176 results on '"RENGO, GIUSEPPE"'
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2. Porphyromonas gingivalis virulence factors induce toxic effects in SH-SY5Y neuroblastoma cells: GRK5 modulation as a protective strategy.
- Author
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Liccardo D, Valletta A, Spagnuolo G, Vinciguerra C, Lauria MR, Perrotta A, Del Giudice C, De Luca F, Rengo G, Rengo S, Rengo C, and Cannavo A
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- Humans, Cell Line, Tumor, Gingipain Cysteine Endopeptidases metabolism, Neuroblastoma, Nitric Oxide Synthase Type II metabolism, Nitric Oxide Synthase Type II genetics, Phosphorylation, Signal Transduction, tau Proteins metabolism, Toll-Like Receptor 2 metabolism, Tumor Suppressor Protein p53 metabolism, G-Protein-Coupled Receptor Kinase 5 metabolism, G-Protein-Coupled Receptor Kinase 5 genetics, Lipopolysaccharides, Porphyromonas gingivalis pathogenicity, Virulence Factors metabolism, Virulence Factors genetics
- Abstract
Periodontitis (PDS) is a chronic inflammatory disease initiated by a dysbiosis of oral pathogenic bacterial species, such as Porphyromonas gingivalis (Pg). These bacteria can penetrate the bloodstream, releasing various endo and exotoxins that fuel the infection, and stimulate toxic inflammation in different compartments, including the brain. However, the specific mechanisms by which PDS/Pg contribute to brain disorders, such as Alzheimer's disease (AD), remain unclear. This study assessed the effects of Pg's virulence factors - lipopolysaccharide (LPS-Pg) and gingipains (gps) K (Kgp) and Rgp - on SH-SY5Y cells. Our results demonstrated that LPS-Pg activated signaling through the Toll-like receptor (TLR)-2/4 induced a significant downregulation of G protein-coupled receptor kinase 5 (GRK5). Additionally, LPS-Pg stimulation resulted in a robust increase in Tau phosphorylation (pTau) and p53 levels, while causing a marked reduction in Bcl2 and increased cell death compared to unstimulated cells (Ns). LPS-Pg also elevated inducible nitric oxide synthase (iNOS) expression, leading to oxidative damage. In cells overexpressing GRK5 via Adenovirus, LPS-Pg failed to increase iNOS and pTau levels compared to GFP control cells. High GRK5 levels also prevented the nuclear accumulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, the overexpression of a GRK5 mutant form lacking the nuclear localization signal (ΔNLS) nearly abolished LPS-Pg induced p53 and iNOS upregulation. Finally, we tested whether Kgp and Rgp mediated similar effects and our data showed that both gps caused a marked downregulation of GRK5 leading to increased p53 and pTau levels. In conclusion, this study provides further insight into the toxic effects elicited by Pg in cells and suggests that preventing GRK5 deficiency may be a valid strategy to mitigate Pg-induced toxic effects (i.e. cell death, oxidative damage, and Tau hyperphosphorylation) in SH-SY5Y cells, which are typical molecular hallmarks of neurodegenerative disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) more...
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- 2024
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3. Correction: Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.
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De Luca M, D'Assante R, Iacoviello M, Triggiani V, Rengo G, De Giorgi A, Limongelli G, Masarone D, Volterrani M, Mancini A, Passantino A, Perrone Filardi P, Sciacqua A, Vriz O, Castello R, Campo M, Lisco G, Modesti PA, Paolillo S, Suzuki T, Salzano A, Marra AM, Bossone E, and Cittadini A more...
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- 2024
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4. Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.
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De Luca M, D'Assante R, Iacoviello M, Triggiani V, Rengo G, De Giorgi A, Limongelli G, Masarone D, Volterrani M, Mancini A, Passantino A, Perrone Filardi P, Sciacqua A, Vriz O, Castello R, Campo M, Lisco G, Modesti PA, Paolillo S, Suzuki T, Salzano A, Marra AM, Bossone E, and Cittadini A more...
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- Humans, Male, Female, Aged, Prospective Studies, Middle Aged, Prognosis, Thyrotropin blood, Thyrotropin analysis, Aged, 80 and over, Hypothyroidism physiopathology, Hypothyroidism complications, Hypothyroidism epidemiology, Heart Failure physiopathology, Heart Failure mortality, Heart Failure complications, Registries statistics & numerical data
- Abstract
Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30 months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5 mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis., (© 2024. The Author(s).) more...
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- 2024
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5. Cognitive profile in burning mouth syndrome versus mild cognitive impairment: A comparative study.
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Femminella GD, Canfora F, Musella G, Di Tella GS, Ugga L, Pecoraro G, Leuci S, Coppola N, De Lucia N, Maldonato NM, Liguori S, Aria M, D'Aniello L, Rengo G, Mignogna MD, and Adamo D
- Abstract
Objectives: This study aims to assess and contrast cognitive and psychological aspects of patients with burning mouth syndrome (BMS-MCI) and geriatric patients (G-MCI) with mild cognitive impairment, focusing on potential predictors like pain, mood disorders, blood biomarkers, and age-related white matter changes (ARWMCs)., Methods: The study enrolled 40 BMS-MCI and 40 geriatric G-MCI, matching them by age, gender, and educational background. Participants underwent psychological, sleepiness, and cognitive assessment including the Mini-Mental State Exam (MMSE), Trail Making Test (TMT), Corsi Block-Tapping Task, Rey Auditory Verbal Learning Test, Copying Geometric Drawings Test, Frontal Assessment Battery, and Digit Cancellation Test., Results: G-MCI patients exhibited higher ARWMCs scores in right (p = 0.005**) and left (p < 0.001**) temporal regions, which may relate to specific neurodegenerative processes. Conversely, BMS-MCI patients showed higher levels of depression and anxiety and lower MMSE scores(p < 0.001**), also struggling more with tasks requiring processing speed and executive function, as evidenced by their higher TMT-A scores (p < 0.001**)., Conclusions: The study highlights particular deficits in global cognition and processing speed for BMS-MCI. The influence of educational background, pain levels, cholesterol, sleep disturbances, and anxiety on these cognitive assessments underscores the need for personalized therapeutic strategies addressing both cognitive and emotional aspects of MCI., (© 2024 The Author(s). Oral Diseases published by John Wiley & Sons Ltd.) more...
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- 2024
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6. Time to negative conversion and cardiopulmonary performance in athletes with COVID-19.
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Mone P, Bencivenga L, Santulli G, Rengo G, Guerra G, and Komici K
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Athletes with longer time to negative conversion for COVID-19 do not present reduction of exercise capacity. However, respiratory and ventilatory parameters are modified. https://bit.ly/3TMdrFL., Competing Interests: Conflicts of interest: The authors declare no conflict of interest., (Copyright ©The authors 2024.) more...
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- 2024
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7. Impact of optimized transcutaneous auricular vagus nerve stimulation on cardiac autonomic profile in healthy subjects and heart failure patients.
- Author
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Maestri R, Pinna GD, Robbi E, Cogliati C, Bartoli A, Gambino G, Rengo G, Montano N, and La Rovere MT
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- Humans, Middle Aged, Male, Female, Healthy Volunteers, Heart physiopathology, Single-Blind Method, Ear, Aged, Cross-Over Studies, Heart Failure physiopathology, Heart Failure therapy, Vagus Nerve Stimulation, Heart Rate physiology, Autonomic Nervous System physiopathology, Transcutaneous Electric Nerve Stimulation
- Abstract
Objective. To determine the optimal frequency and site of stimulation for transcutaneous vagus nerve stimulation (tVNS) to induce acute changes in the autonomic profile (heart rate (HR), heart rate variability (HRV)) in healthy subjects (HS) and patients with heart failure (HF). Approach. We designed three single-blind, randomized, cross-over studies: (1) to compare the acute effect of left tVNS at 25 Hz and 10 Hz ( n = 29, age 60 ± 7 years), (2) to compare the acute effect of left and right tVNS at the best frequency identified in study 1 ( n = 28 age 61 ± 7 years), and (3) to compare the acute effect of the identified optimal stimulation protocol with sham stimulation in HS and HF patients ( n = 30, age 59 ± 5 years, and n = 32, age 63 ± 7 years, respectively). Main results. In study 1, left tragus stimulation at 25 Hz was more effective than stimulation at 10 Hz in decreasing HR (-1.0 ± 1.2 bpm, p < 0.001 and -0.5 ± 1.6 bpm, respectively) and inducing vagal effects (significant increase in RMSSD, and HF power). In study 2, the HR reduction was greater with left than right tragus stimulation (-0.9 ± 1.5 bpm, p < 0.01 and -0.3 ± 1.4 bpm, respectively). In study 3 in HS, left tVNS at 25 Hz significantly reduced HR, whereas sham stimulation did not (-1.1 ± 1.2 bpm, p < 0.01 and -0.2 ± 2.9 bpm, respectively). In HF patients, both active and sham stimulation produced negligible effects. Significance. Left tVNS at 25 Hz is effective in acute modulation of cardiovascular autonomic control (HR, HRV) in HS but not in HF patients (NCT05789147)., (© 2024 Institute of Physics and Engineering in Medicine.) more...
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- 2024
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8. The relationship between muscle strength and epicardial fat in healthy adults.
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Komici K, Bencivenga L, Arganese C, Rengo G, and Guerra G
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- Humans, Adult, Aged, Middle Aged, Male, Female, Aged, 80 and over, Young Adult, Adolescent, Echocardiography, Body Composition physiology, Aging physiology, Muscle Strength physiology, Epicardial Adipose Tissue, Pericardium diagnostic imaging, Pericardium physiology, Hand Strength physiology, Adipose Tissue diagnostic imaging, Adipose Tissue physiology, Electric Impedance
- Abstract
Background: Muscular strength and muscle mass are considered key factors for healthy ageing. Modification of body composition and redistribution of adipose tissue has been described in advanced age. Muscle strength has an important predictive role for health outcomes. However, little is known regarding the relationship between muscle strength and epicardial fat., Methods and Materials: In a cohort of healthy adults following physical capacity evaluations, anthropometric measurements, handgrip strength (HGS), echocardiography and bioimpedance analysis (BIA) were performed. Kruskal-Wallis test, Spearman's correlation and regression analysis adjusted for confounders were applied., Results: A total population of 226 adults, age range 18-83 years, were included. Epicardial fat thickness resulted significantly associated with age p < 0.001, HGS (p < 0.001). Regression analysis adjusted for confounders revealed an independent relationship between handgrip strength and epicardial fat thickness: regression coefficient: -1.34; R2 = 0.27 and p = 0.044., Conclusions: The relationship between epicardial fat and muscle strength is inverse and independent. Implementation of HGS measurement may be useful for the identification of subjects with excessive epicardial fat and cardiovascular risk. Measurement of epicardial fat could be helpful in the early detection of physical decline associated to ageing., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...
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- 2024
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9. Frailty and Parkinson's disease: the role of diabetes mellitus.
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Komici K, Pansini A, Bencivenga L, Rengo G, Pagano G, and Guerra G
- Abstract
Parkinson's disease (PD) is a chronic neurodegenerative disease associated with a progressive loss of dopaminergic neurons, clinically characterized by motor and non-motor signs. Frailty is a clinical condition of increased vulnerability and negative health outcomes due to the loss of multiple physiological reserves. Chronic hyperglycemia and insulin resistance, which characterize diabetes mellitus (DM), have been reported to alter dopaminergic activity, increase the risk of PD, and influence the development of frailty. Even though diabetes may facilitate the development of frailty in patients with PD, this relationship is not established and a revision of the current knowledge is necessary. Furthermore, the synergy between DM, PD, and frailty may drive clinical complexity, worse outcomes, and under-representation of these populations in the research. In this review, we aimed to discuss the role of diabetes in the development of frailty among patients with PD. We summarized the clinical characteristics and outcomes of patients with concomitant DM, PD, and frailty. Finally, interventions to prevent frailty in this population are discussed., Competing Interests: GP is a full-time employee and a shareholder of F. Hoffmann-La Roche Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Komici, Pansini, Bencivenga, Rengo, Pagano and Guerra.) more...
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- 2024
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10. Impact of serum leptin and adiponectin levels on brain infarcts in patients with mild cognitive impairment and Alzheimer's disease: a longitudinal analysis.
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Carbone G, Bencivenga L, Santoro MA, De Lucia N, Palaia ME, Ercolano E, Scognamiglio F, Edison P, Ferrara N, Vitale DF, Rengo G, and Femminella GD
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- Humans, Male, Female, Aged, Longitudinal Studies, Aged, 80 and over, Magnetic Resonance Imaging, Case-Control Studies, Middle Aged, Adiponectin blood, Alzheimer Disease blood, Cognitive Dysfunction blood, Cognitive Dysfunction etiology, Leptin blood, Biomarkers blood, Brain Infarction blood, Brain Infarction diagnostic imaging, Brain Infarction complications
- Abstract
Introduction: The adipokines leptin and adiponectin have been associated with atherosclerosis and the risk of cerebral infarcts. Pre-clinical studies, however, suggest a protective role against ischemic brain damage. In this study we analyzed the relationship between serum leptin and adiponectin levels and the onset or progression of brain infarcts in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD)., Methods: All data were extracted from the ADNI database. The final population included 566 subjects, with 58 healthy controls, 396 MCI and 112 AD. All patients with available serum leptin and adiponectin levels at baseline were selected. Demographics, neuropsychological test results, CSF biomarkers, regional brain metabolism with FDG-PET data and the number of brain infarcts on longitudinal MRI scans were extracted., Results: Leptin levels were significantly lower in patients with MCI than controls at baseline, while adiponectin levels were not different between the groups. Multivariate logistic regression analysis at baseline for the presence of brain infarcts showed a predictive value for leptin but not for adiponectin. Multivariate longitudinal analysis showed that age was the only significant predictor of brain infarcts development at 15-year follow-up, while serum leptin and adiponectin levels did not play a role in this population., Discussion: The evidence on the pathogenetic or protective role of adipokines on ischemic brain damage is mixed. In this MCI and AD population, serum leptin and adiponectin were not associated with the development of brain infarcts; therefore, these results do not support the use of adipokines as biomarkers of cerebrovascular pathology in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision, (Copyright © 2024 Carbone, Bencivenga, Santoro, De Lucia, Palaia, Ercolano, Scognamiglio, Edison, Ferrara, Vitale, Rengo and Femminella.) more...
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- 2024
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11. Atrial Fibrillation and Dementia: Focus on Shared Pathophysiological Mechanisms and Therapeutic Implications.
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Carbone G, Ercolano E, Bencivenga L, Palaia ME, Scognamiglio F, Rengo G, and Femminella GD
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- Humans, Anti-Arrhythmia Agents, Cognition, Atrial Fibrillation drug therapy, Atrial Fibrillation epidemiology, Cognitive Dysfunction etiology, Dementia
- Abstract
Objectives: Atrial fibrillation (AF) and dementia are highly prevalent chronic and debilitating conditions, especially affecting the older population. This review focuses on possible common pathophysiological mechanisms that could explain the association between the 2 conditions., Design: Narrative review., Setting and Participants: Evidence from epidemiologic, observational, and interventional studies evaluating prevalence and incidence of cognitive impairment in patients with AF., Methods: Broad literature search between December 2022 and May 2023. Eligible categories for inclusion comprised interventional studies, observational studies, systematic reviews, and meta-analysis., Results: Evidence from different cohorts has shown that AF increases the risk of dementia, although the association with dementia subtypes is not always unequivocal. According to recent evidence, common pathophysiological mechanisms include thromboembolism and hypercoagulable states, proinflammatory state, infection, cerebral hypoperfusion, and brain atrophy. Moreover, we reviewed the evidence on therapeutic measures to prevent dementia in patients with AF., Conclusions and Implications: Screening for cognition in patients with AF is of paramount importance, given the shared risk factors and common pathophysiological mechanisms. More evidence is needed to clarify whether antiarrhythmic and anticoagulant therapy have an impact on cognitive outcomes in AF patients., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...
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- 2024
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12. Intricate relationship between obstructive sleep apnea and dementia in older adults.
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Ercolano E, Bencivenga L, Palaia ME, Carbone G, Scognamiglio F, Rengo G, and Femminella GD
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- Humans, Aged, Alzheimer Disease epidemiology, Alzheimer Disease complications, Sleep Apnea, Obstructive complications, Sleep Apnea, Obstructive epidemiology, Sleep Apnea Syndromes complications, Sleep Apnea Syndromes epidemiology, Cognitive Dysfunction epidemiology, Cognitive Dysfunction etiology, Cognition Disorders
- Abstract
Numerous evidence reports direct correlation between cognitive impairment, Alzheimer's disease and sleep disorders, in particular obstructive sleep apnea. Both obstructive sleep apnea and Alzheimer's disease are highly prevalent conditions whose incidence increases with age. Several studies demonstrate how sleep-disordered breathing may lead to poor cognition, even though the underlying mechanisms of this association remain partially unclear. According to the most recent studies, obstructive sleep apnea may be considered a modifiable risk factor for cognitive dysfunction. In the present review, the authors aim to integrate recent research examining obstructive sleep apnea and Alzheimer's disease biomarkers, also focusing on the mechanisms that support this correlation, including but not limited to the role of hypoxia and cardiovascular risk. Moreover, the potential favourable effect of obstructive sleep apnea therapy on cognitive function is discussed, to evaluate the benefits deriving from appropriate treatment of sleep-disordered breathing on cognition., (© 2023. The Author(s).) more...
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- 2024
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13. Cystic Fibrosis in Adults: A Paradigm of Frailty Syndrome? An Observational Study.
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Iacotucci P, Carnovale V, Ferrillo L, Somma J, Bocchino M, D'Ippolito M, Sanduzzi Zamparelli A, Rengo G, Ferrara N, Conti V, and Corbi G
- Abstract
This study aimed to assess the main clinical and anamnestic characteristics of adult Cystic Fibrosis (CF) patients and to evaluate the association of frailty with the CF genotyping classification. In an observational cross-sectional study, all ambulatory CF patients over 18 years old who received a diagnosis at the Regional Cystic Fibrosis Center for adults were enrolled and assessed by spirometry for respiratory function, by ADL and IADL for functional status, and by the Study of Osteoporotic Fractures (SOF) Index for frailty. The study population consisted of 139 CF patients (mean age 32.89 ± 10.94 years old, 46% women). Most of the subjects were robust (60.4%). The pre-frail/frail group was more frequently females ( p = 0.020), had a lower BMI ( p = 0.001), worse respiratory function, a higher number of pulmonary exacerbations/years, cycles of antibiotic therapy, and hospitalization (all p < 0.001) with respect to robust patients. The pre-frail/frail subjects used more drugs and were affected by more CF-related diseases (all p < 0.001). In relation to logistic regression, the best predictor of the pre-frail/frail status was a low FEV1 level. The CF patients show similarities to older pre-frail/frail subjects, suggesting that CF might be considered an early expression of this geriatric syndrome. This finding could help to better define the possible progression of CF, but overall, it could also suggest the usefulness employing of some tools used in the management and therapy of frailty subjects to identify the more severe CF subjects. more...
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- 2024
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14. Biomarkers of aging in frailty and age-associated disorders: State of the art and future perspective.
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Salvioli S, Basile MS, Bencivenga L, Carrino S, Conte M, Damanti S, De Lorenzo R, Fiorenzato E, Gialluisi A, Ingannato A, Antonini A, Baldini N, Capri M, Cenci S, Iacoviello L, Nacmias B, Olivieri F, Rengo G, Querini PR, and Lattanzio F more...
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- Humans, Artificial Intelligence, Aging metabolism, Biomarkers metabolism, Inflammation metabolism, Frailty diagnosis
- Abstract
According to the Geroscience concept that organismal aging and age-associated diseases share the same basic molecular mechanisms, the identification of biomarkers of age that can efficiently classify people as biologically older (or younger) than their chronological (i.e. calendar) age is becoming of paramount importance. These people will be in fact at higher (or lower) risk for many different age-associated diseases, including cardiovascular diseases, neurodegeneration, cancer, etc. In turn, patients suffering from these diseases are biologically older than healthy age-matched individuals. Many biomarkers that correlate with age have been described so far. The aim of the present review is to discuss the usefulness of some of these biomarkers (especially soluble, circulating ones) in order to identify frail patients, possibly before the appearance of clinical symptoms, as well as patients at risk for age-associated diseases. An overview of selected biomarkers will be discussed in this regard, in particular we will focus on biomarkers related to metabolic stress response, inflammation, and cell death (in particular in neurodegeneration), all phenomena connected to inflammaging (chronic, low-grade, age-associated inflammation). In the second part of the review, next-generation markers such as extracellular vesicles and their cargos, epigenetic markers and gut microbiota composition, will be discussed. Since recent progresses in omics techniques have allowed an exponential increase in the production of laboratory data also in the field of biomarkers of age, making it difficult to extract biological meaning from the huge mass of available data, Artificial Intelligence (AI) approaches will be discussed as an increasingly important strategy for extracting knowledge from raw data and providing practitioners with actionable information to treat patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2023
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15. Neuropsychiatric symptoms and their neural correlates in individuals with mild cognitive impairment.
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De Lucia N, Carbone G, Muzii B, Ferrara N, Rengo G, Maldonato NM, and Femminella GD
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- Humans, Executive Function, Neuropsychological Tests, Alzheimer Disease psychology, Cognitive Dysfunction diagnosis, Sleep Wake Disorders complications
- Abstract
Objectives: Neuropsychiatric symptoms are common in subjects with MCI and associated with higher risk of progression to AD. The cognitive and neuroanatomical correlates of neuropsychiatric symptoms in MCI have not been fully elucidated. In this study, we sought to evaluate the association between neuropsychiatric symptoms, cognitive function, regional tau deposition, and brain volumes in MCI subjects., Methods: A total of 233 MCI and 305 healthy comparisons were selected from the ADNI-3 cohort. All the subjects underwent a comprehensive neuropsychological assessment, volumetric MR brain scan, and Flortaucipir PET for in vivo assessment of regional tau deposition. Prevalence of neuropsychiatric symptoms was evaluated by means of the NPI questionnaire. Multivariate analyses of variance were used to detect differences in cognitive and imaging markers in MCI subjects with and without neuropsychiatric symptoms., Results: 61.4% MCI subjects showed at least one neuropsychiatric symptom, with the most prevalent ones being depression (26.1%), irritability (23.6%), and sleep disturbances (23.6%). There was a significant effect of neuropsychiatric symptoms on cognitive tests of frontal and executive functions. MCI subjects with neuropsychiatric symptoms showed reduced brain volumes in the orbitofrontal and posterior cingulate cortices, while no effects were detected on regional tau deposition. Posterior cingulate cortex volume was the only predictor of global neuropsychiatric burden in this MCI population., Conclusions: Neuropsychiatric symptoms occur early in the AD trajectory and are mainly related to defects of control executive abilities and to the reduction of gray matter volume in the orbitofrontal and posterior cingulate cortices. A better understanding of the cognitive and neuroanatomical mechanisms of neuropsychiatric symptoms in MCI could help develop more targeted and efficacious treatment alternatives. more...
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- 2023
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16. Ventilatory efficiency in post-COVID-19 athletes.
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Komici K, Bencivenga L, Rengo G, Bianco A, and Guerra G
- Subjects
- Humans, Carbon Dioxide, SARS-CoV-2, Athletes, Echocardiography, COVID-19
- Abstract
Limitation in exercise capacity has not been described in athletes affected by SARS-CoV-2 infection. However, patients who have recovered from COVID-19 without cardiopulmonary impairment show exaggerated ventilatory response during exercise. Therefore, we aimed to evaluate the ventilatory efficiency (VEf) in competitive athletes recovered from COVID-19 and to characterize the ventilation versus carbon dioxide relationship (VE/VCO
2 ) slope in this population. Thirty-seven competitive athletes with COVID-19 were recruited for this study. All participants underwent spirometry, echocardiography, and cardiopulmonary exercise testing (CPET). z-FVC values and end-title pressure of CO2 (PET CO2 ) were lower in the third tertile compared with the first tertile: -0.753 ± 0.473 vs. 0.037 ± 0.911, p = 0.05; 42.2 ± 2.7 vs. 37.1 ± 2.5 mmHg, p < 0.01. VE/VCO2 slope was significantly correlated to maximal VCO2 /VE and maximal VO2 /VE: coefficient = -0.5 R2 = 0.58, p < 0.0001 and coefficient = -0.3 R2 = 0.16, p = 0.008. Competitive athletes affected by SARS-CoV-2 infection, without cardio-respiratory disease sequel, may present ventilatory inefficiency (ViE), without exercise capacity limitation. FVC is higher in athletes with better ventilatory performance during exercise, and increased VE/VCO2 slope is inversely correlated to max VCO2 /VE and max VO2 /VE., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.) more...- Published
- 2023
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17. Identification of Drugs Acting as Perpetrators in Common Drug Interactions in a Cohort of Geriatric Patients from Southern Italy and Analysis of the Gene Polymorphisms That Affect Their Interacting Potential.
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Cataldi M, Celentano C, Bencivenga L, Arcopinto M, Resnati C, Manes A, Dodani L, Comnes L, Vander Stichele R, Kalra D, Rengo G, Giallauria F, Trama U, Ferrara N, Cittadini A, and Taglialatela M
- Abstract
Background: Pharmacogenomic factors affect the susceptibility to drug-drug interactions (DDI). We identified drug interaction perpetrators among the drugs prescribed to a cohort of 290 older adults and analysed the prevalence of gene polymorphisms that can increase their interacting potential. We also pinpointed clinical decision support systems (CDSSs) that incorporate pharmacogenomic factors in DDI risk evaluation., Methods: Perpetrator drugs were identified using the Drug Interactions Flockhart Table, the DRUGBANK website, and the Mayo Clinic Pharmacogenomics Association Table. Allelic variants affecting their activity were identified with the PharmVar, PharmGKB, dbSNP, ensembl and 1000 genome databases., Results: Amiodarone, amlodipine, atorvastatin, digoxin, esomperazole, omeprazole, pantoprazole, simvastatin and rosuvastatin were perpetrator drugs prescribed to >5% of our patients. Few allelic variants affecting their perpetrator activity showed a prevalence >2% in the European population: CYP3A4/5*22, *1G, *3, CYP2C9*2 and *3, CYP2C19*17 and *2, CYP2D6*4, *41, *5, *10 and *9 and SLC1B1*15 and *5. Few commercial CDSS include pharmacogenomic factors in DDI-risk evaluation and none of them was designed for use in older adults., Conclusions: We provided a list of the allelic variants influencing the activity of drug perpetrators in older adults which should be included in pharmacogenomics-oriented CDSSs to be used in geriatric medicine. more...
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- 2023
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18. Pharmacological treatment of type 2 diabetes in elderly patients with heart failure: randomized trials and beyond.
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Sciacqua A, Succurro E, Armentaro G, Miceli S, Pastori D, Rengo G, and Sesti G
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- Humans, Aged, Quality of Life, Randomized Controlled Trials as Topic, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Heart Failure complications, Heart Failure drug therapy, Dipeptidyl-Peptidase IV Inhibitors therapeutic use, Hypoglycemia, Cardiovascular Diseases drug therapy
- Abstract
Heart failure (HF) and type 2 diabetes mellitus (T2DM) represent two important public health problems, and despite improvements in the management of both diseases, they are responsible for high rates of hospitalizations and mortality. T2DM accelerates physiological cardiac aging through hyperglycemia and hyperinsulinemia. Thus, HF and T2DM are chronic diseases widely represented in elderly people who often are affected by numerous comorbidities with important functional limitations making it difficult to apply the current guidelines. Several antidiabetic drugs should be used with caution in elderly individuals with T2DM. For instance, sulfonylureas should be avoided due to the risk of hypoglycemia associated with its use. Insulin should be used with caution because it is associated with higher risk of hypoglycemia, and may determine fluid retention which can lead to worsening of HF. Thiazolindinediones should be avoided due to the increased risk of fluid retention and HF. Biguanides may lead to a slightly increased risk of lactic acidosis in particular in elderly individuals with impaired renal function. Dipeptidyl peptidase 4 (DPP-4) inhibitors are safe having few side effects, minimal risk of hypoglycemia, and a neutral effect on cardiovascular (CV) outcome, even if it has been reported that saxagliptin treatment is associated with increased risk of hospitalizations for HF (hHF). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a CV protection without a significant reduction in hHF. On the other hand, sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown a significant improvement in CV outcome, with a strong reduction of hHF and a positive impact on renal damage progression. However, it is necessary to consider the possible some side effects related to their use in elderly individuals including hypotension, bone fractures, and ketoacidosis.It is important to remark that elderly patients, in particular the very elderly, are not sufficiently represented in the trials; thus, the management and treatment of elderly diabetic patients with HF should be mainly based on the integration of scientific evidence with clinical judgment and patients' condition, with respect to the dignity and quality of life., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...
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- 2023
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19. β3AR-Dependent Brain-Derived Neurotrophic Factor (BDNF) Generation Limits Chronic Postischemic Heart Failure.
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Cannavo A, Jun S, Rengo G, Marzano F, Agrimi J, Liccardo D, Elia A, Keceli G, Altobelli GG, Marcucci L, Megighian A, Gao E, Feng N, Kammers K, Ferrara N, Finos L, Koch WJ, and Paolocci N
- Subjects
- Rats, Mice, Humans, Animals, Brain-Derived Neurotrophic Factor metabolism, Endothelial Cells metabolism, Myocytes, Cardiac metabolism, Receptors, Adrenergic, beta metabolism, Neuroblastoma metabolism, Heart Failure etiology, Heart Failure metabolism, Myocardial Ischemia metabolism, Ventricular Dysfunction, Left metabolism
- Abstract
Background: Loss of brain-derived neurotrophic factor (BDNF)/TrkB (tropomyosin kinase receptor B) signaling accounts for brain and cardiac disorders. In neurons, β-adrenergic receptor stimulation enhances local BDNF expression. It is unclear if this occurs in a pathophysiological relevant manner in the heart, especially in the β-adrenergic receptor-desensitized postischemic myocardium. Nor is it fully understood whether and how TrkB agonists counter chronic postischemic left ventricle (LV) decompensation, a significant unmet clinical milestone., Methods: We conducted in vitro studies using neonatal rat and adult murine cardiomyocytes, SH-SY5Y neuronal cells, and umbilical vein endothelial cells. We assessed myocardial ischemia (MI) impact in wild type, β3AR knockout, or myocyte-selective BDNF knockout (myoBDNF KO) mice in vivo (via coronary ligation [MI]) or in isolated hearts with global ischemia-reperfusion (I/R)., Results: In wild type hearts, BDNF levels rose early after MI (<24 hours), plummeting at 4 weeks when LV dysfunction, adrenergic denervation, and impaired angiogenesis ensued. The TrkB agonist, LM22A-4, countered all these adverse effects. Compared with wild type, isolated myoBDNF KO hearts displayed worse infarct size/LV dysfunction after I/R injury and modest benefits from LM22A-4. In vitro, LM22A-4 promoted neurite outgrowth and neovascularization, boosting myocyte function, effects reproduced by 7,8-dihydroxyflavone, a chemically unrelated TrkB agonist. Superfusing myocytes with the β3AR-agonist, BRL-37344, increased myocyte BDNF content, while β3AR signaling underscored BDNF generation/protection in post-MI hearts. Accordingly, the β1AR blocker, metoprolol, via upregulated β3ARs, improved chronic post-MI LV dysfunction, enriching the myocardium with BDNF. Last, BRL-37344-imparted benefits were nearly abolished in isolated I/R injured myoBDNF KO hearts., Conclusions: BDNF loss underscores chronic postischemic heart failure. TrkB agonists can improve ischemic LV dysfunction via replenished myocardial BDNF content. Direct cardiac β3AR stimulation, or β-blockers (via upregulated β3AR), is another BDNF-based means to fend off chronic postischemic heart failure. more...
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- 2023
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20. Cardiac sympathetic innervation and mortality risk scores in patients with heart failure.
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Bencivenga L, Komici K, Paolillo S, Nappi C, Gargiulo P, Assante R, Gambino G, Santillo F, Femminella GD, Corbi GM, Ferrara N, Cuocolo A, Perrone-Filardi P, and Rengo G
- Subjects
- Humans, Radiopharmaceuticals, Prospective Studies, Heart diagnostic imaging, Risk Factors, Adrenergic Agents, 3-Iodobenzylguanidine, Heart Failure diagnostic imaging, Heart Failure therapy
- Abstract
Introduction: In the risk stratification and selection of patients with heart failure (HF) eligible for implantable cardioverter-defibrillator (ICD) therapy,
123 I-meta-IodineBenzylGuanidine (123 I-mIBG) scintigraphy has emerged as an effective non-invasive method to assess cardiac adrenergic innervation. Similarly, clinical risk scores have been proposed to identify patients with HF at risk of all-cause mortality, for whom the net clinical benefit of device implantation would presumably be lower. Nevertheless, the association between the two classes of tools, one suggestive of arrhythmic risk, the other of all-cause mortality, needs further investigation., Objective: To test the relationship between the risk scores for predicting mortality and cardiac sympathetic innervation, assessed through myocardial123 I-mIBG imaging, in a population of patients with HF., Methods: In HF patients undergoing123 I-mIBG scintigraphy, eight risk stratification models were assessed: AAACC, FADES, MADIT, MADIT-ICD non-arrhythmic mortality score, PACE, Parkash, SHOCKED and Sjoblom. Cardiac adrenergic impairment was assessed by late heart-to-mediastinum ratio (H/M) <1.6., Results: Among 269 patients suffering from HF, late H/M showed significant negative correlation with all the predicting models, although generally weak, ranging from -0.15 (p = .013) for PACE to -0.32 (p < .001) for FADES. The scores showed poor discrimination for cardiac innervation, with areas under the curve (AUC) ranging from 0.546 for Parkash to 0.621 for FADES., Conclusion: A weak association emerged among mortality risk scores and cardiac innervation, suggesting to integrate in clinical practice tools indicative of both arrhythmic and general mortality risks, when evaluating patients affected by HF eligible for device implantation., (© 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.) more...- Published
- 2023
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21. Testosterone deficiency independently predicts mortality in women with HFrEF: insights from the T.O.S.CA. registry.
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Marra AM, D'Assante R, Salzano A, Iacoviello M, Triggiani V, Rengo G, Limongelli G, Masarone D, Perticone M, Cimellaro A, Perrone Filardi P, Paolillo S, Gargiulo P, Mancini A, Volterrani M, Vriz O, Castello R, Passantino A, Campo M, Modesti PA, De Giorgi A, Arcopinto M, D'Agostino A, Raparelli V, Isidori AM, Valente V, Giardino F, Crisci G, Sciacqua A, Savoia M, Suzuki T, Bossone E, and Cittadini A more...
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- Humans, Female, Stroke Volume, Prospective Studies, Registries, Testosterone, Heart Failure, Hypertension, Pulmonary, Ventricular Dysfunction, Left
- Abstract
Aims: Testosterone deficiency (TD) is associated with increased morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). However, data in women are scanty. The aim of this study was to investigate the prognostic impact of TD on women with HFrEF., Methods: Among 480 patients prospectively enrolled in the T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, a prospective, multicentre, nationwide, observational study, 94 women were included in the current analysis. The TD was defined as serum testosterone levels lower than 25 ng/dl. Data regarding clinical status, echocardiography, exercise performance, cardiovascular hospitalization, and survival after an average follow-up of 36 months were analysed., Results: Thirty patients (31.9%) displayed TD. TD was associated with lower tricuspid annular plane excursion (TAPSE) to pulmonary arterial systolic pressure PASP ratio (TAPSE/PASP) (P = 0.008), peak oxygen consumption (VO
2 peak) (P = 0.03) and estimated glomerular filtration rate (P < 0.001). TD was an independent predictor of the combined endpoint of all-cause mortality/cardiovascular hospitalization (HR: 10.45; 95% CI: 3.54-17.01; P = 0.001), all-cause mortality (HR: 8.33; 95%: 5.36-15.11; P = 0.039), and cardiovascular hospitalization (HR: 2.41; 95% CI: 1.13-4.50; P = 0.02)., Conclusions: One-third of women with HFrEF displays TD that impacts remarkably on their morbidity and mortality. TD is associated with a worse clinical profile including exercise capacity, right ventricular-pulmonary arterial coupling, and renal function. These findings lend support to an accurate profiling of women with HF, a problem often overlooked in clinical trials., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.) more...- Published
- 2023
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22. Angiopoietins, vascular endothelial growth factors and secretory phospholipase A 2 in heart failure patients with preserved ejection fraction.
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Varricchi G, Poto R, Ferrara AL, Gambino G, Marone G, Rengo G, Loffredo S, and Bencivenga L
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- Humans, Stroke Volume, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor D, Vascular Endothelial Growth Factor C, Angiopoietins, Endothelial Cells, Prognosis, Phospholipases, Heart Failure, Phospholipases A2, Secretory
- Abstract
Background: Heart failure (HF) is a growing public health burden, with high prevalence and mortality rates. A proportion of patients with HF have a normal ventricular ejection fraction (EF), referred to as HF with preserved EF (HFpEF), as opposed to patients with HF with reduced ejection fraction (HFrEF). HFpEF currently accounts for about 50% of all HF patients, and its prevalence is rising. Angiopoietins (ANGPTs), vascular endothelial growth factors (VEGFs) and secretory phospholipases A
2 (sPLA2 s) are proinflammatory mediators and key regulators of endothelial cells., Methods: The aim of this study was to analyze the plasma concentrations of angiogenic (ANGPT1, ANGPT2, VEGF-A) and lymphangiogenic (VEGF-C, VEGF-D) factors and the plasma activity of sPLA2 in patients with HFpEF and HFrEF compared to healthy controls., Results: The concentration of ANGPT1 was reduced in HFrEF compared to HFpEF patients and healthy controls. ANGPT2 levels were increased in both HFrEF and HFpEF subjects compared to controls. The ANGPT2/ANGPT1 ratio was increased in HFrEF patients compared to controls. The concentrations of both VEGF-A and VEGF-C did not differ among the three groups examined. VEGF-D was increased in both HFrEF and HFpEF patients compared to controls. Plasma activity of sPLA2 was increased in HFrEF but not in HFpEF patients compared to controls., Conclusions: Our results indicate that three different classes of proinflammatory regulators of vascular permeability and smoldering inflammation are selectively altered in HFrEF or HFpEF patients. Studies involving larger cohorts of these patients will be necessary to demonstrate the clinical implications of our findings., Competing Interests: Declaration of Competing Interest All authors declare they have no conflict of interest., (Copyright © 2022 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.) more...- Published
- 2022
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23. Role of frailty on cardiac rehabilitation in hospitalized older patients.
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Bencivenga L, Femminella GD, Ambrosino P, Bosco Q, De Lucia C, Perrotta G, Formisano R, Komici K, Vitale DF, Ferrara N, Maniscalco M, Cacciatore F, Papa A, and Rengo G
- Subjects
- Humans, Aged, Male, Geriatric Assessment, Hospitalization, Syndrome, Cardiac Rehabilitation, Frailty, Coronary Artery Disease
- Abstract
Background: Cardiovascular diseases are the leading cause of mortality, morbidity, and disability in the world, especially in the older adults. A relevant proportion of patients admitted to Cardiac Rehabilitation (CR) may suffer from frailty, a complex geriatric syndrome with multifactorial aetiology., Aims: The hypothesis underlying the study is that frailty complicates the management of older patients undergoing CR. The main objective is, therefore, to determine the relationship between frailty and CR outcomes in hospitalized older adults., Methods: The participants have been recruited among patients aged ≥ 65 years admitted at the hospital for CR. A Comprehensive Geriatric Assessment (CGA)-based Frailty Index (FI) was created following a standard procedure. The outcome was measured as the ratio between 6-min walk test (6MWT) distance at the end of CR and normal predicted values for a healthy adult of same age and gender, according to reference equations., Results: The study population consisted of 559 elderly patients, 387 males (69.2%), with age of 72 (69-76) years. The most frequent diagnosis at admission was ischaemic heart disease (231, 41.5%) and overall 6MWT ratio was 0.62 ± 0.21. At the multivariable regression analysis, gender, diagnosis and FI were significantly and independently associated with 6MWT ratio (p ≤ 0.0001, p ≤ 0.001 and p ≤ 0.0001, respectively), while no significant association emerged for age., Conclusion: FI resulted independently correlated to 6MWT ratio in a population of older patients undergoing in-hospital CR programs. Frailty is a multifactorial geriatric syndrome whose assessment is essential for prognostic evaluation of older patients, also in CR clinical setting., (© 2022. The Author(s).) more...
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- 2022
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24. Impact of Body Composition Parameters on Lung Function in Athletes.
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Komici K, D'Amico F, Verderosa S, Piomboni I, D'Addona C, Picerno V, Bianco A, Caiazzo A, Bencivenga L, Rengo G, and Guerra G
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- Adult, Athletes, Body Mass Index, Female, Forced Expiratory Volume, Humans, Male, Retrospective Studies, Spirometry, Vital Capacity, Body Composition physiology, Lung physiology
- Abstract
Background: Given the potential risk of unhealthy weight management, the monitoring of body composition in athletes is advised. However, limited data reveal how body composition measurements can benefit athlete health and, in particular, respiratory function. The aim of this study is to evaluate the impact of body composition on pulmonary function in a population of adult athletes. Methods: Data from 435 competitive adult athletes regarding body compositions parameters and spirometry are retrospectively analyzed. Results: Our study population consists of 335 males and 100 female athletes. Muscle mass and fat-free mass are significantly and positively associated with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in the male and female population, while waist-to-height ratio is negatively associated with FEV1, FVC, and FEV1/FVC in the male population. In multivariable analysis, muscle mass and fat-free mass show significant association with FEV1 and FVC in both males and females (p < 0.05), and waist-to-height ratio is significantly and inversely associated with FEV1 and FVC in males (p < 0.05). Conclusions: Fat-free mass and muscle mass are positively and independently associated with FEV1 and FVC in athletes of both genders, and waist-to-height ratio is inversely associated with FEV1 and FVC only among male athletes. These findings suggest that body composition in athletes may be helpful in monitoring respiratory function. more...
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- 2022
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25. Serum galectin-3 and aldosterone: potential biomarkers of cardiac complications in patients with COVID-19.
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Cannavo A, Liccardo D, Gelzo M, Amato F, Gentile I, Pinchera B, Femminella GD, Parrella R, DE Rosa A, Gambino G, Marzano F, Ferrara N, Paolocci N, Rengo G, and Castaldo G
- Subjects
- Actins, Aldosterone, Biomarkers, Fibrosis, Humans, SARS-CoV-2, Troponin I, COVID-19 complications, Galectin 3
- Abstract
Background: Despite severe acute respiratory syndrome (SARS)-Coronavirus (CoV-2) primarily targeting the lungs, the heart represents another critical virus target. Thus, the identification of SARS-CoV-2 disease of 2019 (COVID-19)-associated biomarkers would be beneficial to stratify prognosis and the risk of developing cardiac complications. Aldosterone and galectin-3 promote fibrosis and inflammation and are considered a prognostic biomarker of lung and adverse cardiac remodeling. Here, we tested whether galectin-3 and aldosterone levels can predict adverse cardiac outcomes in COVID-19 patients., Methods: To this aim, we assessed galectin-3 and aldosterone serum levels in 51 patients diagnosed with COVID-19, using a population of 19 healthy subjects as controls. In in-vitro studies, we employed 3T3 fibroblasts to assess the potential roles of aldosterone and galectin-3 in fibroblast activation., Results: Serum galectin-3 levels were more elevated in COVID-19 patients than healthy controls and correlated with COVID-19 severity classification and cardiac troponin-I (cTnI) serum levels. Furthermore, we observed an augmented secretion of aldosterone in COVID-19 patients. This adrenal hormone is a direct stimulator of galectin-3 secretion; therefore, we surmised that this axis could perpetrate fibrosis and adverse remodeling in these subjects. Thus, we stimulated fibroblasts with 10% of serum from COVID-19 patients. This challenge markedly rose the expression of smooth muscle alpha (α)-2 actin (ACTA2), a myofibroblast marker., Conclusions: Our study suggests that COVID-19 can affect cardiac structure and function by triggering aldosterone and galectin-3 release that may serve as prognostic and therapeutic biomarkers while monitoring the course of cardiac complications in patients suffering from COVID-19. more...
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- 2022
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26. Insulin-like growth factor-1 (IGF-1) as predictor of cardiovascular mortality in heart failure patients: data from the T.O.S.CA. registry.
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De Giorgi A, Marra AM, Iacoviello M, Triggiani V, Rengo G, Cacciatore F, Maiello C, Limongelli G, Masarone D, Perticone F, Filardi PP, Paolillo S, Mancini A, Volterrani M, Vriz O, Castello R, Passantino A, Campo M, Modesti PA, Salzano A, D'Assante R, Arcopinto M, Raparelli V, Fabbian F, Sciacqua A, Colao A, Suzuki T, Bossone E, and Cittadini A more...
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- Adult, Humans, Prognosis, Registries, Stroke Volume, Heart Failure, Insulin-Like Growth Factor I analysis, Kidney Diseases
- Abstract
Introduction: Data from the "Trattamento Ormonale nello Scompenso CArdiaco" (T.O.S.CA) registry showed that heart failure (HF) represents a complex clinical syndrome with different hormonal alterations. Renal failure represents a frequent complication in HF. We evaluated the relationship between renal function and insuline-like growth factor-1 (IGF-1) deficiency and its impact on cardiovascular mortality (CVM) in patients enrolled in the T.O.S.CA. registry., Methods: At the enrolment, all subjects underwent chemistry examinations, including circulating hormones and cardiovascular functional tests. COX regression analysis was used to evaluate factors related to CVM during the follow-up period in all populations, in high-risk patients and in the young-adult population. Also, we evaluate the effects of renal function on the CVM., Results: 337 patients (41 deceased) were analyzed. CVM was related to severe renal dysfunction (HR stages IV-V = 4.86), high-risk conditions (HR 2.25), serum IGF-1 (HR 0.42), and HF etiology (HR 5.85 and HR 1.63 for valvular and ischemic etiology, respectively). In high-risk patients, CVM was related to IGF-1 levels, severe renal dysfunction and valvular etiology, whereas in young patients CMV was related to the high-risk pattern and serum IGF-1 levels., Conclusions: Our study showed the clinical and prognostic utility of the IGF-1 assay in patients with HF., (© 2022. The Author(s).) more...
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- 2022
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27. Frailty in Patients With Lung Cancer: A Systematic Review and Meta-Analysis.
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Komici K, Bencivenga L, Navani N, D'Agnano V, Guerra G, Bianco A, Rengo G, and Perrotta F
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- Aged, Frail Elderly, Humans, Prevalence, Prognosis, Frailty epidemiology, Lung Neoplasms complications, Lung Neoplasms epidemiology
- Abstract
Background: Previous studies regarding the prevalence of frailty in patients with lung cancer and mortality in frail patients with lung cancer are inconsistent and require clarification., Research Question: What is the prevalence and impact of frailty in patients with lung cancer?, Study Design and Methods: This systematic review and meta-analysis used a combination of free-text terms and medical subject headings terms, according to the database requirements in MEDLINE/PubMed, Scopus, and Cochrane Library from inception until November 15, 2020., Results: A total of 2,571 articles were identified, and 16 articles involving 4,183 patients were included for study. The prevalence of frailty in lung cancer was 45% (95% CI, 28-61; I
2 = 99.5%; P < .0001). In patients with lung cancer, frailty was associated with an increased hazard ratio for mortality (hazard ratio, 3.01; 95% CI, 1.77-5.10; P < .001)., Interpretation: The prevalence of frailty in lung cancer is 45%, which has a significant negative impact on survival of patients with lung cancer. These results highlight the importance of measuring frailty, which provides important prognostic information, and may provide opportunities for interventions to improve outcomes in patients with lung cancer., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2022
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28. Editorial: Post COVID-19 physical performance and functional capacity.
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Komici K, Bencivenga L, and Rengo G
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2022
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29. Relationship between COVID-19 Mortality, Hospital Beds, and Primary Care by Italian Regions: A Lesson for the Future.
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Ferrara N, Campobasso CP, Cocozza S, Conti V, Davinelli S, Costantino M, Cannavo A, Rengo G, Filippelli A, and Corbi G
- Abstract
One of the characteristics of the SARS-CoV-2 infection in Italy is the significant regional difference in terms of lethality and mortality. These geographical variances were clear in the first wave and confirmed in the second one as well. The study aimed to analyze the correlation between regional differences in COVID-19 mortality and different regional care models, by retrospectively analyzing the association between the Italian COVID-19 deaths and the number of hospital beds, long-term care facilities, general practitioners (GPs), and the health expenditure per capita. The period considered was from 1 March 2020 to 1 March 2021. The number of hospital beds (p < 0.0001) and the number of GPs (p = 0.0094) significantly predicted the COVID-19 death rate. The Italian regions with a higher number of hospital beds and a lower number of GPs showed a higher number of deaths. Multivariate analyses confirmed the results. The Italian regions with a higher amount of centralized healthcare, as represented by the number of hospital beds, experienced a higher number of deaths, while the regions with greater community support, as exemplified by the number of the GPs, faced higher survival. These results suggest the need for a change in the current healthcare system organization. more...
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- 2022
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30. Muscle Ultrasound as Imaging Domain of Frailty.
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Bencivenga L, Picaro F, Ferrante L, Komici K, Ruggiero F, Sepe I, Gambino G, Femminella GD, Vitale DF, Ferrara N, Rengo C, and Rengo G
- Abstract
Introduction: Frailty is a geriatric syndrome, a clinical state of vulnerability for developing dependency and/or death. Due to its multidimensional nature, Comprehensive Geriatric Assessment (CGA) constitutes the best strategy to evaluate frailty in older patients. Accumulation of deficits model synthesizes the global assessment of geriatric domains in the Frailty Index (FI) score. Muscle Ultrasound (MUS) has been employed to evaluate muscle mass wasting as tool to assess sarcopenia in late life. The present study aims to evaluate the association between CGA-based FI and MUS measures in a population of hospitalized older adults., Methods: Patients aged ≥65 years underwent CGA for the evaluation of the domains of health and functional status, psycho-cognition, nutritional status, socio-environmental condition. Following standard procedure, a CGA-based FI was elaborated, taking into account 38 multidimensional items. Muscle thicknesses (MT) of rectus femoris plus vastus intermedius were measured through MUS axial cross-section. Multivariable regression analysis was employed to determine factors associated with FI., Results: The study population consisted of 136 older patients, 87 men (63.9%), with median age of 74 (70-81) years, FI of 0.3 (0.21-0.46), and MT of rectus femoris plus vastus intermedius 29.27 (23.08-35.7) mm. At multivariable regression analysis, FI resulted significantly and independently associated with age and MT., Conclusion: Muscle thicknesses of rectus femoris plus vastus intermedius, measured through MUS, resulted to be significantly related to FI in a population of hospitalized older patients. In the CGA-based assessment of frailty, MUS may constitute an additional imaging domain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bencivenga, Picaro, Ferrante, Komici, Ruggiero, Sepe, Gambino, Femminella, Vitale, Ferrara, Rengo and Rengo.) more...
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- 2022
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31. Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry.
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Salzano A, D'Assante R, Iacoviello M, Triggiani V, Rengo G, Cacciatore F, Maiello C, Limongelli G, Masarone D, Sciacqua A, Filardi PP, Mancini A, Volterrani M, Vriz O, Castello R, Passantino A, Campo M, Modesti PA, De Giorgi A, Arcopinto M, Gargiulo P, Perticone M, Colao A, Milano S, Garavaglia A, Napoli R, Suzuki T, Bossone E, Marra AM, and Cittadini A more...
- Subjects
- Exercise Test methods, Humans, Registries, Stroke Volume, Ventricular Function, Right, Diabetes Mellitus, Type 2 complications, Heart Failure, Insulins, Ventricular Dysfunction, Right diagnostic imaging, Ventricular Dysfunction, Right etiology
- Abstract
Background: Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance-IR or diabetes mellitus-T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF., Methods: Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D., Results: Compared with EU and IR, T2D was associated with increased filling pressures (E/e'ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO
2 ) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO2 in the T2D group (+ 13% increase in RV dimension, - 21% decline in TAPSE/PAPS ratio and - 20% decrease in peak VO2 )., Conclusion: The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis. Trial registration ClinicalTrials.gov identifier: NCT023358017., (© 2022. The Author(s).) more...- Published
- 2022
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32. Heart failure with preserved ejection fraction: Squaring the circle between comorbidities and cardiovascular abnormalities.
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Marra AM, Bencivenga L, D'Assante R, Rengo G, and Cittadini A
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- Comorbidity, Forecasting, Humans, Stroke Volume, Cardiovascular Abnormalities, Heart Failure
- Abstract
Heart Failure with preserved Ejection Fraction (HFpEF) is nowadays considered a major healthcare issue. According to forecasts two third of all Heart Failure patients will belong to this phenotype by year 2050, overwhelming those affected by Heart Failure with reduced Ejection Fraction (HFrEF). Both epidemiological and mechanistic studies support the concept that HFpEF represents true HF although aggravated by a collection of comorbidities. There is urgent need of improving its phenotyping due to the high degree of disease heterogeneity within HFpEF that lead to the failure of randomized clinical trials in demonstrating a remarkable impact of drugs in improving its morbidity and mortality., (Copyright © 2022. Published by Elsevier B.V.) more...
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- 2022
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33. Genetic Catalytic Inactivation of GRK5 Impairs Cardiac Function in Mice Via Dysregulated P53 Levels.
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Marzano F, Liccardo D, Elia A, Mucio I, de Lucia C, Lucchese AM, Gao E, Ferrara N, Rapacciuolo A, Paolocci N, Rengo G, Koch WJ, and Cannavo A
- Abstract
GRK5's catalytic activity in regulating basal and stressed cardiac function has not been studied. Herein, we studied knock-in mice in which GRK5 was mutated to render it catalytically inactive (K215R). At baseline, GRK5-K215R mice showed a marked decline in cardiac function with increased apoptosis and fibrosis. In vitro, restriction of GRK5 inside the nucleus of cardiomyocytes resulted in enhanced cell death along with higher p53 levels. Moreover, in fibroblasts, we demonstrated that K215R mutation promoted the transition into myofibroblast phenotype. This study provides novel insight into the biological actions of GRK5, that are essential for its future targeting., Competing Interests: This research was funded by Italian Ministry of Education, Universities and Research “Rita Levi Montalcini 2016” (to Dr Cannavo). The research was also supported by National Institutes of Health grant P01 HL174841 (to Dr Koch), and American Heart Association (Postdoctoral fellowship 17POST33660942 to Dr Lucia). Dr Marzano was supported by a research grant provided by the CardioPaTh PhD program and she was also supported by UniNA and Compagnia San Paolo, in the frame of Programme STAR PLUS. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.) more...
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- 2022
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34. Personal protective equipment in Covid-19: Evidence-based quality and analysis of YouTube videos after one year of pandemic.
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Gerundo G, Collà Ruvolo C, Puzone B, Califano G, La Rocca R, Parisi V, Capece M, Celentano G, Creta M, Rengo G, Leosco D, Abete P, Longo N, Mirone V, and Ferrara N
- Subjects
- Humans, Information Dissemination, Pandemics prevention & control, Personal Protective Equipment, SARS-CoV-2, Video Recording, COVID-19 prevention & control, Social Media
- Abstract
Background: The correct use of personal protective equipment (PPE) during the Covid-19 pandemic is mandatory to minimize the contagion risk. The current study aimed to evaluate quality information of YouTube videos on PPE use during the pandemic., Methods: Using Google Trend tool, the frequency of worldwide YouTube and Google searches for "donning and doffing" was examined. We queried YouTube with terms related to donning and doffing of PPE. Validated quality information assessment tools were used., Results: From the December 1, 2019 to the January 31, 2021, according to YouTube and Google searches, both peaks occurred in April 2020 (69.5% and 72.0%, respectively). Of all videos, 144 were eligible for the analyses. According to misinformation tool, 90 (62.5%) videos contained inaccuracies. The median DISCERN Section 1 ranged from 3 to 5. The median DISCERN Section 3 was 4. According to Global Quality Score, 8.3% (n = 12), 14.6% (n = 21), 22.9% (n = 33), 30.6% (n = 44) and 23.6% (n = 34) were classified as poor, partially poor, moderate, partially good and excellent quality videos, respectively., Conclusions: Nowadays, YouTube may be recommended as a reliable source of information. Nevertheless, a not negligible number of videos contained inaccuracies. Future authors should improve videos contents to provide more complete information., (Copyright © 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.) more...
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- 2022
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35. The Prevalence and the Impact of Frailty in Hepato-Biliary Pancreatic Cancers: A Systematic Review and Meta-Analysis.
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Komici K, Cappuccio M, Scacchi A, Vaschetti R, Delli Carpini G, Picerno V, Avella P, Brunese MC, Rengo G, Guerra G, and Bencivenga L
- Abstract
Background: Frailty has been associated with increased mortality among hepatobiliary pancreatic (HBP) cancer patients. Nevertheless, estimates of frailty prevalence in HBP cancers and the precise average effect regarding mortality remains uncertain. The present systematic review and meta-analysis aimed to quantify: (1) the prevalence of frailty in patients with liver and pancreatic cancers and (2) the impact of frailty on mortality in patients affected by liver and pancreatic cancers., Methods: MEDLINE/PubMed database search was conducted from inception until 1 November 2021, the pooled prevalence and relative risk (RR) estimate were calculated., Results: A total of 34,276 patients were identified and the weighted prevalence of frailty was 39%; (95% [C.I.] 23-56; I2 = 99.9%, p < 0.0001). Frailty was significantly associated with increased mortality RR 1.98 (95% [C.I.] 1.49-2.63; I2 = 75.9%, p = 0.006)., Conclusions: Frailty prevalence is common among HBP cancer patients and exerts a significant negative impact on survival. These findings are characterized by significant heterogeneity and caution is warranted on their interpretation. However, stratification of patients with HBP cancer by frailty status may provide prognostic information and may inform priorities for decision-making strategy. more...
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- 2022
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36. G protein-coupled receptor kinase 5 (GRK5) contributes to impaired cardiac function and immune cell recruitment in post-ischemic heart failure.
- Author
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de Lucia C, Grisanti LA, Borghetti G, Piedepalumbo M, Ibetti J, Lucchese AM, Barr EW, Roy R, Okyere AD, Murphy HC, Gao E, Rengo G, Houser SR, Tilley DG, and Koch WJ
- Subjects
- Animals, Cytokines genetics, Cytokines metabolism, Disease Models, Animal, G-Protein-Coupled Receptor Kinase 5 genetics, Heart Failure immunology, Heart Failure pathology, Heart Failure physiopathology, Inflammation Mediators metabolism, Leukocytes immunology, Mice, Knockout, Myocardial Contraction, Myocardial Infarction immunology, Myocardial Infarction pathology, Myocardial Infarction physiopathology, Myocytes, Cardiac immunology, Myocytes, Cardiac pathology, Signal Transduction, Stroke Volume, Transcriptome, Ventricular Pressure, Mice, Chemotaxis, Leukocyte, G-Protein-Coupled Receptor Kinase 5 metabolism, Heart Failure enzymology, Leukocytes metabolism, Myocardial Infarction enzymology, Myocytes, Cardiac enzymology, Ventricular Function, Left
- Abstract
Aims: Myocardial infarction (MI) is the most common cause of heart failure (HF) worldwide. G protein-coupled receptor kinase 5 (GRK5) is upregulated in failing human myocardium and promotes maladaptive cardiac hypertrophy in animal models. However, the role of GRK5 in ischemic heart disease is still unknown. In this study, we evaluated whether myocardial GRK5 plays a critical role post-MI in mice and included the examination of specific cardiac immune and inflammatory responses., Methods and Results: Cardiomyocyte-specific GRK5 overexpressing transgenic mice (TgGRK5) and non-transgenic littermate control (NLC) mice as well as cardiomyocyte-specific GRK5 knockout mice (GRK5cKO) and wild type (WT) were subjected to MI and, functional as well as structural changes together with outcomes were studied. TgGRK5 post-MI mice showed decreased cardiac function, augmented left ventricular dimension and decreased survival rate compared to NLC post-MI mice. Cardiac hypertrophy and fibrosis as well as fetal gene expression were increased post-MI in TgGRK5 compared to NLC mice. In TgGRK5 mice, GRK5 elevation produced immuno-regulators that contributed to the elevated and long-lasting leukocyte recruitment into the injured heart and ultimately to chronic cardiac inflammation. We found an increased presence of pro-inflammatory neutrophils and macrophages as well as neutrophils, macrophages and T-lymphocytes at 4-days and 8-weeks respectively post-MI in TgGRK5 hearts. Conversely, GRK5cKO mice were protected from ischemic injury and showed reduced early immune cell recruitment (predominantly monocytes) to the heart, improved contractility and reduced mortality compared to WT post-MI mice. Interestingly, cardiomyocyte-specific GRK2 transgenic mice did not share the same phenotype of TgGRK5 mice and did not have increased cardiac leukocyte migration and cytokine or chemokine production post-MI., Conclusions: Our study shows that myocyte GRK5 has a crucial and GRK-selective role on the regulation of leucocyte infiltration into the heart, cardiac function and survival in a murine model of post-ischemic HF, supporting GRK5 inhibition as a therapeutic target for HF., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.) more...
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- 2022
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37. Multiple hormonal and metabolic deficiency syndrome predicts outcome in heart failure: the T.O.S.CA. Registry.
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Cittadini A, Salzano A, Iacoviello M, Triggiani V, Rengo G, Cacciatore F, Maiello C, Limongelli G, Masarone D, Perticone F, Cimellaro A, Perrone Filardi P, Paolillo S, Mancini A, Volterrani M, Vriz O, Castello R, Passantino A, Campo M, Modesti PA, De Giorgi A, Monte IP, Puzzo A, Ballotta A, D'Assante R, Arcopinto M, Gargiulo P, Sciacqua A, Bruzzese D, Colao A, Napoli R, Suzuki T, Eagle KA, Ventura HO, Marra AM, and Bossone E more...
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- Hospitalization, Humans, Prognosis, Prospective Studies, Registries, Stroke Volume, Ventricular Function, Left, Heart Failure diagnosis, Heart Failure drug therapy, Heart Failure epidemiology
- Abstract
Aims: Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients., Methods and Results: The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P < 0.001). Median follow-up was of 36 months. MHDS was independently associated with the occurrence of the primary endpoint [hazard ratio 95% (confidence interval), 1.93 (1.37-2.73), P < 0.001] and identified a group of patients with a higher mortality [2.2 (1.28-3.83), P = 0.01], with a graded relation between HDs and cumulative events (P < 0.01)., Conclusion: MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target., Trial Registration: ClinicalTrials.gov identifier: NCT023358017., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.) more...
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- 2021
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38. Endothelial Progenitor Cells and Rheumatoid Arthritis: Response to Endothelial Dysfunction and Clinical Evidences.
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Komici K, Perna A, Rocca A, Bencivenga L, Rengo G, and Guerra G
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- Arthritis, Rheumatoid therapy, Biomarkers metabolism, Gene Expression Regulation, Humans, Signal Transduction, Arthritis, Rheumatoid immunology, Endothelial Progenitor Cells immunology
- Abstract
Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease characterized by the swelling of multiple joints, pain and stiffness, and accelerated atherosclerosis. Sustained immune response and chronic inflammation, which characterize RA, may induce endothelial activation, damage and dysfunction. An equilibrium between endothelial damage and repair, together with the preservation of endothelial integrity, is of crucial importance for the homeostasis of endothelium. Endothelial Progenitor Cells (EPCs) represent a heterogenous cell population, characterized by the ability to differentiate into mature endothelial cells (ECs), which contribute to vascular homeostasis, neovascularization and endothelial repair. A modification of the number and function of EPCs has been described in numerous chronic inflammatory and auto-immune conditions; however, reports that focus on the number and functions of EPCs in RA are characterized by conflicting results, and discrepancies exist among different studies. In the present review, the authors describe EPCs' role and response to RA-related endothelial modification, with the aim of illustrating current evidence regarding the level of EPCs and their function in this disease, to summarize EPCs' role as a biomarker in cardiovascular comorbidities related to RA, and finally, to discuss the modulation of EPCs secondary to RA therapy. more...
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- 2021
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39. Renal function and cardiac adrenergic impairment in patients affected by heart failure.
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Marsico F, Paolillo S, Gargiulo P, Parisi V, Nappi C, Assante R, Dell'Aversana S, Esposito I, Renga F, Esposito L, Bardi L, Rengo G, Dellegrottaglie S, Marciano C, Leosco D, Cuocolo A, and Filardi PP
- Subjects
- Aged, Female, Heart physiopathology, Heart Failure physiopathology, Humans, Italy, Kidney physiopathology, Kidney Diseases physiopathology, Male, Middle Aged, Statistics, Nonparametric, Adrenergic Agents metabolism, Heart Failure complications, Kidney Diseases etiology
- Abstract
Although in heart failure (HF) there is a strict correlation between heart and kidney, no data are available on the potential relationship in HF between renal dysfunction (RD) and the impaired sympathetic innervation. Aim of the present study was to assess the relationship between RD and cardiac sympathetic innervation in HF patients with reduced ejection fraction. Two hundred and sixty-three patients with mild-to-severe HF underwent iodine-123 meta-iodobenzylguanidine myocardial scintigraphy to assess sympathetic innervation, evaluating early and late heart-to-mediastinum (H/M) ratios and washout rate. In all patients, glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was assessed. A direct association was found between EPI-eGFR and late H/M (r = .215; P < .001). Dividing the population into moderate-to-severe eGFR reduction and normal-to-mildly reduced eGFR (cutoff ≤ 60 mL·min
-1 ·1.73 m-2 ), a statistically significant reduction of late H/M value was found in patients with RD compared to patients with preserved eGFR (P = .030). By multivariable linear regression analysis, eGFR resulted in the prediction of impaired late H/M in patients with RD (P = .005). Patients with RD and HF show more impaired cardiac sympathetic activity than HF patients with preserved renal function, and reduced eGFR is a predictor of reduced late H/M., (© 2019. American Society of Nuclear Cardiology.) more...- Published
- 2021
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40. Letter by Varricchi et al Regarding Article, "Role of IgE-FcεR1 in Pathological Cardiac Remodeling and Dysfunction".
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Varricchi G, Rengo G, and Galli SJ
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- Humans, Immunoglobulin E, Heart, Ventricular Remodeling
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- 2021
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41. Circulating cell-free DNA levels are associated with adverse outcomes in heart failure: testing liquid biopsy in heart failure.
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Salzano A, Israr MZ, Garcia DF, Middleton L, D'Assante R, Marra AM, Arcopinto M, Yazaki Y, Bernieh D, Cassambai S, Page K, Rengo G, Bossone E, Cittadini A, Shaw JA, and Suzuki T
- Subjects
- Humans, Liquid Biopsy, Cell-Free Nucleic Acids, Heart Failure diagnosis
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- 2021
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42. Aging is associated with cardiac autonomic nerve fiber depletion and reduced cardiac and circulating BDNF levels.
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Elia A, Cannavo A, Gambino G, Cimini M, Ferrara N, Kishore R, Paolocci N, and Rengo G
- Abstract
Background: Aging is a multifactorial process associated with an impairment of autonomic nervous system (ANS) function. Progressive ANS remodeling includes upregulation of expression of circulating catecholamines and depletion of cardiac autonomic nerve fibers, and it is responsible, in part, for the increased susceptibility to cardiac diseases observed in elderly subjects. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), are involved in synaptogenesis and neurite outgrowth processes, supporting neuronal cell differentiation and maturation. However, whether and how these factors and their downstream signaling are involved in cardiac aging remains unclear. Here, we tested whether, in the aged heart, the overall extent of autonomic fibers is reduced, owing to lower production of trophic factors such as BDNF and NGF., Methods: In vivo , we used young (age: 3 months; n = 10) and old (age: 24 months; n = 11) male Fisher rats, whereas, we used human neuroblastoma (SH-SY5Y) cells in vitro ., Results: Compared to the young rats, old rats displayed a marked reduction in the overall ANS fiber density, affecting both sympathetic and cholinergic compartments, as indicated by dopamine β-hydroxylase (dβh) and vesicular acetylcholine transporter (VaChT) immunohistochemical staining. In addition, a marked downregulation of GAP-43 and BDNF protein was observed in the left ventricular lysates of old rats compared to those of young rats. Interestingly, we did not find any significant difference in cardiac NGF levels between the young and old groups. To further explore the impact of aging on ANS fibers, we treated SH-SY5Y cells in vitro with serum obtained from young and old rats. Sera from both groups induced a remarkable increase in neuronal sprouting, as evidenced by a crystal violet assay. However, this effect was blunted in cells cultured with old rat serum and was accompanied by a marked reduction in GAP-43 and BDNF protein levels., Conclusions: Our data indicate that physiological aging is associated with an impairment of ANS structure and function and that reduced BDNF levels are responsible, at least in part, for these phenomena., Competing Interests: The authors declare no conflicts of interest., (Copyright and License information: Journal of Geriatric Cardiology 2021.) more...
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- 2021
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43. Clinical Characteristics, Exercise Capacity and Pulmonary Function in Post-COVID-19 Competitive Athletes.
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Komici K, Bianco A, Perrotta F, Dello Iacono A, Bencivenga L, D'Agnano V, Rocca A, Bianco A, Rengo G, and Guerra G
- Abstract
Background: Limited evidence exists regarding adverse modifications affecting cardiovascular and pulmonary function in physical active adults affected by COVID-19, especially in athletic populations. We aimed to describe the clinical presentation of COVID-19 in a cohort of competitive athletes, as well as spirometry and echocardiography findings and cardio-respiratory performance during exercise., Methods: Twenty-four competitive athletes with COVID-19 were recruited for this study after ending self-isolation and confirmation of negative laboratory results. All athletes underwent clinical evaluation, spirometry, echocardiography and cardiopulmonary exercise testing (CPET). These data were compared to a group of healthy control athletes., Results: Anosmia was the most frequent symptom present in 70.83% patients, followed by myalgia, fatigue and ageusia. The most frequent persisting symptoms were anosmia 11 (45.83%) and ageusia 8 (33.33%). Compared to controls, COVID-19 patients presented lower FEV1%: 97.5 (91.5-108) vs. 109 (106-116) p = 0.007. Peak Oxygen Uptake (VO
2 ) in COVID-19 patients was 50.1 (47.7-51.65) vs. 49 (44.2-52.6) in controls ( p = 0.618)., Conclusions: Reduced exercise capacity was not identified and pulmonary and cardiovascular function are not impaired during early recovery phase in a population of physical active adults except FEV1 reduction. more...- Published
- 2021
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44. Infective Endocarditis: A Focus on Oral Microbiota.
- Author
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Del Giudice C, Vaia E, Liccardo D, Marzano F, Valletta A, Spagnuolo G, Ferrara N, Rengo C, Cannavo A, and Rengo G
- Abstract
Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria entering the bloodstream and settling in the heart lining valves or blood vessels. Despite modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Thus, primary prevention and enhanced diagnosis remain the most important strategies to fight this disease. In this regard, it is worth noting that for over 50 years, oral microbiota has been considered one of the significant risk factors for IE. Indeed, among the disparate recommendations from the American heart association and the European Society of Cardiology, there are good oral hygiene and prophylaxis for high-risk patients undergoing dental procedures. Thus, significant interest has grown in the role of oral microbiota and it continues to be a subject of research interest, especially if we consider that antimicrobial treatments can generate drug-resistant mutant bacteria, becoming a severe social problem. This review will describe the current knowledge about the relationship between oral microbiota, dental procedures, and IE. Further, it will discuss current methods used to prevent IE cases that originate from oral pathogens and how these should be focused on improving oral hygiene, which remains the significant persuasible way to prevent bacteremia and systemic disorders. more...
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- 2021
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45. [Prevention Italy 2021 - An update of the 2018 Consensus document and recommendations for the prevention of cardiovascular disease in Italy].
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Battistoni A, Gallo G, Aragona CO, Barchiesi F, Basolo A, Bellone S, Bellotti P, Bertolotti M, Bianco A, Biffi A, Borghi C, Cicero AFG, Consoli A, Corsini A, Desideri G, Di Giacinto B, Fernando F, Ferri C, Galiuto L, Grassi D, Grassi G, Icardi G, Indolfi C, Lodi E, Modena MG, Muiesan ML, Nati G, Orsi A, Palermi S, Parati G, Passantino A, Patelli A, Pelliccia A, Pengo M, Filardi PP, Perseghin G, Pirro M, Pontremoli R, Rengo G, Ricotti R, Rizzoni D, Rocca B, Rotella C, Rubattu S, Salvetti G, Sciacqua A, Serdoz A, Sirico F, Squeo MR, Tocci G, Trimarco B, Vigili de Kreutzenberg S, Volpe R, and Volpe M more...
- Subjects
- Consensus, Humans, Italy, Risk Assessment, Risk Factors, Cardiovascular Diseases prevention & control
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- 2021
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46. Adiponectin and Sarcopenia: A Systematic Review With Meta-Analysis.
- Author
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Komici K, Dello Iacono A, De Luca A, Perrotta F, Bencivenga L, Rengo G, Rocca A, and Guerra G
- Subjects
- Female, Humans, Male, Muscle Strength physiology, Risk Factors, Sarcopenia blood, Sarcopenia epidemiology, Adiponectin blood, Sarcopenia etiology
- Abstract
Background: Sarcopenia is a progressive loss of skeletal muscle mass whose pathophysiology has been proposed to possibly involve mechanisms of altered inflammatory status and endocrine function. Adiponectin has been shown to modulate inflammatory status and muscle metabolism. However, the possible association between adiponectin levels and sarcopenia is poorly understood. In order to fill this gap, in the present manuscript we aimed to summarize the current evidence with a systematic review and a meta-analysis of studies reporting serum adiponectin levels in patients with sarcopenia compared to non-sarcopenic controls., Methods: An electronic search through Medline/PubMed, Cochrane Library, and Science Direct was performed till March 1, 2020. From the included papers, meta-analysis of cross-sectional studies comparing serum levels of adiponectin between patients with sarcopenia and controls was performed., Results: Out of 1,370 initial studies, seven studies were meta-analyzed. Sarcopenic participants had significantly higher levels of adiponectin Hedges' g with 95% confidence interval (CI): 1.20 (0.19-2.22), p = 0.02 than controls. Subgroup analysis, performed in Asian population and focused on identification of the condition based on AWGS criteria, reported higher adiponectin levels in sarcopenic population (2.1 (0.17-4.03), p = 0.03 and I2 = 98.98%. Meta-regression analysis revealed female gender to significantly influence the results as demonstrated by beta = 0.14 (95% CI (0.010-0.280), p = 0.040)., Conclusions: Our meta-analysis found evidence that sarcopenia is associated with higher adiponectin levels. However, caution is warranted on the interpretation of these findings, and future longitudinal research is required to disentangle and better understand the topic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Komici, Dello Iacono, De Luca, Perrotta, Bencivenga, Rengo, Rocca and Guerra.) more...
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- 2021
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47. Impact of the number of comorbidities on cardiac sympathetic derangement in patients with reduced ejection fraction heart failure.
- Author
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Bencivenga L, Komici K, Femminella GD, Paolillo S, Gargiulo P, Formisano R, Assante R, Nappi C, Puzone B, Sepe I, Cittadini A, Vitale DF, Ferrara N, Cuocolo A, Filardi PP, and Rengo G
- Subjects
- 3-Iodobenzylguanidine, Aged, Heart diagnostic imaging, Humans, Middle Aged, Radiopharmaceuticals, Stroke Volume, Sympathetic Nervous System, Heart Failure diagnostic imaging, Heart Failure epidemiology, Ventricular Function, Left
- Abstract
Introduction: Heart failure (HF) is frequently associated with comorbidities.
123 I-metaiodobenzylguanidine (123 I-mIBG) imaging constitutes an effective tool to measure cardiac adrenergic innervation and to improve prognostic stratification in HF patients, including the risk of major arrhythmic events. Although comorbidities have been individually associated with reduced cardiac adrenergic innervation, thus suggesting increased arrhythmic risk, very comorbid HF patients seem to be less likely to experience fatal arrhythmias. We evaluated the impact of the number of comorbidities on cardiac adrenergic innervation, assessed through123 I-mIBG imaging, in patients with systolic HF., Methods: Patients with systolic HF underwent clinical examination, transthoracic echocardiography and cardiac123 I-mIBG scintigraphy. The presence of 7 comorbidities/conditions (smoking, chronic obstructive pulmonary disease, diabetes mellitus, peripheral artery disease, atrial fibrillation, chronic ischemic heart disease and chronic kidney disease) was documented in the overall study population., Results: The study population consisted of 269 HF patients with a mean age of 66±11 years, a left ventricular ejection fraction (LVEF) of 31±7%, and 153 (57%) patients presented ≥3 comorbidities. Highly comorbid patients presented a reduced late heart to mediastinum (H/M) ratio, while no significant differences emerged in terms of early H/M ratio and washout rate. Multiple regression analysis revealed that the number of comorbidities was not associated with mIBG parameters of cardiac denervation, which were correlated with age, body mass index and LVEF., Conclusion: In systolic HF patients, the number of comorbidities is not associated with alterations in cardiac adrenergic innervation. These results are consistent with the observation that very comorbid HF patients suffer lower risk of sudden cardiac death., (Copyright © 2021 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.) more...- Published
- 2021
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48. Myocardial expression of somatotropic axis, adrenergic signalling, and calcium handling genes in heart failure with preserved ejection fraction and heart failure with reduced ejection fraction.
- Author
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D'Assante R, Arcopinto M, Rengo G, Salzano A, Walser M, Gambino G, Monti MG, Bencivenga L, Marra AM, Åberg DN, De Vincentiis C, Ballotta A, Bossone E, Isgaard J, and Cittadini A
- Subjects
- Adrenergic Agents, Calcium, Humans, Stroke Volume, Heart Failure
- Abstract
Aims: Limited data are available regarding cardiac expression of molecules involved in heart failure (HF) pathophysiology. The majority of the studies have focused on end-stage HF with reduced ejection fraction (HFrEF) without comparison with healthy subjects, while no data are available with regard to HF with preserved ejection fraction (HFpEF). HFpEF is a condition whose multiple pathophysiological mechanisms are still not fully defined, with many proposed hypotheses remaining speculative due to limited access to human heart tissue. This study aimed at evaluating cardiac expression levels of key genes of interest in human biopsy samples from patients affected with HFrEF and HFpEF in order to possibly point out distinct phenotypes., Methods and Results: Total RNA was extracted from left ventricular cardiac biopsies collected from stable patients with HFrEF (n = 6) and HFpEF (n = 7) and healthy subjects (n = 9) undergoing elective cardiac surgery for valvular replacement, mitral valvuloplasty, aortic surgery, or coronary artery bypass. Real-time PCR was performed to evaluate the mRNA expression levels of genes involved in somatotropic axis regulation [IGF-1, IGF-1 receptor (IGF-1R), and GH receptor (GHR)], in adrenergic signalling (GRK2, GRK5, ADRB1, and ADRB2), in myocardial calcium handling (SERCA2), and in TNF-α. Patients with HFrEF and HFpEF showed reduced serum IGF-1 circulating levels when compared with controls (102 ± 35.6, 138 ± 11.5, and 160 ± 13.2 ng/mL, P < 0.001, respectively). At myocardial level, HFrEF showed significant decreased GHR and increased IGF-1R expressions when compared with HFpEF and controls (0.54 ± 0.27, 0.94 ± 0.25, and 0.84 ± 0.2, P < 0.05 and 1.52 ± 0.9, 1.06 ± 0.21, and 0.72 ± 0.12, P < 0.05, respectively), while no differences in the local expression of IGF-1 mRNA were detected among the groups (0.80 ± 0.45, 0.97 ± 0.18, and 0.63 ± 0.23, P = 0.09, respectively). With regard to calcium handling and adrenergic signalling, HFrEF displayed significant decreased levels of SERCA2 (0.19 ± 0.39, 0.82 ± 0.15, and 0.87 ± 0.32, P < 0.01) and increased levels of GRK2 (3.45 ± 2.94, 0.93 ± 0.12, and 0.80 ± 0.14, P < 0.01) and GRK5 (1.32 ± 0.70, 0.71 ± 0.14, and 0.77 ± 0.15, P < 0.05), while no significant difference was found in ADRB1 (0.66 ± 0.4, 0.83 ± 0.3, and 0.86 ± 0.4) and ADRB2 mRNA expression (0.65 ± 0.3, 0.66 ± 0.2, and 0.68 ± 0.1) when compared with HFpEF and controls. Finally, no changes in the local expression of TNF-α were detected among groups., Conclusions: Heart failure with reduced ejection fraction and HFpEF patients with stable clinical condition display a distinct molecular milieu of genes involved in somatotropic axis regulation, calcium handling, and adrenergic derangement at a myocardial level. The unique opportunity to compare these results with a control group, as reference population, may contribute to better understand HF pathophysiology and to identify novel potential therapeutic targets that could be modulated to improve ventricular function in patients with HF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.) more...
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- 2021
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49. Antithrombotic therapy in patients undergoing transcatheter aortic valve replacement: the complexity of the elderly.
- Author
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Bencivenga L, Sepe I, Palaia ME, Komici K, Corbi G, Puzone B, Arcopinto M, Cittadini A, Ferrara N, Femminella GD, and Rengo G
- Subjects
- Age Factors, Aged, Aortic Valve Stenosis complications, Humans, Risk Factors, Aortic Valve Stenosis drug therapy, Aortic Valve Stenosis surgery, COVID-19 complications, Fibrinolytic Agents therapeutic use, Transcatheter Aortic Valve Replacement
- Abstract
Along with epidemiologic transitions of the global population, the burden of aortic stenosis (AS) is rapidly increasing and transcatheter aortic valve replacement (TAVR) has quickly spread; indeed, it is nowadays also employed in treating patients with AS at intermediate operative risk. Nonetheless, the less invasive interventional strategy still carries relevant issues concerning post-procedural optimal antithrombotic strategy, given the current indications provided by guidelines are not completely supported by evidence-based data. Geriatric patients suffer from high bleeding and thromboembolic risks, whose balance is particularly subtle due to the presence of concomitant conditions, such as atrial fibrillation and chronic kidney disease, that make the post-TAVR antithrombotic management particularly insidious. This scenario is further complicated by the lack of specific evidence regarding the 'real-life' complex conditions typical of the geriatric syndromes, thus, the management of such a heterogeneous population, ranging from healthy ageing to frailty, is far from being defined. The aim of the present review is to summarize the critical points and the most updated evidence regarding the post-TAVR antithrombotic approach in the geriatric population, with a specific focus on the most frequent clinical settings., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.) more...
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- 2021
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50. Editorial: Smoldering Inflammation in Cardio-Immune-Metabolic Disorders.
- Author
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Varricchi G, Paolocci N, Rivellese F, and Rengo G
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2021
- Full Text
- View/download PDF
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