76 results on '"Bosso, G."'
Search Results
2. Blood lactate in mild and moderate ARDS secondary to SARS COV 2
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Pagano, A., primary, Porta, G., additional, Bosso, G., additional, Allegorico, E., additional, Serra, C., additional, Mercurio, V., additional, Sansone, G., additional, Orefice, S., additional, and Numis, F.G., additional
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- 2023
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3. Clinical features of patients with home isolation SARS-COV-2 infection: A multicenter retrospective study in southern Italy
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Pisaturo M., De Angelis G., Maggi P., Sangiovanni V., Numis F. G., Gentile I., Masullo A., Rescigno C., Calabria G., Megna A. S., Gambardella M., Manzillo E., Giolitto G., Rossomando A., Buonomo A. R., Macera M., Messina V., Pagano A., Pisapia R., Farella N., Bosso G., Coppola N., Monari C., Sagnelli C., Russo G., Esposito V., Allegorico E., Biagio Pinchera, Catalano M., Salzillo A., Porta G., Scotto R., Pinchera B., Zappulo E., Viceconte G., Moriello N. S., Foggia M., Calo F., Rossomando A. M., Russo A., Liorre G., Paradiso L., Liberti A., Serra C., Vicario F. D., Minerva V., Selva V., Simeone F., De Pascalis S., Pontillo V., Pisaturo, M., De Angelis, G., Maggi, P., Sangiovanni, V., Numis, F. G., Gentile, I., Masullo, A., Rescigno, C., Calabria, G., Megna, A. S., Gambardella, M., Manzillo, E., Giolitto, G., Rossomando, A., Buonomo, A. R., Macera, M., Messina, V., Pagano, A., Pisapia, R., Farella, N., Bosso, G., Coppola, N., Monari, C., Sagnelli, C., Russo, G., Esposito, V., Allegorico, E., Biagio, Pinchera, Catalano, M., Salzillo, A., Porta, G., Scotto, R., Pinchera, B., Zappulo, E., Viceconte, G., Moriello, N. S., Foggia, M., Calo, F., Rossomando, A. M., Russo, A., Liorre, G., Paradiso, L., Liberti, A., Serra, C., Vicario, F. D., Minerva, V., Selva, V., Simeone, F., De Pascalis, S., Pontillo, V., Pisaturo, Mariantonietta, De Angelis, Giulia, Maggi, Paolo, Sangiovanni, Vincenzo, Numis, Fabio Giuliano, Gentile, Ivan, Masullo, Alfonso, Rescigno, Carolina, Calabria, Giosuele, Salomone Megna, Angelo, Gambardella, Michele, Manzillo, Elio, Giolitto, Giancarlo, Rossomando, Annamaria, Buonomo, Antonio Riccardo, Macera, Margherita, Messina, Vincenzo, Pagano, Antonio, Pisapia, Raffaella, Farella, Nunzia, Bosso, Giorgio, Coppola, Nicola, and Group, Covicam
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medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Isolation (health care) ,Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Home isolation ,Mild clinical presentation ,Disease ,030204 cardiovascular system & hematology ,Asymptomatic ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,medicine ,030212 general & internal medicine ,Ecology, Evolution, Behavior and Systematics ,business.industry ,SARS-CoV-2 infection ,Home management ,Paleontology ,COVID-19 ,Retrospective cohort study ,Space and Planetary Science ,mild clinical presentation ,home management ,home isolation ,medicine.symptom ,business - Abstract
To describe epidemiological and clinical features of patients confirmed as having SARS-CoV-2 infection and managed in isolation at home. We performed a multicenter retrospective study enrolling all SARS-CoV-2-positive adults evaluated from 28 February to 31 May 2020 at one of nine COVID-19 Units in southern Italy: we included patients receiving care at home and those admitted to hospital. We defined patients with not-severe disease if they were asymptomatic or experienced a mild infection that did not need oxygen (O2) therapy and those with a severe infection if hospitalized and required O2 therapy. We enrolled 415 patients with SARS-CoV-2 infection: 77 were managed in isolation at home, 338 required hospital management. The 77 patients in home isolation were less frequently male than hospitalized patients (55% vs. 64%; < 0.01) and were younger (median age 45 years (IQR:19) vs 62 (IQR 22); p < 0.01), had a lower Charlson comorbidity index (median 0 (IQR2) vs 6 (IQR 3); p < 0.01), and included fewer subjects with an underlying chronic disease (36% vs 59%; p < 0.01). According to a binomial logistic regression analysis, a younger age (OR: 0.96 (95% IC: 0.94–0.98), p < 0.01) and a low Charlson comorbidity index (OR: 0.66 (95% IC: 0.54 –0.83); p < 0.01) were independent factors associated with at-home management. The identification of subjects with SARS-CoV-2 infection who could be managed in home isolation is useful in clinical practice. A younger age and no comorbidities were identified as factors independently associated with home management.
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- 2021
4. Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience
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Diurno, F., Numis, F. G., Porta, G., Cirillo, F., Maddaluno, S., Ragozzino, A., De Negri, P., Di Gennaro, C., Pagano, A., Allegorico, E., Bressy, L., Bosso, G., Ferrara, A., Serra, C., Montisci, A., D'Amico, M., Schiano Lo Morello, S., Di Costanzo, G., Tucci, A. G., Marchetti, P., Di Vincenzo, U., Sorrentino, I., Casciotta, A., Fusco, M., Buonerba, C., Berretta, M., Ceccarelli, M., Nunnari, G., Diessa, Y., Cicala, S., and Facchini, G.
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Treatment ,Coronavirus ,Betacoronavirus ,SARS-CoV-2 ,Pneumonia, Viral ,COVID-19 ,Humans ,Eculizumab ,Antibodies, Monoclonal, Humanized ,Coronavirus Infections ,Severe Acute Respiratory Syndrome ,Complement Activation ,Pandemics - Abstract
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord.This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV).We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days.Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.
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- 2020
5. ALERT-HF: adherence to guidelines in the treatment of patients with chronic heart failure (vol 15, pg 491, 2014)
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Guarnaccia F, Fimiani B, Zito GB, De Simone A, Stabile G, Bossone E, Volpe E, Bosso G, Sacca L, Oliviero U, Guarnaccia, F, Fimiani, B, Zito, Gb, De Simone, A, Stabile, G, Bossone, E, Volpe, E, Bosso, G, Sacca, L, and Oliviero, U
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- 2014
6. Recombinant human thyrotropin enhances endothelial-mediated vasodilatation of conduit arteries
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Napoli R., Apuzzi V., Bosso G., D'Anna C., De Sena A., Pirozzi C., Marano A., Cudemo G., Oliviero U., Matarazzo M., Saccà L., LUPOLI, GIOVANNI, LUPOLI, GELSY, Napoli, R., Apuzzi, V., Bosso, G., D'Anna, C., De Sena, A., Pirozzi, C., Marano, A., Lupoli, Giovanni, Cudemo, G., Oliviero, U., Matarazzo, M., Lupoli, Gelsy, and Saccà, L.
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Recombinant human thyrotropin ,endothelial-mediated vasodilatation ,hypothyroidism - Abstract
CONTEXT: Endothelial cells possess receptors to TSH. Their role is largely unknown. OBJECTIVES: The objective of the study was to determine whether elevated serum TSH levels, as occur in hypothyroidism, affect endothelial function of large arteries and vascular risk biomarkers. SUBJECTS AND METHODS: Thirty-four consecutively recruited patients, who had undergone thyroidectomy for thyroid carcinoma, were studied in connection with one of the monitoring procedures based on recombinant human (rh) TSH administration. Flow-mediated dilation (FMD) of the brachial artery and serum vascular risk markers were measured at baseline and for 5 d after the administration of rhTSH (0.9 mg im on d 1 and 2). Holter electrocardiogram and echocardiography were performed on d 2. RESULTS: rhTSH caused a rapid increase in flow-mediated dilation from the basal value of 10.2 to 15.6% at 6 h (P < 0.0000001), to 16.1% on d 2 (P < 0.0000001), and to 14.9% on d 6 (P = 0.0015). The results were identical when the analysis was made in a subgroup of 19 patients free of vascular risk conditions. Vascular cell adhesion molecule-1, TNFalpha, IL-6, and high sensitive C-reactive protein were unaffected by rhTSH, whereas homocysteine was decreased. Arterial blood pressure, mean 24-h heart rate, and left ventricular function were unaffected by rhTSH. CONCLUSIONS: rhTSH causes marked and persistent activation of the endothelial mediated vasodilation, independent of systemic hemodynamic changes.
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- 2009
7. The Drosophila telomere-capping protein Verrocchio binds single-stranded DNA and protects telomeres from DNA damage response
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Cicconi A, Micheli E, Vernì F, Jackson A, Ac, Gradilla, Cipressa F, Raimondo D, Bosso G, Jg, Wakefield, Ciapponi L, Cenci G, Maurizio Gatti, Cacchione S, and Gd, Raffa
8. Adherence to guidelines in the management of patients with chronic heart failure follow-up
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Giovanni Battista Zito, Antonio Cittadini, Alert-Hf Investigators, Giorgio Bosso, Ugo Oliviero, Franco Guarnaccia, Biagio Fimiani, Antonio Valvano, Vincenzo Carbone, Bosso, G., Valvano, A., Guarnaccia, F., Fimiani, B., Carbone, V., Cittadini, A., Zito, G. B., and Oliviero, U.
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Male ,medicine.medical_specialty ,Time Factors ,030204 cardiovascular system & hematology ,Group B ,law.invention ,Poor adherence ,Electrocardiography ,03 medical and health sciences ,Basal (phylogenetics) ,0302 clinical medicine ,Randomized controlled trial ,Predictive Value of Tests ,law ,Internal medicine ,Humans ,Medicine ,Registries ,030212 general & internal medicine ,Practice Patterns, Physicians' ,Aged ,Aged, 80 and over ,Heart Failure ,Ejection fraction ,business.industry ,General Medicine ,medicine.disease ,Home Care Services ,Hospitalization ,Treatment Outcome ,Italy ,Echocardiography ,Heart failure ,Predictive value of tests ,Chronic Disease ,Practice Guidelines as Topic ,Female ,Guideline Adherence ,Cardiology and Cardiovascular Medicine ,business ,Clinical evaluation - Abstract
Background and aim The Adherence to Guidelines in the Treatment of patients with Chronic Heart Failure trial showed a poor adherence to the current therapeutic guidelines in 660 chronic heart failure (CHF) patients. The second phase, Adherence to Guidelines in the Treatment of patients with Chronic Heart Failure follow-up, was aimed to determine if periodic echocardiographic evaluations could improve the prognosis of CHF patients and/or increase the adherence to the guidelines. Material and methods Among 528 CHF patients with reduced ejection fraction from the ALERT registry, 436 patients accepted to participate in the second phase of the study between February and September 2013 and completed the 3-year follow-up phase between February and September 2016. They were randomized into two groups: Group A (n = 218) followed by clinical evaluation and ECG every 3 months, and echocardiography every 6 months and Group B (n = 218) monitored only with clinical evaluation and ECG every 3 months. Results The number of vascular events that occurred resulted as similar in both the groups: there were 78 hospitalizations (37 in Group A vs. 41 in Group B); 9 home-treated vascular events (4 in Group A and five in Group B); and 16 cardiovascular deaths (9 and 7, respectively). The adherence to the guidelines at the end of the trial resulted as significantly improved in both the groups in comparison with the basal evaluation, without differences between the two groups. Conclusion A strict follow-up of CHF patients was associated with a lower number of events and an improvement in the adherence to the guidelines. Periodic echocardiography does not modify these results.
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- 2020
9. The use of chest ultrasonography in suspected cases of COVID-19 in the emergency department
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Valentina Mercurio, Luca Scafuri, Teresa Russo, Paola Arbo, Alfonso Ragozzino, Gelsomina Gervasio, Nicoletta Franco, Claudia Serra, Giuseppe Di Costanzo, Gianluca Ruffa, Giorgio Bosso, Concetta Altruda, Cinzia Mormile, Pasquale Dolce, Francesca Cannavacciuolo, Carlo Buonerba, Gaetano Facchini, Ferdinando Dello Vicario, Antonio Pagano, Enrico Allegorico, Valentina Minerva, Chiara De Sio, Giovanni Porta, Fabio Giuliano Numis, Allegorico, E., Buonerba, C., Bosso, G., Pagano, A., Porta, G., Serra, C., Dolce, P., Minerva, V., Vicario, F. D., Altruda, C., Arbo, P., Russo, T., Sio, C. D., Franco, N., Ruffa, G., Mormile, C., Cannavacciuolo, F., Mercurio, V., Gervasio, G., Costanzo, G. D., Ragozzino, A., Scafuri, L., Facchini, G., and Numis, F.
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2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,RT-PCR ,COVID-19 ,Emergency department ,Gold standard (test) ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Real-time polymerase chain reaction ,030228 respiratory system ,Chest ultrasonography ,medicine ,030212 general & internal medicine ,Radiology ,business ,Research Article ,lung ultrasound ,Biotechnology ,Coronavirus - Abstract
Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-specific reverse transcriptase-polymerase chain reaction (RT-PCR) represents the diagnostic gold standard. We explored the value of chest ultrasonography to predict positivity to SARS-CoV-2 on RT-PCR in suspected COVID-19 cases. Patients & methods: Consecutive patients with suspect COVID-19 were included if they had fever and/or history of cough and/or dyspnea. Lung ultrasound score (LUSS) was computed according to published methods. Results: A total of 76 patients were included. A 3-variable model based on aspartate transaminase (AST) > upper limit of normal, LUSS >12 and body temperature >37.5°C yielded an overall accuracy of 91%. Conclusion: A simple LUSS-based model may represent a powerful tool for initial assessment in suspected cases of COVID-19., Lay abstract The gold standard for diagnosis of COVID-19 is RT-PCR. During a pandemic emergency, it may be useful to identify suspect symptomatic patients who may safely be observed without undergoing testing for COVID-19. In this work, a simple model based on the findings of lung ultrasound, AST levels and fever showed an overall accuracy of 91% to predict the results of RT-PCR.
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- 2021
10. Atorvastatin-linked rhabdomyolysis caused by the simultaneous intake of amoxicillin clavulanic acid
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Antonio Cittadini, Rosa Lucci, Giorgio Bosso, Olimpia Iacono, Ugo Oliviero, Mariarosaria De Luca, Vincenzo Guardasole, De Luca, M., Iacono, O., Lucci, R., Guardasole, V., Bosso, G., Cittadini, A., and Oliviero, U.
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Drug ,medicine.medical_specialty ,Statin ,Physiology ,medicine.drug_class ,media_common.quotation_subject ,Atorvastatin ,Case presentation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Drug Discovery ,medicine ,In patient ,030223 otorhinolaryngology ,media_common ,Pharmacology ,Kidney ,Amoxicillin/clavulanic acid ,business.industry ,statin ,General Medicine ,atorvastatin ,medicine.disease ,rhabdomyolysi ,medicine.anatomical_structure ,business ,Rhabdomyolysis ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Objectives Rhabdomyolysis is a rare syndrome in which a serious muscle damage suddenly appears, with the possible occurrence of severe complications such as kidney failure, electrolyte imbalances and death, and represents the most severe form of statin-induced muscle injury. Case presentation Here we present the case of a 55-year-old woman who started therapy with amoxicillin clavulanic acid on a background of atorvastatin therapy, resulting in rhabdomyolysis. Conclusions This case highlights the importance of evaluating potential drug interactions in patients taking statin and the need of monitoring clinical and laboratory findings suggestive of rhabdomyolysis.
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- 2021
11. Non-invasive CPAP in mild and moderate ARDS secondary to SARS-CoV-2
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F. Dello Vicario, Giorgio Bosso, Fabio Giuliano Numis, Paola Arbo, Giovanni Porta, Enrico Allegorico, Antonio Pagano, Valentina Mercurio, Claudia Serra, Valentina Minerva, Teresa Russo, Concetta Altruda, Pagano, A., Porta, G., Bosso, G., Allegorico, E., Serra, C., Dello Vicario, F., Minerva, V., Russo, T., Altruda, C., Arbo, P., Mercurio, V., and Numis, F. G.
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Pulmonary and Respiratory Medicine ,Male ,ARDS ,Physiology ,medicine.medical_treatment ,Coronaviru ,Pneumonia, Viral ,medicine.disease_cause ,Article ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,Hypoxic pulmonary vasoconstriction ,SARS COV 2 ,Medicine ,Humans ,Continuous positive airway pressure ,Prospective Studies ,Prospective cohort study ,Pandemics ,Coronavirus ,Aged ,Aged, 80 and over ,Respiratory Distress Syndrome ,Lung ,Continuous Positive Airway Pressure ,business.industry ,SARS-CoV-2 ,General Neuroscience ,COVID-19 ,respiratory system ,Middle Aged ,medicine.disease ,nervous system diseases ,respiratory tract diseases ,Pneumonia ,medicine.anatomical_structure ,030228 respiratory system ,Respiratory failure ,Anesthesia ,Female ,business ,Coronavirus Infections ,therapeutics ,COVID 19 ,030217 neurology & neurosurgery ,circulatory and respiratory physiology - Abstract
Highlights • Helmet CPAP is effective to treat mild and moderate ARDS secondary to SARS COV 2. • Lung recruitment is not the only pathological mechanism responsible of CPAP effect. • Patients that improve PaO2/FiO2 ratio after one hour of CPAP have a lower mortality, Background During the COVID-19 outbreak, a very high number of infected patients developed pneumonia and many of them complicated with acute respiratory distress syndrome. The optimal management of respiratory failure and the role of lung ultrasound imaging in the evaluation of efficacy of treatment are unknown. Methods In March 2020 we treated 18 patients with mild and moderate ARDS secondary to SARS-CoV-2 with non-invasive continuous positive airway pressure therapy (NI-CPAP). All patients underwent lung ultrasound imaging to verify the entity of lung recruitment after NI-CPAP initiation. Results After one hour of treatment we observed a significant improvement in PaO2/FiO2 ratio in 10 patients. Notably, only 50% of them reached an effective improvement in lung aeration detectable with lung ultrasound. In the other 50% or patients the improvement in PaO2/FiO2 might be related to blood redistribution and reverse of hypoxic vasoconstriction. Conclusion NI- CPAP is a valid therapeutic option in mild and moderate ARDS secondary SARS-CoV-2. Lung recruitment detected by means of lung ultrasound is a relevant but not the exclusive mechanism that underlies the therapeutic efficacy of NI-CPAP in this clinical setting.
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- 2020
12. Long-term follow-up in high risk hypertensive patients with carotid dolicoarteriopathies
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Antonio Valvano, Federica Cammarota, Valentina Apuzzi, Mariarosaria De Luca, Giorgio Bosso, Claudio Tomas, Valentina Mercurio, Valeria Di Simone, Antonio Cittadini, Veronica Panicara, Ugo Oliviero, Valvano, A., Bosso, G., Apuzzi, V., Mercurio, V., Di Simone, V., Panicara, V., De Luca, M., Tomas, C., Cammarota, F., Cittadini, A., and Oliviero, U.
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Carotid Artery Diseases ,Male ,Carotid ultrasound ,medicine.medical_specialty ,Long term follow up ,Population ,030204 cardiovascular system & hematology ,030230 surgery ,Carotid Intima-Media Thickness ,Risk Assessment ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Retrospective analysis ,Humans ,cardiovascular diseases ,education ,Stroke ,Aged ,Retrospective Studies ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Carotid Arteries ,Italy ,Ischemic Attack, Transient ,Hypertension ,Angiography ,Cardiology ,Population study ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
BACKGROUND: Carotid dolicoarteriopathies (CDA) are a common finding during the carotid ultrasound or angiography, but their potential role in the development of cerebrovascular diseases is still unclear. Aim of this study is to clarify the possible relationship between CDA and the occurrence of cerebral events. METHODS: We performed a retrospective analysis on 2124 hypertensive patients with high cardiovascular risk that underwent carotid ultrasound from January 2000 to December 2008. Follow-up data on cerebrovascular events (transient ischemic attack and/or stroke occurrence) at 10 years were collected. RESULTS: The global prevalence of CDA in the study population was 12.9% (274/2124), and carotid kinking was more frequent in females and in the left carotid axis. The percentage of cerebrovascular events among hypertensive patients with CDA was similar to those occurred in the group of patients without CDA (10.94% vs. 10.97%, P=NS), with no differences in the number of strokes (8.39% vs. 8.38% P=NS) and TIA (2.55% vs. 2.59% P=NS). CONCLUSIONS: CDA are not associated with a major occurrence of cerebrovascular events in a high-risk population of hypertensives.
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- 2020
13. NBS1 interacts with HP1 to ensure genome integrity
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Jacopo Albanesi, Laura Ciapponi, Fabio Polticelli, Simona Cugusi, Giovanni Cenci, Valentina Brandi, Francesca Cipressa, Antonio Antoccia, Alessandra di Masi, Maria Lina Moroni, Rosa Pennisi, Giuseppe Bosso, Fioranna Renda, Bosso, G, Cipressa, F, Moroni, Ml, Pennisi, R, Albanesi, J, Brandi, V, Cugusi, S, Renda, F, Ciapponi, L, Polticelli, F, Antoccia, A, di Masi, A, and Cenci, G
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Male ,Cancer Research ,Chromosomal Proteins, Non-Histone ,DNA damage ,Genome, Insect ,Immunology ,Diseases ,Cell Cycle Proteins ,Biology ,NBS1 ,Article ,Chromosomes ,Genomic Instability ,NBS1, HP1, Drosophila, genome stability ,Cellular and Molecular Neuroscience ,medicine ,Animals ,Drosophila Proteins ,Humans ,lcsh:QH573-671 ,Nijmegen Breakage Syndrome ,Endodeoxyribonucleases ,lcsh:Cytology ,HP1 ,DNA replication ,Nuclear Proteins ,Cell Biology ,Fibroblasts ,medicine.disease ,Telomere ,Chromatin ,Cell biology ,Drosophila melanogaster ,Exodeoxyribonucleases ,Gene Expression Regulation ,MRN complex ,Chromobox Protein Homolog 5 ,Rad50 ,Mutation ,embryonic structures ,Female ,Drosophila ,Heterochromatin protein 1 ,genome stability ,Nijmegen breakage syndrome ,DNA Damage - Abstract
Heterochromatin Protein 1 (HP1) and the Mre11-Rad50-Nbs1 (MRN) complex are conserved factors that play crucial role in genome stability and integrity. Despite their involvement in overlapping cellular functions, ranging from chromatin organization, telomere maintenance to DNA replication and repair, a tight functional relationship between HP1 and the MRN complex has never been elucidated. Here we show that the Drosophila HP1a protein binds to the MRN complex through its chromoshadow domain (CSD). In addition, loss of any of the MRN members reduces HP1a levels indicating that the MRN complex acts as regulator of HP1a stability. Moreover, overexpression of HP1a in nbs (but not in rad50 or mre11) mutant cells drastically reduces DNA damage associated with the loss of Nbs suggesting that HP1a and Nbs work in concert to maintain chromosome integrity in flies. We have also found that human HP1α and NBS1 interact with each other and that, similarly to Drosophila, siRNA-mediated inhibition of NBS1 reduces HP1α levels in human cultured cells. Surprisingly, fibroblasts from Nijmegen Breakage Syndrome (NBS) patients, carrying the 657del5 hypomorphic mutation in NBS1 and expressing the p26 and p70 NBS1 fragments, accumulate HP1α indicating that, differently from NBS1 knockout cells, the presence of truncated NBS1 extends HP1α turnover and/or promotes its stability. Remarkably, an siRNA-mediated reduction of HP1α in NBS fibroblasts decreases the hypersensitivity to irradiation, a characteristic of the NBS syndrome. Overall, our data provide an unanticipated evidence of a close interaction between HP1 and NBS1 that is essential for genome stability and point up HP1α as a potential target to counteract chromosome instability in NBS patient cells.
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- 2019
14. A nutraceutical combination reduces left ventricular mass in subjects with metabolic syndrome and left ventricular hypertrophy: A multicenter, randomized, double-blind, placebo-controlled trial
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Ferruccio Galletti, Francesca Battista, Giorgio Bosso, Angela Iannuzzi, Giuseppe Schillaci, Giacomo Pucci, Nadia Brambilla, Giampaolo Giacovelli, Cristina Vitalini, Valeria Fazio, Valentina Mercurio, Gaetano Vaudo, Massimo D'Amato, Domenico Bonaduce, Mercurio, V., Pucci, G., Bosso, G., Fazio, V., Battista, F., Iannuzzi, A., Brambilla, N., Vitalini, C., D'Amato, M., Giacovelli, G., Vaudo, G., Schillaci, G., Galletti, F., and Bonaduce, D.
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0301 basic medicine ,Male ,medicine.medical_specialty ,Heart Ventricles ,Placebo-controlled study ,030209 endocrinology & metabolism ,Nutraceutical combination ,Critical Care and Intensive Care Medicine ,Left ventricular hypertrophy ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Nutraceutical ,Double-Blind Method ,Echocardiography ,Metabolic syndrome ,Internal medicine ,medicine ,Humans ,Policosanol ,030109 nutrition & dietetics ,Nutrition and Dietetics ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Blood pressure ,Dietary Supplements ,Cardiology ,Female ,Hypertrophy, Left Ventricular ,Lipid profile ,business ,medicine.drug - Abstract
Increased left ventricular mass (LVM) is often present in metabolic syndrome (MS), also in the setting of well-controlled blood pressure (BP). Aim of the present study was to evaluate the efficacy of a nutraceutical combination of berberine, red yeast rice extract and policosanol (Armolipid Plus™, AP) in reducing LVM in patients with MS and left ventricular hypertrophy (LVH).In this multicenter, randomized, double-blind, placebo-controlled trial, 158 patients with MS (IDF criteria) and LVH (LVM48 g/mOne-hundred-and-forty-five patients (AP n = 74, placebo n = 71) completed the study. A significant percentage reduction in LVM was observed in AP group vs baseline (-2.7%, p 0.0001), and compared to placebo (-4.1%, p 0.0001), and remained significant after adjustment for age, sex, baseline systolic BP and BMI and their changes during the study period. The proportion of subjects showing LVM reduction was higher in AP group than in the placebo group (57% vs 28%, adjusted p = 0.007). Treatment with AP was associated with improvement of lipid profile.24-week of treatment with AP is associated with a significant reduction in LVM in subjects with MS and LVH, in addition to favourable effects on lipid profile, and could represent an effective strategy aiming at reducing the associated cardiovascular risk. The trial was registered at clinicaltrials.gov with ID NCT02295176.
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- 2019
15. Efficacy of a nutraceutical combination on lipid metabolism in patients with metabolic syndrome: A multicenter, double blind, randomized, placebo controlled trial
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Giampaolo Giacovelli, Cristina Vitalini, Ferruccio Galletti, Francesca Battista, Giorgio Bosso, Giacomo Pucci, Valentina Mercurio, Massimo D'Amato, Valeria Fazio, Marco Gentile, Giuseppe Schillaci, Domenico Bonaduce, Nadia Brambilla, Galletti, F., Fazio, V., Gentile, M., Schillaci, G., Pucci, G., Battista, F., Mercurio, V., Bosso, G., Bonaduce, D., Brambilla, N., Vitalini, C., D'Amato, M., and Giacovelli, G.
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Male ,Berberine ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Placebo-controlled study ,030204 cardiovascular system & hematology ,Fatty Alcohol ,Gastroenterology ,Placebos ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,High-density lipoprotein ,lcsh:RC620-627 ,Metabolic Syndrome ,education.field_of_study ,medicine.diagnostic_test ,Middle Aged ,Left Ventricular ,lcsh:Nutritional diseases. Deficiency diseases ,Cholesterol ,Treatment Outcome ,Hypertrophy, Left Ventricular ,Female ,Fatty Alcohols ,Human ,medicine.drug ,Adult ,medicine.medical_specialty ,Population ,030209 endocrinology & metabolism ,Placebo ,LDL ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Lovastatin ,education ,Policosanol ,Aged ,business.industry ,Research ,Biochemistry (medical) ,Cholesterol, LDL ,Hypertrophy ,medicine.disease ,Lipid Metabolism ,chemistry ,Insulin Resistance ,Dietary Supplements ,Metabolic syndrome ,Lipid profile ,business - Abstract
Background Nutraceuticals represent a new therapeutic frontier in the treatment of metabolic syndrom (MetS) and related cardiovascular risk factors. The aim of this study was to evaluate the potential beneficial effects of Armolipid Plus (AP) (berberine 500 mg, red yest rice, monacolin K 3 mg and policosanol 10 mg) on insulin resistance, lipid profile, particularly on small and dense LDL cholesterol (sdLDL-C), representing the most atherogenic components, as well as its effects on high sensitivity C-reactive protein, a notable marker of cardiovascular risk, blood pressure and cardiac remodeling in subjects affected by MetS, with left ventricular hypertrophy. Methods The study was a prospective, multi-center, randomized, double blind, placebo-controlled trial. One hundred and fifty eight patients, aged between 28 and 76 years old, were enrolled and randomized to receive either one tablet of AP or placebo (PL) once daily for 24 weeks. Anthropometric and vital parameters, total cholesterol (tot-C), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceridemia (TG), non-HDL cholesterol (NHDL-C) and sdLDL-C were evaluated. Results After 24 weeks of treatment, the analysis performed on 141 subjects (71 in AP arm and 70 in PL arm), showed a significant improvement of lipid profile in the AP group, with reduction in tot-C (− 13.2 mg/dl), LDL-C (− 13.9 mg/dl) and NHDL-C (− 15.3 mg/dl) and increase in HDL-C (+ 2.0 mg/dl). These changes were equally significant compared with placebo (tot-C: AP − 13.2 mg/dL vs PL + 2.7 mg/dL, p
- Published
- 2019
16. Lactate determination in pleural and abdominal effusions: a quick diagnostic marker of exudate—a pilot study
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Valerio Rosato, Claudia Serra, Fernando Schiraldi, Mario Masarone, Antonio Pagano, Giorgio Bosso, Fiorella Paladino, M.C. Fascione, A. Amelia, Giovanni Porta, Luca Rinaldi, Fabio Giuliano Numis, Porta, G., Numis, F. G., Rosato, V., Pagano, A., Masarone, M., Bosso, G., Serra, C., Rinaldi, L., Fascione, M. C., Amelia, A., Paladino, F., and Schiraldi, F.
- Subjects
Male ,Pathology ,Microbiological culture ,Pleural effusion ,medicine.medical_treatment ,Thoracentesis ,Pilot Projects ,Lactate ratio ,Predictive Value of Test ,Gastroenterology ,Transudate ,Bacterial peritonitis ,0302 clinical medicine ,Paracentesis ,Ascitic Fluid ,030212 general & internal medicine ,Diagnostic Techniques and Procedures ,Aged, 80 and over ,medicine.diagnostic_test ,Exudates and Transudates ,Middle Aged ,Exudates and Transudate ,Bacterial peritoniti ,Delta lactate ,Area Under Curve ,Emergency Medicine ,Female ,Infection ,Human ,medicine.medical_specialty ,Exudate ,Sepsi ,Sepsis ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Diagnostic marker ,Abdominal effusion ,Pilot Project ,Lactic Acid ,Thoracentesi ,Paracentesi ,Aged ,business.industry ,Lactate ,Light’s criteria ,Pneumonia ,Gold standard (test) ,Biomarker ,medicine.disease ,Diagnostic Techniques and Procedure ,030228 respiratory system ,ROC Curve ,Differential diagnosis ,business ,Biomarkers - Abstract
Pleural or abdominal effusions are frequent findings in ICU and Internal Medicine patients. Diagnostic gold standard to distinguish between transudate and exudate is represented by “Light’s Criteria,” but, unfortunately, the chemical–physical examination for their calculation is not a rapid test. Pursuing an acid–base assessment of the fluid by a blood-gas analyzer, an increase of lactate beyond the normal serum range is reported in the exudative effusions. The advantages of this test are that it is a very fast bed-side test, executable directly by the physician. The aim of this study is to evaluate whether the increase in lactate in pleural and abdominal effusions might be used as a criterion for the differential diagnosis of the nature of the fluid. Sixty-nine patients with pleural or abdominal effusions and clinical indication for thoracentesis or paracentesis were enrolled. Acid–base assessment with lactate, total protein, and LDH dosage on the serum, and acid–base assessment with lactate, total protein, and LDH dosage, cytology, and bacterial culture on the fluid were performed to each patient. Fluid–blood lactate difference (ΔLacFB) and fluid–blood lactate ratio (LacFB ratio) were calculated. A statistical analysis was carried out for fluid lactate (LacF), ΔLacFB, and LacFB ratio, performing ROC curves to find the cut-off values with best sensitivity (Sn) and specificity (Sp) predicting an exudate diagnosis: LacF: cut-off value: 2.4mmol/L; AU-ROC 0.854 95% CI 0.756–0.952; Sn 0.77; Sp 0.84. ΔLacFB: cut-off value: 0.95mmol/L; Au-ROC 0.876 95% CI 0.785–0.966; Sn 0.80; Sp 0.92. LacFB ratio: cut-off value: 2mmol/L; Au-ROC 0.730 95% CI 0.609–0.851; Sn 0.74; Sp 0.65. Lactate dosage by blood-gas analyzer on pleural and abdominal effusions seems to be a promising tool to predict a diagnosis of exudate.
- Published
- 2018
17. Human immunodeficiency virus per se exerts atherogenic effects
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Giorgio Bosso, Luigi Saccà, Giovanni Bonadies, Guglielmo Borgia, Maria Foggia, Valentina Apuzzi, Antonio Valvano, Ugo Oliviero, Giuseppe Castello, Raffaele Napoli, Enrico Leonardi, Salvatore Nappa, Oliviero, Ugo, Bonadies, Giovanni, Apuzzi, Valentina, Foggia, Maria, Bosso, G, Nappa, Salvatore, Valvano, A, Leonardi, E, Borgia, Guglielmo, Castello, G, Napoli, Raffaele, and Sacca', Luigi
- Subjects
Adult ,Carotid Artery Diseases ,Male ,medicine.medical_specialty ,Brachial Artery ,Endothelium ,HIV Infections ,Hyperemia ,Risk Assessment ,Gastroenterology ,Virus ,Risk Factors ,Internal medicine ,medicine ,Humans ,Risk factor ,Ultrasonography ,biology ,Tumor Necrosis Factor-alpha ,business.industry ,Vascular disease ,HIV ,virus diseases ,Middle Aged ,Viral Load ,biology.organism_classification ,medicine.disease ,CD4 Lymphocyte Count ,Vasodilation ,Carotid Arteries ,medicine.anatomical_structure ,Case-Control Studies ,Lentivirus ,Immunology ,Circulatory system ,cardiovascular system ,RNA, Viral ,Regression Analysis ,Female ,Tunica Intima ,Tunica Media ,Cardiology and Cardiovascular Medicine ,business ,Blood vessel ,Artery - Abstract
Objective: Premature atherosclerosis in HIV-infected patients has been attributed to highly active antiretroviral therapy (HAART) and the associated metabolic complications. Whether HIV per se plays a role is an unresolved issue. The purpose of this study was to evaluate whether HIV per se exerts atherogenic effects.Methods: We measured carotid intima-media thickness (IMT) and brachial endothelial-dependent (FMD) and endothelial-independent (NMD) vasodilation in 38 naive untreated HIV-infected patients and 41 healthy control subjects.Results: Control subjects were selected as to match the HIV patients for metabolic risk factors. Mean carotid IMT was higher in HIV patients (0.85 +/- 0.2 mm; p < 0.001) than in controls (0.63 +/- 0.1 mm). In a stepwise multiple regression model, the changes in carotid IMT were predicted by the duration of HIV infection (p < 0.001)and CD4T-cells (p = 0.035). Brachial FMD was impaired in HIV patients (8.8 +/- 3% versus 12.2 +/- 3% in controls; p < 0.001). In contrast, NMD values practically overlapped in the HIV patients and controls. Analysis of the data in relation to viral load showed that FMD was significantly more impaired in the subgroup of patients with viral load values above the median (p < 0.001). In addition, there was a highly significant, inverse correlation between FMD and the HIV-RNA copies (p < 0.001).Conclusion: HIV infection causes functional and structural vascular alterations in a very early stage of the infection independent of HAART and metabolic factors. The data lend support to the viral infectious theory of atherosclerosis. Early assessment of the vascular status in HIV-infected patients is suggested.
- Published
- 2009
18. Effects of long-term L-thyroxine treatment on endothelial function and arterial distensibility in young adults with congenital hypothyroidism
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Valentina Apuzzi, Giorgio Bosso, Fabrizia Calabrese, Antonio Cittadini, Donatella Capalbo, Manuela Cerbone, Mariacarolina Salerno, Antonio Valvano, Ugo Oliviero, Teresa Lettiero, Oliviero, U., Cittadini, Antonio, Bosso, G., Cerbone, Manuela, Valvano, A., Capalbo, Donatella, Apuzzi, Valentina, Calabrese, F., Lettiero, Teresa, and Salerno, Mariacarolina
- Subjects
Male ,Long-term L-thyroxine treatment, endothelial function, arterial distensibility, young adults, congenital hypothyroidism ,medicine.medical_specialty ,Adolescent ,Brachial Artery ,Endocrinology, Diabetes and Metabolism ,Levothyroxine ,Young Adult ,Endocrinology ,Risk Factors ,Internal medicine ,medicine.artery ,medicine ,Congenital Hypothyroidism ,Humans ,Longitudinal Studies ,Young adult ,Brachial artery ,Subclinical infection ,business.industry ,Puberty ,Case-control study ,Ultrasonography, Doppler ,General Medicine ,medicine.disease ,Atherosclerosis ,Congenital hypothyroidism ,Vasodilation ,Thyroxine ,medicine.anatomical_structure ,Case-Control Studies ,Circulatory system ,Linear Models ,Female ,Endothelium, Vascular ,business ,Artery ,medicine.drug - Abstract
ObjectivePatients with congenital hypothyroidism (CH) display subclinical abnormalities of the cardiovascular system that are related to unphysiological fluctuations of TSH levels and occur despite careful replacement therapy.DesignThe aim of the present case–control study was to evaluate the effects of long-term levothyroxine (l-T4) replacement therapy on the vascular district in CH patients by assessing endothelial function with flow-mediated dilation (FMD) and brachial artery distensibility with the measurement of the coefficient of distensibility (DC).MethodsThirty-two young adults with CH aged 18.9±0.2 years and 32 age- and sex-matched controls underwent brachial Doppler ultrasound examination to measure FMD and DC at the time of the study. Hypothyroidism was diagnosed by neonatal screening, and l-T4 treatment was initiated within the first month of life.ResultsCompared to healthy controls, CH patients had significantly reduced brachial artery reactivity with lower FMD values (8.9±5.7 vs 14.1±5.1% P=0.003) and decreased vascular distensibility (24.6±1.6 vs 27.3±3 kPa−1×10−3, Pr=0.81 and r=0.87 respectively, PConclusionsYoung adults with CH treated with long-term l-T4 replacement therapy may have significant impairment of both FMD and DC. Our data suggest that high TSH levels, inadequately corrected by l-T4 replacement therapy in CH patients especially during puberty, can exert significant effects on the elastic and functional vessel properties.
- Published
- 2010
19. Differential contribution for ERK1 and ERK2 kinases in BRAF V600E -triggered phenotypes in adult mouse models.
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Bosso G, Cintra Herpst AC, Laguía O, Adetchessi S, Serrano R, and Blasco MA
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- Animals, Mice, Humans, Mice, Inbred C57BL, MAP Kinase Signaling System, Cell Proliferation, Disease Models, Animal, Lymphocytes metabolism, Proto-Oncogene Proteins B-raf metabolism, Proto-Oncogene Proteins B-raf genetics, Mitogen-Activated Protein Kinase 3 metabolism, Mitogen-Activated Protein Kinase 1 metabolism, Phenotype
- Abstract
The BRAF gene is mutated in a plethora of human cancers. The majority of such molecular lesions result in the expression of a constitutively active BRAF variant (BRAF
V600E ) which continuously bolsters cell proliferation. Although we recently addressed the early effects triggered by BRAFV600E -activation, the specific contribution of ERK1 and ERK2 in BRAFV600E -driven responses in vivo has never been explored. Here we describe the first murine model suitable for genetically dissecting the ERK1/ERK2 impact in multiple phenotypes induced by ubiquitous BRAFV600E -expression. We unveil that ERK1 is dispensable for BRAFV600E -dependent lifespan shortening and for BRAFV600E -driven tumor growth. We show that BRAFV600E -expression provokes an ERK1-independent lymphocyte depletion which does not rely on p21CIP1 -induced cell cycle arrest and is unresponsive to ERK-chemical inhibition. Moreover, we also reveal that ERK1 is dispensable for BRAFV600E -triggered cytotoxicity in lungs and that ERK-chemical inhibition abrogates some of these detrimental effects, such as DNA damage, in Club cells but not in pulmonary lymphocytes. Our data suggest that ERK1/ERK2 contribution to BRAFV600E -driven phenotypes is dynamic and varies dependently on cell type, the biological function, and the level of ERK-pathway activation. Our findings also provide useful insights into the comprehension of BRAFV600E -driven malignancies pathophysiology as well as the consequences in vivo of novel ERK pathway-targeted anti-cancer therapies., (© 2024. The Author(s).)- Published
- 2024
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20. Protocol for the generation and purification of high-molecular-weight covalent RNA-DNA hybrids with T4 RNA ligase.
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Laguía O, Bosso G, Martínez-Torrecuadrada J, Míguez-Amil S, Fernández-Leiro R, and Blasco MA
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- RNA Ligase (ATP), RNA, DNA genetics
- Abstract
RNA-DNA covalent hybrids (RDHs) are widely employed in biology. Although RDHs can be manufactured, the synthesis of molecules longer than 120 nucleotides is challenging. Here, we present a protocol for the generation and purification of high-grade purified high-molecular-weight 5'-RNA-DNA-3' hybrids. We describe steps for preparing oligos and buffers, ligation reaction, and high-performance liquid chromatography-based RDH purification. This protocol is executable in standard molecular biology laboratories., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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21. The impact of a non-restrictive Antimicrobial Stewardship Program in the emergency department of a secondary-level Italian hospital.
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Monari C, Onorato L, Allegorico E, Minerva V, Macera M, Bosso G, Calò F, Pagano A, Russo T, Sansone G, D'Isanto M, Casciotta A, Vanni M, Numis FG, and Coppola N
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- Humans, Prospective Studies, Anti-Bacterial Agents therapeutic use, Hospitals, Emergency Service, Hospital, Italy, Antimicrobial Stewardship
- Abstract
Evidence supporting the effectiveness of Antimicrobial Stewardship (AMS) Programs in the emergency department (ED) setting is limited. We conducted a prospective cohort study to assess the efficacy of an AMS program in an ED and a short-stay observation unit. The intervention included periodic prospective audits (twice a week), conducted by four infectious disease consultants. Primary outcomes included the difference in the hospital mortality rate, antibiotic consumption, and the incidence of bloodstream infections (BSI) caused by multidrug resistant (MDR) bacteria, before March 2020-February 2021 and after March 2021-February 2022 when the program was implemented. Interrupted time-series analysis was performed to assess the effect of our program. During the 12-month program, we performed 152 audits and evaluated 366 antibiotic therapies out of a total of 853 patients admitted. In the intervention period, we observed a non-statistically significant decrease in total antibiotic consumption, with a change in level of - 31.2 defined daily dose/100 patient-days (PD) (p = 0.71). Likewise, we found no significant variations in the rate of BSI due to MDR Gram-positive (CT - 0.02 events/PD, p = 0.84), MDR Gram-negative bacteria (CT 0.08, p = 0.71), or Candida spp. (CT 0.008, p = 0.86). Conversely, we found a significant decrease in the mortality rate between the pre- and post-intervention periods (- 1.98 deaths/100 PD, CI - 3.9 to - 0.007, p = 0.049). The Antibiotic Stewardship Program in the ED was associated with a significant decrease in the mortality rate. More high-quality studies are needed to determine the most effective ASP strategies in this unique setting., (© 2023. The Author(s).)
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- 2024
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22. Parinaud's syndrome: a stroke chameleon.
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Barbato F, Allocca R, Bosso G, and Numis FG
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- Humans, Syndrome, Ocular Motility Disorders, Stroke
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- 2024
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23. Simple detecting of elevated ICP through liquor flow after lumbar puncture.
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Barbato F, Troise A, Allocca R, Sansone G, Bosso G, and Numis FG
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- Humans, Adolescent, Young Adult, Adult, Middle Aged, Aged, Aged, 80 and over, Intracranial Pressure, ROC Curve, Manometry methods, Spinal Puncture methods, Intracranial Hypertension diagnosis
- Abstract
Elevated intracranial pressure (ICP) is defined as a cerebrospinal fluid (CSF) opening pressure (OP) greater than 25 cmH2O. When a diagnostic lumbar puncture is performed it is useful to estimate also intracranial pressure. To do this it is required a presence of pressure gauges, which are currently the gold standard, not available in most resource-constrained contexts. We decided to evaluate whether it is possible to estimate it simply by counting the drops of cerebrospinal liquor, which are collected after lumbar puncture, according to Poiseuille's law. Was examined a sample of 52 patients, aged between 18 and 85 years, belonging to the emergency room of "Santa Maria delle Grazie" Hospital in Pozzuoli (Naples) who needed a diagnostic lumbar puncture (LP). The ICP was initially measured using a standard narrow-gauge manometer by attaching it to the spinal needle. After removing the pressure gauge, the number of drops of cerebrospinal fluid flowing from the spinal needle in 30 seconds was counted. A statistical analysis was made with linear regression and ROC analysis. OP as measured by standard manometry was raised on 17 occasions with CSF drop rate median of 47 drops/30 seconds and range 30-74 drops/30 seconds. OP was normal on 35 occasions with CSF drop rate median of 23 drops/30 seconds with range of 14-34 drops/30 seconds. A linear regression analysis was performed which resulted in a Pearson correlation of 0.936 an adjusted R square of 0.874 (see Fig. 1). Analysis through ANOVA documented an F of 355.301 with p < 0.01 and Dubin Watson of 1.642. The analysis through ROC showed an AUC of 0.980, with a sensitivity of 100% and a specificity of 91% if chosen as a limit, 29 drops in 30 seconds (Youden Index of 0.9140). Therefore, we have concluded, that although there are several precautions, like patient's position, it is technically feasible to indirectly estimate cerebrospinal fluid pressure with good accuracy by counting the drops of cerebrospinal fluid flowing from a 22 G spinal needle., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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24. Co-amplification of CBX3 with EGFR or RAC1 in human cancers corroborated by a conserved genetic interaction among the genes.
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Bosso G, Cipressa F, Tullo L, and Cenci G
- Abstract
Chromobox Protein 3 (CBX3) overexpression is a common event occurring in cancer, promotes cancer cell proliferation and represents a poor prognosis marker in a plethora of human cancers. Here we describe that a wide spectrum of human cancers harbors a co-amplification of CBX3 gene with either EGFR or RAC1, which yields a statistically significant increase of both mRNA and protein levels of CBX3, EGFR and RAC1. We also reveal that the simultaneous overexpression of CBX3, RAC1 and EGFR gene products correlates with a worse prognosis compared to the condition when CBX3, RAC1 and EGFR are singularly upregulated. Furthermore, we also show that a co-occurrence of low-grade amplification, in addition to high-grade amplification, between CBX3 and EGFR or RAC1 is associated with a reduced patient lifespan. Finally, we find that CBX3 and RAC1/EGFR genetically interact in the model organism Drosophila melanogaster, suggesting that the simultaneous overexpression as well as well the co-occurrence of high- or low-grade copy number alterations in these genes is not accidental and could reflect evolutionarily conserved functional relationships., (© 2023. Cell Death Differentiation Association (ADMC).)
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- 2023
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25. Lung ultrasound-guided PEEP titration in COVID-19 patients treated with CPAP.
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Bosso G, Sansone G, Papillo M, Giaquinto A, Orefice S, Allegorico E, Serra C, Minerva V, Mercurio V, Cannavacciuolo F, Dello Vicario F, Porta G, Pagano A, and Numis FG
- Subjects
- Humans, Prospective Studies, Lung diagnostic imaging, Ultrasonography, Interventional, Pneumothorax, COVID-19 therapy
- Abstract
Objectives: An increasing number of COVID-19 patients were treated with continuous positive airways pressure (CPAP). To evaluate the clinical effects of personalized positive end-expiratory pressure (PEEP) compared to standard fixed PEEP in COVID-19 patients requiring CPAP., Methods: This is a single center, prospective, randomized clinical study. Sixty-three COVID-19 patients with hypoxemic respiratory failure and bilateral pneumonia were randomized in two Groups: Group A received CPAP with fixed PEEP of 10 cm H
2 O, Group B performed the "PEEP trial", that consists in the evaluation of best PEEP defined as the PEEP value that precedes the echographic appearance of "lung pulse" determining a PaO2 /FiO2 increase. Primary outcome was composite in-hospital mortality + intubation, secondary outcome was the percentage increase of PaO2 /FiO2 . As safety indicator, the incidence of pneumothorax was collected., Results: Thirty-two patients were enrolled in Group A and 31 in Group B . The two groups were comparable for clinical characteristics and laboratory parameters. The primary outcome occurred in 36 (57.1 %) patients: 23 (71.8 %) in Group A and 13 (41.9 %) in Group B (p<0.01). Mortality was higher in Group A (53.1 vs. 19.3 %, p<0.01), while intubation rate was comparable between groups. Group B showed a higher PaO2 /FiO2 increase than Group A (34.9 vs. 13.1 %, p<0.01). Five cases of pneumothorax were reported in Group A , none in Group B ., Conclusions: Lung ultrasound-guided PEEP trial is associated with lower mortality in COVID-19 patients treated with CPAP. Identifying the best PEEP is useful to increase oxygenation and reduce the incidence of complications., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)- Published
- 2023
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26. Alert-LDL-2: adherence to guidelines and goals attainment in the treatment of diabetic patients with dyslipidemia.
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DE Luca M, Bosso G, Alma G, Carbone V, Ferrara F, Fimiani B, Guarnaccia F, Iandolo A, Murolo S, Olivares M, Romeo E, Santoro G, Valvano A, Zito G, and Oliviero U
- Subjects
- Humans, Goals, Cholesterol, LDL, Prospective Studies, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Dyslipidemias drug therapy, Dyslipidemias epidemiology
- Abstract
Background: Type 2 diabetes mellitus is associated with a cluster of lipid and apolipoprotein abnormalities which increase the risk for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the adherence to guidelines-oriented dyslipidemia treatment in diabetic patients and to assess the efficacy of a territorial goal-oriented program., Methods: One thousand seventy-one diabetic patients at very high cardiovascular risk were enrolled in this prospective study. They performed a clinical-laboratory follow-up program, received lifestyle recommendations and optimization of their antihyperlipidemic therapies. At the beginning and the 3-month follow-up visit, LDL-c data were collected, and further therapies were prescribed to the patients that did not reach the target. After 12 month follow-up, LDL-c data were collected again., Results: Diabetic patients significantly improved mean LDL cholesterol levels during one-year follow-up (LDLc mean value 135 mg/dL at baseline, 60 mg/dL at the end of the study), obtaining a greater reduction compared to non-diabetic patients participating in the same program. Accordingly, the percentage of patients that reached the lipid target was significantly higher in diabetic patients after 3-months and 12- follow-ups (P<0.05). Diabetic patients assuming statins, both in monotherapy and in combination with ezetimibe, increased during the follow-up (74.1% at the enrolment vs. 88.2% one year later). GLP1ra-treated patients achieved the greatest reduction in cholesterol levels compared to baseline., Conclusions: The results of the study recommend encouraging strategies and appropriate treatments to achieve a targeted lipid profile in diabetic patients at very high cardiovascular risk.
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- 2023
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27. Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.
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Piñeiro-Hermida S, Bosso G, Sánchez-Vázquez R, Martínez P, and Blasco MA
- Subjects
- Humans, Mice, Animals, Heterografts, Tumor Microenvironment, Telomere metabolism, Lung metabolism, Cell Line, Tumor, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms pathology, Telomerase genetics, Telomerase metabolism
- Abstract
Non-small cell lung cancer (NSCLC) is a leading cause of cancer death. Tumor progression depends on interactions of cancer cells with the tumor microenvironment. Here, we find increased copy number and mRNA expression of the catalytic subunit of telomerase, TERT, in tumors from NSCLC patients, contributing to a lower survival. Moreover, TERT expression in NSCLC patients from the TCGA cohort is mainly associated to the reduced infiltration of CD8
+ T lymphocytes, as well as to increased infiltration of myeloid-derived suppressor cells (MDSCs). We also show that TERT deficiency and dysfunctional telomeres induced by 6-thio-dG treatment in mice reduced lung tumor implantation and vascularization, increased DNA damage response, cell cycle arrest and apoptosis, as well as reduced proliferation, inflammation, lung tumor immunosupression and invasion upon induction of a Lewis lung carcinoma (LLC). Furthermore, 6-thio-dG-treated human NSCLC xenografts exhibited increased telomere damage, cell cycle arrest and apoptosis, as well as reduced proliferation, resulting in a reduced tumor growth. Our results show that targeting telomeres might be an effective therapeutic strategy in NSCLC., (© 2023. The Author(s).)- Published
- 2023
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28. Effects of three-months folate supplementation on early vascular abnormalities in hyperhomocysteinemic patients with epilepsy.
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De Luca M, Valvano A, Striano P, Bosso G, Pirone D, Trinchillo A, Bilo L, and Oliviero U
- Subjects
- Humans, Matrix Metalloproteinase 9, Dietary Supplements, Homocysteine, Folic Acid therapeutic use, Tissue Inhibitor of Metalloproteinase-1, Epilepsy complications, Epilepsy drug therapy
- Abstract
Background: Epilepsy has been associated with an increased risk of cardiovascular events. Anti-seizure medication (ASM) may contribute to vascular risk by several mechanisms, including increased homocysteine levels. This study aims to assess the global vascular burden in hyperhomocysteinemic people with epilepsy (PWE) on long-term ASM before and after folic acid supplementation and in subgroups of PWE treated with single enzyme-inducing or single non-enzyme inducing ASM., Methods: One hundred and seventy-four hyperhomocysteinemic (HHcy) PWE who met the inclusion criteria were enrolled. Carotid Doppler ultrasonography, FMD and ultrasound assessment of the brachial artery properties at the baseline and after 90 days of folic acid supplementation were performed. The vascular biomarkers MMP-9 and TIMP-1 were also detected., Results: After folic acid supplementation, in HHcy patients homocysteine levels reduced from 26.8 ± 10.5 to 20.2 ± 5.3 μmol/L, carotid Intima-Media-Thickness reduced from 0.83+0.06 mm to 0.79±0.05 mm, and FMD, distensibility coefficient and β-stiffness improved (p < 0.05). Moreover, MMP-9 and TIMP-1 reduced after supplementation (p < 0.05). PWE treated with a single enzyme-inducing ASM showed an impairment of vascular parameters compared to patients treated with non-enzyme inducing ASM., Conclusions: The results highlight the importance of assessing homocysteine levels and estimating the cardiovascular risk of PWE, preferring non-enzyme inducing ASM in high cardiovascular-risk patients. An adequate correction of homocysteine levels with folate supplementation should be considered to improve the cardiovascular profile., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest/competing interests., (Published by Elsevier Ltd.)
- Published
- 2022
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29. Consequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development.
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Piñeiro-Hermida S, Martínez P, Bosso G, Flores JM, Saraswati S, Connor J, Lemaire R, and Blasco MA
- Subjects
- Animals, Bleomycin toxicity, Female, Fibroblasts metabolism, Male, Mice, Telomere metabolism, Pulmonary Fibrosis chemically induced, Pulmonary Fibrosis genetics, Pulmonary Fibrosis pathology, Telomeric Repeat Binding Protein 1 genetics
- Abstract
TRF1 is an essential component of the telomeric protective complex or shelterin. We previously showed that dysfunctional telomeres in alveolar type II (ATII) cells lead to interstitial lung fibrosis. Here, we study the lung pathologies upon telomere dysfunction in fibroblasts, club and basal cells. TRF1 deficiency in lung fibroblasts, club and basal cells induced telomeric damage, proliferative defects, cell cycle arrest and apoptosis. While Trf1 deletion in fibroblasts does not spontaneously lead to lung pathologies, upon bleomycin challenge exacerbates lung fibrosis. Unlike in females, Trf1 deletion in club and basal cells from male mice resulted in lung inflammation and airway remodeling. Here, we show that depletion of TRF1 in fibroblasts, Club and basal cells does not lead to interstitial lung fibrosis, underscoring ATII cells as the relevant cell type for the origin of interstitial fibrosis. Our findings contribute to a better understanding of proper telomere protection in lung tissue homeostasis., (© 2022. The Author(s).)
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- 2022
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30. Spontaneous eye movements in myxedematous coma.
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Barbato F, Allocca R, Serra C, Bosso G, and Numis FG
- Subjects
- Humans, Coma etiology, Eye Movements
- Published
- 2022
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31. ALERT-LDL: adherence to guidelines in the treatment of patients with dyslipidemia.
- Author
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Bosso G, De Luca M, Alma G, Carbone V, Ferrara F, Fimiani B, Guarnaccia F, Iandolo A, Murolo S, Olivares M, Romeo E, Santoro G, Valvano A, Zito G, and Oliviero U
- Subjects
- Cholesterol, LDL therapeutic use, Drug Therapy, Combination, Guideline Adherence, Humans, Prospective Studies, Treatment Outcome, Anticholesteremic Agents therapeutic use, Cardiovascular Diseases drug therapy, Cardiovascular Diseases prevention & control, Dyslipidemias drug therapy
- Abstract
The association between LDL-c levels and cardiovascular outcomes suggests tailoring lipid-lowering therapies according to total cardiovascular risk. We aimed to evaluate the adherence to guidelines-oriented dyslipidaemia's treatment in an outpatient population referring to ARCA cardiologists, and assess the efficacy of treatment's optimization for each specific level of risk. Three thousand seventy-five patients enrolled in this prospective study were classified according to cardiovascular risk category, and their therapies were optimized. At the beginning and the 3 month follow-up visit, LDL-c data were collected, and further therapies were prescribed to the patients that did not reach the target. A significant LDL-c reduction was observed in all subgroups at different cardiovascular risk at the end of the study (p < 0.05). The number of patients assuming statins, both in monotherapy and in combination with ezetimibe, increased during the follow-up (63% at the enrollment vs 89% after 12 months). At the enrollment, only 1.4% of patients were treated with PCSK-9 inhibitors while after 12 months the percentage increased both in high (5.8%) and very high-risk (18.4%) patients. At the beginning of the study, only 698/3075 patients (22.7%) reached lipid targets. At the end of the study, carried out by the referring cardiologists in the pertaining healthcare districts and specifically aimed to control the lipid profile, the percentage of patients on target increased in all risk categories (68.5%). Our results suggest carefully implementing measures that encourage outpatients and their cardiologists to achieve the targeted lipid profile according to cardiovascular risk., (© 2021. The Author(s).)
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- 2022
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32. Early differential responses elicited by BRAF V600E in adult mouse models.
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Bosso G, Lanuza-Gracia P, Piñeiro-Hermida S, Yilmaz M, Serrano R, and Blasco MA
- Subjects
- Animals, Carcinogenesis genetics, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Disease Models, Animal, Mice, Mutation genetics, Oncogenes, Tumor Suppressor Protein p53 genetics, Adenoma genetics, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf metabolism
- Abstract
The BRAF gene is frequently mutated in cancer. The most common genetic mutation is a single nucleotide transition which gives rise to a constitutively active BRAF kinase (BRAF
V600E ) which in turn sustains continuous cell proliferation. The study of BRAFV600E murine models has been mainly focused on the role of BRAFV600E in tumor development but little is known on the early molecular impact of BRAFV600E expression in vivo. Here, we study the immediate effects of acute ubiquitous BRAFV600E activation in vivo. We find that BRAFV600E elicits a rapid DNA damage response in the liver, spleen, lungs but not in thyroids. This DNA damage response does not occur at telomeres and is accompanied by activation of the senescence marker p21CIP1 only in lungs but not in liver or spleen. Moreover, in lungs, BRAFV600E provokes an acute inflammatory state with a tissue-specific recruitment of neutrophils in the alveolar parenchyma and macrophages in bronchi/bronchioles, as well as bronchial/bronchiolar epithelium transdifferentiation and development of adenomas. Furthermore, whereas in non-tumor alveolar type II (ATIIs) pneumocytes, acute BRAFV600E induction elicits rapid p53-independent p21CIP1 activation, adenoma ATIIs express p53 without resulting in p21CIP1 gene activation. Conversely, albeit in Club cells BRAFV600E -mediated proliferative cue is more exacerbated compared to that occurring in ATIIs, such oncogenic stimulus culminates with p21CIP1 -mediated cell cycle arrest and apoptosis. Our findings indicate that acute BRAFV600E expression drives an immediate induction of DNA damage response in vivo. More importantly, it also results in rapid differential responses of cell cycle and senescence-associated proteins in lung epithelia, thus revealing the early molecular changes emerging in BRAFV600E -challenged cells during tumorigenesis in vivo., (© 2022. The Author(s).)- Published
- 2022
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33. Surgical tracheotomy in COVID-19 patients: an Italian single centre experience.
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Briatore R, Aprile F, Roasio A, Bianchi A, Bosso S, Carmino L, Lorenzelli L, Scanu M, Zanin M, Bosso G, Torchia V, and Pisani P
- Subjects
- Humans, Intensive Care Units, Italy epidemiology, Male, Middle Aged, RNA, Viral, Respiration, Artificial, SARS-CoV-2, Tracheotomy adverse effects, COVID-19, Pandemics
- Abstract
Purpose: Coronavirus infection disease 2019 (COVID-19) causes in 10% of patients a severe respiratory distress syndrome managed with invasive mechanical ventilation (IMV), sometimes difficult to wean. The role of tracheotomy is debated for the possible risks for patients and staff. We are going to describe here our experience with surgical tracheotomy in COVID-19 positive patients., Methods: We enrolled all intensive care unit (ICU) patients requiring longer than 10 days of IMV. Demographic, clinical, respiratory, complications, and outcomes data were collected, in a particular length of weaning from sedation and IMV, in-ICU and in-hospital mortality rate. All healthcare operators involved were tested for SARS-CoV2 by pharyngeal swab and blood test (antibody test)., Results: 13 out of 68 ICU patients (19.1%) underwent surgical tracheotomy after a median intubation period of 14 days. The mean age was 60 (56-65) years. 85% were male patients. Postoperative mild bleeding was seen in 30.7%, pneumothorax in 7.7%. Mean weaning from sedation required 3 days, 19 days from IMV. In-ICU and in-hospital COVID-infection-related mortality was 23.1% and 30.7%, respectively. None of the healthcare operators was found SARS-CoV2 positive during the period of the study., Conclusions: In COVID-19 pandemic surgical tracheotomy enables to wean from sedation and subsequently from IMV in a safe way for both patients and personnel., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)
- Published
- 2021
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34. Correction to: Management of patients with chronic heart failure and type 2 diabetes mellitus: the SCODIAC-II study.
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De Luca M, Bosso G, Valvano A, Guardasole V, Botta A, Carbone V, Carella G, Del Buono A, Di Giovanni G, Fimiani B, Guarnaccia F, Lapice E, Martedì E, Memoli G, Oliva D, Romano G, Cittadini A, Zito GB, and Oliviero U
- Published
- 2021
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35. Management of patients with chronic heart failure and type 2 diabetes mellitus: the SCODIAC-II study.
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De Luca M, Bosso G, Valvano A, Guardasole V, Botta A, Carbone V, Carella G, Del Buono A, Di Giovanni G, Fimiani B, Guarnaccia F, Lapice E, Martedì E, Memoli G, Oliva D, Romano G, Cittadini A, Zito GB, and Oliviero U
- Subjects
- Aged, Biomarkers blood, Diabetes Mellitus, Type 2 complications, Drug Combinations, Echocardiography, Female, Heart Failure complications, Heart Failure diagnostic imaging, Humans, Italy, Male, Aminobutyrates therapeutic use, Angiotensin Receptor Antagonists therapeutic use, Biphenyl Compounds therapeutic use, Diabetes Mellitus, Type 2 drug therapy, Heart Failure drug therapy, Valsartan therapeutic use
- Abstract
SCODIAC was a pilot study which revealed an increasing use of SGLT2i in 123 outpatients affected with Heart Failure (HF) and Type 2 Diabetes Mellitus. SCODIAC-II study, the second phase of the program, has been carried out to determine diagnostic and therapeutic pathways in a larger group of patients and to verify whether the use of innovative antidiabetic therapies could modify echocardiographic parameters and cardiovascular therapies. 406 HF-diabetic patients, referred to Cardiologists and Diabetologists of pertaining healthcare districts in Campania, were enrolled in this retrospective study and divided in Group A, composed of 136 patients with preserved Ejection Fraction (HF-pEF)(> 45%) and Group B, formed of 270 patients with reduced EF (HF-rEF)(≤ 45%). All patients had performed periodic clinical and echocardiographic evaluations. The antidiabetic therapies resulted modified after 1 year with a greater use of GLP1-AR, gliptins and SGLT2i. Cardiovascular therapies resulted also modified with a greater use of sacubitril/valsartan and a reduction of ACEi and ARBs in HF-rEF patients. Echocardiography E velocity, A velocity and E/e' ratio resulted markedly reduced in 25 HF-pEF and in 60 HF-rEF patients treated with SGLT2i, in respect to both the whole sample of subjects at beginning and the other diabetic patients. LAVi resulted reduced only in HF-pEF patients and EF increased only in HF-rEF patients. The approach to the patients with HF and diabetes must necessarily take place in the healthcare districts, be multidisciplinary and integrated. SGLT2i could improve left ventricular function in HF-rEF patients and modify cardiovascular therapies, almost in this setting of patients.Trial registration The protocol was approved by the University of Naples Federico II Ethics Committee and registered at ClinicalTrial.gov (CT04375943). The principles outlined in the Declaration of Helsinki were followed.
- Published
- 2021
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36. Clinical Features of Patients with Home Isolation Sars-Cov-2 Infection: A Multicenter Retrospective Study in Southern Italy.
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Pisaturo M, De Angelis G, Maggi P, Sangiovanni V, Numis FG, Gentile I, Masullo A, Rescigno C, Calabria G, Salomone Megna A, Gambardella M, Manzillo E, Giolitto G, Rossomando A, Buonomo AR, Macera M, Messina V, Pagano A, Pisapia R, Farella N, Bosso G, Coppola N, and Group C
- Abstract
To describe epidemiological and clinical features of patients confirmed as having SARS-CoV-2 infection and managed in isolation at home. We performed a multicenter retrospective study enrolling all SARS-CoV-2-positive adults evaluated from 28 February to 31 May 2020 at one of nine COVID-19 Units in southern Italy: we included patients receiving care at home and those admitted to hospital. We defined patients with not-severe disease if they were asymptomatic or experienced a mild infection that did not need oxygen (O
2 ) therapy and those with a severe infection if hospitalized and required O2 therapy. We enrolled 415 patients with SARS-CoV-2 infection: 77 were managed in isolation at home, 338 required hospital management. The 77 patients in home isolation were less frequently male than hospitalized patients (55% vs. 64%; <0.01) and were younger (median age 45 years (IQR:19) vs. 62 (IQR 22); p < 0.01), had a lower Charlson comorbidity index (median 0 (IQR2) vs. 6 (IQR 3); p < 0.01), and included fewer subjects with an underlying chronic disease (36% vs. 59%; p < 0.01). According to a binomial logistic regression analysis, a younger age (OR: 0.96 (95% IC: 0.94-0.98), p < 0.01) and a low Charlson comorbidity index (OR: 0.66 (95% IC: 0.54-0.83); p < 0.01) were independent factors associated with at-home management. The identification of subjects with SARS-CoV-2 infection who could be managed in home isolation is useful in clinical practice. A younger age and no comorbidities were identified as factors independently associated with home management.- Published
- 2021
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37. Lung ultrasound as diagnostic tool for SARS-CoV-2 infection.
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Bosso G, Allegorico E, Pagano A, Porta G, Serra C, Minerva V, Mercurio V, Russo T, Altruda C, Arbo P, De Sio C, Dello Vicario F, and Numis FG
- Subjects
- Aged, COVID-19 epidemiology, COVID-19 Testing, Female, Humans, Italy epidemiology, Male, Pneumonia, Viral epidemiology, Pneumonia, Viral virology, SARS-CoV-2, Sensitivity and Specificity, COVID-19 diagnostic imaging, Pneumonia, Viral diagnostic imaging, Ultrasonography methods
- Abstract
The aim of this study was to explore the role of lung ultrasound (LUS) in the diagnosis of SARS-CoV-2 infection and to verify its utility in the prediction of lung disease's severity and outcome. Fifty-three consecutive patients presenting to the Emergency Department of Santa Maria delle Grazie Hospital with high suspicion of SARS-CoV-2 infection underwent diagnostic test for SARS-CoV-2 on samples obtained from nasopharyngeal swab as well as complete proper diagnostic work-up that included clinical evaluation, laboratory tests, blood gas analyses, chest CT and LUS. A semiquantitative analysis of B-lines distribution was performed to calculate the LUS score. Patients were divided into two groups according to the results of both SARS-CoV-2 diagnostic test and other exams (Group A = pneumonia due to SARS-CoV2 infection vs Group B = no SARS-CoV2 infection and another definite diagnosis). LUS showed an excellent accuracy in predicting the diagnosis of SARS-CoV-2 infection (area under the ROC curve of 0.92 with a sensibility of 73% and a specificity of 89% a the cut-off of 12.5). LUS score was more impaired in SARS-CoV-2 patients (18.1 ± 6.0 vs 7.6 ± 5.9, p < 0.00001) and it is significantly negatively correlated with PF ratio values (r = - 0.719, p < 0.0001). An intrahospital mortality rate of 46% was found; patients with adverse outcome had significant higher value of LUS, PF, LDH, and APACHE II score. None of these parameters was predictive of mortality. LUS is a useful tool for the early detection of SARS-CoV-2 infection and for the evaluation of the disease severity, but does not predict mortality. Further studies with repeated evaluations of LUS score are needed to further explore the role of LUS in the assessment of severity in SARS-CoV-2 disease and in the monitoring of the response to treatments.
- Published
- 2021
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38. Time-weighted lactate as a predictor of adverse outcome in acute heart failure.
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Bosso G, Mercurio V, Diab N, Pagano A, Porta G, Allegorico E, Serra C, Guiotto G, Numis FG, Tocchetti CG, and Schiraldi F
- Subjects
- Hospitalization, Humans, Intensive Care Units, Italy epidemiology, Heart Failure diagnosis, Lactic Acid
- Abstract
Aims: The role of dynamic changes in lactate concentrations on prognosis in acute heart failure has been poorly investigated. The aim of this study was to explore the predictive value of 24 h time-weighted lactate (LAC
TW ) in patients with acute heart failure., Methods and Results: Ninety-six consecutive acute heart failure patients presenting to the Emergency Department of San Paolo Hospital, Naples, Italy, were prospectively enrolled. Arterial blood lactate was measured at admission and during the following 24 h at random time intervals. LACTW was obtained by the sum of the average lactate values among consecutive time points multiplied by the intervals between consecutive time points and dividing the sum by the total time (24 h). The outcome was a composite of need of admission to the intensive care unit, hospitalization duration >7 days, or intra-hospital death. Admission lactate, maximum measured lactate, and LACTW were collected. Univariate and multivariate Cox regression analysis was applied to determine the hazard ratio (HR) of developing the outcome. Forty-three patients experienced the pre-specified outcome. In sex-adjusted and age-adjusted multivariable analysis, LACTW predicted the outcome occurrence (HR: 1.51, 95% confidence interval: 1.24, 1.84, P < 0.001). Risk stratification analysis based on LACTW tertiles demonstrated a gradual increase in risk of developing the outcome (HR: 17.32, 95% confidence interval: 2.30, 130.23, P = 0.006) for the highest LACTW tertile., Conclusions: In acute heart failure patients, 24 h LACTW had a significant independent predictive value for adverse intra-hospital outcome. LACTW could be a useful index at identifying high-risk patients who may require a more aggressive treatment during hospitalization., (©2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)- Published
- 2021
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39. Echocardiographic assessment of aortic pulse wave velocity for left ventricular diastolic dysfunction.
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Bosso G, DE Luca M, and Oliviero U
- Subjects
- Echocardiography, Humans, Prognosis, Pulse Wave Analysis, Ventricular Dysfunction, Left diagnostic imaging
- Published
- 2021
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40. The use of chest ultrasonography in suspected cases of COVID-19 in the emergency department.
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Allegorico E, Buonerba C, Bosso G, Pagano A, Porta G, Serra C, Dolce P, Minerva V, Vicario FD, Altruda C, Arbo P, Russo T, Sio C, Franco N, Ruffa G, Mormile C, Cannavacciuolo F, Mercurio V, Gervasio G, Costanzo GD, Ragozzino A, Scafuri L, Facchini G, and Numis F
- Abstract
Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-specific reverse transcriptase-polymerase chain reaction (RT-PCR) represents the diagnostic gold standard. We explored the value of chest ultrasonography to predict positivity to SARS-CoV-2 on RT-PCR in suspected COVID-19 cases., Patients & Methods: Consecutive patients with suspect COVID-19 were included if they had fever and/or history of cough and/or dyspnea. Lung ultrasound score (LUSS) was computed according to published methods., Results: A total of 76 patients were included. A 3-variable model based on aspartate transaminase (AST) > upper limit of normal, LUSS >12 and body temperature >37.5°C yielded an overall accuracy of 91%., Conclusion: A simple LUSS-based model may represent a powerful tool for initial assessment in suspected cases of COVID-19., Competing Interests: Financial & competing interests disclosure C Buonerba is a member of the Future Science OA Editorial Board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2020 Enrico Allegorico.)
- Published
- 2020
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41. Atorvastatin-linked rhabdomyolysis caused by the simultaneous intake of amoxicillin clavulanic acid.
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De Luca M, Iacono O, Lucci R, Guardasole V, Bosso G, Cittadini A, and Oliviero U
- Abstract
Objectives Rhabdomyolysis is a rare syndrome in which a serious muscle damage suddenly appears, with the possible occurrence of severe complications such as kidney failure, electrolyte imbalances and death, and represents the most severe form of statin-induced muscle injury. Case presentation Here we present the case of a 55-year-old woman who started therapy with amoxicillin clavulanic acid on a background of atorvastatin therapy, resulting in rhabdomyolysis. Conclusions This case highlights the importance of evaluating potential drug interactions in patients taking statin and the need of monitoring clinical and laboratory findings suggestive of rhabdomyolysis.
- Published
- 2020
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42. Peripheral Vascular Function in Dilated Cardiomyopathy of Different Etiology.
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Bosso G, Valvano A, Apuzzi V, Mercurio V, Di Simone V, Cittadini A, Napoli R, and Oliviero U
- Subjects
- Aged, Brachial Artery diagnostic imaging, Cardiomyopathy, Dilated diagnostic imaging, Case-Control Studies, Female, Humans, Male, Middle Aged, Myocardial Ischemia diagnosis, Myocardial Ischemia physiopathology, Prognosis, Risk Assessment, Risk Factors, Brachial Artery physiopathology, Cardiomyopathy, Dilated etiology, Cardiomyopathy, Dilated physiopathology, Myocardial Ischemia complications, Vascular Stiffness, Vasodilation
- Abstract
Vascular function in dilated cardiomyopathy of different etiology has been poorly investigated. Moreover, reference values of flow-mediated dilation (FMD) in chronic heart failure (CHF) need to be updated according to the new standardized protocols. We characterized the vascular impairment in different stages of post-ischemic dilated cardiomyopathy (PI-DC) or idiopathic dilated cardiomyopathy (I-DC). Eighty consecutive outpatients with CHF in different New York Heart Association (NYHA) classes (45 PI-DC, 35 I-DC) and 50 control subjects underwent FMD and brachial distensibility coefficient measurement. Patients with CHF showed a marked impairment in FMD compared with controls that worsened from classes NYHA I-II to III-IV, independently of etiology ( P < .05). New York Heart Association I-II PI-DC patients showed a worse FMD compared with NYHA I-II I-DC patients ( P < .05). Brachial distensibility coefficient values were significantly lower in patients with CHF compared with controls ( P < .001) without differences between PI-DC and I-DC. In conclusion, advanced CHF is characterized by vascular impairment that is independent of etiology. In the early stages of CHF, endothelial dysfunction is more severe in patients with PI-DC compared with I-DC probably due to the high cardiovascular risk profile. In I-DC, vascular function impairment is independent of cardiovascular risk factors and could participate in the pathogenesis of I-DC.
- Published
- 2020
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43. A nutraceutical combination reduces left ventricular mass in subjects with metabolic syndrome and left ventricular hypertrophy: A multicenter, randomized, double-blind, placebo-controlled trial.
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Mercurio V, Pucci G, Bosso G, Fazio V, Battista F, Iannuzzi A, Brambilla N, Vitalini C, D'Amato M, Giacovelli G, Vaudo G, Schillaci G, Galletti F, and Bonaduce D
- Subjects
- Double-Blind Method, Female, Humans, Male, Middle Aged, Dietary Supplements, Heart Ventricles pathology, Hypertrophy, Left Ventricular diet therapy
- Abstract
Background & Aims: Increased left ventricular mass (LVM) is often present in metabolic syndrome (MS), also in the setting of well-controlled blood pressure (BP). Aim of the present study was to evaluate the efficacy of a nutraceutical combination of berberine, red yeast rice extract and policosanol (Armolipid Plus™, AP) in reducing LVM in patients with MS and left ventricular hypertrophy (LVH)., Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 158 patients with MS (IDF criteria) and LVH (LVM > 48 g/m
2.7 in men and > 44 g/m2.7 in women), were randomized 1:1 to receive AP or placebo for 24 weeks. Reduction of LVM, regression of LVH, and changes in lipids were analysed., Results: One-hundred-and-forty-five patients (AP n = 74, placebo n = 71) completed the study. A significant percentage reduction in LVM was observed in AP group vs baseline (-2.7%, p < 0.0001), and compared to placebo (-4.1%, p < 0.0001), and remained significant after adjustment for age, sex, baseline systolic BP and BMI and their changes during the study period. The proportion of subjects showing LVM reduction was higher in AP group than in the placebo group (57% vs 28%, adjusted p = 0.007). Treatment with AP was associated with improvement of lipid profile., Conclusions: 24-week of treatment with AP is associated with a significant reduction in LVM in subjects with MS and LVH, in addition to favourable effects on lipid profile, and could represent an effective strategy aiming at reducing the associated cardiovascular risk. The trial was registered at clinicaltrials.gov with ID NCT02295176., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)- Published
- 2020
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44. Adherence to guidelines in the management of patients with chronic heart failure follow-up: role of periodic echocardiographic examinations.
- Author
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Bosso G, Valvano A, Guarnaccia F, Fimiani B, Carbone V, Cittadini A, Zito GB, and Oliviero U
- Subjects
- Aged, Aged, 80 and over, Chronic Disease, Electrocardiography trends, Female, Heart Failure diagnostic imaging, Heart Failure mortality, Heart Failure physiopathology, Home Care Services trends, Hospitalization trends, Humans, Italy, Male, Predictive Value of Tests, Registries, Time Factors, Treatment Outcome, Echocardiography trends, Guideline Adherence trends, Heart Failure therapy, Practice Guidelines as Topic, Practice Patterns, Physicians' trends
- Abstract
Background and Aim: The Adherence to Guidelines in the Treatment of patients with Chronic Heart Failure trial showed a poor adherence to the current therapeutic guidelines in 660 chronic heart failure (CHF) patients. The second phase, Adherence to Guidelines in the Treatment of patients with Chronic Heart Failure follow-up, was aimed to determine if periodic echocardiographic evaluations could improve the prognosis of CHF patients and/or increase the adherence to the guidelines., Material and Methods: Among 528 CHF patients with reduced ejection fraction from the ALERT registry, 436 patients accepted to participate in the second phase of the study between February and September 2013 and completed the 3-year follow-up phase between February and September 2016. They were randomized into two groups: Group A (n = 218) followed by clinical evaluation and ECG every 3 months, and echocardiography every 6 months and Group B (n = 218) monitored only with clinical evaluation and ECG every 3 months., Results: The number of vascular events that occurred resulted as similar in both the groups: there were 78 hospitalizations (37 in Group A vs. 41 in Group B); 9 home-treated vascular events (4 in Group A and five in Group B); and 16 cardiovascular deaths (9 and 7, respectively). The adherence to the guidelines at the end of the trial resulted as significantly improved in both the groups in comparison with the basal evaluation, without differences between the two groups., Conclusion: A strict follow-up of CHF patients was associated with a lower number of events and an improvement in the adherence to the guidelines. Periodic echocardiography does not modify these results.
- Published
- 2020
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45. Long-term follow-up in high risk hypertensive patients with carotid dolicoarteriopathies.
- Author
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Valvano A, Bosso G, Apuzzi V, Mercurio V, Di Simone V, Panicara V, De Luca M, Tomas C, Cammarota F, Cittadini A, and Oliviero U
- Subjects
- Aged, Carotid Intima-Media Thickness, Female, Follow-Up Studies, Humans, Italy epidemiology, Male, Middle Aged, Retrospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, Carotid Arteries pathology, Carotid Artery Diseases epidemiology, Hypertension complications, Ischemic Attack, Transient epidemiology, Stroke epidemiology
- Abstract
Background: Carotid dolicoarteriopathies (CDA) are a common finding during the carotid ultrasound or angiography, but their potential role in the development of cerebrovascular diseases is still unclear. Aim of this study is to clarify the possible relationship between CDA and the occurrence of cerebral events., Methods: We performed a retrospective analysis on 2124 hypertensive patients with high cardiovascular risk that underwent carotid ultrasound from January 2000 to December 2008. Follow-up data on cerebrovascular events (transient ischemic attack and/or stroke occurrence) at 10 years were collected., Results: The global prevalence of CDA in the study population was 12.9% (274/2124), and carotid kinking was more frequent in females and in the left carotid axis. The percentage of cerebrovascular events among hypertensive patients with CDA was similar to those occurred in the group of patients without CDA (10.94% vs. 10.97%, P=NS), with no differences in the number of strokes (8.39% vs. 8.38% P=NS) and TIA (2.55% vs. 2.59% P=NS)., Conclusions: CDA are not associated with a major occurrence of cerebrovascular events in a high-risk population of hypertensives.
- Published
- 2020
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46. NBS1 interacts with HP1 to ensure genome integrity.
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Bosso G, Cipressa F, Moroni ML, Pennisi R, Albanesi J, Brandi V, Cugusi S, Renda F, Ciapponi L, Polticelli F, Antoccia A, di Masi A, and Cenci G
- Subjects
- Animals, Chromobox Protein Homolog 5, DNA Damage genetics, Drosophila melanogaster genetics, Female, Fibroblasts metabolism, Fibroblasts pathology, Gene Expression Regulation, Genome, Insect genetics, Humans, Male, Mutation genetics, Nijmegen Breakage Syndrome genetics, Nijmegen Breakage Syndrome pathology, Cell Cycle Proteins genetics, Chromosomal Proteins, Non-Histone genetics, Drosophila Proteins genetics, Endodeoxyribonucleases genetics, Exodeoxyribonucleases genetics, Genomic Instability genetics, Nuclear Proteins genetics
- Abstract
Heterochromatin Protein 1 (HP1) and the Mre11-Rad50-Nbs1 (MRN) complex are conserved factors that play crucial role in genome stability and integrity. Despite their involvement in overlapping cellular functions, ranging from chromatin organization, telomere maintenance to DNA replication and repair, a tight functional relationship between HP1 and the MRN complex has never been elucidated. Here we show that the Drosophila HP1a protein binds to the MRN complex through its chromoshadow domain (CSD). In addition, loss of any of the MRN members reduces HP1a levels indicating that the MRN complex acts as regulator of HP1a stability. Moreover, overexpression of HP1a in nbs (but not in rad50 or mre11) mutant cells drastically reduces DNA damage associated with the loss of Nbs suggesting that HP1a and Nbs work in concert to maintain chromosome integrity in flies. We have also found that human HP1α and NBS1 interact with each other and that, similarly to Drosophila, siRNA-mediated inhibition of NBS1 reduces HP1α levels in human cultured cells. Surprisingly, fibroblasts from Nijmegen Breakage Syndrome (NBS) patients, carrying the 657del5 hypomorphic mutation in NBS1 and expressing the p26 and p70 NBS1 fragments, accumulate HP1α indicating that, differently from NBS1 knockout cells, the presence of truncated NBS1 extends HP1α turnover and/or promotes its stability. Remarkably, an siRNA-mediated reduction of HP1α in NBS fibroblasts decreases the hypersensitivity to irradiation, a characteristic of the NBS syndrome. Overall, our data provide an unanticipated evidence of a close interaction between HP1 and NBS1 that is essential for genome stability and point up HP1α as a potential target to counteract chromosome instability in NBS patient cells.
- Published
- 2019
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47. EXPRESS: Cardiac Sympathetic Dysfunction in Pulmonary Arterial Hypertension: Lesson from Left-sided Heart Failure.
- Author
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Mercurio V, Pellegrino T, Bosso G, Campi G, Parrella P, Piscopo V, Tocchetti CG, Hassoun P, Petretta M, Cuocolo A, and Bonaduce D
- Published
- 2019
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48. Multiple cancer pathways regulate telomere protection.
- Author
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Bejarano L, Bosso G, Louzame J, Serrano R, Gómez-Casero E, Martínez-Torrecuadrada J, Martínez S, Blanco-Aparicio C, Pastor J, and Blasco MA
- Subjects
- Animals, Cell Line, Tumor, Female, Gene Deletion, Glioma genetics, Glioma metabolism, Glioma pathology, Humans, MAP Kinase Signaling System genetics, Mice, Mice, Nude, Telomere genetics, Telomere pathology, Telomeric Repeat Binding Protein 1 genetics, Telomeric Repeat Binding Protein 1 metabolism, Xenograft Model Antitumor Assays, Glioma drug therapy, MAP Kinase Signaling System drug effects, Neoplasm Proteins antagonists & inhibitors, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Protein Kinase Inhibitors pharmacology, Telomere metabolism
- Abstract
Telomeres are considered as universal anti-cancer targets, as telomere maintenance is essential to sustain indefinite cancer growth. Mutations in telomerase, the enzyme that maintains telomeres, are among the most frequently found in cancer. In addition, mutations in components of the telomere protective complex, or shelterin, are also found in familial and sporadic cancers. Most efforts to target telomeres have focused in telomerase inhibition; however, recent studies suggest that direct targeting of the shelterin complex could represent a more effective strategy. In particular, we recently showed that genetic deletion of the TRF1 essential shelterin protein impairs tumor growth in aggressive lung cancer and glioblastoma (GBM) mouse models by direct induction of telomere damage independently of telomere length. Here, we screen for TRF1 inhibitory drugs using a collection of FDA-approved drugs and drugs in clinical trials, which cover the majority of pathways included in the Reactome database. Among other targets, we find that inhibition of several kinases of the Ras pathway, including ERK and MEK, recapitulates the effects of Trf1 genetic deletion, including induction of telomeric DNA damage, telomere fragility, and inhibition of cancer stemness. We further show that both bRAF and ERK2 kinases phosphorylate TRF1 in vitro and that these modifications are essential for TRF1 location to telomeres in vivo. Finally, we use these new TRF1 regulatory pathways as the basis to discover novel drug combinations based on TRF1 inhibition, with the goal of effectively blocking potential resistance to individual drugs in patient-derived glioblastoma xenograft models., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2019
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49. Efficacy of a nutraceutical combination on lipid metabolism in patients with metabolic syndrome: a multicenter, double blind, randomized, placebo controlled trial.
- Author
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Galletti F, Fazio V, Gentile M, Schillaci G, Pucci G, Battista F, Mercurio V, Bosso G, Bonaduce D, Brambilla N, Vitalini C, D'Amato M, and Giacovelli G
- Subjects
- Adult, Aged, Berberine therapeutic use, Cholesterol, LDL blood, Double-Blind Method, Fatty Alcohols therapeutic use, Female, Humans, Hypertrophy, Left Ventricular diet therapy, Insulin Resistance, Lovastatin therapeutic use, Male, Metabolic Syndrome metabolism, Middle Aged, Placebos, Treatment Outcome, Dietary Supplements, Lipid Metabolism drug effects, Metabolic Syndrome diet therapy
- Abstract
Background: Nutraceuticals represent a new therapeutic frontier in the treatment of metabolic syndrom (MetS) and related cardiovascular risk factors. The aim of this study was to evaluate the potential beneficial effects of Armolipid Plus (AP) (berberine 500 mg, red yest rice, monacolin K 3 mg and policosanol 10 mg) on insulin resistance, lipid profile, particularly on small and dense LDL cholesterol (sdLDL-C), representing the most atherogenic components, as well as its effects on high sensitivity C-reactive protein, a notable marker of cardiovascular risk, blood pressure and cardiac remodeling in subjects affected by MetS, with left ventricular hypertrophy., Methods: The study was a prospective, multi-center, randomized, double blind, placebo-controlled trial. One hundred and fifty eight patients, aged between 28 and 76 years old, were enrolled and randomized to receive either one tablet of AP or placebo (PL) once daily for 24 weeks. Anthropometric and vital parameters, total cholesterol (tot-C), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceridemia (TG), non-HDL cholesterol (NHDL-C) and sdLDL-C were evaluated., Results: After 24 weeks of treatment, the analysis performed on 141 subjects (71 in AP arm and 70 in PL arm), showed a significant improvement of lipid profile in the AP group, with reduction in tot-C (- 13.2 mg/dl), LDL-C (- 13.9 mg/dl) and NHDL-C (- 15.3 mg/dl) and increase in HDL-C (+ 2.0 mg/dl). These changes were equally significant compared with placebo (tot-C: AP - 13.2 mg/dL vs PL + 2.7 mg/dL, p < 0.01; LDL-C: AP -13.9 mg/dl vs PL + 1.5 mg/dl, p < 0.01; NHDL-C: AP -15.3 mg/dl vs PL + 2.8 mg/dl, p < 0.01), Although no significant difference was observed between the two arms in the reduction of HDL-C nevertheless it increased significantly in the AP group (AP + 2 mg/dL p < 0.05, PL 0.13 mg/dL)., Conclusion: The results of this study, applicable to a specific local population show that, in a population of subjects affected by MetS, treatment with AP improves the lipid profile and the most atherogenic factors, thus suggesting a reduction in the risk of development and progression of atherosclerosis, particularly in subjects with high atherogenic risk, due to the presence of sdLDL-C.
- Published
- 2019
- Full Text
- View/download PDF
50. Lactate determination in pleural and abdominal effusions: a quick diagnostic marker of exudate-a pilot study.
- Author
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Porta G, Numis FG, Rosato V, Pagano A, Masarone M, Bosso G, Serra C, Rinaldi L, Fascione MC, Amelia A, Paladino F, and Schiraldi F
- Subjects
- Aged, Aged, 80 and over, Area Under Curve, Biomarkers analysis, Biomarkers blood, Diagnostic Techniques and Procedures, Exudates and Transudates chemistry, Female, Humans, Lactic Acid blood, Male, Middle Aged, Pilot Projects, Pleural Effusion diagnosis, Predictive Value of Tests, ROC Curve, Ascitic Fluid chemistry, Lactic Acid analysis, Pleural Effusion chemically induced
- Abstract
Pleural or abdominal effusions are frequent findings in ICU and Internal Medicine patients. Diagnostic gold standard to distinguish between transudate and exudate is represented by "Light's Criteria," but, unfortunately, the chemical-physical examination for their calculation is not a rapid test. Pursuing an acid-base assessment of the fluid by a blood-gas analyzer, an increase of lactate beyond the normal serum range is reported in the exudative effusions. The advantages of this test are that it is a very fast bed-side test, executable directly by the physician. The aim of this study is to evaluate whether the increase in lactate in pleural and abdominal effusions might be used as a criterion for the differential diagnosis of the nature of the fluid. Sixty-nine patients with pleural or abdominal effusions and clinical indication for thoracentesis or paracentesis were enrolled. Acid-base assessment with lactate, total protein, and LDH dosage on the serum, and acid-base assessment with lactate, total protein, and LDH dosage, cytology, and bacterial culture on the fluid were performed to each patient. Fluid-blood lactate difference (ΔLacFB) and fluid-blood lactate ratio (LacFB ratio) were calculated. A statistical analysis was carried out for fluid lactate (LacF), ΔLacFB, and LacFB ratio, performing ROC curves to find the cut-off values with best sensitivity (Sn) and specificity (Sp) predicting an exudate diagnosis: LacF: cut-off value: 2.4 mmol/L; AU-ROC 0.854 95% CI 0.756-0.952; Sn 0.77; Sp 0.84. ΔLacFB: cut-off value: 0.95 mmol/L; Au-ROC 0.876 95% CI 0.785-0.966; Sn 0.80; Sp 0.92. LacFB ratio: cut-off value: 2 mmol/L; Au-ROC 0.730 95% CI 0.609-0.851; Sn 0.74; Sp 0.65. Lactate dosage by blood-gas analyzer on pleural and abdominal effusions seems to be a promising tool to predict a diagnosis of exudate.
- Published
- 2018
- Full Text
- View/download PDF
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