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Article ; Online: Frequencies of Combined Dysfunction of Cytochromes P450 2C9, 2C19, and 2D6 in an Italian Cohort: Suggestions for a More Appropriate Medication Prescribing Process.

Gentile, Giovanna / De Luca, Ottavia / Del Casale, Antonio / Salerno, Gerardo / Simmaco, Maurizio / Borro, Marina

International journal of molecular sciences

2023 Volume 24, Issue 16

Abstract: Improper drug prescription is a main cause of both drug-related harms (inefficacy and toxicity) and ineffective spending and waste of the healthcare system's resources. Nowadays, strategies to support an improved, informed prescription process may ... ...

Abstract	Improper drug prescription is a main cause of both drug-related harms (inefficacy and toxicity) and ineffective spending and waste of the healthcare system's resources. Nowadays, strategies to support an improved, informed prescription process may benefit from the adequate use of pharmacogenomic testing. Using next-generation sequencing, we analyzed the genomic profile for three major cytochromes P450 (CYP2C9, CYP2C19, CYP2D6) and studied the frequencies of dysfunctional isozymes (e.g., poor, intermediate, or rapid/ultra-rapid metabolizers) in a cohort of 298 Italian subjects. We found just 14.8% of subjects with a fully normal set of cytochromes, whereas 26.5% of subjects had combined cytochrome dysfunction (more than one isozyme involved). As improper drug prescription is more frequent, and more burdening, in polytreated patients, since drug-drug interactions also cause patient harm, we discuss the potential benefits of a more comprehensive PGX testing approach to support informed drug selection in such patients.
MeSH term(s)	Humans ; Cytochrome P-450 CYP2C9/genetics ; Drug Prescriptions ; Cytochrome P-450 CYP2D6 ; Genetic Profile ; High-Throughput Nucleotide Sequencing
Chemical Substances	Cytochrome P-450 CYP2C9 (EC 1.14.13.-) ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1)
Language	English
Publishing date	2023-08-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241612696
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Acquired Hemophilia A Treated with Recombinant Porcine Factor VIII: Case Report and Literature Review on Its Efficacy.

Borro, Matteo / Tassara, Riccardo / Paris, Luca / Artom, Nathan / Brignone, Marcello / Rebella, Lara / Tassara, Rodolfo

Hematology reports

2023 Volume 15, Issue 1, Page(s) 17–22

Abstract: Acquired hemophilia A (AHA) is a bleeding disorder due to the presence of neutralizing autoantibodies named inhibitors in patients with a previously normal hemostasis. Recent international recommendations suggest the use of bypassing agents or ... ...

Abstract	Acquired hemophilia A (AHA) is a bleeding disorder due to the presence of neutralizing autoantibodies named inhibitors in patients with a previously normal hemostasis. Recent international recommendations suggest the use of bypassing agents or substitutive therapy as the first-line treatment, usually preferring the former. The adequate hemostatic therapy needs an accurate balance between bleeding and thrombotic risks. We report a clinical case of acquired hemophilia A successfully treated with recombinant porcine factor VIII (Susoctocog alfa) as the first-line treatment. Despite the patient having a high-risk thrombotic score and a history of recent myocardial infarction, our experience showed the absence of thrombotic complications related to the use of Susoctocog alfa and a complete restoration of hemostatic parameters. Limited literature is present on the use of recombinant porcine factor VIII as a first-line treatment, and our report supports its use, especially when the thrombotic risk is high.
Language	English
Publishing date	2023-01-06
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2586645-X
ISSN	2038-8330 ; 2038-8322
ISSN (online)	2038-8330
ISSN	2038-8322
DOI	10.3390/hematolrep15010003
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Article ; Online: A Simple Method to Quantify Outward Leakage of Medical Face Masks and Barrier Face Coverings: Implication for the Overall Filtration Efficiency.

Chiera, Silvia / Cristoforetti, Alessandro / Benedetti, Luca / Nollo, Giandomenico / Borro, Luca / Mazzei, Lorenzo / Tessarolo, Francesco

International journal of environmental research and public health

2022 Volume 19, Issue 6

Abstract: Face masking proved essential to reduce transmission of COVID-19 and other respiratory infections in indoor environments, but standards and literature do not provide simple quantitative methods for quantifying air leakage at the face seal. This study ... ...

Abstract	Face masking proved essential to reduce transmission of COVID-19 and other respiratory infections in indoor environments, but standards and literature do not provide simple quantitative methods for quantifying air leakage at the face seal. This study reports an original method to quantify outward leakage and how wearing style impacts on leaks and filtration efficiency. The amount of air leakage was evaluated on four medical masks and four barrier face coverings, exploiting a theoretical model and an instrumented dummy head in a range of airflows between 30 and 160 L/min. The fraction of air leaking at the face seal of the medical masks and barrier face coverings ranged from 43% to 95% of exhaled air at 30 L/min and reduced to 10-85% at 160 L/min. Filter breathability was the main driver affecting both leak fraction and total filtration efficiency that varied from 5% to 53% and from 15% to 84% at 30 and 160 L/min, respectively. Minor changes were related to wearing style, supporting indications on the correct mask use. The fraction of air leaking from medical masks and barrier face coverings during exhalation is relevant and varies according to design and wearing style. The use of highly breathable filter materials reduces air leaks and improve total filtration efficiency.
MeSH term(s)	COVID-19/prevention & control ; Filtration ; Humans ; Masks
Language	English
Publishing date	2022-03-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19063548
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Article ; Online: Combining 3-Dimensional Electroanatomic Mapping and Cardiac Magnetic Resonance: A New Tool for Arrhythmogenic Cardiomyopathy.

Narducci, Maria Lucia / Scacciavillani, Roberto / Pelargonio, Gemma / Borro, Luca / Secinaro, Aurelio

JACC. Case reports

2022 Volume 4, Issue 18, Page(s) 1200–1202

Abstract: We present the case of a 17-year-old asymptomatic boy with a diagnosis of arrhythmogenic cardiomyopathy. Merging of cardiac magnetic resonance imaging and three-dimensional electroanatomic mapping provided striking visualization of the association ... ...

Abstract	We present the case of a 17-year-old asymptomatic boy with a diagnosis of arrhythmogenic cardiomyopathy. Merging of cardiac magnetic resonance imaging and three-dimensional electroanatomic mapping provided striking visualization of the association between structural and electrical alterations and guided the decision to implant an implantable cardioverter defibrillator. (
Language	English
Publishing date	2022-09-21
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-0849
ISSN (online)	2666-0849
DOI	10.1016/j.jaccas.2022.07.021
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Article: The Modern Surgical Approach to Pulmonary Atresia with Ventricular Septal Defect and Major Aortopulmonary Collateral Arteries.

Trezzi, Matteo / Cetrano, Enrico / Albanese, Sonia B / Borro, Luca / Secinaro, Aurelio / Carotti, Adriano

Children (Basel, Switzerland)

2022 Volume 9, Issue 4

Abstract: Pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals is a complex congenital heart defect that includes a heterogeneous subgroup of patients. Variation in the sources of pulmonary blood flow contributes to the complexity ... ...

Abstract	Pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals is a complex congenital heart defect that includes a heterogeneous subgroup of patients. Variation in the sources of pulmonary blood flow contributes to the complexity of the lesion and the diversity of approaches to its management. Unifocalization and rehabilitation focus on mobilization of collateral arteries and growth of native pulmonary arteries, respectively, with the ultimate surgical goal of achieving separated systemic and pulmonary circulations with the lowest possible right ventricular pressure. Regardless of the strategy, outcomes have altered the natural history of the disease, with a complete repair rate of approximately 80% and low early and late mortality rates. Given this heterogeneity of pulmonary vasculature, a tailored approach should be adopted for each patient, using all diagnostic methods currently offered by technical developments.
Language	English
Publishing date	2022-04-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children9040515
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Article ; Online: Predicting Dihydropyrimidine Dehydrogenase Deficiency and Related 5-Fluorouracil Toxicity: Opportunities and Challenges of

De Luca, Ottavia / Salerno, Gerardo / De Bernardini, Donatella / Torre, Maria Simona / Simmaco, Maurizio / Lionetto, Luana / Gentile, Giovanna / Borro, Marina

International journal of molecular sciences

2022 Volume 23, Issue 22

Abstract: Deficiency of dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is associated with severe toxicity induced by the anti-cancer drug 5-Fluorouracil (5-FU). DPYD genotyping of four recommended polymorphisms is widely used to predict toxicity, ...

Abstract	Deficiency of dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is associated with severe toxicity induced by the anti-cancer drug 5-Fluorouracil (5-FU). DPYD genotyping of four recommended polymorphisms is widely used to predict toxicity, yet their prediction power is limited. Increasing availability of next generation sequencing (NGS) will allow us to screen rare variants, predicting a larger fraction of DPD deficiencies. Genotype−phenotype correlations were investigated by performing DPYD exon sequencing in 94 patients assessed for DPD deficiency by the 5-FU degradation rate (5-FUDR) assay. Association of common variants with 5-FUDR was analyzed with the SNPStats software. Functional interpretation of rare variants was performed by in-silico analysis (using the HSF system and PredictSNP) and literature review. A total of 23 rare variants and 8 common variants were detected. Among common variants, a significant association was found between homozygosity for the rs72728438 (c.1974+75A>G) and decreased 5-FUDR. Haplotype analysis did not detect significant associations with 5-FUDR. Overall, in our sample cohort, NGS exon sequencing allowed us to explain 42.5% of the total DPD deficiencies. NGS sharply improves prediction of DPD deficiencies, yet a broader collection of genotype−phenotype association data is needed to enable the clinical use of sequencing data.
MeSH term(s)	Humans ; Dihydrouracil Dehydrogenase (NADP)/genetics ; Dihydrouracil Dehydrogenase (NADP)/metabolism ; Dihydropyrimidine Dehydrogenase Deficiency/diagnosis ; Dihydropyrimidine Dehydrogenase Deficiency/genetics ; Fluorouracil/adverse effects ; Fluorouracil/metabolism ; Floxuridine ; Antimetabolites, Antineoplastic/adverse effects ; Antimetabolites, Antineoplastic/metabolism ; Exons
Chemical Substances	Dihydrouracil Dehydrogenase (NADP) (EC 1.3.1.2) ; Fluorouracil (U3P01618RT) ; Floxuridine (039LU44I5M) ; Antimetabolites, Antineoplastic
Language	English
Publishing date	2022-11-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232213923
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Article: The role of air conditioning in the diffusion of Sars-CoV-2 in indoor environments: A first computational fluid dynamic model, based on investigations performed at the Vatican State Children's hospital

Borro, Luca / Mazzei, Lorenzo / Raponi, Massimiliano / Piscitelli, Prisco / Miani, Alessandro / Secinaro, Aurelio

Environmental research. 2021 Feb., v. 193

2021

Abstract: About 15 million people worldwide were affected by the Sars-Cov-2 infection, which already caused 600,000 deaths. This virus is mainly transmitted through exhalations from the airways of infected persons, so that Heating, Ventilation and Air Conditioning ...

Abstract	About 15 million people worldwide were affected by the Sars-Cov-2 infection, which already caused 600,000 deaths. This virus is mainly transmitted through exhalations from the airways of infected persons, so that Heating, Ventilation and Air Conditioning (HVAC) systems might play a role in increasing or reducing the spreading of the infection in indoor environments.We modeled the role of HVAC systems in the diffusion of the contagion through Computational Fluid Dynamics (CFD) simulations of cough at the “Bambino Gesù” Vatican State Children's Hospital. Both waiting and hospital rooms were modeled as indoor scenarios. A specific Infection-Index (η) parameter was used to estimate the amount of contaminated air inhaled by each person present in the simulated indoor scenarios. The potential role of exhaust air ventilation systems placed above the coughing patient's mouth was also assessed.Our CFD-based simulations of the waiting room show that HVAC air-flow remarkably enhances infected droplets diffusion in the whole indoor environment within 25 s from the cough event, despite the observed dilution of saliva particles containing the virus. At the same time also their number is reduced due to removal through the HVAC system or deposition on the surfaces. The proper use of Local Exhaust Ventilation systems (LEV) simulated in the hospital room was associated to a complete reduction of infected droplets spreading from the patient's mouth in the first 0.5 s following the cough event. In the hospital room, the use of LEV system completely reduced the η index computed for the patient hospitalized at the bed next to the spreader, with a decreased possibility of contagion.CFD-based simulations for indoor environment can be useful to optimize air conditioning flow and to predict the contagion risk both in hospitals/ambulatories and in other public/private settings.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; air ; air flow ; air pollution ; cough ; dynamic models ; heat ; hospitals ; mouth ; patients ; people ; research ; risk ; saliva ; viruses ; Vatican
Language	English
Dates of publication	2021-02
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2020.110343
Database	NAL-Catalogue (AGRICOLA)

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Article: Advanced 3D "Modeling" and "Printing" for the Surgical Planning of a Successful Case of Thoraco-Omphalopagus Conjoined Twins Separation.

Inserra, Alessandro / Borro, Luca / Spada, Marco / Frediani, Simone / Secinaro, Aurelio

Frontiers in physiology

2020 Volume 11, Page(s) 566766

Abstract: Background: The surgical separation of two Conjoined Twins is a particularly complex operation. Surgical times are particularly long and post-operative complications are very frequent in this type of procedure. We report a clinical case of surgical ... ...

Abstract	Background: The surgical separation of two Conjoined Twins is a particularly complex operation. Surgical times are particularly long and post-operative complications are very frequent in this type of procedure. We report a clinical case of surgical separation of two thoraco-omphalopagus conjoined twins in which, thanks to the use of (3D) three dimensional technologies, we were able to significantly reduce operative times and improve clinical outcomes. Methods: We performed a 3D reconstruction of the anatomical parts involved in congenital fusion using Computer Tomography (CT) images.We obtained virtual anatomical models of the patients which allowed us to estimate essential details as the residual post-operative thoracic volume as well as the exact position of resection planes for both the general separation and for the hepatic splitting procedure. Subsequently, we printed 3D anatomical models of the thoracic cage and sternum and of the liver with the plane of resection. Finally, we printed an additional 3D anatomical model of the two patients representing different organs with multiple colors and materials. Results: The use of 3D printing reduced the duration of surgery by 30% with a favorable patient outcome. Two years after the operation, the patients do not present any type of deficit and have a normal life without any significant complication. Conclusion: Virtual anatomical 3D models and 3D printing represent a valid technological tool to support complex surgical operations, especially in pre-surgical planning. 3D models are important tools to better understand complex anatomy and to discuss clinical cases among members of the surgical team.
Language	English
Publishing date	2020-11-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2020.566766
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Article: DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs.

Del Casale, Antonio / Simmaco, Maurizio / Modesti, Martina Nicole / Zocchi, Clarissa / Arena, Jan Francesco / Bilotta, Irene / Alcibiade, Alessandro / Sarli, Giuseppe / Cutillo, Lorenzo / Antonelli, Giulia / La Spina, Enrico / De Luca, Ottavia / Preissner, Robert / Borro, Marina / Gentile, Giovanna / Girardi, Paolo / Pompili, Maurizio

Biomedicines

2023 Volume 11, Issue 7

Abstract: Background: The objective of this study was to investigate the : Methods: We divided 129 participants into a high treatment resistance (HTR) group (current treatment with two SGAs, or clozapine, or classic neuroleptics for a failure of previous SGAs ... ...

Abstract	Background: The objective of this study was to investigate the Methods: We divided 129 participants into a high treatment resistance (HTR) group (current treatment with two SGAs, or clozapine, or classic neuroleptics for a failure of previous SGAs trials) and a low treatment resistance (LTR) group (current treatment with one atypical antipsychotic). We used Next-Generation Sequencing on DNA isolated from peripheral blood samples to analyze the polymorphisms. We performed logistic regression to search for predictors of HTR membership. Results: A diagnosis of schizophrenia significantly predicted the HTR membership compared to other diagnoses. Other predictors were the Conclusions: A diagnosis of schizophrenia and the
Language	English
Publishing date	2023-07-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11072088
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Article: Vertical Hemispherotomy: Contribution of Advanced Three-Dimensional Modeling for Presurgical Planning and Training.

De Benedictis, Alessandro / Marasi, Alessandra / Rossi-Espagnet, Maria Camilla / Napolitano, Antonio / Parrillo, Chiara / Fracassi, Donatella / Baldassari, Giulia / Borro, Luca / Bua, Antonella / de Palma, Luca / Luisi, Concetta / Pepi, Chiara / Savioli, Alessandra / Luglietto, Davide / Marras, Carlo E

Journal of clinical medicine

2023 Volume 12, Issue 11

Abstract: Vertical hemispherotomy is an effective treatment for many drug-resistant encephalopathies with unilateral involvement. One of the main factors influencing positive surgical results and long-term seizure freedom is the quality of disconnection. For this ... ...

Abstract	Vertical hemispherotomy is an effective treatment for many drug-resistant encephalopathies with unilateral involvement. One of the main factors influencing positive surgical results and long-term seizure freedom is the quality of disconnection. For this reason, perfect anatomical awareness is mandatory during each step of the procedure. Although previous groups attempted to reproduce the surgical anatomy through schematic representations, cadaveric dissections, and intraoperative photographs and videos, a comprehensive understanding of the approach may still be difficult, especially for less experienced neurosurgeons. In this work, we reported the application of advanced technology for three-dimensional (3D) modeling and visualization of the main neurova-scular structures during vertical hemispherotomy procedures. In the first part of the study, we built a detailed 3D model of the main structures and landmarks involved during each disconnection phase. In the second part, we discussed the adjunctive value of augmented reality systems for the management of the most challenging etiologies, such as hemimegalencephaly and post-ischemic encephalopathy. We demonstrated the contribution of advanced 3D modeling and visualization to enhance the quality of anatomical representation and interaction between the operator and model according to a surgical perspective, optimizing the quality of presurgical planning, intraoperative orientation, and educational training.
Language	English
Publishing date	2023-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12113779
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