Publications by authors named "Francesco Rossi"

277 Publications

Bronchoscopy in COVID-19 patients: When, how and why. Experience in clinical practice.

Monaldi Arch Chest Dis 2021 Mar 2;91(2). Epub 2021 Mar 2.

Unit of Bronchology, Monaldi Hospital, Azienda Ospedaliera dei Colli, Naples.

Severe Acute Respiratory Syndrome due to Coronavirus-19 (SARS-CoV-2) is caused by combined alveolar-capillary lung damage, with bilateral pneumonia and thrombosis, which often causes respiratory failure. Proper COVID-19 management requires high skills in airway control and the need to perform aerosol-generating procedures such as bronchoscopy, which can increase the possibility of virus spreading among healthcare professionals. In an epidemiologically delicate moment, the multidisciplinary decision on "WHEN, HOW and WHY" to perform bronchoscopies minimizing the risk of COVID-19 transmission, represented a great challenge for all specialists engaged in bronchoscopic procedures. In this work authors want to share all technical aspects of 87 videobronchoscopies performed in confirmed or suspected COVID-19 patients, from 3rd to 6th January 2020, describing the reason, the organizational and operational model and patients characteristics. Was also evaluated the impact of high-risk procedures such as bronchoscopy on the personnel involved. The disclosure of all technical details, represents, in the opinion of the authors, an important contribution, capable of providing support to all physicians engaged in bronchoscopy procedures in confirmed or suspected COVID-19 patients.
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http://dx.doi.org/10.4081/monaldi.2021.1744DOI Listing
March 2021

Impact of the COVID-19 pandemic on the Emergency Department of a tertiary children's hospital.

Ital J Pediatr 2021 Jan 29;47(1):21. Epub 2021 Jan 29.

Medical Direction, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Background: Italy was the first country in Europe affected by COVID-19: the emergency started on February 20, 2020, culminating with national lockdown on March 11, which terminated on May 4, 2020. We describe how the pandemic affected Emergency Department (ED) accesses in a tertiary children's hospital, composed by two different pediatric centers, one located in Rome's city center and the second, Palidoro (regional COVID-19 center), in its surrounding metropolitan area, both in the Lazio region, analyzing the profile of admitted patients during the pandemic period in terms of their general characteristics (at presentation in the ED's) and urgent hospitalizations compared to prepandemic period.

Methods: The study compare the period between the 21st of February and the 30th of April 2020, covering the three phases of the national responses (this period will be referred to as the pandemic period) with the same period of 2019 (prepandemic period). The study analyzes the number of ED visits and urgent hospitalizations and their distribution according to selected characteristics.

Results: The reduction of ED visits was 56 and 62%, respectively in Rome and Palidoro centers. The higher relative decline was encountered for Diseases of Respiratory System, and for Diseases of the Nervous System and Sense Organs. A doubling of the relative frequency of hospitalizations was observed, going from 14.2 to 24.4% in Rome and from 6.4 to 10.3% in Palidoro. In terms of absolute daily numbers the decrease of urgent hospitalizations was less sharp than ED visits. For pathologies such as peritonitis, tumors or other possible life-treathening conditions we did not observe a significative increase due to delayed access.

Conclusions: In the pandemic period there was a general reduction in the number of children referred to ED, such reduction was greater in low-acuity levels. The reduction for respiratory tract infections and other communicable diseases during school closure and the national lockdown must make us reflect on the possible impact that these conditions may have on the health system, in particular the ED, at the reopening of schools. The major problem remains the fear for possible diagnostic delays in life-threatening or crippling diseases; our study doesn't demonstrate an increase in number or significant delay in some serious conditions such as tumors, peritonitis, diabetic ketoacidosis, ileo-colic intussusception and testis/ovary torsion. A continuous, deep re-organizational process step by step of the ED is nececessary in the present and upcoming pandemic situation.
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http://dx.doi.org/10.1186/s13052-021-00976-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844808PMC
January 2021

Structural Health Monitoring Based on Acoustic Emissions: Validation on a Prestressed Concrete Bridge Tested to Failure.

Sensors (Basel) 2020 Dec 18;20(24). Epub 2020 Dec 18.

Department of Civil, Environmental and Mechanical Engineering, University of Trento, 38123 Trento, Italy.

The increasing number of bridges approaching their design life has prompted researchers and operators to develop innovative structural health monitoring (SHM) techniques. An acoustic emissions (AE) method is a passive SHM approach based on the detection of elastic waves in structural components generated by damages, such as the initiation and propagation of cracks in concrete and the failure of steel wires. In this paper, we discuss the effectiveness of AE techniques by analyzing records acquired during a load test on a full-size prestressed concrete bridge span. The bridge is a 1968 structure currently decommissioned but perfectly representative, by type, age, and deterioration state of similar bridges in operation on the Italian highway network. It underwent a sequence of loading and unloading cycles with a progressively increasing load up to failure. We analyzed the AE signals recorded during the load test and examined how far their features (number of hits, amplitude, signal strength, and peak frequency) allow us to detect, quantify, and classify damages. We conclude that AE can be successfully used in permanent monitoring to provide information on the cracking state and the maximum load withstood. They can also be used as a non-destructive technique to recognize whether a structural member is cracked. Finally, we noticed that AE allow classifying different types of damage, although further experiments are needed to establish and validate a robust classification procedure.
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http://dx.doi.org/10.3390/s20247272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766546PMC
December 2020

PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database.

Drug Saf 2021 Mar 22;44(3):337-349. Epub 2020 Dec 22.

Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

Introduction: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9Is) were associated with a risk of neurocognitive adverse drug reactions (ADRs).

Objective: We aimed to investigate the occurrence of neuropsychiatric ADRs related to PCSK9Is.

Methods: We analyzed Individual Case Safety Reports (ICSRs) sent through the European pharmacovigilance database that reported alirocumab or evolocumab as the suspected drug and at least one neurological or psychiatric ADR. The reporting odds ratio (ROR) was computed to compare the probability of reporting ICSRs with neuropsychiatric ADRs between alirocumab, evolocumab and statins.

Results: Overall, 2041 ICSRs with alirocumab and/or evolocumab as the suspected drug described the occurrence of neuropsychiatric ADRs. The most reported preferred terms for both drugs were headache, insomnia and depression. No difference between alirocumab and evolocumab was observed for the RORs of ICSRs with ADRs belonging to the System Organ Classes (SOCs) 'Nervous system disorders' or 'Psychiatric disorders' (ROR 1.02, 95% confidence interval 0.91-1.14; and 1.12, 95% CI 0.94-1.34, respectively), while evolocumab and alirocumab had a higher reporting probability of ICSRs with ADRs belonging to the SOC 'Nervous system disorders' compared with atorvastatin and fluvastatin. A lower reporting probability was instead found for ICSRs with ADRs belonging to the SOC 'Psychiatric disorders' for evolocumab and alirocumab versus simvastatin, pravastatin and rosuvastatin.

Conclusion: Our results demonstrated that 22.7% of all ICSRs reporting alirocumab or evolocumab as suspect drugs described the occurrence of neuropsychiatric ADRs. The ROR showed that evolocumab and alirocumab had a higher reporting probability of neurological ADRs compared with statins. Further data from real-life contexts are needed.
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http://dx.doi.org/10.1007/s40264-020-01021-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892743PMC
March 2021

We Really Need Clear Guidelines and Recommendations for Safer and Proper Use of Aripiprazole and Risperidone in a Pediatric Population: Real-World Analysis of EudraVigilance Database.

Front Psychiatry 2020 2;11:550201. Epub 2020 Dec 2.

Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania "Luigi Vanvitelli", Naples, Italy.

Although aripiprazole and risperidone are used widespread in pediatrics, there are still limited pieces of evidence on their actual safety profile. By using the EudraVigilance database, we carried out an analysis to perform a comprehensive overview of reported adverse events among children and adolescents treated with aripiprazole and risperidone. Descriptive analysis was performed of all individual case safety reports (ISCRs) submitted to EudraVigilance associated with aripiprazole and risperidone and related to the pediatric population from 2016 to 2018. A total of 855 and 2,242 ISCRs for aripiprazole and risperidone, respectively, were recorded for a total of 11,042 suspected adverse drug reactions (2,993 for aripiprazole and 8,049 for risperidone). Most ISCRs were related to male patients (65.0 and 86.3% for aripiprazole and risperidone, respectively) and were serious (81.0 and 94.1% for aripiprazole and risperidone, respectively). Schizophrenia spectrum and other psychotic disorders, such as disruptive, impulse-control, and conduct disorders, and autism spectrum disorder were the top three clinical indications for aripiprazole (19.0, 16.1, and 11.6%, respectively). For risperidone, attention-deficit/hyperactivity disorder (25.4%), disruptive, impulse-control, and conduct disorders (17.1%), and bipolar and related disorders (14.2%) were more commonly reported as clinical indications. Data also showed a high proportion of use for clinical conditions not authorized in children. Psychiatric disorders were the main related adverse events for aripiprazole (20.2%), and among these, suicidal behavior was one of the most reported (14.9%). Reproductive system and breast disorders were the main related adverse events for risperidone (19.8%), and gynecomastia was the most reported event; metabolism and nutrition disorders, mainly reported as weight gain disorders, were more reported in children (3-11 years) than in adolescents (12-17 years). Our results demonstrate that spontaneously reported adverse events associated with aripiprazole and risperidone reflect what is already known in terms of safety profile, although with about 90% of them being serious. This analysis stresses the need for further studies and effective training and information activities to better define the actual benefit/risk ratio of these drugs in pediatric patients.
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http://dx.doi.org/10.3389/fpsyt.2020.550201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738432PMC
December 2020

Deficit of glucocorticoid-induced leucine zipper amplifies angiotensin-induced cardiomyocyte hypertrophy and diastolic dysfunction.

J Cell Mol Med 2021 Jan 28;25(1):217-228. Epub 2020 Nov 28.

Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.

Poor prognosis in heart failure and the lack of real breakthrough strategies validate targeting myocardial remodelling and the intracellular signalling involved in this process. So far, there are no effective strategies to counteract hypertrophy, an independent predictor of heart failure progression and death. Glucocorticoid-induced leucine zipper (GILZ) is involved in inflammatory signalling, but its role in cardiac biology is unknown. Using GILZ-knockout (KO) mice and an experimental model of hypertrophy and diastolic dysfunction, we addressed the role of GILZ in adverse myocardial remodelling. Infusion of angiotensin II (Ang II) resulted in myocardial dysfunction, inflammation, apoptosis, fibrosis, capillary rarefaction and hypertrophy. Interestingly, GILZ-KO showed more evident diastolic dysfunction and aggravated hypertrophic response compared with WT after Ang II administration. Both cardiomyocyte and left ventricular hypertrophy were more pronounced in GILZ-KO mice. On the other hand, Ang II-induced inflammatory and fibrotic phenomena, cell death and reduction in microvascular density, remained invariant between the WT and KO groups. The analysis of regulators of hypertrophic response, GATA4 and FoxP3, demonstrated an up-regulation in WT mice infused with Ang II; conversely, such an increase did not occur in GILZ-KO hearts. These data on myocardial response to Ang II in mice lacking GILZ indicate that this protein is a new element that can be mechanistically involved in cardiovascular pathology.
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http://dx.doi.org/10.1111/jcmm.15913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810940PMC
January 2021

Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells.

Int J Mol Sci 2020 Oct 26;21(21). Epub 2020 Oct 26.

Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert pleiotropic effects on cardiac cell biology which are not yet fully understood. Here we tested whether statin treatment affects resident endogenous cardiac stem/progenitor cell (CSC) activation in vitro and in vivo after myocardial infarction (MI). Statins (Rosuvastatin, Simvastatin and Pravastatin) significantly increased CSC expansion in vitro as measured by both BrdU incorporation and cell growth curve. Additionally, statins increased CSC clonal expansion and cardiosphere formation. The effects of statins on CSC growth and differentiation depended on Akt phosphorylation. Twenty-eight days after myocardial infarction by permanent coronary ligation in rats, the number of endogenous CSCs in the infarct border zone was significantly increased by Rosuvastatin-treatment as compared to untreated controls. Additionally, commitment of the activated CSCs into the myogenic lineage (c-kit/Gata4 CSCs) was increased by Rosuvastatin administration. Accordingly, Rosuvastatin fostered new cardiomyocyte formation after MI. Finally, Rosuvastatin treatment reversed the cardiomyogenic defects of CSCs in c-kit haploinsufficient mice, increasing new cardiomyocyte formation by endogenous CSCs in these mice after myocardial infarction. In summary, statins, by sustaining Akt activation, foster CSC growth and differentiation in vitro and in vivo. The activation and differentiation of the endogenous CSC pool and consequent new myocyte formation by statins improve myocardial remodeling after coronary occlusion in rodents. Similar effects might contribute to the beneficial effects of statins on human cardiovascular diseases.
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http://dx.doi.org/10.3390/ijms21217927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663580PMC
October 2020

[The specialist skills of the nurse in hemodialysis: report of an explorative survey. A challenge for professional recognition].

G Ital Nefrol 2020 Oct 5;37(5). Epub 2020 Oct 5.

Università Vita-Salute San Raffaele, Milano, Italy.

Nursing requires a complex set of skills encompassing professional clinical judgment, values and attitudes. In order to outline the future career path of the specialist nurse, the European Federation of Nurses Association compared the EU Directive 2013/55/EU with the Competency Framework, an important document on guidelines written by a group of experts and focusing on the recognition of nurses' educational requirements. The aim of our research is to identify the special skill set required from nurses on haemodialysis wards through the development of an exploratory survey and the comparison of its results with the EFN guidelines and the Directive 2013/55/EU. The survey was conducted across eighteen dialysis centers in Tuscany. Through focus groups, debates and reflections, 28 skills were identified as pertaining exclusively to nurses working with haemodialysis patients. This preliminary study aims at demonstrating the need to define and recognize these specialist skills in order to ensure an effective and integrated nursing leadership in disease management.
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October 2020

Tisagenlecleucel in Children and Young Adults: Reverse Translational Research by Using Real-World Safety Data.

Pharmaceuticals (Basel) 2020 Sep 21;13(9). Epub 2020 Sep 21.

Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania "Luigi Vanvitelli", Via Costantinopoli 16, 80138 Naples, Italy.

Tisagenlecleucel has revolutionized the pharmacological approach of relapsed or refractory B-cell acute lymphoblastic leukaemialeukaemia in paediatrics. The safety profile of tisagenlecleucel still needs to be better defined. The aim of this study was a post-marketing evaluation of the safety of tisagenlecleucel through the analysis of the Eudravigilance database with focus on the paediatric population. From 2017 to 2020, one third of Individual Case Safety Reports referring to tisagenlecleucel (117/364) have been collected in paediatrics, on average nine year-old boys. Overall, 92% of the638 adverse events were serious and caused or prolonged hospitalisation. A total of 55 adverse events presented a fatal outcome, mainly due to progression of malignant neoplasm ( = 10; 18.2%), recurrence of acute lymphocytic leukaemia ( = 6; 10.9%) or occurrence of acute lymphocytic leukaemia ( = 5; 9.1%). Cytokine release syndrome was commonly reported after tisagenlecleucel infusion (54/638), followed by pyrexia (45/638) and hypotension (27/638). Only 18/638 events referred to neurotoxicity, none of them resulted in death. More than one third of cases (41/117) were suggestive of therapeutic failure. This first post-marketing analysis confirms pre-approval evidence of the safety profile of tisagenlecleucel in paediatrics. Since only a few years of marketing is available, further followed-up studies need to be performed to investigate longer-term safety of tisagenlecleucel.
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http://dx.doi.org/10.3390/ph13090258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558916PMC
September 2020

Traceability of Pediatric Antibiotic Purchasing Pathways in Italy: A Nationwide Real-World Drug Utilization Analysis.

Front Pharmacol 2020 12;11:1232. Epub 2020 Aug 12.

Department of Clinical and Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy.

Purpose: The aim of the present study was to describe the purchasing patterns of a set of antibiotics used exclusively in an out-patient pediatric setting in Italy using the Farma360 wholesale drug database (IQVIA Solutions Italy), identifying the proportion of medications which are not captured by Italian National Health Service (NHS) pharmacy claims databases and examining the implications of such findings from a public health and pharmaceutical policy perspective.

Methods: Using a systematic approach, sixty-six antibiotic pediatric formulations were selected for the 5 most commonly used antibiotics in Italy in children and adolescents: amoxicillin in combination with clavulanic acid, amoxicillin, azithromycin, clarithromycin and cefixime. The Farma360 wholesale drug purchasing database was used to identify the yearly proportion of antibiotics not purchased based on NHS reimbursement in primary care from 2015-2017 at the national level. The relationship between product cost and purchase outside the NHS was assessed by a scatterplot. All analyses were stratified by geographic area: Northwest, Northeast, Central and Southern Italy.

Results: The proportion of antibiotics not reimbursed by the NHS increased nationally from 24% in 2015 to 29% in 2017. The antibiotic with the highest proportion of purchases outside the NHS was amoxicillin, with almost two-thirds of all amoxicillin purchases in Southern Italy being made in this way in 2017. The relationship between antibiotic price and antibiotic purchase outside the NHS was almost linear for many geographic areas.

Conclusions: This study showed that a large proportion of antibiotics with a pediatric formulation is purchased outside the NHS drug purchasing pathway, especially in Southern Italy, indicating that it is not possible to fully monitor drug utilization, including appropriateness, for these antibiotics. A better strategy is needed to improve drug utilization monitoring, such as better data collection or data linkage.
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http://dx.doi.org/10.3389/fphar.2020.01232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435014PMC
August 2020

Renin-Angiotensin System and Coronavirus Disease 2019: A Narrative Review.

Front Cardiovasc Med 2020 11;7:143. Epub 2020 Aug 11.

Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

Although clinical manifestations of the 2019 novel coronavirus disease pandemic (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), are mainly respiratory symptoms, patients can also develop severe cardiovascular damage. Therefore, understanding the damage caused by SARS-COV-2 to the cardiovascular system and the underlying mechanisms is fundamental. The cardiovascular damage may be related to the imbalance of the renin-angiotensin-system (RAS) as this virus binds the Angiotensin-Converting-Enzyme 2 (ACE2), expressed on the lung alveolar epithelial cells, to enter into cells. Virus internalization may cause a downregulation of ACE2 on host cell surface that could lead to a local increased level of angiotensin II (AII) and a reduced level of angiotensin 1-7 (A1-7). An imbalance between these angiotensins may be responsible for the lung and heart damage. Pharmacological strategies that interfere with the viral attachment to ACE2 (umifenovir and hydroxychloroquine/chloroquine) or that modulate the RAS (analogous of A1-7 and ACE2, losartan) are in clinical development for COVID-19. The use of RAS inhibitors has also become a matter of public concern as these drugs may increase the mRNA expression and levels of ACE2 and impact the virulence and transmission of SARS-COV-2. Data on the effect of RAS inhibitors on ACE2 mRNA expression are scarce. Scientific societies expressed their opinion on continuing the therapy with RAS inhibitors in patients with COVID-19 and underlying cardiovascular diseases. In conclusion, RAS may play a role in SARS-COV-2-induced cardiac and pulmonary damage. Further studies are needed to better understand the role of RAS in COVID-19 and to guide decision on the use of RAS inhibitors.
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http://dx.doi.org/10.3389/fcvm.2020.00143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431661PMC
August 2020

Covid-19 Kills More Men Than Women: An Overview of Possible Reasons.

Front Cardiovasc Med 2020 17;7:131. Epub 2020 Jul 17.

Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.

The high mortality observed in Covid-19 patients may be related to unrecognized pulmonary embolism, pulmonary thrombosis, or other underlying cardiovascular diseases. Recent data have highlighted that the mortality rate of Covid-19 seems to be higher in male patients compared to females. In this paper, we have analyzed possible factors that may underline this sex difference in terms of activity of the immune system and its modulation by sex hormones, coagulation pattern, and preexisting cardiovascular diseases as well as effects deriving from smoking and drinking habits. Future studies are needed to evaluate the effects of sex differences on the prevalence of infections, including Covid-19, its outcome, and the responses to antiviral treatments.
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http://dx.doi.org/10.3389/fcvm.2020.00131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380096PMC
July 2020

Cardioprotective effects of miR-34a silencing in a rat model of doxorubicin toxicity.

Sci Rep 2020 07 23;10(1):12250. Epub 2020 Jul 23.

Department of Experimental Medicine, Section of Pharmacology, University of Campania "Luigi Vanvitelli", Via Costantinopoli 16, 80138, Naples, Italy.

Cardiotoxicity remains a serious problem in anthracycline-treated oncologic patients. Therapeutic modulation of microRNA expression is emerging as a cardioprotective approach in several cardiovascular pathologies. MiR-34a increased in animals and patients exposed to anthracyclines and is involved in cardiac repair. In our previous study, we demonstrated beneficial effects of miR-34a silencing in rat cardiac cells exposed to doxorubicin (DOXO). The aim of the present work is to evaluate the potential cardioprotective properties of a specific antimiR-34a (Ant34a) in an experimental model of DOXO-induced cardiotoxicity. Results indicate that in our model systemic administration of Ant34a completely silences miR-34a myocardial expression and importantly attenuates DOXO-induced cardiac dysfunction. Ant34a systemic delivery in DOXO-treated rats triggers an upregulation of prosurvival miR-34a targets Bcl-2 and SIRT1 that mediate a reduction of DOXO-induced cardiac damage represented by myocardial apoptosis, senescence, fibrosis and inflammation. These findings suggest that miR-34a therapeutic inhibition may have clinical relevance to attenuate DOXO-induced toxicity in the heart of oncologic patients.
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http://dx.doi.org/10.1038/s41598-020-69038-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378226PMC
July 2020

Correction to: Angiotensin II and angiotensin 1-7: which is their role in atrial fibrillation?

Heart Fail Rev 2020 Sep;25(5):897

Department of Experimental Medicine, Section of Pharmacology L. Donatelli, University of Campania "Luigi Vanvitelli", Via Santa Maria di Costantinopoli 16, 80138, Naples, Italy.

There was a mistake in Prof. Giuseppe Massimo Claudio Rosano's affiliation.
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http://dx.doi.org/10.1007/s10741-020-10000-wDOI Listing
September 2020

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database.

Front Pharmacol 2020 9;11:830. Epub 2020 Jun 9.

Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: The introduction of immune checkpoint inhibitors (ICIs) in clinical practice has brought significant benefits for patients. Seven ICIs are available in Europe: nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, and ipilimumab. Despite their proven clinical efficacy, these innovative drugs may cause serious immune-related adverse drugs reactions (irADRs). Given the significance of these ADRs for patients' health, we analyzed individual case safety reports (ICSRs) related to ICIs, focusing on those reporting irADRs, collected in the Italian spontaneous reporting database.

Methods: We analyzed ICI-induced irADRs collected in the Italian Pharmacovigilance database (Rete Nazionale di Farmacovigilanza [RNF]) from January 1, 2002, to February 28, 2019, focusing on those reported in the Campania Region. We retrieved from an open-access Italian pharmacovigilance system, the RAM system (for national safety data), and from the RNF (for Campania safety data) all ICSRs reporting ADRs related to ICIs authorized until the analysis date. Focusing on irADRs, we performed descriptive and disproportionality analyses through the reporting odds ratio (ROR) with 95% confidence interval.

Results: . Among 2,088 ICI-related ICSRs, 801 reported irADRs. The majority of such ADRs occurred in male patients reporting gastrointestinal and skin toxicities. Nivolumab and pembrolizumab were drugs most commonly reported as suspect drugs. Compared to other ICIs, ROR was statistically significant for pembrolizumab and ipilimumab.. Out of 253 ICI-related ICSRs sent to Regional Pharmacovigilance Center of Campania Region, 121 reported at least one ICI-induced irADR. These were serious in 37.2% of cases and had an unfavorable outcome in 32.2% of cases. Overall, out of 8 ICSRs reported ADR with a fatal outcome, four reported irADRs. From disproportionality analyses on Campania Region ICSRs, statistically significant ROR emerged only for ipilimumab.

Conclusions: Our results showed that during the study period several serious irADRs were reported, some of which had fatal outcome. Given the clinical relevance of irADRs, further investigations in real-life context are necessary for a better characterization of ICIs safety profiles. Oncologists should be trained to early recognize and adequately manage irADRs. Patients should also be educated to immediately report any new symptom or worsening of pre-existed ones during the ICI treatment.
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http://dx.doi.org/10.3389/fphar.2020.00830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295943PMC
June 2020

Treatment with Class A CpG Oligodeoxynucleotides in Cats with Naturally Occurring Feline Parvovirus Infection: A Prospective Study.

Viruses 2020 06 12;12(6). Epub 2020 Jun 12.

AniCura Istituto Veterinario di Novara, Strada Provinciale 9, 28060 Granozzo con Monticello (NO), Italy.

Feline parvovirus (FPV) causes severe gastroenteritis and leukopenia in cats; the outcome is poor. Information regarding specific treatments is lacking. Class A CpG oligodeoxynucleotides (CpG-A) are short single-stranded DNAs, stimulating type I interferon production. In cats, CpG-A induced an antiviral response in vivo and inhibited FPV replication in vitro. The aim was to prospectively investigate the effects of CpG-A on survival, clinical score, hematological findings, antiviral response (cytokines), viremia, and fecal shedding (real-time qPCR) in cats naturally infected with FPV. Forty-two FPV-infected cats were randomized to receive 100 µg/kg of CpG-A ( = 22) or placebo ( = 20) subcutaneously, on admission and after 48 h. Blood and fecal samples were collected on admission, after 1, 3, and 7 days. All 22 cats showed short duration pain during CpG-A injections. The survival rate, clinical score, leukocyte and erythrocyte counts, viremia, and fecal shedding at any time-point did not differ between cats treated with CpG-A (50%) and placebo (40%). Antiviral myxovirus resistance () gene transcription increased in both groups from day 1 to 3 ( = 0.005). Antibodies against FPV on admission were associated with survival in cats ( = 0.002). In conclusion, CpG-A treatment did not improve the outcome in cats with FPV infection. FPV infection produced an antiviral response.
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http://dx.doi.org/10.3390/v12060640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354499PMC
June 2020

Identification of cofilin 1 as a candidate protein associated to mouse visual cortex plasticity.

Neurosci Lett 2020 07 22;731:135056. Epub 2020 May 22.

Laboratorio de Neurociencias "Neuroplasticity Unit", Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay. Electronic address:

In order to characterize the mechanisms controlling plasticity in the mouse visual cortex, we used, for the first time on brain samples, an unconventional proteomic approach to separate acid-extracted proteins by bi-dimensional electrophoresis (AUT/SDS or AUT/AU gels). The analysis was performed on high plasticity critical period young vs. low plasticity adult, and on fluoxetine-induced high plasticity vs. low plasticity untreated adult mice. Mass spectrometry allowed for the identification of 11 proteins that are differentially expressed between critical period and adult mice, and 5 between fluoxetine-treated and control adult mice. We then focused on cofilin 1, as the intensity level of the corresponding spot on 2D gels was higher in both high plasticity conditions. Western blot showed that cofilin 1 expression is dynamically regulated during postnatal life, reaching a peak at the critical period, and decreasing at adult stage, and that it increases in fluoxetine-treated vs. untreated adult mice. In summary, by using a 2D gel electrophoresis differential approach on basic proteins followed by mass spectrometry and immunoblot analysis, we identified cofilin 1 as a potential candidate controlling plasticity levels of the mouse visual cortex.
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http://dx.doi.org/10.1016/j.neulet.2020.135056DOI Listing
July 2020

Amelioration of diastolic dysfunction by dapagliflozin in a non-diabetic model involves coronary endothelium.

Pharmacol Res 2020 07 28;157:104781. Epub 2020 Apr 28.

Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via Costantinopoli 16, 80138 Naples, Italy.

The results of trials with sodium-glucose cotransporter 2 (SGLT2) inhibitors raised the possibility that this class of drugs provides cardiovascular benefits independently from their anti-diabetic effects, although the mechanisms are unknown. Therefore, we tested the effects of SGLT2 inhibitor dapagliflozin on the progression of experimental heart disease in a non-diabetic model of heart failure with preserved ejection fraction. Dahl salt-sensitive rats were fed a high-salt diet to induce hypertension and diastolic dysfunction and were then treated with dapagliflozin for six weeks. Dapagliflozin ameliorated diastolic function as documented by echo-Doppler and heart catheterization, while blood pressure remained markedly elevated. Chronic in vivo treatment with dapagliflozin reduced diastolic Ca and Na overload and increased Ca transient amplitude in ventricular cardiomyocytes, although no direct action of dapagliflozin on isolated cardiomyocytes was observed. Dapagliflozin reversed endothelial activation and endothelial nitric oxide synthase deficit, with reduced cardiac inflammation and consequent attenuation of pro-fibrotic signaling. The potential involvement of coronary endothelium was supported by the endothelial upregulation of Na/H exchanger 1in vivo and direct effects on dapagliflozin on the activity of this exchanger in endothelial cells in vitro. In conclusions, several mechanisms may cumulatively play a significant role in the dapagliflozin-associated cardioprotection. Dapagliflozin ameliorates diastolic function and exerts a positive effect on the myocardium, possibly targeting coronary endothelium. The lower degree of endothelial dysfunction, inflammation and fibrosis translate into improved myocardial performance.
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http://dx.doi.org/10.1016/j.phrs.2020.104781DOI Listing
July 2020

Current pharmacological treatments for COVID-19: What's next?

Br J Pharmacol 2020 11 15;177(21):4813-4824. Epub 2020 May 15.

Department of Experimental Medicine, Università degli studi della Campania "Luigi Vanvitelli", Naples, Italy.

Since December 2019 SARS-Cov-2 was found responsible for the disease COVID-19, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID-19, focusing on their antiviral, immune-modulatory and/or anti-inflammatory actions. Where available, data from clinical trials involving patients with COVID-19 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID-19 and reducing its symptoms and complications. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.
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http://dx.doi.org/10.1111/bph.15072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264618PMC
November 2020

SARS-Cov-2 infection: Response of human immune system and possible implications for the rapid test and treatment.

Int Immunopharmacol 2020 Jul 16;84:106519. Epub 2020 Apr 16.

Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Regional Centre of Pharmacovigilance, Campania Region, Naples, Italy.

The new coronavirus outbreak is an ongoing pandemic that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new coronavirus SARS-Cov-2 belongs to the subfamily of β-coronaviruses and shares 79.5% of the genetic sequence of SARS-CoV, the causative agent of the epidemic that started in 2002 and ended in 2004. Considering the clinical impact of the new outbreak, it is highly important to study the potential responses of the human immune system during the SARS-CoV-2 infection as well as the role of virus-specific T cells and by B-lymphocytes. Moreover, specific data on the production of IgG and IgM is crucial to allow the rapid identification of the infection. In this paper we also described the importance of sensitive and specific rapid test for SARS-CoV-2. Indeed, this test represents an important immunological tool aimed at identifying the precise phase of the infection in order to undertake a more appropriate pharmacological treatment. Lastly, we provided an overview of pharmacological treatments aimed to reduce inflammatory processes underlying the infection and the need for the discovery of a new vaccine against SARS-CoV-2.
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http://dx.doi.org/10.1016/j.intimp.2020.106519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161502PMC
July 2020

Gold Nanorods Embedded in Polymeric Film for Killing Bacteria by Generating Reactive Oxygen Species with Light.

ACS Appl Bio Mater 2019 Jul 14;2(7):3059-3067. Epub 2019 May 14.

Institute of Materials Research and Engineering, ASTAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, #8-03, Singapore 138634, Singapore.

For the first time, anisotropic gold nanorods (AuNRs) were embedded with a photosensitizer dye (crystal violet) in polyurethane (PU) matrix to create the effective antimicrobial film, capable of killing Gram-negative bacteria on its surface when exposed to white light. The dye, when activated with white light, interacts with the AuNRs to generate reactive oxygen species (ROS), which kill bacteria. With a proper control of the aspect ratio (2.1-2.4) and coating of the AuNRs, the film can be tuned to reduce the bacteria population of one to four orders of magnitude (1-log to 4-log) under 11 klux of light, for an exposure to light between 1 to 3 h. Particularly it could reduce 10 cfu/cm to the level of 1-5 cfu/cm in 3 h of light exposure. This was a desired performance for use on hospital surfaces. In addition, the system showed antimicrobial effect only when exposed to light, which eliminated the concern for a cumulative toxic effect on subjects exposed to the material for a long period of time and limited the time given to the bacteria to develop resistance against the system. Furthermore, this process of sterilization could be carried out by a commercially available white light lamp, which when in use did not interrupt the normal routine operation of the environment.
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http://dx.doi.org/10.1021/acsabm.9b00343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009025PMC
July 2019

SMC5/6 acts jointly with Fanconi anemia factors to support DNA repair and genome stability.

EMBO Rep 2020 02 23;21(2):e48222. Epub 2019 Dec 23.

The FIRC Institute of Molecular Oncology, IFOM, Milan, Italy.

SMC5/6 function in genome integrity remains elusive. Here, we show that SMC5 dysfunction in avian DT40 B cells causes mitotic delay and hypersensitivity toward DNA intra- and inter-strand crosslinkers (ICLs), with smc5 mutants being epistatic to FANCC and FANCM mutations affecting the Fanconi anemia (FA) pathway. Mutations in the checkpoint clamp loader RAD17 and the DNA helicase DDX11, acting in an FA-like pathway, do not aggravate the damage sensitivity caused by SMC5 dysfunction in DT40 cells. SMC5/6 knockdown in HeLa cells causes MMC sensitivity, increases nuclear bridges, micronuclei, and mitotic catastrophes in a manner similar and non-additive to FANCD2 knockdown. In both DT40 and HeLa systems, SMC5/6 deficiency does not affect FANCD2 ubiquitylation and, unlike FANCD2 depletion, RAD51 focus formation. SMC5/6 components further physically interact with FANCD2-I in human cells. Altogether, our data suggest that SMC5/6 functions jointly with the FA pathway to support genome integrity and DNA repair and may be implicated in FA or FA-related human disorders.
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http://dx.doi.org/10.15252/embr.201948222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001510PMC
February 2020

The Role of Viral Coinfection in Bronchiolitis Treated With High-Flow Nasal Cannula at Pediatric Emergency Department During 2 Consecutive Seasons: An Observational Study.

Pediatr Infect Dis J 2020 02;39(2):102-107

From the Pediatric Emergency Department.

Background: The role of multiple respiratory viruses in bronchiolitis treated with high-flow nasal cannula (HFNC) has not been thoroughly investigated. We evaluated the contribution of coinfection on clinical course of bronchiolitis treated with HFNC and on response to this treatment.

Methods: We selected 120 children with bronchiolitis, younger than 12 months, admitted to Emergency Department between 2016 and 2018 and treated with HFNC. We compared single and multiple virus infections in relation to specific outcomes such as the clinical response to HFNC and the HFNC failure. The multiple virus infection was defined by the detection of 2 or more viruses in nasopharyngeal aspirates. The HFNC failure was defined as escalation to higher level of care, including Helmet-Continuous Positive Airway Pressure, invasive ventilation or transfer to pediatric intensive care unit within 48 hours from the time of HFNC initiation. We also performed a comparison between HFNC failure and HFNC not-failure groups according to the number of virus and the type of virus.

Results: The severity score post-HFNC initiation was significantly associated with coinfection [odds ratio (OR): 1.361; 95% confidence interval (CI): 1.036-1.786; P = 0.027]. The likelihood of coinfection decreased by 23.1% for each increase of saturation O2 after HFNC initiation (OR: 0.769; 95% CI: 0.609-0.972; P = 0.028). Atelectasis was more likely to occur in coinfection (OR: 2.923; 95% CI: 1.049-8.148; P = 0.04). The duration of HFNC treatment increased significantly in coinfection (OR: 1.018; 95% CI: 1.006-1.029; P = 0.002). No significant differences were described between HFNC failure and the number and the type of detected viruses.

Conclusions: The detection of multiple viruses and the type of virus did not influence the HFNC failure, although the coinfection was associated with a deterioration of severity score, a longer HFNC treatment and a major presence of atelectasis. The role of coinfection on HFNC treatment might subtend a complex interplay between multiple viruses and host susceptibility.
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http://dx.doi.org/10.1097/INF.0000000000002512DOI Listing
February 2020

The European clinical trials regulation (No 536/2014): changes and challenges.

Expert Rev Clin Pharmacol 2019 Nov 21;12(11):1027-1032. Epub 2019 Oct 21.

Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology - Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy.

: In recent years, a significant decrease in the number of clinical trials was observed among EU countries. This decline could be attributed to several factors, including the financial crisis of EU countries, the requirements introduced by the Directive 2001/20/EC and the increased market attractiveness of not EU countries.: The EU Clinical Trials Regulation (CTR) 536/2014 was adopted in April 2014 by the European Parliament. The main changes arising from the CTR, including but not limited to the activation of a new EU portal, the potentiation of the already existing EU database and the requirement to provide plain language summaries of clinical trials, are aimed to improve the competitiveness of Europe in clinical research scenario and promote a faster approval of clinical trials. In this review, data related to the CTR 536/2014 and its potential implications in terms of transparency are based on pertinent papers that were retrieved by the PubMed database and the internet.: The full implementation of the CTR 536/2014 requires close cooperation between EU member states and regulatory agencies. Some aspects should be carefully considered such as the interaction with ethics committees, the insurance coverage and the protection of personal data issues.
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http://dx.doi.org/10.1080/17512433.2019.1680282DOI Listing
November 2019

Immune-complex glomerulonephritis in cats: a retrospective study based on clinico-pathological data, histopathology and ultrastructural features.

BMC Vet Res 2019 Aug 20;15(1):303. Epub 2019 Aug 20.

Istituto Veterinario di Novara, Strada Provinciale 9, 28060 Granozzo con Monticello (NO), Novara, Italy.

Background: Chronic kidney disease (CKD) has typically a non-immune mediated origin in cats and immune-complex glomerulonephritis (ICGN) is scarcely described. Aims of this study were to characterize ICGN by light and electron microscopy and identify associations with clinico-pathological findings. In addition, comparisons between cats with ICGN and non immune-complex glomerulonephritis (non-ICGN) were performed. Renal samples examined between 2010 and 2019 were considered if both light and electron microscopy were performed. Signalment, feline immunodeficiency virus (FIV) and leukemia virus (FeLV) status, serum creatinine concentration, urine protein-to-creatinine (UPC) ratio, systolic blood pressure (SBP) and International Renal Interest Society (IRIS) stage were retrieved and used for comparisons.

Results: Sixty-eight client-owned cats were included. Thirty-seven cats (54.4%) had ICGN and 31 (45.6%) non-ICGN. Eighteen (48.6%) with ICGN had membranous glomerulonephropathy (MGN), 14 (37.8%) membranoproliferative glomerulonephritis (MPGN), and 5 (13.5%) mesangioproliferative glomerulonephritis (MeGN). Clinico-pathological data were not associated with any type of ICGN. Among cats with non-ICGN, 11 (35.5%) had end-stage CKD, 9 (29%) focal segmental glomerulosclerosis, 6 (19.4%) global and multifocal mesangiosclerosis, 2 (6.5%) glomerular atrophy, 2 (6.5%) renal dysplasia and 1 (3.1%) amyloidosis. Eight (25.8%) cats with non-ICGN had chronic interstitial nephritis (CIN) grade 1, 13 (41.9%) grade 2 and 10 (32.3%) grade 3; creatinine and UPC ratio increased with CIN grades (p = 0.001, p < 0.001). Cats with ICGN were more frequently FIV or FeLV-infected (OR:11.4; 95%CI:1.4-94.4; p = 0.024), had higher UPC ratio (OR:6.8; 95%CI:2.5-18.2; p < 0.001) and were younger (OR:0.9; 95%CI:0.7-1.0; p = 0.042) than cats with non-ICGN.

Conclusions: MGN and MPGN were the most common morphological diagnoses of ICGN in cats. Unfortunately, none of the investigated findings differentiated ICGN morphological diagnoses. Serum creatinine concentration and UPC ratio were directly associated with grades of CIN (p = 0.001 and p < 0.001, respectively), confirming previous literature. More ICGN than non-ICGN was observed in cats with retroviral infections, younger cats and higher UPC ratio.
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http://dx.doi.org/10.1186/s12917-019-2046-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702729PMC
August 2019

Beta-blocker choice and exchangeability in patients with heart failure and chronic obstructive pulmonary disease: an Italian register-based cohort study.

Sci Rep 2019 08 7;9(1):11465. Epub 2019 Aug 7.

Campania Pharmacovigilance and Pharmacoepidemiology Regional Centre, Department of Experimental Medicine, University of Campania "L. Vanvitelli", Via Santa Maria di Costantinopoli 16, 80138, Naples, Italy.

Clinical guidelines suggest that for patients with heart failure and concurrent chronic obstructive pulmonary disease (COPD), metoprolol/bisoprolol/nebivolol should be preferred over carvedilol. However, studies suggest a high proportion of carvedilol usage that remains unexplained. Therefore, we aimed to investigate the predictors of carvedilol choice in patients with heart failure and COPD that were naïve to carvedilol or metoprolol/bisoprolol/nebivolol. Caserta Local Health Unit databases (Italy) were used as data sources. Age, sex, chronic/acute comorbidities, and co-medications were included in a logistic regression model to assess predictors of carvedilol choice. Chronic comorbidities include those defined in the Elixhauser comorbidity index and all hospitalizations within two years prior to the first beta-blocker prescription. Comedications include all redeemed prescriptions within one year prior to the beta-blocker prescription. Kernel density estimations were used to assess the overlap in propensity and preference scores distributions for receiving carvedilol and thereby potential beta-blocker exchangeability. Totally, 10091 patients composed the study population; 2011 were exposed to carvedilol. The overlapping of propensity scores distributions was 57%. Accordingly, the exchangeability was not reached. Atrioventricular block (Odds Ratio, OR 8.20; 95% Confidence Interval, 95% CI 1.30-51.80), cerebrovascular thrombosis (OR 7.06; 95% CI 1.14-43.68), chronic kidney disease (OR 4.32; 95% CI 1.16-16.02), and acute heart failure (OR 1.97; 95% CI 1.28-3.03) hospitalizations were statistically significantly associated with carvedilol choice. Analogously, human insulin (OR 3.00; 95% CI 1.24-7.24), fondaparinux (OR 2.47; 95% CI 1.17-5.21) or strontium ranelate (OR 2.03; 95% CI 1.06-3.90) redeemed prescriptions. In conclusion, this study suggests the absence of beta-blockers exchangeability and a preferential choice of carvedilol in patients with heart failure, COPD and concurrent chronic kidney disease, atrioventricular block, cerebrovascular thrombosis, acute heart failure or redeeming human insulin, fondaparinux or strontium ranelate prescriptions. Therefore, it suggests that choice of prescribing carvedilol over metoprolol/bisoprolol/nebivolol is driven by differences in comorbidities and co-treatments.
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http://dx.doi.org/10.1038/s41598-019-47967-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685956PMC
August 2019

Yellow sac spider bite in pediatric patient.

Clin Toxicol (Phila) 2020 05 6;58(5):427-428. Epub 2019 Aug 6.

Regional Paediatric Poison Center, IRCCS Bambino Gesu Children's Hospital, Rome, Italy.

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http://dx.doi.org/10.1080/15563650.2019.1648821DOI Listing
May 2020

Good Pharmacovigilance Practice in Paediatrics: An Overview of the Updated European Medicines Agency Guidelines.

Paediatr Drugs 2019 10;21(5):317-321

Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", Naples, Italy.

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http://dx.doi.org/10.1007/s40272-019-00350-wDOI Listing
October 2019

Angiotensin II and angiotensin 1-7: which is their role in atrial fibrillation?

Heart Fail Rev 2020 03;25(2):367-380

Department of Experimental Medicine, Section of Pharmacology L. Donatelli, University of Campania "Luigi Vanvitelli", Via Santa Maria di Costantinopoli 16, 80138, Naples, Italy.

Atrial fibrillation (AF) is a significant cause of morbidity and mortality as well as a public health burden considering the high costs of AF-related hospitalizations. Pre-clinical and clinical evidence showed a potential role of the renin angiotensin system (RAS) in the etiopathogenesis of AF. Among RAS mediators, angiotensin II (AII) and angiotensin 1-7 (A1-7) have been mostly investigated in AF. Specifically, the stimulation of the pathway mediated by AII or the inhibition of the pathway mediated by A1-7 may participate in inducing and sustaining AF. In this review, we summarize the evidence showing that both RAS pathways may balance the onset of AF through different biological mechanisms involving inflammation, epicardial adipose tissue (EAT) accumulation, and electrical cardiac remodeling. EAT is a predictor for AF as it may induce its onset through direct (infiltration of epicardial adipocytes into the underlying atrial myocardium) and indirect (release of inflammatory adipokines, the stimulation of oxidative stress, macrophage phenotype switching, and AF triggers) mechanisms. Classic RAS blockers such as angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) may prevent AF by affecting the accumulation of the EAT, representing a useful therapeutic strategy for preventing AF especially in patients with heart failure and known left ventricular dysfunction. Further studies are necessary to prove this benefit in patients with other cardiovascular diseases. Finally, the possibility of using the A1-7 or ACE2 analogues, to enlarge current therapeutic options for AF, may represent an important field of research.
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http://dx.doi.org/10.1007/s10741-019-09837-7DOI Listing
March 2020