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1. Persistence of both reversible airway obstruction and higher blood eosinophils may predict lung function decline in severe asthma

Author

Sposato B., Scalese M., Ricci A., Rogliani P., Paggiaro P., Migliorini M. G., Di Tomassi M., Olivieri C., Perrella A., Camiciottoli G., Maselli R., Pelaia G., Busceti M. T., Sabato E., Cagnazzo M. G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Caiaffa M. F., Berra A., Calabrese C., Stanziola A. A., Schino P., Di Gioacchino M., Cazzola M., Segreti A., Pastorello E. A., Scibilia G., Vianello A., Marchi M. R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Matucci A., Vultaggio A., Maggi E., Maestrelli P., Guarnieri G., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Macchia L., Bellia V., Scichilone N., Novelli F., Latorre M., Vergura L., Masieri S., Rosati Y., Milanese M., Folletti I., Pio R., Pio A., Maccari U., Maggiorelli C., Scala R., Vignale L., Pulera N., Carpagnano G. E., Foschino Barbaro M. P., Sposato B., Scalese M., Ricci A., Rogliani P., Paggiaro P., Migliorini M.G., Di Tomassi M., Olivieri C., Perrella A., Camiciottoli G., Maselli R., Pelaia G., Busceti M.T., Sabato E., Cagnazzo M.G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Caiaffa M.F., Berra A., Calabrese C., Stanziola A.A., Schino P., Di Gioacchino M., Cazzola M., Segreti A., Pastorello E.A., Scibilia G., Vianello A., Marchi M.R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Matucci A., Vultaggio A., Maggi E., Maestrelli P., Guarnieri G., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Macchia L., Bellia V., Scichilone N., Novelli F., Latorre M., Vergura L., Masieri S., Rosati Y., Milanese M., Folletti I., Pio R., Pio A., Maccari U., Maggiorelli C., Scala R., Vignale L., Pulera N., Carpagnano G.E., Foschino Barbaro M.P., Sposato, B., Scalese, M., Ricci, A., Rogliani, P., Paggiaro, P., Migliorini, M. G., Di Tomassi, M., Olivieri, C., Perrella, A., Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Caiaffa, M. F., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Cazzola, M., Segreti, A., Pastorello, E. A., Scibilia, G., Vianello, A., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Scichilone, N., Novelli, F., Latorre, M., Vergura, L., Masieri, S., Rosati, Y., Milanese, M., Folletti, I., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Scala, R., Vignale, L., Pulera, N., Carpagnano, G. E., Foschino Barbaro, M. P., and Et, Al

Subjects
Pulmonary and Respiratory Medicine, severe asthma, medicine.medical_specialty, medicine.drug_class, Severe asthma, Eosinophil, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Gastroenterology, Persistence (computer science), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Bronchodilator, allergic asthma, blood eosinophil, bronchodilator reversibility, lung function decline, severe asthma, salbutamol, Forced Expiratory Volume, medicine, Settore MED/10, Immunology and Allergy, Humans, 030212 general & internal medicine, Blood eosinophil, Lung, Genetics (clinical), Lung function, Bronchodilator Agent, allergic asthma, blood eosinophil, bronchodilator reversibility, lung function decline, salbutamol, bronchodilator agents, eosinophils, forced expiratory volume, humans, lung, airway obstruction, asthma, business.industry, Airway obstruction, medicine.disease, Asthma, Bronchodilator Agents, Airway Obstruction, Eosinophils, 030228 respiratory system, Salbutamol, Blood eosinophils, business, medicine.drug, Human
Abstract

Objective: This study analysed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics. Methods: About 202 severe asthmatics were studied after 12–120months of step-5 treatment associated to anti-IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV1>12% or ≤12% changes differentiated RAO+ from RAO− subjects. Blood eosinophil (BE) counts after treatment were considered. Results: Pre-/post-treatment bronchodilator FEV1% and ACT were lower (61% [50–71], 74.4% [62.5–83.7] and 20[18–22]), whereas BE were higher (380 cells/µl [170–590]) in RAO+ compared to RAO− subjects (77% [64–88], p=0.0001, 81.8% [66.1–94.3], p=0.0001, 21[18–23], p=0.045 and 230 cells/µl [80–360], p=0.003). A negative relationship between SABA-induced FEV1% changes and pre-bronchodilator FEV1% (β=−0.551%; p=0.0001) and ACT (β=−0.059; p=0.038) was found. Conversely, post-treatment BE levels were positively related (β=145.565 cells/µl; p=0.003) to FEV1>12% increases. A rising trend of pre-/post-bronchodilator FEV1% in time was observed in RAO− subjects with BE300 cells/µl reaching lower values after more than 36months of step-5 treatment (59.6% [39.9–72.1] vs 74[66.5–89.2] of RAO+ individuals with BE300 cells/µl [p=0.009]). Conclusion: Persistent SABA-induced FEV1>12%, especially when associated to BE>300 cells/ml, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step-5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline.

Published
2020

2. Higher blood eosinophil levels after omalizumab treatment may be associated with poorer asthma outcomes

Author

Sposato, B, Scalese, M, Milanese, M, Masieri, S, Cavaliere, C, Latorre, M, Scichilone, N, Ricci, A, Cresti, A, Santus, P, Olivieri, C, Perrella, A, Rogliani, P, Paggiaro, P, Migliorini, M. G, Di Tomassi, M, Camiciottoli, G, Maselli, R, Pelaia, G, Busceti, M. T, Sabato, E, Cagnazzo, M. G, Colombo, F, Palumbo, L, Ravazzi, A, Bucca, C, Caiaffa, M. F, Berra, A, Calabrese, C, Stanziola, A. A, Schino, P, Di Gioacchino, M, Cazzola, M, Segreti, A, Pastorello, E. A, Scibilia, G, Vianello, A, Marchi, M. R, Paladini, L, Baglioni, S, Abbritti, M, Almerigogna, F, Matucci, A, Vultaggio, A, Maggi, E, Maestrelli, P, Guarnieri, G, Steinhilber, G, Bonavia, M, Rottoli, P, Bargagli, E, Senna, G, Caminati, M, Macchia, L, Bellia, V, Novelli, F, Vergura, L, Rosati, Y, Folletti, I, Pio, R, Pio, A, Maccari, U, Maggiorelli, C, Scala, R, Vignale, L, Pulerà, N, Carpagnano, G. E, Foschino Barbaro, M. P, The Omalizumab Italian Study Group, Sposato, B, Scalese, M, Milanese, M, Masieri, S., Cavaliere, C, Latorre, M., Scichilone, N., Ricci, A., Cresti, A., Santus, P., Olivieri, C., Perrella, A., Rogliani, P., Paggiaro, P., Sposato, B., Migliorini, M. G., Di Tomassi, M., Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Caiaffa, M. F., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Cazzola, M., Segreti, A., Pastorello, E. A., Scibilia, G., Vianello, A., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Novelli, F., Vergura, L., Scalese, M., Rosati, Y., Milanese, M., Folletti, I., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Scala, R., Vignale, L., Pulera, N., Carpagnano, G. E., Foschino Barbaro, M. P., Cavaliere, C., Sposato B., Scalese M., Milanese M., Masieri S., Cavaliere C., Latorre M., Scichilone N., Ricci A., Cresti A., Santus P., Olivieri C., Perrella A., Rogliani P., Paggiaro P., Migliorini M.G., Di Tomassi M., Camiciottoli G., Maselli R., Pelaia G., Busceti M.T., Sabato E., Cagnazzo M.G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Caiaffa M.F., Berra A., Calabrese C., Stanziola A.A., Schino P., Di Gioacchino M., Cazzola M., Segreti A., Pastorello E.A., Scibilia G., Vianello A., Marchi M.R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Matucci A., Vultaggio A., Maggi E., Maestrelli P., Guarnieri G., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Macchia L., Bellia V., Novelli F., Vergura L., Rosati Y., Folletti I., Pio R., Pio A., Maccari U., Maggiorelli C., Scala R., Vignale L., Pulera N., Carpagnano G.E., and Foschino Barbaro M.P.

Subjects
Adult, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Treatment outcome, MEDLINE, Omalizumab, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Immunoglobulin E, eosinophil, Omalizumab, anti-IgE, asthma, Leukocyte Count, Text mining, Forced Expiratory Volume, Internal medicine, Eosinophilia, medicine, Humans, Immunology and Allergy, Anti-Asthmatic Agents, Blood eosinophil, Aged, Retrospective Studies, Asthma, biology, business.industry, Retrospective cohort study, Middle Aged, asthma, Prognosis, medicine.disease, Eosinophils, Treatment Outcome, inflammation, biology.protein, Female, business, medicine.drug
Published
2019

3. Effects of omalizumab in severe asthmatics across ages: A real life Italian experience

Author

Sposato, B., Scalese, M., Latorre, M., Scichilone, N., Matucci, A., Milanese, M., Masieri, Simonetta, Rolla, G., Steinhilber, G., Rosati, Y., Vultaggio, A., Folletti, I., Baglioni, S., Bargagli, E., Di Tomassi, M., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Migliorini, M. G., Vignale, L., PulerÃ&nbsp, Carpagnano, G. E., Foschino Barbaro, M. P., Perrella, A., Paggiaro, P. L., Sposato, B., Scalese, M., Latorre, M., Scichilone, N., Matucci, A., Milanese, M., Masieri, S., Rolla, G., Steinhilber, G., Rosati, Y., Vultaggio, A., Folletti, I., Baglioni, S., Bargagli, E., Di Tomassi, M., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Migliorini, M., Vignale, L., Pulerà, N., Carpagnano, G., Foschino Barbaro, M., Perrella, A., and Paggiaro, P.

Subjects
Male, Severe asthma, Pediatrics, Comorbidity, Omalizumab, Overweight, Immunoglobulin E, Severity of Illness Index, Elderly, 0302 clinical medicine, Adrenal Cortex Hormones, Forced Expiratory Volume, Age effect, Anti-Asthmatic Agents, asthma, allergy, elderly, omalizumab, 030212 general & internal medicine, Young adult, biology, Real-life, Adrenergic beta-Agonists, Middle Aged, Treatment Outcome, Italy, Female, medicine.symptom, medicine.drug, Adult, Pulmonary and Respiratory Medicine, age effect, elderly, omalizumab, real-life, severe asthma, medicine.medical_specialty, Adolescent, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Antibodies, Monoclonal, Humanized, Young Adult, 03 medical and health sciences, Administration, Inhalation, Severity of illness, medicine, Humans, Aged, Retrospective Studies, Asthma, business.industry, Retrospective cohort study, asthma, allergy, medicine.disease, 030228 respiratory system, biology.protein, business
Abstract

Background This retrospective study aimed at evaluating long-term effects of Omalizumab in elderly asthmatics in a real-life setting. Methods 105 consecutive severe asthmatics (GINA step 4–5; mean FEV1% predicted:66 ± 15.7) treated with Omalizumab for at least 1 year (treatment mean duration 35.1 ± 21.7 months) were divided into 3 groups according to their age at Omalizumab treatment onset: 18–39, 40–64 and ≥ 65 years. Results Comorbidities, number of overweight/obese subjects and patients with late-onset asthma were more frequent among older people. A similar reduction of inhaled corticosteroids dosage and SABA on-demand therapy was observed in all groups during Omalizumab treatment; a similar FEV1 increased was also observed. Asthma Control Test (ACT) improved significantly (p

Published
2016
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4. Clinical presentation and management of patients with primary hyperparathyroidism in Italy

Author

Serena Palmieri, Alfredo Scillitani, Salvatore Minisola, Elda Kara, Luisella Cianferotti, Cristiana Cipriani, Sabrina Corbetta, Federica Saponaro, Andrea Palermo, Giorgio Borretta, Giuseppe Vezzoli, Claudio Marcocci, Antonio Stefano Salcuni, Laura Gianotti, Uberto Pagotto, Valentina Camozzi, Fabio Maino, Antongiulio Faggiano, Francesco Romanelli, Jessica Pepe, Cristina Eller-Vainicher, Filomena Cetani, Marco Scalese, M. L. Brandi, C. Cipri, Andrea Repaci, Elena Castellano, Iacopo Chiodini, Fabio Vescini, Bruno Madeo, M. L. De Feo, Saponaro, F, Cetani, F, Repaci, A, Pagotto, U, Cipriani, C, Pepe, J, Minisola, S, Cipri, C, Vescini, F, Scillitani, A, Salcuni, A, Palmieri, S, Eller-Vainicher, C, Chiodini, I, Madeo, B, Kara, E, Castellano, E, Borretta, G, Gianotti, L, Romanelli, F, Camozzi, V, Faggiano, A, Corbetta, S, Cianferotti, L, Brandi, M L, De Feo, M L, Palermo, A, Vezzoli, G, Maino, F, Scalese, M, Marcocci, C, Saponaro, F., Cetani, F., Repaci, A., Pagotto, U., Cipriani, C., Pepe, J., Minisola, S., Cipri, C., Vescini, F., Scillitani, A., Salcuni, A., Palmieri, S., Eller-Vainicher, C., Chiodini, I., Madeo, B., Kara, E., Castellano, E., Borretta, G., Gianotti, L., Romanelli, F., Camozzi, V., Faggiano, A., Corbetta, S., Cianferotti, L., Brandi, M. L., De Feo, M. L., Palermo, A., Vezzoli, G., Maino, F., Scalese, M., and Marcocci, C.

Subjects
Male, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Parathyroid hormone, Parathyroid Gland, 0302 clinical medicine, Endocrinology, Prospective Studies, Prospective cohort study, diabetes and metabolism, health care economics and organizations, Parathyroid adenoma, Ultrasonography, Hyperparathyroidism, parathyroid adenoma, parathyroid imaging, parathyroidectomy, serum calcium, endocrinology, diabetes and metabolism, endocrinology, Middle Aged, Hyperparathyroidism, Primary, Urinary calcium, Italy, Parathyroid Hormone, 030220 oncology & carcinogenesis, Female, medicine.symptom, Presentation (obstetrics), Primary, Human, Parathyroidectomy, medicine.medical_specialty, education, 030209 endocrinology & metabolism, Parathyroid imaging, Serum calcium, Aged, Calcium, Follow-Up Studies, Humans, Parathyroid Glands, Asymptomatic, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, business.industry, medicine.disease, Prospective Studie, business, Primary hyperparathyroidism
Abstract

Purpose: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. Method: From January 2014–January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. Results: Over the first year we enrolled 604 patients (age 61 ± 14years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13 years), the remaining 38 (6.3%, age 41 ± 17 years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2–81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1–37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. Conclusions: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.

Published
2018

5. Pediatric ranges of normality for 2D speckle‐tracking echocardiography atrial strain: differences between p‐ and r‐gating and among new (Atrial Designed) and conventional (Ventricular Specific) software's

Author

Pietro Marchese, Antonio Ravaglioli, Massimiliano Cantinotti, Raffaele Giordano, Shelby Kutty, Marco Scalese, Martin Koestenberger, Eliana Franchi, Nadia Assanta, Marchese, P., Scalese, M., Giordano, R., Assanta, N., Franchi, E., Koestenberger, M., Ravaglioli, A., Kutty, S., and Cantinotti, M.

Subjects
Adult, Male, medicine.medical_specialty, Heart Ventricles, media_common.quotation_subject, Gating, strain, Software, Internal medicine, Heart rate, medicine, Humans, Radiology, Nuclear Medicine and imaging, Heart Atria, Child, Normality, media_common, Body surface area, congenital pediatric, business.industry, atrial, Nomogram, Healthy Volunteer, Healthy Volunteers, Atrial strain, medicine.anatomical_structure, Echocardiography, Ventricle, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Human
Abstract

Background: 2D speckle tracking echocardiography (STE) atrial strain (ε) analysis in children is gaining interest; however, pediatric nomograms remain limited. Comparison among conventional software's (designed for left ventricle and adapted to atria and using R-gating analysis) and new software's (designed for atria and allowing for both R- and P-gating) are lacking. The present study aims to establish pediatric nomograms for atrial ε using an atrial dedicated software and to compare values obtained by (a) R- and P-gating and, (b) R-gating with new and conventional software. Methods: Echocardiographic measurements included STE left (LA) and right (RA) atrial longitudinal reservoir, conduit and contractile ε. Age/weigh/height/heart rate, and body surface area (BSA) were used as independent variables in the statistical analysis. Results: In all, 580 healthy subjects (age range, 31 days-18 years; mean age 7.5 years; median age 7.1 years; inter-quartile range, 4.3–10.7 months; 45.5% female) were included. Feasibility of atrial ε measurements was high (98.9–96.8%). At lower age, atrial conduit ε was lower (p

Published
2021
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6. Left Ventricular Systolic Impairment after Pediatric Cardiac Surgery Assessed by STE Analysis

Author

Massimiliano Cantinotti, Vivek Jani, Pak Vitali, Pietro Marchese, Marco Scalese, Martin Koestenberger, Eliana Franchi, Raffaele Giordano, Giuseppe Santoro, Cecilia Viacava, Paola Medino, Shelby Kutty, Nadia Assanta, Cantinotti, M., Marchese, P., Scalese, M., Medino, P., Jani, V., Franchi, E., Vitali, P., Santoro, G., Viacava, C., Assanta, N., Kutty, S., Koestenberger, M., and Giordano, R.

Subjects
endocrine system, medicine.medical_specialty, Ejection fraction, Leadership and Management, business.industry, Health Policy, Health Informatics, Speckle tracking echocardiography, Mean age, congenital heart disease, Article, Cardiac surgery, Basal (phylogenetics), Health Information Management, Internal medicine, medicine, Cardiology, Medicine, echocardiography, cardiovascular diseases, business, speckle tracking echocardiography, cardiac surgery
Abstract

Background: Speckle-tracking echocardiography (STE) has gained increasing value in the evaluation of congenital heart diseases (CHD), however, its use in pediatric cardiac surgery is limited. Aim: To evaluate left ventricular (LV) systolic impairment after biventricular pediatric cardiac surgery by STE strain (ε) analysis. Methods: We prospectively enrolled 117 children undergoing cardiac surgery for CHD. Echocardiography was performed at four different times: pre-operatively, 12–36 h (Time 1), 3–5 days (Time 2), and 6–8 days (Time 3). Images were obtained in the 4-2-and 3 apical chamber’s views to derive LV global and regional (basal/mid/apical) ε values. Results: At different postoperative times, we performed 320 examinations in 117 children (mean age: 2.4 ± 3.9, range: 0–16 years), 117 age-matched healthy children served as controls. All global, basal, and mid LVε values decreased after surgery, the lowest values being at Time 1 (p &lt, 0.0001), which increased thereafter. At discharge, all global, basal, and mid LVε values remained lower than in pre-operative and healthy children (p &lt, 0.05). Instead, apical segments (lowest at baseline) increased after surgery (p &lt, 0.0001) but remained lower compared to controls. LV ejection fraction (LVEF) decreased at Time 1 (p = 0.0004) but promptly recovered to Time 2 and normalized at Time 3. Conclusions: STE ε analysis revealed a significant LV systolic impairment after surgery with amelioration thereafter but incomplete normalization at discharge. Base-apex differences emerged with apical segments that, contrary to all the other regions, showed relative hypercontractility after surgery. The slower recovery of LVε values compared to LVEF suggests that STE ε analysis may be more accurate for the follow-up of mild LV post-surgical impairment.

Published
2021

7. A real-world efficacy and safety analysis of combined carfilzomib, lenalidomide, and dexamethasone (KRd) in relapsed/refractory multiple myeloma

Author

Giulia Marzocchi, Luca Dozza, Angela Bonalumi, Elisabetta Antonioli, Lucia Pantani, Chiara Di Giovanni Bezzi, Marina Martello, Anna Furlan, Michela Staderini, Elena Zamagni, Mario Petrini, Paola Tacchetti, Michele Cavo, Katia Mancuso, Marco Scalese, Ilaria Rizzello, Gregorio Barilà, Gabriele Buda, Michele Cea, Serena Rocchi, Micol Quaresima, Rocchi S., Tacchetti P., Pantani L., Mancuso K., Rizzello I., di Giovanni Bezzi C., Scalese M., Dozza L., Marzocchi G., Martello M., Barila G., Antonioli E., Staderini M., Buda G., Petrini M., Cea M., Quaresima M., Furlan A., Bonalumi A., Cavo M., and Zamagni E.

Subjects
Oncology, Male, safety, Cancer Research, medicine.medical_specialty, efficacy, Neutropenia, Dexamethasone, Disease-Free Survival, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Refractory, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, real-life, Adverse effect, Lenalidomide, Multiple myeloma, Aged, Chromosome Aberrations, relapse, business.industry, Bortezomib, carfilzomib–lenalidomide–dexamethasone, multiple myeloma, Hematology, General Medicine, Middle Aged, medicine.disease, Carfilzomib, Survival Rate, chemistry, 030220 oncology & carcinogenesis, Female, business, Oligopeptides, 030215 immunology, medicine.drug
Abstract

Carfilzomib–lenalidomide–dexamethasone (KRd) has been approved for the treatment of relapsed/refractory multiple myeloma (RRMM). We conducted a retrospective analysis of 197 RRMM patients (pts) between January 2016 and March 2018 in six Italian hematologic centers, with the aim to evaluate efficacy and safety of KRd in real-life. At KRd initiation 27% carried high risk cytogenetic abnormalities (HRCA) [del17p and/or t(4;14) and/or t(14;16)], median number of prior lines of therapy was 2 (1–8), nearly all pts (96%) received prior bortezomib (18% refractory) while 45% were exposed to lenalidomide (R; 22% refractory). At the median of 12.5 months, 52% of the pts had discontinued treatment, mainly (66%) for progression. Main grade 3–4 adverse events were neutropenia (21%), infections (11%), and hypertension (6%). Overall, the response rate was 88%. The median progression-free survival (PFS) was 19.8 months and 1-year overall survival (OS) rate was 80.6%. By subgroup analysis, extended PFS and OS were observed for pts who received ≤2 prior lines of therapy (HR = 0.42, p < 0.001 and HR = 0.35, p = 0.001, respectively), not refractory to prior R (HR = 0.37, p < 0.001, and HR = 0.47, p = 0.024), without HRCA (HR = 0.33, p = 0.005 and HR = 0.26, p = 0.016) and achieving ≥ very good partial response (VGPR; HR = 0.17, p < 0.001 and HR = 0.18, p < 0.001). In conclusion, KRd demonstrated to be effective in RRMM pts treated in real-world setting, without new safety concerns. Better survival outcomes emerged for pts with ≤2 prior lines of therapy, achieving at least a VGPR, and without HRCA.

Published
2021

8. Factors reducing omalizumab response in severe asthma

Author

Manuela Latorre, Andrea Matucci, Marco Scalese, Pierachille Santus, Bruno Sposato, Alberto Cresti, Simonetta Masieri, Nicola Scichilone, Manlio Milanese, Pierluigi Paggiaro, Alessandra Vultaggio, Carlo Cavaliere, Alberto Ricci, Antonio Perrella, Sposato, B., Scalese, M., Milanese, M., Masieri, S., Cavaliere, C., Latorre, M., Scichilone, N., Matucci, A., Vultaggio, A., Ricci, A., Cresti, A., Santus, P., Perrella, A., and Paggiaro, P.L.

Subjects
Male, Severe asthma, Drug Resistance, Comorbidity, Omalizumab, Adrenal Cortex Hormone, Comorbidities, 0302 clinical medicine, Retrospective Studie, Adrenal Cortex Hormones, Risk Factors, Forced Expiratory Volume, Age Factor, Nasal polyps, Anti-Asthmatic Agents, 030212 general & internal medicine, Multivariate Analysi, Smoking, Age Factors, Real-life, Middle Aged, Treatment Outcome, Italy, Female, Comorbiditie, Human, medicine.drug, Adult, age, comorbidities, obesity, omalizumab, real-life, severe asthma, therapeutic response, internal medicine, medicine.medical_specialty, Logistic Model, Therapeutic response, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Nitric Oxide, 03 medical and health sciences, FEV1/FVC ratio, Nasal Polyps, Age, Internal medicine, Internal Medicine, medicine, Anti-Asthmatic Agent, Humans, Obesity, Risk factor, Retrospective Studies, Asthma, business.industry, Risk Factor, medicine.disease, respiratory tract diseases, Logistic Models, 030228 respiratory system, Concomitant, Multivariate Analysis, Exhaled nitric oxide, Nasal Polyp, business
Abstract

Background: Despite adding Omalizumab to conventional therapy, several severe asthmatics still show poor disease control. We investigated the factors that may affect a reduced Omalizumab response in a large population of severe asthmatics. Methods: 340 patients were retrospectively evaluated. FEV1%, FVC%, Asthma Control Test (ACT), fractional exhaled nitric oxide (FENO), possible step-downs/step-ups of concomitant therapies, exacerbations, disease control levels, ICS doses and SABA use, observed at the end of treatment, were considered as a response to Omalizumab. Results: Age was an independent risk factor for a reduced response concerning FEV1%, FVC%, ACT and for a lower asthma control. Obesity (vs normal weight) was a determinant condition for exacerbations (OR:3.114[1.509–6.424], p = 0.002), for a disease partial/no control (OR:2.665[1.064–6.680], p = 0.036), for excessive SABA use (OR:4.448[1.837–10.768], p = 0.002) and for an unchanged/increased level of concomitant asthma medications. Furthermore, obesity also reduced the response in FEV1 (β = −6.981,p = 0.04), FVC (β = −11.689,p = 0.014) and ACT (β = −2.585, p = 0.027) and was associated with a higher FENO level (β = 49.045,p = 0.040). Having at least one comorbidity was a risk factor for exacerbations (OR:1.383[1.128–1.697], p = 0.008) and for an ACT

Published
2018
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9. Pediatric nomograms for left ventricle biplane 2D volumes in healthy Caucasian children

Author

Pietro Marchese, Nadia Assanta, Marco Scalese, Martin Koestenberger, Shelby Kutty, Massimiliano Cantinotti, Cecilia Vicava, Giorgio Iervasi, Raffaele Giordano, Eliana Franchi, Cantinotti, M., Scalese, M., Giordano, R., Franchi, E., Marchese, P., Vicava, C., Assanta, N., Iervasi, G., Kutty, S., and Koestenberger, M.

Subjects
Male, medicine.medical_specialty, left ventricle, Heart Ventricles, Population, 030204 cardiovascular system & hematology, Biplane, Ventricular Function, Left, Heart Ventricle, nomogram, 03 medical and health sciences, 0302 clinical medicine, Reference Values, 030225 pediatrics, Internal medicine, Heart rate, medicine, Humans, Radiology, Nuclear Medicine and imaging, Reference Value, education, Child, Body surface area, education.field_of_study, Ventricular size, business.industry, Infant, Newborn, Nomogram, medicine.disease, Hypoplasia, Nomograms, medicine.anatomical_structure, pediatric, Italy, Ventricle, Echocardiography, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Human
Abstract

Background Left ventricular (LV) volumes are basic parameters used to estimate ventricular size and function; however, normal values are not available in children. The aim of our study is to provide normal values for LV volumes (measured with the biplane Simpson method) in healthy children. Materials and methods We prospectively studied 1320 healthy Caucasian Italian children (age 0 days-17 years, 49.4% female). Echocardiographic measurements on LV volumes were performed. Age, heart rate (HR), and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. Results Models with exponential (ln[y] = a + b*ln[x]) equations resulted in the best fit for LV volumes. The association with BSA was found to be stronger than the association of HR and age. Thus BSA was used for normalization of our data. Predicted values and Z-score boundaries by BSA are provided. Conclusions We report normal values for 2D biplane LV volumes in a population of healthy children. These data cover a gap in current pediatric echocardiographic nomograms and may serve as baseline for evaluation of children with cardiac defects characterized by LV dilatation or hypoplasia.

Published
2020

10. Prognostic Value of a New Lung Ultrasound Score to Predict Intensive Care Unit Stay in Pediatric Cardiac Surgery

Author

Nadia Assanta, Pietro Marchese, Sabrina Molinaro, Marco Scalese, Eliana Franchi, Cecilia Viacava, Luna Gargani, Massimiliano Cantinotti, Lamia Ait-Ali, Raffaele Giordano, Shelby Kutty, Martin Koestenberger, Cantinotti, M., Giordano, R., Scalese, M., Marchese, P., Franchi, E., Viacava, C., Molinaro, S., Assanta, N., Koestenberger, M., Kutty, S., Gargani, L., and Ait-Ali, L.

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, 030204 cardiovascular system & hematology, Brain natriuretic peptide, Intensive care unit, law.invention, Surgery, Lung ultrasound, Cardiac surgery, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Interquartile range, law, Predictive value of tests, Medicine, Cardiology and Cardiovascular Medicine, Risk assessment, business, Prospective cohort study
Abstract

Background: Lung ultrasound (LUS) in pediatric cardiac surgery is gaining consensus. We (1) evaluated the prognostic value of a new LUS-score in pediatric cardiac surgery, and (2) compared LUS-score to conventional risk factors including age, The Society of Thoracic Surgeons/European Association of Cardio-Thoracic Surgery (STAT) score, cardiopulmonary bypass time, and prognostic biomarkers including brain natriuretic peptide and cystatin-C. Methods: LUS examinations were performed in 237 children (median age, 0.55 years; interquartile range, 0.09-4.15 years) at 12 to 36 hours after surgery. For each hemithorax, 3 areas (anterior/lateral/posterior) were evaluated in the upper and lower halves, constituting 12 total scanning areas. For each site a score was assigned: 0 (rare B lines), 1 (separated B lines), 2 (coalescent B lines), 3 (loss of aeration), and total LUS score was calculated as sum of all sites. The primary endpoints were intensive care unit length of stay and extubation time. Results: The mean total LUS score was 12.88 ± 6.41 (range, 0-26) and was higher in newborns (16.77 ± 5.25) compared with older children (5.36 ± 5.57; P < .001). On univariate analysis, LUS score was associated inversely with age (beta 0.26; P = .004) and body surface area (beta 3.41 P = .006) and positively with brain natriuretic peptide (beta 1.65; P < .001) and cystatin-C (beta 2.41; P < .001). The LUS score, when added as continuous predictor to a conventional risk model (age, STAT score, and cardiopulmonary bypass time) emerged significant both for intensive care unit length of stay (beta 0.145, P = .047) and extubation time (beta 1.644; P = .024). When single quadrants were analyzed, only anterior LUS score was significant (intensive care unit length of stay beta, 0.471; P = .020; extubation time beta 5.530; P = .007). Conclusions: Our data show the prognostic incremental value of a new LUS score over traditional risk factors in pediatric cardiac surgery.

Published
2020

11. Mepolizumab effectiveness and allergic status in real life

Author

Carlo Cavaliere, Giovanna Elisiana Carpagnano, Mauro Maniscalco, Simonetta Masieri, Alberto Ricci, Bruno Sposato, Pierachille Santus, Amelia Grosso, Ilenia Folletti, Pierluigi Paggiaro, Corrado Pelaia, Antonino Musarra, Angelo Corsico, Elena Bargagli, Stefano Baglioni, Manuela Latorre, Paola Rogliani, Marco Scalese, Gianna Camiciottoli, Nicola Murgia, Girolamo Pelaia, Sposato, B., Scalese, M., Camiciottoli, G., Carpagnano, G. E., Pelaia, C., Santus, P., Maniscalco, M., Corsico, A., Grosso, A., Baglioni, S., Murgia, N., Folletti, I., Pelaia, G., Masieri, S., Cavaliere, C., Musarra, A., Bargagli, E., Ricci, A., Latorre, M., Paggiaro, P., and Rogliani, P.

Subjects
severe asthma, medicine.medical_specialty, Severe asthma, Immunology, Eosinophilic asthma, allergic, Antibodies, Monoclonal, Humanized, Immunoglobulin E, medicine.disease_cause, outcomes, Severity of Illness Index, Gastroenterology, NO, Diagnosis, Differential, Allergen, real life, Internal medicine, Anti-Allergic Agents, Eosinophilic, Hypersensitivity, Odds Ratio, medicine, Settore MED/10, Humans, Immunology and Allergy, In real life, Retrospective Studies, biology, business.industry, eosinophilic, mepolizumab, General Medicine, Asthma, Mepolizumab, Severe asthma, Eosinophilic, Allergic, Outcomes, Real life, Respiratory Function Tests, Discontinuation, Eosinophils, Treatment Outcome, biology.protein, business, Mepolizumab, Biomarkers, medicine.drug
Abstract

Background: It is not clear whether mepolizumab is differently effective in allergic and nonallergic severe eosinophilic asthmatics (SEA) in real life. Objective: We tested mepolizumab effectiveness in allergic/nonallergic SEA in real life. A strict criterion to identify the 2 phenotypes was used. Method: We retrospectively considered 134 consecutive patients divided into allergic, with a positivity to at least 1 allergen to prick tests and/or IgE values ≥100 UI/mL (severe allergic eosinophilic asthma [SAEA]; n: 97–72.4%), and nonallergic, with no prick test results and normal IgE levels n: 37–27.6%). They had taken mepolizumab for at least 6 months. Results: After 10.9 ± 3.7 months, improvements in FEV1%, FEF25–75%, exacerbation numbers, blood eosinophil (BE) counts, fractional exhaled nitric oxide (FENO) (ppb), percentages of patients that stopped/reduced short-acting β2-agonists (SABAs) or oral corticosteroid (OC), observed after treatment, were similar in both groups. Only Asthma Control Test (ACT) increases were higher in SNAEA (8 [5–9]) than in SAEA (5 [2.5–8.5]; p = 0.016). However, no differences were found after treatment in percentages of subjects with ACT ≥20, as well as with FEV1 >80%, FEF25–75 >65%, exacerbations ≤2, BE 1% (β = −0.110; p = 0.266), FEF25–75% (β = −0.228; p = 0.06), BE counts (β = −0.012; p = 0.918), FENO (β = 0.234; p = 0.085), ACT (β = 0.046; p = 0.660), and exacerbations (β = −0.070; p = 0.437). No different associations between lung function and SNAEA occurrence when compared to SAEA condition (FEV1 >80%: OR = 1.04 [95% CI: 0.43–2.55], p = 0.923; FEF25–75 >65%: OR = 0.41 [95% CI: 0.08–2.03], p = 0.272) were detected. Neither all other parameters, such as ACT >20 (OR = 0.73 [95% CI: 0.32–1.63], p = 0.440), presence of exacerbations (OR = 1.35 [95% CI: 0.55–3.27], p = 0.512), SABA discontinuation (OR = 1.16 [95% CI: 0.40–3.39], p = 0.790), and OC cessation/reduction (OR = 3.44 [95% CI: 0.40–29.27], p = 0.258), were differently associated with 1 or the other phenotype. Conclusion: Mepolizumab can be considered as a valid therapeutic choice for either allergic or nonallergic SEA in real life.

Published
2020

12. Nomograms of pulsed Doppler velocities, times, and velocity time integrals for semilunar valves and great arteries in healthy Caucasian children

Author

Martin Koestenberger, Marco Scalese, Sabrina Molinaro, Eliana Franchi, Nadia Assanta, Massimiliano Cantinotti, Giorgio Iervasi, Raffaele Giordano, Shelby Kutty, Marco Paterni, Pietro Marchese, Cantinotti, M, Giordano, R, Scalese, M, Franchi, E, Assanta, N, Molinaro, S, Marchese, P, Paterni, M, Iervasi, G, Kutty, S, and Koestenberger, M

Subjects
Heart Defects, Congenital, Male, Adolescent, White People, Reference Values, Medicine, Humans, Semilunar valves, Child, Pulsed doppler, business.industry, Infant, Newborn, Infant, Anatomy, Arteries, Nomogram, Nomograms, Italy, Great arteries, Ultrasonography, Doppler, Pulsed, Aortic Valve, Child, Preschool, Female, Cardiology and Cardiovascular Medicine, business, Blood Flow Velocity
Published
2019

13. LIMITATIONS OF CURRENT FETAL ECHOCARDIOGRAPHY NOMOGRAMS FOR 2D MEASURES: A CRITICAL OVERVIEW AND ANALYSIS FOR FUTURE RESEARCH

Author

Martin Köstenberger, Nadia Assanta, Massimiliano Cantinotti, Shelby Kutty, Giorgio Iervasi, Raffaele Giordano, Marco Scalese, Marco Paterni, Enrico Chiappa, Giuseppe Santoro, Cantinotti, M, Scalese, M, Giordano, R, Assanta, N, Santoro, G, Paterni, M, Iervasi, G, Chiappa, E, Kutty, S, and Koestenberger, M.

Subjects
Heart Defects, Congenital, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, 030204 cardiovascular system & hematology, Nomogram, Ultrasonography, Prenatal, 03 medical and health sciences, Nomograms, 0302 clinical medicine, Fetal Heart, Echocardiography, Pregnancy, medicine, Humans, Radiology, Nuclear Medicine and imaging, Medical physics, Female, Current (fluid), Cardiology and Cardiovascular Medicine, business, Fetal echocardiography
Published
2018

14. Nomograms for echocardiographic right ventricular sub-costal view dimensions in healthy Caucasian children: A new approach to measure the right ventricle

Author

Giorgio Iervasi, Raffaele Giordano, Massimiliano Cantinotti, Eliana Franchi, Marco Scalese, Martin Koestenberger, Sabrina Molinaro, Marotta Marco, Giulia Corana, Crocetti Maura, Nadia Assanta, Cantinotti, M, Giordano, R, Scalese, M, Franchi, E, Corana, G, Assanta, N, Maura, C, Marco, M, Molinaro, S, Koestenberger, M, and Iervasi, G

Subjects
Male, medicine.medical_specialty, Adolescent, Body Surface Area, Systole, Heart Ventricles, Diastole, 030204 cardiovascular system & hematology, Standard score, White People, 030218 nuclear medicine & medical imaging, Infundibulum, 03 medical and health sciences, 0302 clinical medicine, 2d echocardiography, Internal medicine, Heart rate, medicine, Humans, Child, Body surface area, business.industry, Infant, Newborn, Infant, Nomogram, Nomograms, medicine.anatomical_structure, Italy, Echocardiography, Ventricle, Child, Preschool, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background The sub-costal examination of the heart is part of routine examination in pediatric echocardiography, and has the advantage to visualize also the infundibulum part of the right ventricle (RV). Despite this fact, currently nomograms for sub-costal RV dimensions are lacking. Methods We prospectively studied healthy Caucasian Italian children by two-dimensional echocardiography. Measurements included: sub-costal end diastolic basal-apical and latero-lateral diameters, end diastolic and end systolic area, 4 chamber end diastolic and end systolic area and length, end diastolic basal (RV1) and mid-cavity (RV2) diameters. Age, weight, height, heart rate (HR), and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. Structured Z scores were then computed. Agreement of RV diameters and areas in subcostal view and 4-chamber view were investigated. Results 732 subjects (age 0 days-17 years; 48% female; BSA 0.12-2.12 m2) were studied. The Haycock formula was used when presenting data as predicted values (mean ± 2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. The predicted values and Z-score boundaries for all measurements are presented. Excellent correlations were found among two-dimensional diameters and area calculated in sub-costal view with those evaluated in 4-chamber view. Conclusions We report echocardiographic nomograms for RV diameters and areas measured in the sub-costal view. Our data may implement normative data for 2D echocardiography evaluation of the RV in children.

Published
2018

15. Incidence and natural history of neonatal isolated ventricular septal defects: Do we know everything? A 6-year single-center Italian experience follow-up

Author

Ugo Limbruno, Raffaele Giordano, Massimiliano Cantinotti, Susanna Falorini, Andrea Picchi, Martin Koestenberger, Angela Malandrino, Isabella Spadoni, Marco Scalese, Alberto Cresti, Stefania Stefanelli, Francesco De Sensi, Cresti, A, Giordano, R, Koestenberger, M, Spadoni, I, Scalese, M, Limbruno, U, Falorini, S, Stefanelli, S, Picchi, A, De Sensi, F, Malandrino, A, and Cantinotti, M

Subjects
Heart Septal Defects, Ventricular, Male, Pediatrics, medicine.medical_specialty, Time Factors, Remission, Spontaneous, 030204 cardiovascular system & hematology, Single Center, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, medicine, Humans, Radiology, Nuclear Medicine and imaging, Caucasian population, Male gender, Retrospective Studies, business.industry, Incidence (epidemiology), Incidence, Spontaneous closure, Infant, Newborn, Expert consensus, Disease Management, General Medicine, Middle Aged, Natural history, Italy, Echocardiography, Pediatrics, Perinatology and Child Health, Disease Progression, Surgery, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

Background Despite ventricular septal defects (VSDs) are the most common congenital heart diseases (CHDs) in the neonatal period, their incidence and natural history are still debated and their follow-up and management strategies remain controversial. Our aim was to evaluate the incidence and natural history of isolated VSDs. Methods From January 1996 to December 2015 all neonates with a CHD suspicion were referred to the Cardiological Department of Grosseto Misericordia Hospital. Only newborns with confirmed isolated VSD were enrolled in this study and followed for 6 years. Results Our 343 newborns with an isolated VSD (incidence of 10.45/1000/births) account for 64% of all detected CHDs. VSDs location were as follows: muscular (73.8%), perimembranous (11.3%), inlet (1%), and outlet (0.8%). Of the located VSDs, 90% were small, 7.5% moderate, and 2.5% large, respectively. Spontaneous closure was observed in 96 (29.2%) of the VSD patients at 6-month, 198 (60.2%) at 1-year, 261 (79.3%) at 2-year, and in 302 (91.8%) at 6-year follow-up. Risk factors for defect persistence were a perimembranous location (P = .001; HR: 0.508, CI: 0.342-0.755), detection of multiple defects (P = .043; HR: 0.728, CI: 0.536-0.990), and male gender (P

Published
2017

16. Diagnostic accuracy and prognostic valued of plasmatic Cystatin-C in children undergoing pediatric cardiac surgery

Author

Vincenzo Poli, Bruno Murzi, Massimiliano Cantinotti, Giorgio Iervasi, Raffaele Giordano, Marco Scalese, Sabrina Molinaro, Simona Storti, Aldo Clerico, Vitali Pak, Cantinotti, M, Giordano, R, Scalese, M, Molinaro, S, Storti, S, Murzi, B, Pak, V, Poli, V, Iervasi, G, and Clerico, A.

Subjects
Male, medicine.medical_specialty, Clinical Biochemistry, 030204 cardiovascular system & hematology, urologic and male genital diseases, Biochemistry, Sensitivity and Specificity, 03 medical and health sciences, chemistry.chemical_compound, Basal (phylogenetics), 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Cardiac Surgical Procedures, Cystatin C, Body surface area, Creatinine, biology, business.industry, Biochemistry (medical), Hazard ratio, Acute kidney injury, Infant, General Medicine, Acute Kidney Injury, medicine.disease, Prognosis, Cardiac surgery, chemistry, Child, Preschool, Cardiology, biology.protein, Biomarker (medicine), Female, business, Biomarkers
Abstract

Background Diagnosis and treatment of acute kidney injury (AKI) is often delayed in children after cardiac surgery due to the lack of an early biomarker of renal damage. Our aim was to evaluate the diagnostic accuracy of plasma cystatin-C as an early biomarker of AKI and its prognostic value in pediatric cardiac surgery. Methods Cystatin-C and creatinine were measured pre-operatively and at 2–6–12 h post-surgery. The primary outcome was: AKI (defined as an increase of ≥ 1.5 of plasma creatinine from baseline) and a composite marker, including major complications and/or extubation time > 15 days. Risk was evaluated using Cox proportional hazards regression analysis, considering some continuous predictors in the basal model (i.e., age, body surface area and Aristotle-score) to which cystatin-C peak values were added. Discrimination, calibration, and reclassification tests were also performed. Results 248 children (140 males) undergoing cardiac surgery (median age 6.5 months; IQR: 1.7–40.1 months; range 0–17 years) have been enrolled. Post operatory Cystatin-C values were found to be an early diagnostic marker of AKI showing the best area under the ROC curve value (AUC) at 12 h (0.746, CI 95% 0.674–0.818). In the multivariable analyses, peak cystatin-C values showed a significant hazard ratio (HR = 2.665, CI 95% 1.750–4.059, p < 0.001). Finally, post operatory cystatin-C at 12 h significantly improved the AUC (p = 0.017) compared to basal model, resulting a net gain in reclassification proportion (NRI = 0.417, p < 0.001). Conclusions Our data show that cystatin-C should be considered an early biomarker of AKI, improving the risk prediction for complicated outcome in pediatric cardiac surgery.

Published
2017

17. Different skin prick test sensitization patterns do not influence the response to omalizumab in severe asthma

Author

Manlio Milanese, Simonetta Masieri, Bruno Sposato, Nicola Scichilone, Andrea Matucci, Alberto Ricci, Marco Scalese, Carlo Cavaliere, Alberto Cresti, Pierluigi Paggiaro, Alessandra Vultaggio, Manuela Latorre, Sposato, Bruno, Scalese, M., Milanese, M., Masieri, S., Cavaliere, C., Latorre, M., Scichilone, N., Matucci, A., Vultaggio, A., Ricci, A., Cresti, A., and Paggiaro, P.L.

Subjects
Male, medicine.medical_specialty, Severe asthma, Immunology, Effectiveness, Omalizumab, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Severity of Illness Index, medicine, Humans, Immunology and Allergy, Anti-Asthmatic Agents, Sensitization, Retrospective Studies, Skin Tests, business.industry, Effectivene, Real-life, Immunoglobulin E, Pollen sensitized, Dermatology, Asthma, Test (assessment), Respiratory Function Tests, medicine.anatomical_structure, Treatment Outcome, effectiveness, omalizumab, pollen sensitized, real-life, severe asthma, Female, Immunization, business, medicine.drug
Published
2017

18. Nomograms for two-dimensional echocardiography derived valvular and arterial dimensions in Caucasian children

Author

Massimiliano Cantinotti, Bruno Murzi, Giorgio Iervasi, Marco Scalese, Raffaele Giordano, Marotta Marco, Crocetti Maura, Nadia Assanta, Isabella Spadoni, Shelby Kutty, Sabrina Molinaro, Cantinotti, M, Giordano, R, Scalese, M, Murzi, B, Assanta, N, Spadoni, I, Crocetti, M, Marotta, M, Molinaro, S, Kutty, S, and Iervasi, G

Subjects
Male, medicine.medical_specialty, Adolescent, Body Surface Area, Large population, 030204 cardiovascular system & hematology, White People, 03 medical and health sciences, 0302 clinical medicine, Reference Values, Internal medicine, Heart rate, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Child, Body surface area, business.industry, Two dimensional echocardiography, Body Weight, Infant, Newborn, Infant, Arteries, Nomogram, Heart Valves, Healthy Volunteers, Nomograms, Italy, Echocardiography, Child, Preschool, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background Despite recent advances, current pediatric echocardiographic nomograms for valvular and arterial dimensions remain limited. Methods We prospectively studied healthy Caucasian Italian children by two-dimensional (2D) echocardiography. Echocardiographic measurements for 18 valvular and arterial dimensions were performed and models were generated testing for linear, logarithmic, exponential, and square root relationships. Heteroscedasticity was accounted for by White or Breusch–Pagan test. Age, weight, height, heart rate, and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. Structured Z -scores were then computed. Results In all, 1151 subjects (age 0 days to 17 years; 45% females; BSA 0.12–2.12 m 2 ) were studied. The Haycock formula was used when presenting data as predicted values (mean ± 2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. The predicted values and Z -score boundaries for all measurements are presented. Conclusions We report echocardiographic nomograms for valvular and arterial dimensions derived from a large population of children. Integration of these data with those of previous reports would allow for a comprehensive coverage of pediatric 2D echocardiographic nomograms for measurement of 2D cardiac structures.

Published
2017

19. Smoking and Obesity Increase Airway Hyperesponsiveness Risk In the Elderly

Author

Raffaele Scala, Marco Scalese, Manlio Milanese, Nicola Scichilone, Antonio Perrella, Bruno Sposato, Sposato, B., Scalese, M., Milanese, M., Scichilone, N., Scala, R., and Perrella, A.

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Aging, Adolescent, Vital Capacity, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Bronchial Provocation Tests, 03 medical and health sciences, FEV1/FVC ratio, Young Adult, 0302 clinical medicine, Interquartile range, Risk Factors, Internal medicine, Forced Expiratory Volume, medicine, Respiratory Hypersensitivity, Humans, Obesity, Young adult, Methacholine Chloride, Asthma, Aged, Retrospective Studies, business.industry, Smoking, 030206 dentistry, respiratory system, Middle Aged, medicine.disease, respiratory tract diseases, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Physical therapy, asthma, aging, Methacholine, Female, Airway, business, Body mass index, medicine.drug
Abstract

Objective of our study was assessing whether smoking and obesity might affect airways hyperresponsiveness (AHR) differently in younger and older subjects and whether this influence might be due to their different impacts on baseline lung function values at different ages. Methods 3,903 consecutive adult subjects with normal lung function (1,920 males; mean age 35.1±16.2; median FEV1:97.3% of predicted [interquartile range (IQR):89.7-105.2] and FEV1/FVC:84.6% of predicted [IQR:79.8-89.2]), having performed a methacholine test, were considered. They were subdivided into three groups according to age (18-39, 40-64 and ≥65 years) and into different sub-groups according to body mass index (BMI) and smoking habits, considering two AHR level cut-offs (PD20≤1600 µg and PD20≤800 µg). Results PD20 was significantly lower (p65 (OR:12.786 [IQR:1.450-112.753];p65 years) (OR:3.120 [IQR:1.144-8.509];p65 years. A small airway age-related reduction may cause the increased smoking/obesity induced AHR risk in older people.

Published
2016

20. Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors

Author

Marco Scalese, Aldo Clerico, Sabrina Molinaro, Shelby Kutty, Massimiliano Cantinotti, Francesca Della Pina, Vitali Pak, Luigi Arcieri, Vincenzo Poli, Simona Storti, Giorgio Iervasi, Raffaele Giordano, Marco Marotta, Bruno Murzi, Cantinotti, M, Giordano, R, Scalese, M, Molinaro, S, Della Pina, F, Storti, S, Arcieri, L, Murzi, B, Marotta, M, Pak, V, Poli, V, Iervasi, G, Kutty, S, and Clerico, A

Subjects
Adult, Heart Defects, Congenital, Male, medicine.medical_specialty, Adolescent, Clinical Biochemistry, law.invention, Young Adult, Predictive Value of Tests, Risk Factors, Interquartile range, law, Internal medicine, Natriuretic Peptide, Brain, Humans, Medicine, Child, Body surface area, business.industry, Proportional hazards model, Biochemistry (medical), Hazard ratio, Infant, General Medicine, Prognosis, Brain natriuretic peptide, Intensive care unit, Surgery, Cardiac surgery, Intensive Care Units, Child, Preschool, Predictive value of tests, Cardiology, Female, business
Abstract

The routine use of brain natriuretic peptide (BNP) in pediatric cardiac surgery remains controversial. Our aim was to test whether BNP adds information to predict risk in pediatric cardiac surgery.In all, 587 children undergoing cardiac surgery (median age 6.3 months; 1.2–35.9 months) were prospectively enrolled at a single institution. BNP was measured pre-operatively, on every post-operative day in the intensive care unit, and before discharge. The primary outcome was major complications and length ventilator stay >15 days. A first risk prediction model was fitted using Cox proportional hazards model with age, body surface area and Aristotle score as continuous predictors. A second model was built adding cardiopulmonary bypass time and arterial lactate at the end of operation to the first model. Then, peak post-operative log-BNP was added to both models. Analysis to test discrimination, calibration, and reclassification were performed.BNP increased after surgery (pOur data indicates that BNP may improve the risk prediction in pediatric cardiac surgery, supporting its routine use in this setting.

Published
2015
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21. Pharmacogenetic interaction analysis of VEGFR-2 and IL-8 polymorphisms in advanced breast cancer patients treated with paclitaxel and bevacizumab

Author

Giacomo Allegrini, Virginia Casadei, Sara Lucchesi, Marco Scalese, Lorenzo Marcucci, Paola Orlandi, Marco Di Lieto, Marina Cazzaniga, Barbara Salvadori, Chiara Finale, Anna Fioravanti, Antonella Ferro, I. Ferrarini, Luigi Coltelli, R. Triolo, I. Pazzagli, F. Villa, E. Bona, Teresa Di Desidero, Alfredo Falcone, Domenico Amoroso, Romano Danesi, Giada Arrighi, Andrea Fontana, Orlando Goletti, Andrea Camerini, S. Donati, Guido Bocci, Sabrina Molinaro, Marzia Del Re, Allegrini, G, Coltelli, L, Orlandi, P, Fontana, A, Camerini, A, Ferro, A, Cazzaniga, M, Casadei, V, Lucchesi, S, Bona, E, Di Lieto, M, Pazzagli, I, Villa, F, Amoroso, D, Scalese, M, Arrighi, G, Molinaro, S, Fioravanti, A, Finale, C, Triolo, R, Di Desidero, T, Donati, S, Marcucci, L, Goletti, O, Del Re, M, Salvadori, B, Ferrarini, I, Danesi, R, Falcone, A, and Bocci, G

Subjects
Oncology, Vascular Endothelial Growth Factor A, pharmacogenetics, VEGF, IL-8, bevacizumab, Bioinformatics, Thrombospondin 1, chemistry.chemical_compound, paclitaxel, single nucleotide polymorphism, Basic Helix-Loop-Helix Transcription Factors, advanced breast cancer, education.field_of_study, Metastatic breast cancer, Treatment Outcome, Paclitaxel, pharmacogenetic, Molecular Medicine, Female, medicine.drug, medicine.medical_specialty, Bevacizumab, Population, Breast Neoplasms, Antibodies, Monoclonal, Humanized, Polymorphism, Single Nucleotide, Disease-Free Survival, Breast cancer, Internal medicine, multifactor dimensionality reduction methodology, Genetics, medicine, Humans, education, Genetic Association Studies, Neoplasm Staging, Pharmacology, Multifactor dimensionality reduction, business.industry, Interleukin-8, Cancer, angiogenesi, medicine.disease, Hypoxia-Inducible Factor 1, alpha Subunit, Vascular Endothelial Growth Factor Receptor-2, first-line chemotherapy, chemistry, business, Pharmacogenetics
Abstract

Aim: To investigate pharmacogenetic interactions among VEGF-A, VEGFR-2, IL-8, HIF-1α, EPAS-1 and TSP-1 SNPs and their role on progression-free survival in a population of metastatic breast cancer patients treated with bevacizumab in combination with first-line paclitaxel. Patients & methods: Analyses were performed on germline DNA obtained from blood samples and SNPs were investigated by real-time polymerase chain reaction technique. The multifactor dimensionality reduction methodology was applied to investigate the interaction between SNPs. Results: One hundred and thirteen patients were enrolled from eight Italian Oncology Units ( clinicaltrial.gov : NCT01935102). The multifactor dimensionality reduction software provided two pharmacogenetic interaction profiles consisting of the combination between specific VEGFR-2 rs11133360 and IL-8 rs4073 genotypes. The median progression-free survival was 14.1 months (95% CI: 11.4–16.8) and 10.2 months (95% CI: 8.8–11.5) for the favorable and the unfavorable genetic profile, respectively (HR: 0.44, 95% CI: 0.29–0.66, p < 0.0001). Conclusion: The pharmacogenetic statistical interaction between VEGFR-2 rs11133360 and IL-8 rs4073 genotypes may identify a population of patients with a better outcome.

Published
2014

22. BMI can influence adult males' and females' airway hyperresponsiveness differently

Author

Raffaele Scala, Andrea Pammolli, Bruno Sposato, Marco Scalese, Maria Giovanna Migliorini, Nicola Scichilone, Massimo Tosti Balducci, Sposato, B, Scalese, M, Scichilone, N, Pammolli, A, Balducci, M, Migliorini, M, and Scala, R

Subjects
Pulmonary and Respiratory Medicine, obesity, medicine.medical_specialty, Pathology, Airway hyperresponsiveness, Physiology, body mass index, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Epidemiology, medicine, males and females, obesity, hyperreactivity, lung function, gender, Original Research Article, 030212 general & internal medicine, Risk factor, Suspected asthma, Asthma, lcsh:RC705-779, 2. Zero hunger, business.industry, methacholine test, lcsh:Diseases of the respiratory system, asthma, respiratory system, medicine.disease, Obesity, respiratory tract diseases, 030228 respiratory system, business, Body mass index
Abstract

Background Epidemiological data indicate that obesity is a risk factor for asthma, but scientific literature is still debating the association between changes in body mass index (BMI) and airway hyperresponsiveness (AHR). Methods This study aimed at evaluating the influence of BMI on AHR, in outpatients with symptoms suggestive of asthma. 4,217 consecutive adult subjects (2,439 M; mean age: 38.2±14.9 yrs; median FEV1 % predicted: 100 [IQR:91.88-107.97] and FEV1/FVC % predicted: 85.77% [IQR:81.1-90.05]), performed a methacholine challenge test for suspected asthma. Subjects with PD20 < 200 or 200 < PD20 < 800 or PD20 > 800 were considered affected by severe, moderate or mild AHR, respectively. Results A total of 2,520 subjects (60% of all cases) had a PD20 < 3,200 μg, with a median PD20 of 366 μg [IQR:168–1010.5]; 759, 997 and 764 patients were affected by mild, moderate and severe AHR, respectively. BMI was not associated with increasing AHR in males. On the contrary, obese females were at risk for AHR only when those with moderate AHR were considered (OR: 1.772 [1.250-2.512], p = 0.001). A significant reduction of FEV1/FVC for unit of BMI increase was found in moderate AHR, both in males (β = −0.255; p =0.023) and in females (β = −0.451; p =0.017). Conclusions Our findings indicate that obesity influences AHR only in females with a moderate AHR level. This influence may be mediated by obesity-associated changes in baseline lung function.

Published
2012

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