfully solved using AI algorithms. Specifically, the use of AI techniques in setting up or building precision medicine is significant in terms of the accuracy of disease discovery and tailored treatment. Moreover, with the use of technology, clinical personnel can deliver a very much efficient healthcare service.

Objective: This article reviews AI state-of-the-art in cardiovascular disease management, focusing on diagnostic and therapeutic improvements.

Methods: To that end, we conducted a detailed PubMed search on AI application from distinct areas of cardiology: heart failure, arterial hypertension, atrial fibrillation, syncope and cardiovascular rehabilitation. Particularly, to assess the impact of these technologies in clinical decision-making, this research considers technical and medical aspects.

Results: On one hand, some devices in heart failure, atrial fibrillation and cardiac rehabilitation represent an inexpensive, not invasive or not very invasive approach to long-term surveillance and management in these areas. On the other hand, the availability of large datasets (big data) is a useful tool to predict the development and outcome of many cardiovascular diseases. In summary, with this new guided therapy, the physician can supply prompt, individualised, and tailored treatment and the patients feel safe as they are continuously monitored, with a significant psychological effect.

Conclusion: Soon, tailored patient care via telemonitoring can improve the clinical practice because AI-based systems support cardiologists in daily medical activities, improving disease detection and treatment. However, the physician-patient relationship remains a pivotal step.
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http://dx.doi.org/10.2174/0929867328666201218122633DOI Listing
December 2020

Cardiotoxicity of Novel Targeted Hematological Therapies.

Life (Basel) 2020 Dec 11;10(12). Epub 2020 Dec 11.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, 84081 Salerno, Italy.

Chemotherapy-related cardiac dysfunction, also known as cardiotoxicity, is a group of drug-related adverse events negatively affecting myocardial structure and functions in patients who received chemotherapy for cancer treatment. Clinical manifestations can vary from life-threatening arrythmias to chronic conditions, such as heart failure or hypertension, which dramatically reduce quality of life of cancer survivors. Standard chemotherapy exerts its toxic effect mainly by inducing oxidative stress and genomic instability, while new targeted therapies work by interfering with signaling pathways important not only in cancer cells but also in myocytes. For example, Bruton's tyrosine kinase (BTK) inhibitors interfere with class I phosphoinositide 3-kinase isoforms involved in cardiac hypertrophy, contractility, and regulation of various channel forming proteins; thus, off-target effects of BTK inhibitors are associated with increased frequency of arrhythmias, such as atrial fibrillation, compared to standard chemotherapy. In this review, we summarize current knowledge of cardiotoxic effects of targeted therapies used in hematology.
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http://dx.doi.org/10.3390/life10120344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763613PMC
December 2020

Sirt1 Activity in PBMCs as a Biomarker of Different Heart Failure Phenotypes.

Biomolecules 2020 11 23;10(11). Epub 2020 Nov 23.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.

Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been exhaustively investigated. Sirt1 plays a crucial role in biological processes strongly related to HF. This study aimed to evaluate whether Sirt1 activity was correlated with EF and other parameters in HFpEF, HFmrEF, and HFrEF. Seventy patients, HFpEF ( = 23), HFmrEF ( = 23) and HFrEF ( = 24), were enrolled at the Cardiology Unit of the University Hospital of Salerno. Sirt1 activity was measured in peripheral blood mononuclear cells (PBMCs). Angiotensin-Converting Enzyme 2 (ACE2) activity, Tumor Necrosis Factor-alpha (TNF-α) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF ( < 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r = 0.899 and r = 0.909, respectively), and between ACE2 activity and Sirt1 (r = 0.801 and r = 0.802, respectively). HFrEF showed the highest TNF-α levels without reaching statistical significance. Significant differences in BNP were found among the groups, with the highest levels in the HFrEF. Determining Sirt1 activity in PBMCs is useful to distinguish the HF patients' phenotypes from each other, especially HFmrEF/HFrEF from HFpEF.
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http://dx.doi.org/10.3390/biom10111590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700185PMC
November 2020

A Novel Promising Frontier for Human Health: The Beneficial Effects of Nutraceuticals in Cardiovascular Diseases.

Int J Mol Sci 2020 Nov 18;21(22). Epub 2020 Nov 18.

Department of Angio-Cardio-Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy.

Cardiovascular diseases (CVDs) such as hypertension, atherosclerosis, myocardial infarction, and diabetes are a significant public health problem worldwide. Although several novel pharmacological treatments to reduce the progression of CVDs have been discovered during the last 20 years, the better way to contain the onset of CVDs remains prevention. In this regard, nutraceuticals seem to own a great potential in maintaining human health, exerting important protective cardiovascular effects. In the last years, there has been increased focus on identifying natural compounds with cardiovascular health-promoting effects and also to characterize the molecular mechanisms involved. Although many review articles have focused on the individual natural compound impact on cardiovascular diseases, the aim of this manuscript was to examine the role of the most studied nutraceuticals, such as resveratrol, cocoa, quercetin, curcumin, brassica, berberine and Spirulina platensis, on different CVDs.
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http://dx.doi.org/10.3390/ijms21228706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698807PMC
November 2020

Role of multimodality imaging in evaluation of cardiovascular involvement in COVID-19.

Trends Cardiovasc Med 2021 01 13;31(1):8-16. Epub 2020 Oct 13.

University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.

The management of patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be difficult due to the need for dedicated in-hospital pathways, protective measures for healthcare professionals and isolated beds of intensive care, particularly in areas overwhelmed by wide viral spread. Although pneumonia is the most common clinical manifestation in coronavirus disease 2019 (COVID-19), a variety of cardiovascular complications have been reported. An integrated diagnostic algorithm in SARS-CoV-2-infected patients with suspected cardiac involvement (laboratory findings of myocardial injury and electrocardiographic changes) may help to avoid unnecessary examinations and minimize the risk of operator infection. Due to its mobility and bedside feasibility, echocardiography is the first-line imaging technique in this clinical setting. It quickly provides information on ventricular functions, pulmonary hypertension, valve disease and pericardial effusion. In case of ST-segment elevation (STE), urgent coronary angiography should be performed. Cardiac ultrasound helps distinguish between ischemic and non-ischemic myocardial disease and may detect pericardial disease. Transmural ischemic electrocardiographic changes, with or without early elevated troponin levels or echocardiographic wall motion abnormalities, will determine the need for early invasive coronary angiography. Computed tomography (CT) through its multiple applications (chest CT; CT pulmonary angiography and coronary CT angiography; late iodine enhancement CT) and cardiac magnetic resonance might be helpful in reinforcing or redirecting diagnostic hypothesis emerged by other clinical, electrocardiographic and echocardiographic findings. The current pandemic makes it challenging to perform serial invasive and non-invasive diagnostic testing in COVID-19 patients and high serum troponin level. Nevertheless, thoughtful and systematic use of an appropriate multimodality imaging strategy is clinically relevant to detect cardiac injury and distinguish myocardial infarction from, myocarditis, takotsubo syndrome and pulmonary embolism.
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http://dx.doi.org/10.1016/j.tcm.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553143PMC
January 2021

High TARC plasma levels confer protection to long living individuals by inducing M2 profile.

Cytokine 2021 01 29;137:155305. Epub 2020 Sep 29.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Via Salvatore Allende, 84081 Baronissi, Salerno, Italy. Electronic address:

A way to delay aging and the related low-grade chronic inflammatory state is to study the model of positive physiology such as the Long-Living Individuals (LLIs). Our recent studies have shown higher levels of the host defense BPI Fold-Containing Family B Member 4 (BPIFB4) protein in the LLIs' blood. Notably, BPIFB4 has been shown to influence monocytes typesetting and M2 anti-inflammatory phenotype (CD206+CD163++) macrophages skewing. According to the role of a complex cytokine milieu in guiding the macrophage polarization, here we found that circulating concentrations of thymus and activation regulated chemokine (TARC)/CCL17 and small-inducible cytokine B10 (IP-10)/CXCL10) cytokines, were additionally associated with the LLIs' state. In a differentiation process in vitro, the addition of LLIs' plasma to the cell culture medium, enhanced the ability of monocytes, either from LLIs or controls, to acquire a M2 phenotype. Interestingly, a neutralizing antibody against TARC blunted the M2 skewing effect of the LLIs' plasma. Collectively, these data indicate that exceptional longevity may associate with a peculiar anti-inflammatory myeloid profile responsible for improved reparative processes and reduced inflammatory status mediated in part by TARC and M2 generation.
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http://dx.doi.org/10.1016/j.cyto.2020.155305DOI Listing
January 2021

It is easy to see, but it is better to foresee: a case report on the favourable alliance between CardioMEMS and levosimendan.

Eur Heart J Case Rep 2020 Aug 30;4(4):1-5. Epub 2020 Jun 30.

Department of Medicine, Surgery and Dentistry, University of Salerno, Via Salvador Allende, 84081 Salerno, Italy.

Background: In the past years, different devices have been investigated to help in identifying early decompensation events in patients with heart failure (HF) and reduced ejection fraction (EF), reducing hospital admissions. In this report, we present the first patient experience with levosimendan infusion led by CardioMEMS.

Case Summary: A 68-year-old man with HF and reduced EF with more than 20 hospitalizations for exacerbation of HF was enrolled in our HF Clinic from October 2017. Echocardiogram showed a dilated left ventricle with severely reduced EF (29%) and increased pulmonary artery systolic pressure (40 mmHg). From October 2017 to May 2019, the patient went through numerous hospitalizations, despite optimal medical therapy; subsequently, was adopted a strategy of levosimendan infusions guided by CardioMEMS. Levosimendan infusions improved haemodynamic and pressure profiles. The patient was monitored daily by CardioMEMS, and from June to December 2019, he had only two hospitalizations scheduled for levosimendan infusion and none for HF exacerbation.

Discussion: Our case supports the combination of CardioMEMS and levosimendan for the optimal management of patients with advanced HF. These results further strengthen the development of a randomized clinical trial to demonstrate the clinical usefulness of this device in combination with the levosimendan infusion programme in advanced HF patients.
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http://dx.doi.org/10.1093/ehjcr/ytaa205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501887PMC
August 2020

Correlation of the two most frequent HLA haplotypes in the Italian population to the differential regional incidence of Covid-19.

J Transl Med 2020 09 15;18(1):352. Epub 2020 Sep 15.

Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Via Salvatore Allende, 84081, Baronissi, SA, Italy.

Background: Understanding how HLA polymorphisms may affect both susceptibility, course and severity of Covid-19 infection could help both at the clinical level to identify individuals at higher risk from the disease and at the epidemiological one to explain the differences in the epidemic trend among countries or even within a specific country. Covid-19 disease in Italy showed a peculiar geographical distribution from the northern most affected regions to the southern ones only slightly touched.

Methods: In this study we analysed the regional frequencies for the most common Italian haplotypes from the Italian Bone Marrow Donor Registry (HLA-A, -B, -C and -DRB1 at four-digit level). Then we performed Pearson correlation analyses among regional haplotypes estimated frequency in the population and Covid-19 incidence and mortality.

Results: In this study we found that the two most frequent HLA haplotypes in the Italian population, HLA-A*:01:01g-B*08:01 g-C*07:01g-DRB1*03:01g and HLA-A*02.01g-B*18.01g-C*07.01g-DRB1*11.04g, had a regional distribution overlapping that of Covid-19 and showed respectively a positive (suggestive of susceptibility) and negative (suggestive of protection) significant correlation with both Covid-19 incidence and mortality.

Conclusions: Based on these results, in order to define such HLA haplotypes as a factor effectively associated to the disease susceptibility, the creation of national networks that can collect patients' samples from all regions for HLA typing should be highly encouraged.
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http://dx.doi.org/10.1186/s12967-020-02515-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491019PMC
September 2020

Timing of national lockdown and mortality in COVID-19: The Italian experience.

Int J Infect Dis 2020 Nov 5;100:193-195. Epub 2020 Sep 5.

Department of Medicine, Surgery, and Dentistry, University of Salerno, Baronissi, Salerno, Italy.

Objective: To evaluate if the pandemic mitigation effects of lockdown in Italy have been influenced by the level of penetration of COVID-19 in Italian Regions at the onset of containment (March 9, 2020).

Methods: We collected data published day by daily from the first COVID-19 case until May 3, 2020, the end of lockdown, by Italy's Protezione Civile Department. Linear regression analyses were performed to evaluate possible correlations between the number of confirmed cases/100.000 residents and the number of new cases/100.000/day before lockdown, with the number of deaths/100.000 residents at sixty days, in each Italian region.

Results: We found a significant positive correlation between the number of confirmed cases before lockdown and mortality up to sixty days (p < 0.001; R = 0.57) as well as between the incidence rate of new cases per day and mortality up to sixty days (p < 0.001; R = 0.73). Regression coefficients indicated about two deaths up to sixty days for every new patient with confirmed COVID-19 before lockdown, and 37 deaths for every new infected subject per day until the lockdown decree of March 9, 2020.

Conclusions: Every new infected subject before lockdown counted on the death toll of the COVID-19 pandemic in Italy.
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http://dx.doi.org/10.1016/j.ijid.2020.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833935PMC
November 2020

Prevalence and Predictors of Out-of-Target LDL Cholesterol 1 to 3 Years After Myocardial Infarction. A Subanalysis From the EYESHOT Post-MI Registry.

J Cardiovasc Pharmacol Ther 2021 Mar 6;26(2):149-157. Epub 2020 Aug 6.

Division of Cardiology, A.O. San Camillo-Forlanini, Roma, Italy.

Background: There is an incomplete understanding of the prevalence and predictors of attainment of low-density lipoprotein cholesterol (LDL-C) goal after myocardial infarction (MI).

Aim: To evaluate the prevalence of achievement of LDL-C goal of 70 mg/dL, to identify the baseline features associated with suboptimal lipid control, and to assess the use of LDL-C-lowering drug therapies (LLT) beyond the first year after MI.

Methods: The EYESHOT Post-MI was a prospective, cross-sectional, Italian registry, which enrolled patients presenting to cardiologist 1 to 3 years after MI. In this retrospective post-hoc analysis, patients were categorized in 2 groups according to the achievement or not of the LDL-C goal of 70 mg/dL. Univariable and multivariable logistic regression analyses were performed to identify the baseline features associate with LDL-C≥70 mg/dL.

Results: The study population included 903 patients (mean age 65.5 ± 11.5 years). Among them, LDL-C was ≥70 mg/dL in 474 (52.5%). Male sex ( = 0.031), hypertension ( = 0.024), prior percutaneous coronary intervention ( = 0.016) and high education level ( = 0.008) were higher in the LDL-C <70 group. At multivariable analysis, low education level was an independent predictor of LDL-C≥70 mg/dL (OR:1.582; 95%CI, 1.156-2.165; = 0.004). Conversely, hypertension increased the probability to achieve the LDL-C goal (OR:0.650; 95%CI, 0.443-0.954; = 0.028). Among off-target patients, LLT was not modified in the majority of cases (67.3%), intensified in 85 (18.6%), and actually reduced in 63 patients (13.8%).

Conclusions: In patients presenting to cardiologists 1 to 3 years from the last MI event, LDL-C is not under control in a large proportion of patients, particularly in those with a low education level or without hypertension. LLT is underused in this very-high-risk setting.
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http://dx.doi.org/10.1177/1074248420947633DOI Listing
March 2021

The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum-microglia crosstalk preventing disease progression in a mouse model of Huntington's disease.

Cell Death Dis 2020 07 18;11(7):546. Epub 2020 Jul 18.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081, Baronissi, Italy.

The longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been found significantly enriched in long-living individuals. Neuroinflammation is a key player in Huntington's disease (HD), a neurodegenerative disorder caused by neural death due to expanded CAG repeats encoding a long polyglutamine tract in the huntingtin protein (Htt). Herein, we showed that striatal-derived cell lines with expanded Htt (STHdh Q) expressed and secreted lower levels of BPIFB4, when compared with Htt expressing cells (STHdh Q), which correlated with a defective stress response to proteasome inhibition. Overexpression of LAV-BPIFB4 in STHdh Q cells was able to rescue both the BPIFB4 secretory profile and the proliferative/survival response. According to a well-established immunomodulatory role of LAV-BPIFB4, conditioned media from LAV-BPIFB4-overexpressing STHdh Q111 cells were able to educate Immortalized Human Microglia-SV40 microglial cells. While STHdh Q dying cells were ineffective to induce a CD163 + IL-10 pro-resolving microglia compared to normal STHdh Q, LAV-BPIFB4 transduction promptly restored the central immune control through a mechanism involving the stromal cell-derived factor-1. In line with the in vitro results, adeno-associated viral-mediated administration of LAV-BPIFB4 exerted a CXCR4-dependent neuroprotective action in vivo in the R6/2 HD mouse model by preventing important hallmarks of the disease including motor dysfunction, body weight loss, and mutant huntingtin protein aggregation. In this view, LAV-BPIFB4, due to its pleiotropic ability in both immune compartment and cellular homeostasis, may represent a candidate for developing new treatment for HD.
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http://dx.doi.org/10.1038/s41419-020-02754-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368858PMC
July 2020

Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study.

Front Pharmacol 2020 5;11:857. Epub 2020 Jun 5.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana" University of Salerno, Baronissi, Italy.

To date, there are no specific therapeutic strategies for treatment of COVID-19. Based on the hypothesis that complement and coagulation cascades are activated by viral infection, and might trigger an acute respiratory distress syndrome (ARDS), we report clinical outcomes of 17 consecutive cases of SARS-CoV-2-related ARDS treated (N = 7) with the novel combination of ruxolitinib, a JAK1/2 inhibitor, 10 mg/twice daily for 14 days and eculizumab, an anti-C5a complement monoclonal antibody, 900 mg IV/weekly for a maximum of three weeks, or with the best available therapy (N = 10). Patients treated with the combination showed significant improvements in respiratory symptoms and radiographic pulmonary lesions and decrease in circulating D-dimer levels compared to the best available therapy group. Our results support the use of combined ruxolitinib and eculizumab for treatment of severe SARS-CoV-2-related ARDS by simultaneously turning off abnormal innate and adaptive immune responses.
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http://dx.doi.org/10.3389/fphar.2020.00857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291857PMC
June 2020

Circulating BPIFB4 Levels Associate With and Influence the Abundance of Reparative Monocytes and Macrophages in Long Living Individuals.

Front Immunol 2020 29;11:1034. Epub 2020 May 29.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.

Long-Living Individuals (LLIs) delay aging and are less prone to chronic inflammatory reactions. Whether a distinct monocytes and macrophages repertoire is involved in such a characteristic remains unknown. Previous studies from our group have shown high levels of the host defense BPI Fold Containing Family B Member 4 (BPIFB4) protein in the peripheral blood of LLIs. Moreover, a polymorphic variant of the gene associated with exceptional longevity () confers protection from cardiovascular diseases underpinned by low-grade chronic inflammation, such as atherosclerosis. We hypothesize that BPIFB4 may influence monocytes pool and macrophages skewing, shifting the balance toward an anti-inflammatory phenotype. We profiled circulating monocytes in 52 LLIs (median-age 97) and 52 healthy volunteers (median-age 55) using flow cytometry. If the frequency of total monocyte did not change, the intermediate CD14++CD16+ monocytes counts were lower in LLIs compared to control adults. Conversely, non-classical CD14+CD16++ monocyte counts, which are M2 macrophage precursors with an immunomodulatory function, were found significantly associated with the LLIs' state. In a differentiation assay, supplementation of the LLIs' plasma enhanced the capacity of monocytes, either from LLIs or controls, to acquire a paracrine M2 phenotype. A neutralizing antibody against the phosphorylation site (ser 75) of BPIFB4 blunted the M2 skewing effect of the LLIs' plasma. These data indicate that LLIs carry a peculiar anti-inflammatory myeloid profile, which is associated with and possibly sustained by high circulating levels of BPIFB4. Supplementation of recombinant BPIFB4 may represent a novel means to attenuate inflammation-related conditions typical of unhealthy aging.
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http://dx.doi.org/10.3389/fimmu.2020.01034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272600PMC
April 2021
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