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1. Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy

Author

A. Fassio, G. Porciello, G. Carioli, E. Palumbo, S. Vitale, A. Luongo, C. Montagnese, M. Prete, M. Grimaldi, R. Pica, E. Rotondo, L. Falzone, I. Calabrese, A. Minopoli, B. Grilli, M. Cuomo, P.C. Fiorillo, C. Evangelista, E. Cavalcanti, M. De Laurentiis, D. Cianniello, C. Pacilio, M. Pinto, G. Thomas, M. Rinaldo, M. D’Aiuto, D. Serraino, S. Massarut, A. Steffan, F. Ferraù, R. Rossello, F. Messina, F. Catalano, G. Adami, F. Bertoldo, M. Libra, A. Crispo, E. Celentano, C. La Vecchia, L.S.A. Augustin, and D. Gatti

Subjects
Vitamin D, cholecalciferol, supplementation, breast cancer, chemotherapy, obesity, Medicine, Internal medicine, RC31-1245
Abstract

Objective. To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. Methods. Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects’ characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D30, and ≥35 versus

Published
2024
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2. Empathy at school project: Effects of didactics of emotions® on emotional competence, cortisol secretion and inflammatory profile in primary school children. A controlled longitudinal psychobiological study

Author

A.G. Bottaccioli, U. Mariani, R. Schiralli, M.G. Mari, M. Pontani, M. Bologna, P. Muzi, S.D. Giannoni, V. Ciummo, S. Necozione, V. Cofini, L. Chiariotti, M. Cuomo, D. Costabile, and F. Bottaccioli

Subjects
Stress, Didactics of emotion, Coping, Cortisol, PNEI, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Psychology, BF1-990
Abstract

Background: There is mounting evidence of the presence of chronic stress among children during primary school: girls and boys under the age of 15 years often experience anxiety, irritability and sleeping problems with negative consequences on scholastic climate and the spread of bullying and dropping out of school. The promotion of emotion regulation within school environment through innovative didactic methodologies represents a valuable tool for teachers and parents to reduce emotional distress and associated risk behaviours and to promote wellbeing. Aim: Our research aims to explore the psychological and biological consequences of teaching emotional training in an experimental group of Italian Primary School children. Methods: A sample of pupils (81 children aged between 6 and 8) was divided into an experimental group (33 subjects) and a control group (30 subjects). A further advanced group of 18 subjects, who have experienced the method in the previous school year, was also included. The experimental study lasted one school year (from October 2021 to May 2022). The following psychological tests were administered to all groups: TEC (Test of Emotion Comprehension) to measure the children's different emotional abilities and the Projective test (PT) 'A person in the rain', to identify the coping skills of children in a stressful condition. Morning salivary cortisol, IL-6 and TNF-alpha assays were conducted in all three groups. Psychological and biological tests were administered at the beginning of the study and at the end of the study. Results: The MR-Anova model for TEC score showed that there was not a significant group effect [Fgroup = 2.24, p = 0.114]. Pairwise comparisons showed that mean score significantly increased only in the Experimental group (pB

Published
2023
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3. Starting dose and dose adjustment of non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation

Author

L. Gozzo, A. Di Lenarda, F. Mammarella, P. P. Olimpieri, A. Cirilli, M. Cuomo, M. M. Gulizia, F. Colivicchi, G. Murri, S. K. Kunutsor, D. Gabrielli, and F. Trotta

Subjects
Medicine, Science
Abstract

Abstract This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with atrial fibrillation (AF). In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. During the reference period, treatment was commenced for 866,539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA2DS2-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low dose apixaban and edoxaban increased progressively among elderly patients. Evidence based on real-world data shows a high frequency of low dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

Published
2021
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4. SARS-CoV-2 mRNA vaccine BNT162b2 triggers a consistent cross-variant humoral and cellular response

Author

D. Mileto, C. Fenizia, M. Cutrera, G. Gagliardi, A. Gigantiello, A. De Silvestri, A. Rizzo, A. Mancon, M. Bianchi, F. De Poli, M. Cuomo, I. Burgo, M. Longo, S. G. Rimoldi, C. Pagani, S. Grosso, V. Micheli, G. Rizzardini, R. Grande, M. Biasin, M. R. Gismondo, and A. Lombardi

Subjects
SARS-CoV-2 bnt162b2 mRNA vaccine, Humoral response, T-cell mediated respone, SARS-CoV-2 variants of concern, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

As the SARS-CoV-2 pandemic continues to rage worldwide, the emergence of numerous variants of concern (VOC) represents a challenge for the vaccinal protective efficacy and the reliability of commercially available high-throughput immunoassays. Our study demonstrates the administration of two doses of the BNT162b2 vaccine that elicited a robust SARS-CoV-2-specific immune response which was assessed up to 3 months after full vaccination in a cohort of 37 health care workers (HCWs). SARS-CoV-2-specific antibody response, evaluated by four commercially available chemiluminescence immunoassays (CLIA), was qualitatively consistent with the results provided by the gold-standard in vitro neutralization assay (NTA). However, we could not observe a correlation between the quantity of the antibody detected by CLIA assays and their neutralizing activity tested by NTA. Almost all subjects developed a SARS-CoV-2-specific T-cell response. Moreover, vaccinated HCWs developed a similar protective neutralizing antibodies response against the EU (B.1), Alpha (B.1.1.7), Gamma (P.1), and Eta (B.1.525) SARS-CoV-2 variants, while Beta (B.1.351) and Delta (B.1.617.2) strains displayed a consistent partial immune evasion. These results underline the importance of a solid vaccine-elicited immune response and a robust antibody titre. We believe that these relevant results should be taken into consideration in the definition of future vaccinal strategies.

Published
2021
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5. Non-vitamin K antagonist oral anticoagulation agents in patients with atrial fibrillation: Insights from Italian monitoring registries

Author

P.P. Olimpieri, A. Di Lenarda, F. Mammarella, L. Gozzo, A. Cirilli, M. Cuomo, M.M. Gulizia, F. Colivicchi, G. Murri, D. Gabrielli, and F. Trotta

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased risk of stroke and thromboembolism. Anticoagulation with Vitamin K antagonists (VKAs) or with novel oral anti-coagulants (NOACs) represents the cornerstone of the pharmacological treatment to reduce the risk of thromboembolism. This study aims to provide real-world data from a whole large European country about NOAC use in “non-valvular atrial fibrillation” (NVAF). Methods: We analysed the Italian Medicines Agency (AIFA) monitoring registries collecting data of a nationwide cohort of patients with “NVAF” treated with NOACs. Using logistic regression analysis, baseline characteristics and treatment discontinuation information were compared among initiators of the 4 NOACs. Results: In the reference period, the NOAC database collected data for 683,172 patients. The median age was 78 years with 19.5% aged 85 or older. Overall, the treatments were in accordance with guidelines. About 1/3 of patients switched from a prior VKA treatment; in the 72.3% of cases, these patients had a labile International Normalized Ratio (INR) at first prescription. The most prescribed NOAC was rivaroxaban, followed by apixaban, dabigatran and edoxaban. Conclusions: This study is the largest European real-world study ever published on NOACs. It includes all Italian patients treated with NOACs since 2013 accounting for about 1/3 of subjects with AF. The enrolled population consisted of very elderly patients, at high risk of ischemic adverse events. The AIFA registries are consolidated tools that guarantee the appropriateness of prescription and provide important information for the governance of National Health System by collecting real-world data. Keywords: Monitoring registries, Real world data, NOACs, AF, Appropriateness

Published
2020
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6. Evaluation of 'Steroid-Sparing' Effects of Xanthena® Cream in Patients with Mild to Moderate Atopic Dermatitis

Author

N. Cassano, A. Amoruso, S. Masci, S. De Paola, S. Salvatori, C. P. Agnusdei, S. Calabretta, A. Callea, F. Cellini, S. Centofanti, M. Cuomo, S. Curia, S. Dattola, C. De Caro, L. Del Brocco, L. Donato, A. Ferrari, R. Lopreiato, A. Puglisi, G. Ruggiero, F.M. Russo, G. Valenti, R. Vernaci, F. Verrina, G. Liotti, and G.A. Vena

Subjects
Medicine
Abstract

Emollients play an important role in the management of atopic dermatitis (AD). The aim of this study was to evaluate the efficacy and the “steroid-sparing” activity of an emollient cream (Xanthena® cream) in patients with mild to moderate AD. Patients were asked to apply twice a day for 7 days a cream containing hydrocortisone butyrate on the lesionai skin and then to apply Xanthena® cream only on the left side of affected areas. During the 2-month study period, the use of the corticosteroid cream was resumed in case of flare-up in any side. The results obtained show significant differences of both the total severity score and the intensity of each symptom and sign of AD between the skin areas treated with Xanthena® cream and the control areas (P

Published
2003
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9. Monitoring for arrhythmia in transthyretin cardiac amyloidosis with remote patch devices

Author

S Bruce, M Cuomo, H Yarmohammadi, E Y Wan, D Saluja, R Sciacca, H Garan, J M Griffin, M S Maurer, and A B Biviano

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Funding Acknowledgements Type of funding sources: None. Background/Introduction Transthyretin cardiac amyloidosis (ATTR-CA) is associated with an increased incidence of arrhythmias. We hypothesized that non-invasive, two-week outpatient cardiac rhythm monitoring of patients with ATTR-CA would detect high rates of ventricular tachycardia and atrial fibrillation/flutter (AF). Purpose To characterize arrhythmia in patients with ATTR-CA on two-week, non-invasive cardiac rhythm monitors. Methods 38 patients with ATTR-CA (mean age 76.9 SD 10.0 years, 89.5% male) who underwent two-week remote external patch monitoring were included in this single center retrospective study. An age-matched control group included 38 patients (mean age 73.9 SD 12.3, 76.3% male) who underwent the same cardiac rhythm monitoring as part of neurological workups. Results NSVT was detected on the remote monitor in 81.6% of ATTR-CA patients and AF was detected in 26.3% of patients. ATTR-CA was associated with higher rates of NSVT and AF compared to the control group (28.9% with NSVT and 5.3% with AF). As seen in Figure 1, there were only three ATTR-CA patients without either AF, NSVT, advanced atrioventricular block, or a significant pause detected on remote monitor. Among the ATTR-CA group, at median 45 weeks follow-up, there were 4 heart failure hospitalizations, 2 cardiovascular events (1 episode of sustained VT and 1 stroke), 6 permanent pacemakers placed, and 3 implantable cardioverter-defibrillators placed, including one for sustained VT. NSVT and AF were not associated with a composite of these adverse outcome. Conclusion ATTR-CA was associated with high rates of NSVT and AF on noninvasive remote monitors. While evidence regarding the management of arrhythmias, particularly NSVT/VT, in ATTR-CA remains limited, two-week noninvasive cardiac monitoring can be considered to aid in risk stratification for both atrial and ventricular arrhythmias in ATTR-CA.

Published
2023
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10. Design of architected materials composed by periodic surfaces

Author

M. Cuomo

Abstract

Architected materials possess extraordinary mechanical properties, that cannot be met by natural materials, either in the static and in the dynamic range. For this reason, the study of metamaterials is a very active field of research. Although lattice architectures are commonly preferred, especially for the relative simplicity of manufacturing, geometries based on thin shells may present considerable advantages. Indeed it has been shown that shell metamaterials, still preserving lightness and versatility, can present excellent stiffness and strength properties, and ability to absorb strain energy by means of very large deformations, that make them useful for the design of shock absorbing elements. In the contribution will be examined a class of shell metamaterials, composed of triple periodic minimal surfaces TPMS, that having zero mean curvature can be in equilibrium with an isotropic state of stress. Two particular surfaces, the Schwarz P and the Schwarz G minimal surfaces, the first centro-symmetric, the second chiral, are examined.

Published
2023
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13. A composite index of avoidable hospitalization to assess primary care quality: an Italian experience

Author

G Damiani, M Cuomo, C Mencancini, A Burgio, A Solipaca, D Catania, A Heidar Alizadeh, P Arcaro, and G Baglio

Subjects
Public Health, Environmental and Occupational Health
Abstract

Background In Italy, primary care (PC) ensures universal health coverage while containing costs. However, the assessment of its quality still remains an issue. Evidence has shown that high-quality outpatient care, through timely interventions to prevent complications of “ambulatory care sensitive conditions”, may avoid hospitalization. Aim of the study is to analyse the performance of PC in the Italian regions, using a composite and synthetic index of avoidable hospitalizations. Methods Hospital discharge data from 119 Italian geopolitical areas were analysed for the 2017-2019 triennium and for 2020, separately. According to the “Italian National Outcomes Evaluation Programme” methodology, 9 avoidable hospitalization indicators covering 5 nosological fields (infectious, respiratory, metabolic, cardiovascular and mental diseases) were combined in a synthetic index, calculated as the weighted mean of their standardized scores (with equal weights for each field). Using “natural breaks” technique, the areas were grouped into 5 clusters: “high”, “medium-high”, “medium”, “medium-low” and “low”. Results The analysis showed a marked heterogeneity at intra-regional level for the pre-pandemic triennium, with areas of homogeneity in regions with higher levels of hospitalization. The “medium” cluster, which is the widest, included 36 areas variously distributed across regions. The comparison with 2020 confirmed the geographical patterns observed for the previous triennium, despite a general reduction in hospitalizations due to the pandemic. Conclusions As a proxy indicator of PC quality, this index can aid decision makers in prioritizing quality improvement actions. However, in order to obtain a comprehensive evaluation, a joint reading of this index with other healthcare indicators is recommended. Key messages • High-quality PC is essential in maintaining appropriate hospitalization levels. • The composite synthetic index proposed could aid PC quality assessment.

Published
2022
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16. C73 COVID–19 DIAGNOSIS AND MORTALITY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION ADMITTED IN ITALY DURING THE NATIONAL OUTBREAK

Author

P D’Errigo, L De Luca, S Rosato, B Giordani, M Cuomo, G Duranti, G Mureddu, A Tavilla, G Badoni, F Seccareccia, and G Baglio

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background and objective: There are limited data on the clinical impact of Covid–19 in patients with acute myocardial infarction (AMI). Aim of this work is to assess the impact of Covid–19 infection on mortality in AMI patients admitted during the national outbreak in Italy. Methods Retrospective nationwide cohort study enrolling consecutive AMI patients admitted between March,11st and May 3rd, 2020 (national outbreak) and the equivalent periods of the previous 5 years in Italy. The main outcomes were 30–day and 6–month all–cause mortality. Results The actual number of AMI admission during the 2020 outbreak in Italy was significantly reduced as compared to that expected based on the trend of the previous 5 years (STEMI: 4048 vs 5523, p Conclusion During the 2020 national outbreak in Italy, a concomitant diagnosis of Covid–19 was associated with a significantly higher rate of mortality in both STEMI and NSTEMI patients. Excluding patients diagnosed with Covid–19, the mortality rates become consistent with the previous 5–year trend for STEMI, while they remain higher for NSTEMI.

Published
2023
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21. Systematic Evaluation of CRISPRa and CRISPRi Modalities Enables Development of a Multiplexed, Orthogonal Gene Activation and Repression System

Author

Andrea Martella, Robert G. Roth, Benjamin J. M. Taylor, Anne Göppert, Emanuela M. Cuomo, Alan J. Dickson, David I Fisher, and Mike Firth

Subjects
0106 biological sciences, Biomedical Engineering, Gene regulatory network, Computational biology, Biology, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), 03 medical and health sciences, Downregulation and upregulation, 010608 biotechnology, Humans, CRISPR, Gene Regulatory Networks, Promoter Regions, Genetic, Transcription factor, Gene, 030304 developmental biology, Gene Editing, Regulation of gene expression, 0303 health sciences, Tissue Engineering, Drug discovery, General Medicine, Cellular Reprogramming, HCT116 Cells, Gene Expression Regulation, CRISPR-Cas Systems, Reprogramming, RNA, Guide, Kinetoplastida, Signal Transduction
Abstract

The ability to manipulate the expression of mammalian genes using synthetic transcription factors is highly desirable in both fields of basic research and industry for diverse applications, including stem cell reprogramming and differentiation, tissue engineering, and drug discovery. Orthogonal CRISPR systems can be used for simultaneous transcriptional upregulation of a subset of target genes while downregulating another subset, thus gaining control of gene regulatory networks, signaling pathways, and cellular processes whose activity depends on the expression of multiple genes. We have used a rapid and efficient modular cloning system to build and test in parallel diverse CRISPRa and CRISPRi systems and develop an efficient orthogonal gene regulation system for multiplexed and simultaneous up- and downregulation of endogenous target genes.

Published
2019
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22. Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Author

Bauer, M. Glenn, T. Achtyes, E.D. Alda, M. Agaoglu, E. Altınbaş, K. Andreassen, O.A. Angelopoulos, E. Ardau, R. Vares, E.A. Aydin, M. Ayhan, Y. Baethge, C. Bauer, R. Baune, B.T. Balaban, C. Becerra-Palars, C. Behere, A.P. Behere, P.B. Belete, H. Belete, T. Belizario, G.O. Bellivier, F. Belmaker, R.H. Benedetti, F. Berk, M. Bersudsky, Y. Bicakci, Ş. Birabwa-Oketcho, H. Bjella, T.D. Brady, C. Cabrera, J. Cappucciati, M. Castro, A.M.P. Chen, W.-L. Cheung, E.Y.W. Chiesa, S. Crowe, M. Cuomo, A. Dallaspezia, S. Del Zompo, M. Desai, P. Dodd, S. Donix, M. Etain, B. Fagiolini, A. Fellendorf, F.T. Ferensztajn-Rochowiak, E. Fiedorowicz, J.G. Fountoulakis, K.N. Frye, M.A. Geoffroy, P.A. Gonzalez-Pinto, A. Gottlieb, J.F. Grof, P. Haarman, B.C.M. Harima, H. Hasse-Sousa, M. Henry, C. Høffding, L. Houenou, J. Imbesi, M. Isometsä, E.T. Ivkovic, M. Janno, S. Johnsen, S. Kapczinski, F. Karakatsoulis, G.N. Kardell, M. Kessing, L.V. Kim, S.J. König, B. Kot, T.L. Koval, M. Kunz, M. Lafer, B. Landén, M. Larsen, E.R. Lenger, M. Lewitzka, U. Licht, R.W. Lopez-Jaramillo, C. MacKenzie, A. Madsen, H.Ø. Madsen, S.A.K.A. Mahadevan, J. Mahardika, A. Manchia, M. Marsh, W. Martinez-Cengotitabengoa, M. Martiny, K. Mashima, Y. McLoughlin, D.M. Meesters, Y. Melle, I. Meza-Urzúa, F. Ming, M.Y. Monteith, S. Moorthy, M. Morken, G. Mosca, E. Mozzhegorov, A.A. Munoz, R. Mythri, S.V. Nacef, F. Nadella, R.K. Nakanotani, T. Nielsen, R.E. O‘Donovan, C. Omrani, A. Osher, Y. Ouali, U. Pantovic-Stefanovic, M. Pariwatcharakul, P. Petite, J. Pfennig, A. Ruiz, Y.P. Pilhatsch, M. Pinna, M. Pompili, M. Porter, R. Quiroz, D. Rabelo-da-Ponte, F.D. Ramesar, R. Rasgon, N. Ratta-apha, W. Ratzenhofer, M. Redahan, M. Reddy, M.S. Reif, A. Reininghaus, E.Z. Richards, J.G. Ritter, P. Rybakowski, J.K. Sathyaputri, L. Scippa, Â.M. Simhandl, C. Severus, E. Smith, D. Smith, J. Stackhouse, P.W., Jr. Stein, D.J. Stilwell, K. Strejilevich, S. Su, K.-P. Subramaniam, M. Sulaiman, A.H. Suominen, K. Tanra, A.J. Tatebayashi, Y. Teh, W.L. Tondo, L. Torrent, C. Tuinstra, D. Uchida, T. Vaaler, A.E. Veeh, J. Vieta, E. Viswanath, B. Yoldi-Negrete, M. Yalcinkaya, O.K. Young, A.H. Zgueb, Y. Whybrow, P.C.

Abstract

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed. © 2021, The Author(s).

Published
2021

25. P385 Tailoring induction treatment for children with Crohn’s disease

Author

M Cuomo, A Carobbio, M Aloi, P Alvisi, C Banzato, L Bosa, M Bramuzzo, A Campanozzi, G Catassi, L D’Antiga, M Di Paola, E Felici, M T Fioretti, S Gatti, F Graziano, S Lega, P Lionetti, A Marseglia, M Martinelli, F Musto, N Sansotta, L Scarallo, G Zuin, and L Norsa

Subjects
Gastroenterology, General Medicine
Abstract

Background Multiple clinical studies in children with Crohn’s disease (CD) have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission and even to promote mucosal healing. However, EEN as inductive treatment may be not tolerated or inefficient and we are well aware of the paramount importance of a well conducted induction treatment for paediatric CD with the goal of an individualized induction treatment to improve the prognosis and the quality of life of inflammatory bowel disease (IBD) children. Methods A retrospective multicentre study including newly diagnosed children with CD treated with EEN as induction therapy was designed. The primary aim of the study was to study predictive factors of non- adherence to treatment. The secondary endpoint were predictive factors of clinical non-remission at the end of induction treatment. Those data together were analysed with the ultimate goal of trying to define an individualized induction treatment for children with CD. Results 376 CD children from, 14 IBD paediatric referral centres were enrolled in the study. The rate of EEN adherence was, 89 %. Colonic involvement and FC >, 600 μg/g at diagnosis were found associated with a reduced EEN adherence in univariate and multivariate analysis. The remission rate of those who completed induction treatment was, 67%. A multivariate analysis showed that factor determining lower remission rate were age >, 15 years and PCDAI >, 50. With those results we were able to create a decisional algorithm which is provided in figure 1. Conclusion EEN administered for, 8 weeks is effective for inducing clinical remission. The rate of adherence is high but there is a group of patients (colonic involvement + hight FC) which are at risk of non-adherence and thus may be candidate for alternative dietary induction regimens. Moreover, older patients with moderate to severe active disease (PCDAI>40), are at higher risk of failing clinical remission achievement after EEN and may benefit from an early anti-TNF alpha treatment. Personalized treatment strategies should be proposed weighing the benefits and risks based on each patient’s disease location, phenotype and disease activity with the overall aim of obtaining rapid control of inflammation to reduce long-term bowel damage.

Published
2022
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26. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Author

Kirmeier E. a, Eriksson L. I. c, Lewald H. a, Jonsson Fagerlund, M. c Hoeft, A. f Hollmann, M. g Meistelman, C. e Hunter, J. M. d Ulm, K. b Blobner, M. aEmail Author, Abad Gurumeta, A. Abernethy, C. Abigail, P. Achaibar, K. Adam, E. Afshari, Agudelo Montoya, M. E. Akgün, F. N. Aletti, G. Alkış, N. Allan, K. Allan, A. Allaouchiche, B. Allcock, C. Almasy, E. Amey, I. Amigoni, M. Andersen, E. Andersson, P. Anipchenko, N. Antunes, P. Armstrong, E. Aslam, T. N. Aslin, B. Assunção, J. P. Ausserer, J. Avvai, M. Awad, Ayas Montero, B. Ayuso, M. Azevedo, P. Badarau, V. Badescu, Baiardo Redaelli, M. Baird, C. Baird, Y. Baker, T. Balaji, P. Bălan, C. Balandin, A. Balescu-Arion, C. Baliuliene, Baltasar Isabel, J. Baluch, S. N. Bandrabur, D. Bankewitz, C. Barber, K. Barbera, F. Barcraft-Barnes, H. Barletti, V. Barnett, G. Baron, K. Barros, A. Barsan, V. Bartlett, P. Batistaki, C. Baumgarten, G. Baytas, V. Beauchamp, Becerra Cayetano, I. A. Bell, S. Bellandi, M. Belletti, Belmonte Cuenca, J. Benitez-Cano, A. Beretta, L. Berger, M. Bergmann, N. Bergmark, Bermudez Lopez, M. Bernotaite, M. Beurskens, C. Bidd, H. Bifulco, F. Bignami, E. Bilic, A. Bilskiene, D. Bischoff, P. Bishop, L. Bjonness, T. Blaylock, H. Blethyn, K. Blincoe, T. Blokhin, I. Blunt, N. Boer, C. Bois, G. Bonicolini, E. Booth, J. Borecka-Kedzierska, M. Borstnar, K. Borys, M. Boselli, E. Bouvet, L. Bouwman, A. Bowen, L. Bowrey, S. Boxall, L. Božić, T. Bradley, T. Branco, T. Brazzi, L. Brazzoni, M. Brear, T. Brogly, N. Brohi, F. Broms, J. Bubliauskas, A. Bucolo, G. E. Buerkle, H. Buggy, D. Buhre, W. Bukauskas, T. Butturini, F. Byttner, Cabrera Díaz, I. Calderon, A. Calhau, R. Callejo, A. Cammu, G. Campesato, M. Can, Ö. S. Candeias, M. Cantor, A. Carise, E. Carmona, C. Carreteiro, J. Carrieri, C. Carter, A. Casal, M. Casanova, I. Cascella, M. Casero, L. M. Casiraghi, G. M. Castelo-Branco, Castro Arranz, C. Cernea, D. D. Cervantes, J. Chandler, B. Charnock, R. Chatzimicali, A. Chinery, E. Chishti, A. 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Ewa, Gosavi, Smita, Gottfridsson, peter, Gottschalk, André, Granell, Manuel, Granstrom, Anna, Grassetto, Alberto, Greenwood, Anna, Grigoras, Ioana, Grintescu, Ioana, Gritsan, Alexey, Gritsan, Galina, Grynyuk, Andriy, Guadagnin, Giovanni Maria, Guarnieri, Marcello, Güçlü, Çiğdem, Guerrero Diez, Maria, Gunenc, Ferim, Günther, Ulf, Gupta, Pawan, Guttenthaler, Vera, Hack, Yvonne, Hafisayena, Ade, Hagau, Natalia, Haldar, Jagannath, Hales, Dawn, Hancı, Volkan, Hanna-Jumma, Sameer, Harazim, Hana, Harlet, Pierre, Harper, Daniel, Harris, Benjamin, Harvey, Orla, Hashimi, Medita, Hawkins, Lesley, Hayes, Conrad, Heaton, Jame, Heier, Tom, Helliwell, Laurence, Hemmes, Sabrine, Henderson, Kate, Hermanides, Jeroen, Hermanns, Henning, Herrera Hueso, Berta, Hestenes, Siv, Hettiarachchi, Roshane, Highgate, Judith, Hodgson, Keith, Hoelbling, Daniel, Holland, Jonathan, Horhota, Lucian, Hormis, Anil, Hribar, Renata, Hua, Alina, Humphreys, Sally, Humphries, Ryan, Humpliková, Simona, Hunt, Janez, Husnain, Ali, Hussein, Ahmed, Hyams, Benjamin, Iannuccelli, Fabrizio, Ilette, Katie, Ilyas, Carl, Inan, Turgay, India, Immaculada, Ionițăv, Victor, Irwin, Foo, Jain, Vipul, Janez, Benedikt, Jankovic, Radmilo, Jenkins, Sarah, Jenko, Matej, Jimenez, Raquel, Jiménez Gomez, Bárbara, Joachim, Sugganthi, Joelsson-Alm, Eva, John, John, Jonikaite, Lina, Jovic, Miomir, Jungwirth, Bettina, Junke, Etienne, Kabakov, Bory, Kadaoui, Salah-Din, Kanski, Andrzej, Karadag, Süheyla, Karbonskiene, Aurika, Karjagin, Juri, Kasnik, Darja, Katanolli, Fato, Katsika, Eleni, Kaufmann, Kai, Keane, Helen, Kelly, Martin, Kent, Melanie, Keraitiene, Grazina, Khudhur, Ahmed, Khuenl-Brady, Karin, Kidd, Laurie, King, Siobhan, Kirchgäßner, Katharina, Klancir, Tino, Klucniks, Andri, Knotzer, Johann, Knowlden, Peter, Koers, Lena, Kompan, Janez, Koneti, Kiran K, Kooij, Fabian, Koolen, Eric, Koopman - van Gemert, Anna Wilhelmina Margaretha Maria, Kopp, Kristen, Korfiotis, Dimitrio, Korolkov, Oleg, Kosinová, Martina, Köstenberger, Marku, Kotzinger, Oskar, Kovačević, Marko, Kranke, Peter, Kranke, Eva, Kraus, Christiane, Kraus, Stephanie, Kubitzek, Christiane, Kucharski, Rafal, Kucukguclu, Semih, Kudrashou, Allaksandr, Kumar, Vinayak, Kummen, Live, Kunit, Cornelia, Kushakovsky, Vlad, Kuvaki, Bahar, Kuzmanovska, Biljana, Kyttari, Aikaterina, Landoni, Giovanni, Lau, Gary, Lazarev, Konstantin, Legett, Samantha, Legrottaglie, Anna Maria, Leonardi, Silvia, Leong, Maria, Lercher, Helene, Leuvrey, Matthieu, Leva, Brigitte, Levstek, Meta, Limb, Jame, Lindholm, Espen, Linton, Fiona, Liperi, Corradero, Lipski, Fabian, Lirk, Philipp, Lisi, Alberto, Lišková, Katarina, Lluch Oltra, Aitana, Loganathan, Vinothan, Lombardi, Stefania, Lopez, Eloisa, Lopez Rodríguez, Maria, Lorenzini, Laura, Lowicka, Malgorzata, Lugovoy, Alexander, Luippold, Madeleine, Lumb, Andrew, Macas, Andriu, Macgregor, Mark, Machado, Humberto, Maciariello, Maria, Madeira, Isabel, Maitan, Stefan, Majewski, Jacek, Maldini, Branka, Malewski, Georgia, Manfredini, Livia, Männer, Olja, Marchand, Bahareh, Marcu, Alexandra, Margalef, Jordi, Margarson, Michael, Marinheiro, Lucia, Markic, Ana, Markovic Bozic, Jasmina, Marrazzo, Francesco, Martin, Jane, Martin Ayuso, Maria, Martinez, Esteher, Martino, Enrico Antonio, Martinson, Victoria, Marusic-Gaser, Katarina, Mascarenhas, Catia, Mathis, Cindy, Matsota, Paraskevi, Mavrommati, Eleni, Mazul Sunko, Branka, McCourt, Killian, McGill, Neil, McKee, Raymond, Meço, Başak Ceyda, Meier, Sonja, Melbourne, Susan, Melbybråthen, Grethe, Meli, Andrea, Melia, Aiden, Melotti, Rita Maria, Menga, Maria Rosaria, Mercer, Pauline, Merotra, Susan, Mescolini, Silvia, Metterlein, Thoma, Michalov, Martin, Michlig, Sam, Midgley, Susan, Milić, Morena, Milojevic, Milan, Miñana, Amanda, Minto, Gary, Mirabella, Lucia, Mirea, Liliana, Mittelstädt, Ludger, Moeglen, Aude, Moise, Alida, Mokini, Zhirajr, Molin, Anna, Moltó, Lui, Monea, Maria Concetta, Montalto, Francesca, Montgomery, Jane, Montgomery, Claire, Montillo, Gerardo, Moore, Sally, Moore, Faye, Moreira, Zelia, Moreno, Tania, Moreno, Ricardo, Moret, Enrique, Moreton, Sarah, Morgan, Marianne, Moro Velasco, Concepción, Morri, Davide, Moull, Alice, Moura, Fernando, Mráz, Peter, Mrozek, Katarzyna, Mukhtar, Karim, Muniyappa, Sudeshkumar, Murray, Heather, Murthy, Burra VS, Mushambi, Mary, Nadolski, Maria, Nardelli, Pasquale, Nardin, Giordano, Navarro Pérez, Rosalía, Naveiro, Andrea, Negri, Manuela, Nesek Adam, Visnja, Neskovic, Vojislava, Neuwersch, Stefan, Neves, Miriam, Nguyen, Bavinh, Ní Eochagáin, Aisling, Nicholas, Caroline, Nightingale, Jeremy, Norrie, Kylie, Novak-Jankovic, Vesna, Novakova, Andrea, Novillo, Marta, Numan, Sandra, Oduro-Dominah, Louise, Oldner, Ander, Oliveira, Isabel, Ologoiu, Daniela, Oloktsidou, Irini, O'Reilly, Rosalind, Orlando, Alessandro, Ovezov, Alexey, Ozbilgin, Sule, Paal, Peter, Padin Barreiro, Lidia, Palugniok, Ryszard, Papaioannou, Alexandra, Papapostolou, Konstantino, Paranthaman, Prabhakar, Pardey Bracho, Gilda, Parente, Suzana, Parfeni, Alexandru, Pasin, Laura, Passey, Samuel, Pastor, Ernesto, Patch, Sarah, Patil, Andan, Paunescu, Marilena-Alina, Pehboeck, Daniel, Pereira, Manuela, Pereira, Carla, Perez Caballero, Paula, Pérez García, Aníbal, Pérez Soto, Antonia, Perez Tejero, Gisela, Perez-Cerda, Francisco, Pesenti, Antonio, Petta, Rocco, Philippe, Simon, Pickering, David, Pico Veloso, Jandro, Pina, Pedro, Pinho-Oliveira, Vítor, Pinol, Santiago, Pinto, Rita, Pistidda, Laura, Pitterle, Manuela, Piwowarczyk, Paweł, Plotnikova, Olga, Pohl, Holger, Poldermann, Jorinde, Polkovicová, Lucia, Pompei, Livia, Popescu, Mihai, Popović, Radmila, Pota, Vincenzo, Potocnik, Miriam, Potręć, Beata, Potter, Alison, Pramod, Nalwaya, Prchalova, Martina, Preckel, Benedikt, Pugh, Richard, Pulletz, Mark, Radoeshki, Aleksandar, Rafi, Amir, Ragazzi, Riccardo, Raineri Santi, Maurizio, Rajamanickam, Tamiselvan, Rajput, Zahra, Ramachandran, Rajeskar, Ramasamy, Radhika, Ramessur, Suneil, Rao, Roshan, Rasmussen, Ander, Rato, André, Razaque, Usman, Real Navacerrada, M. Isabel, Reavley, Caroline, Reid, Jame, Reschreiter, Henrik, Rial, Erick, Ribas Carrasco, Patricia, Ribeiro, Sandy, Rich, Nathalie, Richardson, Lydia, Rimaitis, Kestuti, Rimaitis, Mariu, Ringvold, Else-Marie, Ripke, Fabian, Ristescu, Irina, Ritchie, Keith, Ródenas, Frederic, Rodrigues, Patrícia, Rogers, Emma, Rogerson, David, Romagnoli, Stefano, Romero, Esther, Rondovic, Goran, Rose, Bernd Oliver, Roth, Winfried, Rotter, Marie-Therese, Rousseau, Guy, Rudjord, Ander, Rueffert, Henrik, Rundgren, Malin, Rupprecht, Korbinian, Rushton, Andrew, Russotto, Vincenzo, Rypulak, Elżbieta, Ryszka, Maciej, Sà, Jacinta, Sà Couto, Paula, Saby, Sandrine, Sagic, Jelena, Saleh, Omar, Sales, Gabriele, Sánchez Sánchez, Yván, Sanghera, Sumayer, Şanli Karip, Ceren, Santiveri Papiol, Francisco Javier, Santos, Sofia, Sarno, Stephen, Saul, Daniel, Saunders, David, Savic, Nenad, Scalco, Loïc, Scanlon, Deborah, Schaller, Stefan, Schax, Christoph, Scheffer, Gert Jan, Schening, Anna, Schiavone, Vincenzo, Schmidt-Ehrenberg, Florian, Schmidt-Mutter, Catherine, Schönberg, Christina, Schopflin, Christian, Schreiber, Jan-Uwe, Schultz, Marcu, Schurig, Marlen, Scott, Carmen, Sebestian, Siby, Sehgal, Selena, Sem, Victoria, Semenas, Egidiju, Serafini, Elena, Serchan, Pashalitsa, Shields, Martin, Shobha, Ramakrishnan, Shosholcheva, Mirjana, Siamansour, Tanja, Siddaiah, Narendra, Siddiqi, Khalid, Sinclair, Rhona, Singh, Permendra, Singh, Rajendra, Sinha, Aneeta, Sinha, Ashok, Skinner, Amanda, Smee, Elizabeth, Smekalova, Olga, Smith, Neil, Smith, Thoma, Smitz, Carine, Smole, Daniel, Sojčić, Nataša, Soler Pedrola, Maria, Somanath, Sameer, Sonksen, Julian, Sorella, Maria Christina, Sörmus, Alar, Soro, Marina, Soto, Carmen, Spada, Anna, Spadaro, Savino, Spaeth, Johanne, Sparr, Harald, Spielmann, Annika, Spindler-Vesel, Alenka, Stamelos, Matthaio, Stancombe L, Liucia, Stanculescu, Andreea, Standl, Thoma, Standley, Tom, Stanek, Ondrej, Stanisavljević, Snežana, Starczewska, Malgorzata, Stäuble, Christiane, Steen, Julie, Stefan, Oana Maria, Stell, Elizabeth, Stera, Caterina, Stevens, Marku, Stoerckel, Marlène, Stošić, Biljana, Stourac, Petr, Stroumpoulis, Konstantino, Struck, Rafael, Suarez de la Rica, Alejandro, Sultanpori, Altaf, Sundara Rajan, Rajinikanth, Suying, Ong, Svensen, Christer, Swan, Louise, Syrogianni, Paulina, Sysiak, Justyna, Szederjesi, Jano, Taddei, Stefania, Tan Hao, Ern, Tanou, Virginia, Tarabová, Katarina, Tardaguila Sancho, Paula, Tarroso, Maria, Tartaglione, Marco, Taylor, Emma, Tbaily, Lee, Telford, Richard, Terenzoni, Massimo, Theodoraki, Kassiani, Thornley, Helen, Tiganiuc, Liviu, Toim, Hardo, Tomescu, Dana, Tommasino, Concezione, Toni, Jessica, Toninelli, Arturo, Toretti, Ilaria, Townley, Stephen, Trepenaitis, Dariu, Trethowan, Brian, Tsaousi, Georgia, Tsiftsi, Aikaterini, Tudor, Adrada, Turan, Güldem, Turhan, Sanem Çakar, Unic-Stojanovic, Dragana, Unterbuchner, Christoph, Unzueta, Carmen, Uranjek, Jasna, Ursic, Tomaz, Vaida, Simona, Valldeperas Ferrer, Silvia, Valldeperas Hernandez, Maria Inmaculada, Valsamidis, Dimitri, Van Beek, Rienk, Van dasselaer, Nick, Van Der Beek, Tim, Van Duivenvoorde, Yoni, van Klei, Wilton A., Van Poorter, Fran, Van Zaane, Ba, Van Zundert, Tom, Van Zyl, Rebekka, Vargas Munoz, Ana Milena, Varsani, Nimu, Vasconcelos, Pedro, Vassilakis, Georgio, Vecchiatini, Tommaso, Vecera, Lubomir, Vercauteren, Marcel, Verdouw, Ba, Verheyen, Veerle, Verri, Marco, Vicari Sottosanti, Luigi Giancarlo, Vico, Manuel, Vidal Mitjans, Patricia, Vilardi, Anna, Vissicchio, Daniela, Vitale, Giovanni, Vitković, Bibiana, Vizcaychipi, Marcela Paola, Voicu, Alexandra, Voje, Minca, Volfová, Ivana, Volta, Carlo Alberto, Von Lutterotti, Theresa, von Tiesenhausen, Anna, Vrecic-Slabe, Simona, Vukcevic, Dejan, Vukovic, Rade, Vullo, P. Agostina, Wade, Andrew, Wallberg, Hanna, Wallden, Jakob, Wallner, Johann, Walther Sturesson, Louise, Watson, Davina, Weber, Stefan, Wegiel Leskiewiq, Anna, Weller, Debbie, Wensing, Carine, Werkmann, Marku, Westberg, Henrik, Wikström, Erik, Williams, Benedict, Wilson, Robin, Wirth, Steffen, Wittmann, Maria, Wood, Laura, Wright, Stella, Zachoval, Christian, Zambon, Massimo, Zampieri, Silvia, Zampone, Salvatore, Zangrillo, Alberto, Zani, Gianluca, Zavackiene, Asta, Zieglerder, Raphael, Zonneveldt, Harry, Zsisku, Lajo, Zucker, Tom-Philipp, Żukowski, Maciej, Zuleika, Mehrun, and Zupanĕiĕ, Darja

Subjects
Pulmonary and Respiratory Medicine, pulmonary complications, muscle relaxants, Post-anaesthesia complications, Neuromuscular Blockade, pulmonary complication, muscle relaxant, neuromuscular block, postoperative pulmonary complication, business.industry, Retrospective cohort study, post-operative pulmonary complications, Neuromuscular monitoring, Neuromuscular Blocking Agents, Sugammadex, NO, Anaesthesia, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Anesthesia, Medicine, General anaesthesia, Neuromuscular Agents, 030212 general & internal medicine, MED/41 - ANESTESIOLOGIA, Prospective cohort study, business, medicine.drug
Abstract

Background: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj −4·4%, 95% CI −5·5 to −3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj −2·6%, 95% CI −3·9 to −1·4) and the administration of reversal agents (1·23, 1·07–1·41; −1·9%, −3·2 to −0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj −0·3%, 95% CI −2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; −0·4%, −3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation: We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications. Funding: European Society of Anaesthesiology.

Published
2019
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27. Analysis of Aortic Calcifications in 4 Different Transcatheter Heart Valve Prostheses in Order to Reduce Paravalvular Aortic Leak

Author

Steffen Pfeiffer, Ferdinand Vogt, A.M. Dell'Aquila, Theodor Fischlein, Francesco Pollari, M. Cuomo, Jürgen Jessl, and Johannes Schwab

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Leak, medicine.anatomical_structure, business.industry, Internal medicine, medicine, Cardiology, Surgery, Aortic calcifications, Heart valve, Cardiology and Cardiovascular Medicine, business
Published
2018
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29. Effect of a low glycemic index Mediterranean diet on cardiovascular risk factors in women diagnosed with breast cancer: preliminary data from DEDiCa study

Author

C. Montagnese, G. Porciello, S. Vitale, E. Palumbo, I. Calabrese, A. Crispo, M. Grimaldi, R. Pica, V. Marotta, N. Esindi, M. Prete, S. Cubisino, L. Falzone, M. De Laurentiis, M. Rinaldo, M. D’Aiuto, D. Cianniello, C. Pacilio, M. Pinto, G. Thomas, F. Catalano, G. Banna, V. Ursino, F. Ferrau’, R. Rossello, D. Serraino, S. Massarut, L. Poletto, V. Martinuzzo, G. Guerra, A. Farina, F. Messina, E. Cavalcanti, A. Minopoli, P. Fiorillo, B. Grilli, M. Cuomo, C. Comegna, S. Cervo, C. Evangelista, D. Bolzicco, A. Steffan, G. Riccardi, D.J.A. Jenkins, D. Gatti, M. Libra, E. Celentano, G. Botti, and L.S.A. Augustin

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Cardiology and Cardiovascular Medicine
Published
2020
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30. Design of a Membrane Structure Subjected to Blast Load

Author

S. Lanza and M. Cuomo

Subjects
Blast load, business.industry, Membrane structure, Environmental science, Structural engineering, Vapor cloud, business
Abstract

The dynamic analysis of a tent structure subjected to an external blast load is presented. The case studied refers to temporary structures employed in petrochemical facilities that need to resist to vapor cloud explosions that can happen in the vicinity of the tent. The structure can undergo severe permanent deformations but must not collapse and the maximum displacements have to be limited in order not to harm the occupants.

Published
2020
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31. Implicit $$\mathrm{G}^1$$-Conforming Plate Elements

Author

Loredana Contrafatto, L. Greco, and M. Cuomo

Subjects
Pure mathematics, Computer Science::Graphics, Quadrilateral, Polygon mesh, Isogeometric analysis, Finite element method, Mathematics
Abstract

A family of quadrilateral and triangular \(\mathrm{G}^1\)-conforming finite elements, based on the Gregory patch suitable for the analysis of the Kirchhoff plate model are analyzed. In the CAGD-literature Gregory Patch indicates a rational enhancement of the base-polynomial spaces, useful for designing \(\mathrm{G}^1\)-conforming elements on general \(\mathrm{C}^0\)-conforming unstructured meshes.

Published
2020
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32. Long-Term Results after Fallot’s Repair

Author

M. Cuomo, S. Dittrich, M. Alkassar, R. Cesnjevar, R. Blumauer, J. Kleinöder, and A. Purbujo

Subjects
medicine.medical_specialty, business.industry, Internal medicine, medicine, Cardiology, Long term results, business
Published
2020
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35. Recent Advancements and Applications of Human Immune System Mice in Preclinical Immuno-Oncology

Author

Maelle Mairesse, Bethany Bareham, Alba Matas-Céspedes, Emanuela M. Cuomo, Giovanni Pellegrini, Michelle Curran, Ardi Liaunardy, Kourosh Saeb-Parsy, Edward Powell, Rebecca Sargeant, Richard Stebbings, and Catherine J. Betts

Subjects
Toxicology, Medical Oncology, Pathology and Forensic Medicine, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Combined treatment, Immunopathology, Allergy and Immunology, Medicine, Animals, Humans, Immunologic Factors, Molecular Biology, 030304 developmental biology, 0303 health sciences, business.industry, Cancer, Cell Biology, medicine.disease, Disease Models, Animal, Drug development, 030220 oncology & carcinogenesis, Immune System, Cancer research, Immunologic Techniques, business
Abstract

Significant advances in immunotherapies have resulted in the increasing need of predictive preclinical models to improve immunotherapeutic drug development, treatment combination, and to prevent or minimize toxicity in clinical trials. Immunodeficient mice reconstituted with human immune system (HIS), termed humanized mice or HIS mice, permit detailed analysis of human immune biology, development, and function. Although this model constitutes a great translational model, some aspects need to be improved as the incomplete engraftment of immune cells, graft versus host disease and the lack of human cytokines and growth factors. In this review, we discuss current HIS platforms, their pathology, and recent advances in their development to improve the quality of human immune cell reconstitution. We also highlight new technologies that can be used to better understand these models and how improved characterization is needed for their application in immuno-oncology safety, efficacy, and new modalities therapy development.

Published
2019

37. Aortic valve calcification as a risk factor for major complications and reduced survival after transcatheter replacement

Author

Ferdinand Vogt, Christian Langhammer, Johannes Schwab, Theodor Fischlein, M. Cuomo, Wolfgang Hitzl, Francesco Pollari, Claudius Söhn, Jurij M. Kalisnik, Thomas Bertsch, and Steffen Pfeiffer

Subjects
Aortic valve, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, 030204 cardiovascular system & hematology, Risk Assessment, Severity of Illness Index, 030218 nuclear medicine & medical imaging, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, 0302 clinical medicine, Valve replacement, Interquartile range, Risk Factors, Internal medicine, Multidetector Computed Tomography, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Hospital Mortality, Stroke, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Hazard ratio, Calcinosis, Odds ratio, Aortic Valve Stenosis, medicine.disease, medicine.anatomical_structure, Treatment Outcome, Aortic Valve, Cardiology, Female, Aortic valve calcification, Cardiology and Cardiovascular Medicine, business, Calcification
Abstract

Aortic valve calcification is supposed to be a possible cause of embolic stroke or subclinical valve thrombosis after transcatheter aortic valve replacement (TAVR). We aimed to assess the role of aortic valve calcification in the occurrence of in-hospital clinical complications and survival after TAVR.We retrospectively analyzed preoperative contrast-enhanced multidetector computed tomography scans of patients who underwent TAVR on the native aortic valve in our center. Calcium volume was calculated for each aortic cusp, above and below the aortic annulus. Outcomes were recorded according to VARC-2 criteria.Overall, 581 patients were included in the study (SapienXT = 192; Sapien3 = 228; CoreValve/EvolutR = 45; Engager = 5; Acurate = 111). Median survival was 4.98 years (interquartile range 4.41-5.54). Logistic regression identified calcium load beneath the right coronary cusp in left ventricular outflow tract (LVOT) as significantly associated with stroke (odds ratio [OR] 1.2; 95% confidence interval [CI] 1.03-1.3; p = 0.0019) and in-hospital mortality (OR 1.1; 95% CI 1.004-1.2; p = 0.04), whereas total calcium volume of the LVOT was associated with both in-hospital and 30 day-mortality (OR 1.2; 95% CI 1.01-1.4; p = 0.03, and OR 1.2; 95% CI 1.02-1.43; p = 0.029, respectively). Cox regression identified total calcium of LVOT (hazard ratio [HR] 1.18; 95% CI 1.02-1.38; p = 0.026), male sex (HR 1.88; 95% CI 1.06-3.32; p = 0.031), baseline creatinine clearance (HR 0.96; 95% CI 0.93-0.98; p 0.001), and baseline severe aortic regurgitation (HR 7.48; 95% CI 2.76-20.26; p 0.001) as risk factors associated with lower survival.LVOT calcification is associated with increased risk of peri-procedural stroke and mortality as well as shorter long-term survival.

Published
2019

38. Double-Transcatheter Staged Approach for Aorto-Mitral Valve Disease

Author

Ferdinand Vogt, Francesco Pollari, M. Cuomo, Theodor Fischlein, Steffen Pfeiffer, Giuseppe Santarpino, Jürgen Jessl, and J. Sirch

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.anatomical_structure, business.industry, Mitral valve, Internal medicine, Cardiology, Medicine, Surgery, Disease, Cardiology and Cardiovascular Medicine, business
Published
2017
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40. Risk factors for atrioventricular block after transcatheter aortic valve implantation: a single-centre analysis including assessment of aortic calcifications and follow-up

Author

Jurij M. Kalisnik, M. Cuomo, Francesco Pollari, Ferdinand Vogt, Johannes Schwab, Steffen Pfeiffer, Theodor Fischlein, and Irena Großmann

Subjects
Aortic valve, Male, medicine.medical_specialty, Bundle of His, medicine.medical_treatment, 030204 cardiovascular system & hematology, Risk Assessment, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, Electrocardiography, 0302 clinical medicine, Postoperative Complications, Predictive Value of Tests, Risk Factors, Physiology (medical), Internal medicine, Germany, Multidetector Computed Tomography, medicine, Ventricular outflow tract, Humans, 030212 general & internal medicine, Atrioventricular Block, Intraoperative Complications, Aged, Retrospective Studies, business.industry, Cardiac Pacing, Artificial, Percutaneous coronary intervention, Calcinosis, Odds ratio, Aortic Valve Stenosis, Right bundle branch block, medicine.disease, medicine.anatomical_structure, Aortic Valve, Preoperative Period, Cardiology, Female, Aortic valve calcification, Cardiology and Cardiovascular Medicine, business, Atrioventricular block, Calcification
Abstract

AIMS To assess the contribution of aortic valve calcification to the occurrence of transient or permanent atrioventricular block (AVB) and the need for permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) in a large single-centre cohort. METHODS AND RESULTS We retrospectively analysed pre-operative contrast-enhanced multidetector computed tomography scans of patients who underwent TAVI in our centre between 2012 and 2016. Calcium volume was calculated for each aortic cusp above (aortic valve), and below [left ventricular outflow tract (LVOT)] the basal plane. Clinical and procedural data as well as pre-operative electrocardiograms were evaluated. Multivariate analysis was performed to evaluate risk factors for transient and permanent AVB. A total of 342 patients receiving a balloon-expandable prosthesis were included in the study. Overall incidence of transient and permanent AVB was 4% (n = 14) and 7.6% (n = 26), respectively. On logistic regression analysis, baseline right bundle branch block [odds ratio (OR) 7.36, 95% confidence interval (CI) 2.6-20.6; P

Published
2018

41. Lactobacillus paracaseiCBA L74 interferes with gliadin peptides entrance in Caco-2 cells

Author

Francesca Fasano, Roberto Nigro, M. Sarno, Riccardo Troncone, M. Cuomo, Federica Nigro, Francesca Passannanti, Maria Vittoria Barone, Giuliana Lania, Andrea Budelli, Salvatore Auricchio, Merlin Nanayakkara, Sarno, M, Lania, G, Cuomo, M, Nigro, F, Passannanti, F, Budelli, A, Fasano, F, Troncone, Riccardo, Auricchio, S, Barone, MARIA VITTORIA, Nigro, Roberto, and Nanayakkara, M.

Subjects
Lactobacillus paracasei, Colon, Biological effect, Gliadin, law.invention, Microbiology, Pathogenesis, Probiotic, law, Humans, Intestinal Mucosa, Cells, Cultured, Biological Products, biology, Probiotics, food and beverages, biology.organism_classification, Acquired immune system, Celiac disease, Lactobacillus paracasei CBA L74, fermented food, gliadin peptides, vesicular trafficking, Celiac Disease, Lactobacillus, Enterocytes, Biochemistry, Caco-2, Fermentation, biology.protein, Caco-2 Cells, Edible Grain, Peptides, Food Science
Abstract

Several recent reports describe a role of probiotics as a therapeutic approach for celiac disease (CD). Two undigested A-gliadin peptides, P31-43 and P57-68, are central to CD pathogenesis, inducing an innate and an adaptive immune response, respectively. They enter enterocytes and localize to vesicular compartment to induce their toxic/immunogenics effects. In this article, we tested the effect of probiotic Lactobacillus paracasei (LP) CBA L74 (International Depository Accession Number LMG P-24778), its supernatant and LP-fermented cereals on gliadin peptides, P31-43 and P57-68, entrance in Caco-2 cells. Both LP CBA L74 and its supernatant inhibit P31-43 (intensity of fluorescence; FI: 75%) and P57-68 (FI: 50%) entrance in Caco2 cells, indicating that this biological effect is due to some product included in LP CBA L74 supernatant. This effect was present also after fermentation of cereals. This study describes a novel effect of probiotics in the prevention of undigested gliadin peptides toxic effects.

Published
2014
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42. Abstract 4813: Comparative activity profiling of tyrosine kinase inhibitors (TKIs) against exon 20 insertions and the wild-type form of epidermal growth factor receptor (EGFR)

Author

Martina Fitzek, Jelena Urosevic, Emanuela M. Cuomo, Darren Mckerrecher, Ambra Bianco, Nicolas Floc'h, Sladjana Gagrica, M. Raymond V. Finlay, Matthew J. Martin, Beverley Hammond, Richard A. Ward, Jonathan P. Orme, Darren Cross, Paul D. Smith, James W.T. Yates, Nicky Whalley, Nicola Colclough, Daniel O'Neill, and Anna Staniszewska

Subjects
0301 basic medicine, Cancer Research, Cetuximab, biology, business.industry, Afatinib, Poziotinib, Cancer, medicine.disease, 03 medical and health sciences, Exon, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, medicine, Cancer research, biology.protein, Osimertinib, Epidermal growth factor receptor, business, Tyrosine kinase, medicine.drug
Abstract

Exon 20 insertions (Ex20Ins) have been identified in approximately 5% of epidermal growth factor receptor (EGFR)-mutated lung tumours in patients presenting with non-small cell lung cancer (NSCLC). Several small molecule tyrosine kinase inhibitors (TKIs) have been reported to have pre-clinical activity against such insertions including afatinib, poziotinib, osimertinib, nazartinib, AP32788/TAK-788 and TAS6417. However, there remains a lack of approved treatments for patients with Ex20Ins with early approved EGFR agents appearing to be ineffective in this setting. Poziotinib, osimertinib and AP32788/TAK-788 are undergoing clinical evaluation in patients whose tumours carry Ex20Ins and in some cases clinical responses have been reported giving hope that such insertions can be targeted by small molecules. There is however a need for comparable data across such compounds that would enable understanding of the relative activity of these compounds between Ex20Ins and the wild-type form of EGFR. As many of the Exon 20 insertions are not part of the ATP binding pocket achieving selectivity over wild type EGFR is highly challenging and may limit the clinical utility of agents due to dose limiting EGFR wild-type driven toxicity. A selection of TKIs were profiled for Ex20Ins and wild-type EGFR activity using biochemical, in vitro cellular phosphorylation and proliferation assays. This has enabled us to differentiate the Ex20Ins versus wild-type EGFR selectivity profiles of a range of pre-clinical, clinical and proprietary compounds. As part of this evaluation we utilized a CRISPR CAS9 approach in H2073 EGFR wild-type NSCLC cell line, where we have established cellular disease models against the most prevalent insertions including D770-N771insSVD (22%). Finally, we will show anti-tumour efficacy data for a selection of these inhibitors along with a potential combination approach of osimertinib and cetuximab. EGFR D770-N771InsSVD cell phospho IC50 (µM)EGFR WT (H2073) cell phospho IC50 (µM)Fold-EGFR WT margin (cell)afatinib0.0060.00330.5osimertinib0.0940.414.4poziotinib0.00340.00351TAS64170.0230.0672.9AZ62810.0972.223 Citation Format: Richard A. Ward, Ambra Bianco, Nicola Colclough, Darren Cross, Emanuela M. Cuomo, M. Raymond V. Finlay, Martina Fitzek, Nicolas Floc’h, Sladjana Gagrica, Beverley Hammond, Matthew J. Martin, Darren McKerrecher, Daniel J. O’Neill, Jonathan P. Orme, Paul D. Smith, Anna D. Staniszewska, Jelena Urosevic, Nicky Whalley, James W. Yates. Comparative activity profiling of tyrosine kinase inhibitors (TKIs) against exon 20 insertions and the wild-type form of epidermal growth factor receptor (EGFR) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4813.

Published
2019
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43. Abstract 4451: Evaluation of the therapeutic potential of phosphine oxide pyrazole inhibitors in tumors harboring EGFR C797S mutation

Author

Nicolas Floch, M. Raymond V. Finlay, Ambra Bianco, Sue Bickerton, Nicola Colclough, Darren A. Cross, Emanuela M. Cuomo, Carine M. Guerot, David Hargreaves, Matthew J. Martin, Darren McKerrecher, Daniel J. O’Neill, Jonathan P. Orme, Amar Rahi, Paul D. Smith, and Richard A. Ward

Subjects
Cancer Research, Oncology
Abstract

Osimertinib is a next-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with activity against both the activating and the ‘gatekeeper’ T790M EGFR mutations. An acquired EGFR C797S mutation has been reported to mediate osimertinib resistance in approximately 15% and 7% of patients in second-line and first-line treatment respectively. This percentage in the first-line setting will likely evolve as the first line data mature. The C797S mutation leads to the loss of covalent binding of osimertinib to mutant EGFR. The high affinity of the EGFR triple mutant for ATP presents a challenge for reversible inhibitor design, particularly as the loss of the cysteine at position 797 precludes the previously exploited covalent approaches. We have explored various approaches to address this challenge, including an effort to maximise reversible affinity to target the C797S mutation without requiring a covalent bond. We describe herein the therapeutic potential of reversible phosphine oxide pyrazole inhibitors in tumors harboring C797S. Using structure-based design, we were able to design a series of phosphine oxide pyrazole inhibitors that displayed exceptionally high biochemical potency against EGFR C797S mutation, which translated into good activity in cell-based assays. Using CRISPR-Cas 9 genome editing technology, we engineered cellular disease-relevant models to express the C797S mutation to evaluate potency in vitro and in vivo. By modulating the physicochemical properties of our in vitro leads, we were able to achieve good oral exposure of cellularly active EGFR C797S inhibitors such as AZ’7608. We showed that AZ’7608 inhibits signalling pathways and cellular growth of C797S EGFR cell lines in vitro and demonstrated an improved WT EGFR margin. This translated into 52% (p The work presented herein shows a proof of concept for reversible phosphine oxide pyrazole inhibitors to target tumors harboring C797S. The emergence of the C797S EGFR mutation remains a key area of unmet need and warrants further efforts in drug discovery. Citation Format: Nicolas Floch, M. Raymond V. Finlay, Ambra Bianco, Sue Bickerton, Nicola Colclough, Darren A. Cross, Emanuela M. Cuomo, Carine M. Guerot, David Hargreaves, Matthew J. Martin, Darren McKerrecher, Daniel J. O’Neill, Jonathan P. Orme, Amar Rahi, Paul D. Smith, Richard A. Ward. Evaluation of the therapeutic potential of phosphine oxide pyrazole inhibitors in tumors harboring EGFR C797S mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4451.

Published
2019
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44. Genetic risk factors for insidious equine recurrent uveitis in Appaloosa horses

Author

Candice Brinkmeyer-Langford, James R. Mickelson, F. M. Cuomo, S. J. Valberg, M. L. Wagner, M. Lucio, K. M. Dynes, Molly E. McCue, Loren C. Skow, Mark S. Rutherford, Krista L. Fritz, Aaron Rendahl, Heather J. Kaese, Rebecca R. Bellone, and Julie A. Hendrickson

Subjects
Genetic Markers, Genetics, education.field_of_study, Models, Genetic, Population, General Medicine, Equine recurrent uveitis, Biology, Polymorphism, Single Nucleotide, Uveitis, Risk Factors, Animals, SNP, Eye disorder, Microsatellite, Horse Diseases, Animal Science and Zoology, Horses, Allele, education, Alleles, TRPM1, Microsatellite Repeats, Genetic association
Abstract

Appaloosa horses are predisposed to equine recurrent uveitis (ERU), an immune-mediated disease characterized by recurring inflammation of the uveal tract in the eye, which is the leading cause of blindness in horses. Nine genetic markers from the ECA1 region responsible for the spotted coat color of Appaloosa horses, and 13 microsatellites spanning the equine major histocompatibility complex (ELA) on ECA20, were evaluated for association with ERU in a group of 53 Appaloosa ERU cases and 43 healthy Appaloosa controls. Three markers were significantly associated (corrected P-value

Published
2014
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47. EP08 CALCIUM LOADING AS RISK FACTOR FOR CONDUCTION DISTURBANCE AFTER TAVI

Author

Theodor Fischlein, Jürgen Jessl, Jill Marianowicz, Irena Großmann, Steffen Pfeiffer, Francesco Pollari, M. Cuomo, and Ferdinand Vogt

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Cardiology, Medicine, General Medicine, Calcium loading, Risk factor (computing), Cardiology and Cardiovascular Medicine, business, Conduction disturbance
Published
2018
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48. RF11 CALCIUM LOADING AS RISK FACTOR FOR POST IMPLANTATION LEAKAGE IN TAVI PROCEDURES

Author

Johannes Schwab, Ferdinand Vogt, A.M. Dell'Aquila, M. Cuomo, Francesco Pollari, Theodor Fischlein, Jurij M. Kalisnik, and Steffen Pfeiffer

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Cardiology, medicine, General Medicine, Calcium loading, Cardiology and Cardiovascular Medicine, Post implantation, business, Leakage (electronics)
Published
2018
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