94 results on '"Raffaeli G."'
Search Results
2. Thromboelastographic profiles of healthy very low birthweight infants serially during their first month
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Raffaeli G., Tripodi A., Cavallaro G., Cortesi V., Scalambrino E., Pesenti N., Artoni A., Mosca F., Ghirardello S., Raffaeli, G, Tripodi, A, Cavallaro, G, Cortesi, V, Scalambrino, E, Pesenti, N, Artoni, A, Mosca, F, and Ghirardello, S
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Male ,Neonatal intensive care unit ,030204 cardiovascular system & hematology ,Fibrinogen ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,medicine ,thrombosi ,Humans ,Infant, Very Low Birth Weight ,Prospective Studies ,Prospective cohort study ,hemostasi ,Blood Coagulation ,Prothrombin time ,Analysis of Variance ,medicine.diagnostic_test ,business.industry ,Infant, Newborn ,Obstetrics and Gynecology ,thromboelastography ,General Medicine ,medicine.disease ,bleeding ,Thrombosis ,Thromboelastography ,Thrombelastography ,Prospective Studie ,Anesthesia ,Hemostasis ,Pediatrics, Perinatology and Child Health ,Female ,neonate ,business ,Partial thromboplastin time ,medicine.drug ,Human - Abstract
ObjectiveWe determined thromboelastographic (TEG) profiles of healthy very low birthweight infants (VLBWIs) of the day of birth and at set intervals during their first month.DesignProspective observational study with blinded clinical and laboratory follow-up.SettingLevel III neonatal intensive care unit (June 2015 to June 2018).PatientsConsecutive qualifying VLBWIs were enrolled at birth and followed up for 30 days.Interventions and main outcomes measuresLaboratory (citrated-native TEG, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, blood count) and clinical variables were retrieved at birth, 3rd–5th, 10th and 30th day of life. Blood samples temporally related to events with a potential hemostatic impact (sepsis, bleeding, platelets/plasma transfusions, ibuprofen/indomethacin administration) were excluded from analysis.ResultsWe enrolled 201 VLBWIs and 72 full-term neonates. Sixty-seven of the healthy VLBWIs completed the 30-day follow-up. 541 TEG traces were analysed.On day 1, the median (minimum–maximum) TEG values were as follows: reaction time (R), 8.2 min (1–21.8); kinetics (K), 2.8 min (0.8–16); α angle, 51° (14.2–80.6); maximum amplitude (MA), 54.9 mm (23.9–76.8). PT and APTT were 15.9 s (11.7–51.2) and 59 s (37.8–97.5), respectively. The above parameters suggest minor hypocoagulability compared with term infants. On day 30, the median (minimum–maximum) R was 5 (1–16.9), K 1 (0.8–4.1), α 74.7 (41.1–86.7) and MA 70.2 (35.8–79.7). PT and APTT were 12.1 (10.4–16.6) and 38.8 (29.6–51.4), respectively. Those parameters are consistent with a relatively hypercoagulable phenotype, compared with term infants.ConclusionsHealthy VLBWIs have a prolonged PT and APTT, but their TEG profiles suggest a relatively balanced hemostatic system, with slight hypocoagulability initially (compared with term neonates), gradually evolving to a somewhat more procoagulant phenotype over the first month.
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- 2019
3. The effect of delayed umbilical cord clamping on cord blood gas analysis in vaginal and caesarean‐delivered term newborns without fetal distress: a prospective observational study
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Giovannini, N, primary, Crippa, BL, additional, Denaro, E, additional, Raffaeli, G, additional, Cortesi, V, additional, Consonni, D, additional, Cetera, GE, additional, Parazzini, F, additional, Ferrazzi, E, additional, Mosca, F, additional, and Ghirardello, S, additional
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- 2019
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4. CYCLIC NUCLEOTIDE-DEPENDENT RELAXATION IN HUMAN UMBILICAL VESSELS
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Provitera, L., Cavallaro, G., Griggio, A., Raffaeli, G., Amodeo, I., Gulden, S., Lattuada, D., Ercoli, G., Lonati, C., Tomaselli, A., Mosca, F., Villamor, E., RS: GROW - R4 - Reproductive and Perinatal Medicine, Kindergeneeskunde, and MUMC+: MA Medische Staf Kindergeneeskunde (9)
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soluble guanylate cyclase ,VASORELAXATION ,BAY 41-2272 ,DYNAMIC PLACENTA ,PROTEIN-KINASE ,GATED K+ CHANNELS ,VASCULAR SMOOTH-MUSCLE ,MECHANISMS ,PULMONARY-ARTERY ,beta-adrenoceptor ,cardiovascular system ,phosphodiesterase inhibitors ,human umbilical vein ,NITRIC-OXIDE SYNTHASE ,nitric oxide donor ,SOLUBLE-GUANYLATE-CYCLASE ,adenylate cyclase ,human umbilical artery - Abstract
Umbilical vessels have a low sensitivity to dilate, and this property is speculated to have physiological implications. We aimed to investigate the different relaxing responses of human umbilical arteries (HUAs) and veins (HUVs) to agonists acting through the cAMP and cGMP pathways. Vascular rings were suspended in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U44069, concentration-response curves to the nitric oxide (NO) donor sodium nitroprusside (SNP), the soluble guanylate cyclase (sGC) stimulator BAY 41-2272, the adenylate cyclase (AC) activator forskolin, the beta-adrenergic receptor agonists isoproterenol (ADRB1), salmeterol (ADRB2), and BRL37344 (ADRB3), and the phosphodiesterase (PDE) inhibitors milrinone (PDE3), rolipram (PDE4), and sildenafil (PDE5) were performed. None of the tested drugs induced a relaxation higher than 30% of the U44069-induced tone. Rings from HUAs and HUVs showed a similar relaxation to forskolin, SNP, PDE inhibitors, and ADRB agonists. BAY 41-2272 was significantly more efficient in relaxing veins than arteries. ADRB agonists evoked weak relaxations (
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- 2019
5. The effect of delayed umbilical cord clamping on cord blood gas analysis in vaginal and caesarean-delivered term newborns without fetal distress: a prospective observational study.
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Giovannini, N, Crippa, BL, Denaro, E, Raffaeli, G, Cortesi, V, Consonni, D, Cetera, GE, Parazzini, F, Ferrazzi, E, Mosca, F, Ghirardello, S, Crippa, B L, and Cetera, G E
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UMBILICAL cord clamping ,CORD blood ,FETAL distress ,LACTATES ,BICARBONATE ions ,CESAREAN section ,BLOOD testing ,ACIDOSIS ,BLOOD gases analysis ,DELIVERY (Obstetrics) ,LABOR complications (Obstetrics) ,MEDICAL care ,PATIENTS ,UMBILICAL cord ,PREGNANCY outcomes - Abstract
Objective: To determine variations in cord blood gas (CBG) parameters after 3-minute delayed cord clamping (DCC) in vaginal deliveries (VDs) and caesarean deliveries (CDs) at term without fetal distress.Design: Prospective observational study.Setting: University hospital.Sample: CBG from 97 VDs and 124 CDs without fetal distress.Methods: Comparison of paired arterial-venous CBG parameters drawn at birth from the unclamped cord and after 3-minutes DCC for VDs and CDs.Main Outcome Measures: Base excess, bicarbonate, haematocrit and haemoglobin from both arterial and venous cord blood, lactate, neonatal outcomes, partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ), pH, and postpartum haemorrhage.Results: Arterial cord blood pH, bicarbonate ( HCO3- , mmol/l), and base excess (BE, mmol/l) decreased significantly after 3-minute DCC both in VDs (pH = 7.23 versus 7.27; P < 0.001; HCO3- = 23.3 versus 24.3; P = 0.004; BE = -5.1 versus -2.9; P < 0.001) and CDs (pH = 7.28 versus 7.34; P < 0.001; HCO3- = 26.2 versus 27.2; P < 0.001; BE = -1.5 versus 0.7; P < 0.001). After 3-minute DCC, pCO2 increased in CDs only (57 versus 51; P < 0.001), whereas lactate increased more in CDs compared with VDs (lactate, +1.1 [0.9, 1.45] versus +0.5 [-0.65, 2.35]; P = 0.01). Postpartum maternal haemorrhage, neonatal maximum bilirubin concentration, and need for phototherapy were similar between the two groups. Newborns born by CD more frequently required postnatal clinical monitoring or admission to a neonatal intensive care unit.Conclusions: After 3-minute DCC, the acid-base status shifted towards mixed acidosis in CDs and prevalent metabolic acidosis in VDs. CDs were associated with a more pronounced increase in arterial lactate, compared with VDs.Tweetable Abstract: By 3-minute DCC, acid-base status shifts towards mixed and metabolic acidosis in caesarean and vaginal delivery, respectively. [ABSTRACT FROM AUTHOR]- Published
- 2020
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6. Cerebral hemodynamics monitoring during extracorporeal membrane oxygenation in piglets.
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Amendola, C., Cavallaro, G., Amelio, G. S., Provitera, L., Raffaeli, G., Mosca, F., Spinelli, L., Torricelli, A., and Contini, D.
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- 2023
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7. EDIN Scale Implemented by Gestational Age for Pain Assessment in Preterms: A Prospective Study
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Raffaeli, G., primary, Cristofori, G., additional, Befani, B., additional, De Carli, A., additional, Cavallaro, G., additional, Fumagalli, M., additional, Plevani, L., additional, and Mosca, F., additional
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- 2017
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8. A19 Gastro-oesophageal reflux in symptomatic preterm infants: lack of efficacy of a new preterm thickened formula
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Legnani, E., primary, Mariani, E., additional, Raffaeli, G., additional, Corvaglia, L., additional, and Faldella, G., additional
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- 2012
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9. PP18 EFFECT OF A THICKENED FORMULA SPECIFICALLY DESIGNED FOR PRETERM INFANTS ON GASTROESOPHAGEAL REFLUX
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Legnani, E., primary, Mariani, E., additional, Aceti, A., additional, Raffaeli, G., additional, Ferlini, M., additional, and Corvaglia, L., additional
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- 2011
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10. MAPS - a computerized management analysis and planning system
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Packe, D. R and Raffaeli, G. A
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Mathematics And Information Sciences - Abstract
Program lists work structure of projects at all levels. System integrates work item, its schedule, its status against the schedule, responsible personnel, and explanatory comments. structure of MAPS promotes natural organization of project work elements, project features and uses are given.
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- 1971
11. A maChine and deep Learning Approach to predict pulmoNary hyperteNsIon in newbornS with congenital diaphragmatic Hernia (CLANNISH): Protocol for a retrospective study
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Isabella Fabietti, Valentina Condò, Benedetta Tafuri, Nicola Persico, Mariarosa Colnaghi, Stefano Ghirardello, Giuseppe Como, Donato Cascio, Genny Raffaeli, Maria Pierro, Ilaria Amodeo, Francesco Macchini, Fabio Mosca, Giacomo Cavallaro, Irene Borzani, Alice Griggio, Giorgio De Nunzio, Luana Conte, Amodeo, I., De Nunzio, G., Raffaeli, G., Borzani, I., Griggio, A., Conte, L., Macchini, F., Condo, V., Persico, N., Fabietti, I., Ghirardello, S., Pierro, M., Tafuri, B., Como, G., Cascio, D., Colnaghi, M., Mosca, F., Cavallaro, G., Amodeo I., De Nunzio G., Raffaeli G., Borzani I., Griggio A., Conte L., Macchini F., Condo V., Persico N., Fabietti I., Ghirardello S., Pierro M., Tafuri B., Como G., Cascio D., Colnaghi M., Mosca F., and Cavallaro G.
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Pediatrics ,medicine.medical_treatment ,retrospective study ,Diagnostic Radiology ,Cohort Studies ,Study Protocol ,Mathematical and Statistical Techniques ,Pregnancy ,Medicine and Health Sciences ,Lung volumes ,Multidisciplinary ,medicine.diagnostic_test ,Radiology and Imaging ,Statistics ,Software Engineering ,Magnetic Resonance Imaging ,Pulmonary Imaging ,machine learning ,Obstetric Procedures ,Physical Sciences ,Engineering and Technology ,Medicine ,Female ,Cohort study ,Computer and Information Sciences ,medicine.medical_specialty ,Imaging Techniques ,Hypertension, Pulmonary ,Science ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,Pulmonary hypertension ,Computer Software ,Diagnostic Medicine ,Artificial Intelligence ,Congenital Diaphragmatic Hernia, Pulmonary Ipertension, Deep Learning, protocol ,medicine ,Extracorporeal membrane oxygenation ,Humans ,Hernia ,Statistical Methods ,Retrospective Studies ,Fetal surgery ,business.industry ,diaphragmatic hernia ,segmentation ,Infant, Newborn ,Biology and Life Sciences ,Neonates ,Congenital diaphragmatic hernia ,deep learning ,Retrospective cohort study ,Magnetic resonance imaging ,medicine.disease ,Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin) ,Hernias, Diaphragmatic, Congenital ,business ,Mathematics ,Developmental Biology ,Forecasting - Abstract
Introduction Outcome predictions of patients with congenital diaphragmatic hernia (CDH) still have some limitations in the prenatal estimate of postnatal pulmonary hypertension (PH). We propose applying Machine Learning (ML), and Deep Learning (DL) approaches to fetuses and newborns with CDH to develop forecasting models in prenatal epoch, based on the integrated analysis of clinical data, to provide neonatal PH as the first outcome and, possibly: favorable response to fetal endoscopic tracheal occlusion (FETO), need for Extracorporeal Membrane Oxygenation (ECMO), survival to ECMO, and death. Moreover, we plan to produce a (semi)automatic fetus lung segmentation system in Magnetic Resonance Imaging (MRI), which will be useful during project implementation but will also be an important tool itself to standardize lung volume measures for CDH fetuses. Methods and analytics Patients with isolated CDH from singleton pregnancies will be enrolled, whose prenatal checks were performed at the Fetal Surgery Unit of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (Milan, Italy) from the 30th week of gestation. A retrospective data collection of clinical and radiological variables from newborns’ and mothers’ clinical records will be performed for eligible patients born between 01/01/2012 and 31/12/2020. The native sequences from fetal magnetic resonance imaging (MRI) will be collected. Data from different sources will be integrated and analyzed using ML and DL, and forecasting algorithms will be developed for each outcome. Methods of data augmentation and dimensionality reduction (feature selection and extraction) will be employed to increase sample size and avoid overfitting. A software system for automatic fetal lung volume segmentation in MRI based on the DL 3D U-NET approach will also be developed. Ethics and dissemination This retrospective study received approval from the local ethics committee (Milan Area 2, Italy). The development of predictive models in CDH outcomes will provide a key contribution in disease prediction, early targeted interventions, and personalized management, with an overall improvement in care quality, resource allocation, healthcare, and family savings. Our findings will be validated in a future prospective multicenter cohort study. Registration The study was registered at ClinicalTrials.gov with the identifier NCT04609163.
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- 2021
12. NeoAPACHE II. Relationship Between Radiographic Pulmonary Area and Pulmonary Hypertension, Mortality, and Hernia Recurrence in Newborns With CDH
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Ilaria Amodeo, Nicola Pesenti, Genny Raffaeli, Francesco Macchini, Valentina Condò, Irene Borzani, Nicola Persico, Isabella Fabietti, Giulia Bischetti, Anna Maria Colli, Stefano Ghirardello, Silvana Gangi, Mariarosa Colnaghi, Fabio Mosca, Giacomo Cavallaro, Amodeo, I, Pesenti, N, Raffaeli, G, Macchini, F, Condo, V, Borzani, I, Persico, N, Fabietti, I, Bischetti, G, Colli, A, Ghirardello, S, Gangi, S, Colnaghi, M, Mosca, F, and Cavallaro, G
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medicine.medical_specialty ,Pediatrics ,RJ1-570 ,congenital diaphragmatic hernia ,Perimeter ,03 medical and health sciences ,Pulmonary hypoplasia ,recurrence of the hernia ,0302 clinical medicine ,030225 pediatrics ,Internal medicine ,medicine.artery ,pulmonary hypertension ,medicine ,030212 general & internal medicine ,Original Research ,Lung ,business.industry ,Congenital diaphragmatic hernia ,radiographic lung area ,medicine.disease ,Pulmonary hypertension ,mortality ,Clinical trial ,stomatognathic diseases ,FETO ,medicine.anatomical_structure ,lung hypoplasia ,Pediatrics, Perinatology and Child Health ,Pulmonary artery ,Cardiology ,business ,Rare disease - Abstract
Congenital diaphragmatic hernia is a rare disease with high mortality and morbidity due to pulmonary hypoplasia and pulmonary hypertension. The aim of the study is to investigate the relationship between radiographic lung area and systolic pulmonary artery pressure (sPAP) on the first day of life, mortality, and hernia recurrence during the first year of life in infants with a congenital diaphragmatic hernia (CDH). A retrospective data collection was performed on 77 CDH newborns. Echocardiographic sPAP value, deaths, and recurrence cases were recorded. Lung area was calculated by tracing the lung's perimeter, excluding mediastinal structures, and herniated organs, on the preoperative chest X-ray performed within 24 h after birth. Logistic and linear regression analyses were performed. Deceased infants showed lower areas and higher sPAP values. One square centimeter of rising in the total, ipsilateral, and contralateral area was associated with a 22, 43, and 24% reduction in mortality risk. sPAP values showed a decreasing trend after birth, with a maximum of 1.84 mmHg reduction per unitary increment in the ipsilateral area at birth. Recurrence patients showed lower areas, with recurrence risk decreasing by 14 and 29% per unit increment of the total and ipsilateral area. In CDH patients, low lung area at birth reflects impaired lung development and defect size, being associated with increased sPAP values, mortality, and recurrence risk.Clinical Trial Registration: The manuscript is an exploratory secondary analysis of the trial registered at ClinicalTrials.gov with identifier NCT04396028.
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- 2021
13. The NeoAPACHE Study Protocol I: Assessment of the Radiographic Pulmonary Area and Long-Term Respiratory Function in Newborns With Congenital Diaphragmatic Hernia
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Ilaria Amodeo, Mariarosa Colnaghi, Irene Borzani, Stefano Ghirardello, Silvana Gangi, Nicola Persico, Marijke Ophorst, Giacomo Cavallaro, Nicola Pesenti, Francesco Macchini, Fabio Mosca, Isabella Fabietti, Genny Raffaeli, Valentina Condò, Amodeo, I, Raffaeli, G, Pesenti, N, Macchini, F, Condo, V, Borzani, I, Persico, N, Fabietti, I, Ophorst, M, Ghirardello, S, Gangi, S, Colnaghi, M, Mosca, F, and Cavallaro, G
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medicine.medical_specialty ,Diaphragmatic breathing ,Pediatrics ,neonatology ,congenital diaphragmatic hernia ,Pulmonary function testing ,Functional residual capacity ,Internal medicine ,medicine ,Respiratory function ,Neonatology ,Tidal volume ,Original Research ,Lung ,long term respiratory function ,business.industry ,respiratory function tests ,lcsh:RJ1-570 ,Congenital diaphragmatic hernia ,lcsh:Pediatrics ,radiographic lung area ,respiratory system ,medicine.disease ,respiratory tract diseases ,FETO ,medicine.anatomical_structure ,lung hypoplasia ,Pediatrics, Perinatology and Child Health ,Cardiology ,business - Abstract
In newborns with congenital diaphragmatic hernia (CDH), the radiographic lung area is correlated with functional residual capacity (FRC) and represents an alternative method to estimate lung hypoplasia. In a cohort of newborn CDH survivors, we retrospectively evaluated the relationship between radiographic lung area measured on the 1st day of life and long-term respiratory function. As a secondary analysis, we compared radiographic lung areas and respiratory function between patients undergoing fetal endoscopic tracheal occlusion (FETO) and patients managed expectantly (non-FETO). Total, ipsilateral, and contralateral radiographic areas were obtained by tracing lung perimeter as delineated by the diaphragm and rib cage, excluding mediastinal structures and herniated organs. Tidal volume (VT), respiratory rate (RR), and their Z-Scores when compared to the norm were collected from pulmonary function tests (PFTs) performed at 12 ± 6 months of age. Linear regression analyses using the absolute Z-Score values for each parameter were performed. In CDH survivors, an increase in total and ipsilateral lung area measured at birth was related to a reduction in the absolute Z-Score for VT in PFTs (p = 0.046 and p = 0.023, respectively), indicating a trend toward an improvement in pulmonary volumes and VT normalization. Radiographic lung areas were not significantly different between FETO and non-FETO patients, suggesting a volumetric lung increase due to prenatal intervention. However, the mean Z-Score value for RR was significantly higher in the FETO group (p < 0.001), probably due to impaired diaphragmatic motility in the most severe cases. Further analyses are necessary to better characterize the role of the radiographic pulmonary area in the prognostic evaluation of respiratory function in patients with CDH. Clinical Trial Registration: This trial was registered at ClinicalTrials.gov with the identifier NCT04396028.
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- 2020
14. Robotic therapy: Cost, accuracy, and times. New challenges in the neonatal intensive care unit
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Ilaria Amodeo, Nicola Pesenti, Genny Raffaeli, Gabriele Sorrentino, Alessia Zorz, Silvia Traina, Silvia Magnani, Maria Teresa Russo, Salvatore Muscolo, Laura Plevani, Fabio Mosca, Giacomo Cavallaro, Amodeo, I, Pesenti, N, Raffaeli, G, Sorrentino, G, Zorz, A, Traina, S, Magnani, S, Russo, M, Muscolo, S, Plevani, L, Mosca, F, and Cavallaro, G
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0301 basic medicine ,medicine.medical_specialty ,Neonatal intensive care unit ,medicine.medical_treatment ,Time ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,High complexity ,Robotic cost ,medicine ,Pharmacology (medical) ,Lead (electronics) ,Robotic therapy ,Accuracy ,Original Research ,Pharmacology ,Descriptive statistics ,business.industry ,lcsh:RM1-950 ,Newborn ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,Safety therapy ,Intravenous therapy ,Compounding ,030220 oncology & carcinogenesis ,Emergency medicine ,business - Abstract
Background: The medication process in the Neonatal Intensive Care Unit (NICU), can be challenging in terms of costs, time, and the risk of errors. Newborns, especially if born preterm, are more vulnerable to medication errors than adults. Recently, robotic medication compounding has reportedly improved the safety and efficiency of the therapeutic process. In this study, we analyze the advantages of using the I.V. Station® system in our NICU, compared to the manual preparation of injectable drugs in terms of accuracy, cost, and time. Method: An in vitro experimental controlled study was conducted to analyze 10 injectable powdered or liquid drugs. Accuracy was calculated within a 5% difference of the bottle weight during different stages of preparation (reconstitution, dilution, and final product). The overall cost of manual and automated preparations were calculated and compared. Descriptive statistics for each step of the process are presented as mean ± standard deviation or median (range). Results: The median error observed during reconstitution, dilution, and final therapy of the drugs prepared by the I.V. Station® ranged within ±5% accuracy, with narrower ranges of error compared to those prepared manually. With increasing preparations, the I.V. Station® consumed less materials, reduced costs, decreased preparation time, and optimized the medication process, unlike the manual method. In the 10 drugs analyzed, the time saved from using the I.V. Station® ranged from 16 s for acyclovir to 2 h 57 min for teicoplanin, and cost savings varied from 8% for ampicillin to 66% for teicoplanin. These advantages are also capable of continually improving as the total amount of final product increases. Conclusions: The I.V. Station® improved the therapeutic process in our NICU. The benefits included increased precision in drug preparation, improved safety, lowered cost, and saved time. These advantages are particularly important in areas such as the NICU, where the I.V. Station® could improve the delivery of the high complexity of care and a large amount of intravenous therapy typically required. In addition, these benefits may lead to the reduction in medication errors and improve patient and family care; however, additional studies will be required to confirm this hypothesis.
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- 2019
15. Is the new, noninvasive, continuous cardiorespiratory monitoring reliable during neonatal ECMO?
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Stefano Ghirardello, Laura Plevani, Nicola Pesenti, Mara Vanzati, Federico Schena, Fabio Mosca, Francesco Canesi, Chiara Baracetti, Genny Raffaeli, Federica Conigliaro, Giacomo Cavallaro, Fabrizio Ciralli, Monica Fumagalli, Raffaeli, G, Canesi, F, Conigliaro, F, Ghirardello, S, Vanzati, M, Baracetti, C, Fumagalli, M, Ciralli, F, Schena, F, Pesenti, N, Plevani, L, Mosca, F, and Cavallaro, G
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Respiratory failure ,Hematocrit ,Critical Care and Intensive Care Medicine ,Oxygen extraction ratio ,03 medical and health sciences ,Hemoglobins ,0302 clinical medicine ,Extracorporeal Membrane Oxygenation ,Oxygen Consumption ,030225 pediatrics ,Internal medicine ,Cardiorespiratory monitoring ,medicine ,Extracorporeal membrane oxygenation ,Humans ,Blood gas analysis ,Monitoring, Physiologic ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Pulmonary Gas Exchange ,Blood gas analyzer ,Continuous monitoring ,Infant, Newborn ,Reproducibility of Results ,Cardiorespiratory fitness ,Oxygen ,030228 respiratory system ,Cardiology ,Neonatal ECMO ,Female ,Blood Gas Analysis ,Cardiology and Cardiovascular Medicine ,business ,Respiratory Insufficiency ,Noninvasive monitoring ,Oxygenator performance - Abstract
Background Advances in cardiorespiratory monitoring have made the extracorporeal membrane oxygenation (ECMO) technique safer for the patient. Noninvasive, continuous tools are available, although data on their applications in the neonatal ECMO setting are lacking. Objective We retrospectively described the neonatal clinical application of this continuous, noninvasive ECMO monitor and compared the analyzed parameters from those derived from blood gas analysis. Materials and methods We performed 897 h of cardiorespiratory monitoring during neonatal venoarterial-ECMO (VA-ECMO) for four patients affected by (cardio-) respiratory failure, to compare the reliability of a noninvasive, continuous monitoring Spectrum M4® (M4) (Spectrum Medical, Gloucester, England) to an invasive, intermittent co-monitoring with blood gas analyzer (Radiometer Medical ApS, Bronshoj, Denmark). Results A range of 117 pairs (time-matched BGA-derived vs. M4-derived parameters) was retrospectively analyzed. T-test, linear regression and Bland–Altman analysis for hemoglobin, hematocrit, venous oxygen saturation, oxygen delivery, oxygen consumption, oxygen extraction ratio, oxygen partial pressure, and carbon dioxide partial pressure showed a strong relationship between the two monitors for all parameters analyzed (p Conclusions Continuous, noninvasive cardiorespiratory monitoring appears to be feasible and reliable, although its accuracy needs to be verified in a more extensive cohort.
- Published
- 2018
16. Lack of efficacy of a starch-thickened preterm formula on gastro-oesophageal reflux in preterm infants: a pilot study
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Genny Raffaeli, Giacomo Faldella, Marianna Ferlini, E. Legnani, Luigi Corvaglia, Arianna Aceti, Elisa Mariani, Corvaglia L., Aceti A., Mariani E., Legnani E., Ferlini M., Raffaeli G., and Faldella G.
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Male ,medicine.medical_specialty ,Pediatrics ,Treatment outcome ,Gestational Age ,Pilot Projects ,Infant, Premature, Diseases ,Gastroenterology ,Esophagus ,Gastro ,Internal medicine ,PRETERM INFANTS ,Electric Impedance ,medicine ,Lack of efficacy ,Humans ,gastro-esophageal reflux ,business.industry ,Infant, Newborn ,Reflux ,Obstetrics and Gynecology ,Gestational age ,Starch ,Hydrogen-Ion Concentration ,Infant Formula ,feed thickening ,Treatment Outcome ,Dietary Supplements ,Food, Fortified ,Pediatrics, Perinatology and Child Health ,Gastroesophageal Reflux ,Female ,business ,Infant, Premature - Abstract
BACKGROUND: Gastro-oesophageal reflux (GOR) is common in preterm infants; conservative interventions (i.e. dietary changes) should represent the first-line approach. AIM: To evaluate by combined pH and impedance monitoring (pH-MII) the effect of a new preterm formula thickened with amylopectin (TPF) on GOR features in symptomatic preterm infants. METHODS: Twenty-eight symptomatic preterm newborns underwent a 24-hour pH-MII; each baby received eight meals (four of TPF and four of a preterm formula [PF]). GOR indexes (number, acidity, duration and height of GORs) after TPF and PF meals were compared by Wilcoxon Signed Ranks Test. Viscosity of PF and TPF was measured. RESULTS: TPF significantly decreased the number of acid GORs detected by pH-monitoring (TPF vs. PF: median 20 vs. 24.5, p = 0.009), while it had no influence on Reflux Index (RIpH), nor on acid and non-acid GOR indexes detected by MII, GOR physical features, and GOR height. TPF's viscosity was extremely higher than PF's, and further increased at pH 3 after the addition of pepsin. CONCLUSIONS: The new formula was found to reduce the number of acid GORs detected by pH-monitoring; it did not reduce neither total oesophageal acid exposure nor non-acid GORs. At present its extended clinical use cannot be recommended.
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- 2012
17. Hyperbilirubinemia and retinopathy of prematurity: a retrospective cohort study.
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Gulden S, Cervellini G, Colombo M, Marangoni MB, Taccani V, Pesenti N, Raffaeli G, Araimo G, Osnaghi S, Fumagalli M, Garrido F, Villamor E, and Cavallaro G
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- Humans, Infant, Newborn, Retrospective Studies, Male, Female, Italy epidemiology, Risk Factors, Infant, Premature, Phototherapy methods, Incidence, Hyperbilirubinemia, Neonatal therapy, Hyperbilirubinemia, Neonatal etiology, Hyperbilirubinemia, Neonatal epidemiology, Gestational Age, Intensive Care Units, Neonatal, Retinopathy of Prematurity epidemiology, Retinopathy of Prematurity etiology, Retinopathy of Prematurity blood
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Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g. Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP. Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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18. Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial.
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Teofili L, Papacci P, Dani C, Cresi F, Remaschi G, Pellegrino C, Bianchi M, Ansaldi G, Campagnoli MF, Vania B, Lepore D, Franco FGS, Fabbri M, de Vera d' Aragona RP, Molisso A, Beccastrini E, Dragonetti A, Orazi L, Pasciuto T, Mozzetta I, Baldascino A, Locatelli E, Valentini CG, Giannantonio C, Carducci B, Gabbriellini S, Albiani R, Ciabatti E, Nicolotti N, Baroni S, Mazzoni A, Besso FG, Serrao F, Purcaro V, Coscia A, Pizzolo R, Raffaeli G, Villa S, Mondello I, Trimarchi A, Beccia F, Ghirardello S, and Vento G
- Subjects
- Humans, Infant, Newborn, Female, Male, Double-Blind Method, Erythrocyte Transfusion, Infant, Extremely Premature, Gestational Age, Treatment Outcome, Severity of Illness Index, Retinopathy of Prematurity prevention & control, Fetal Blood
- Abstract
Background: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP., Methods: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions., Results: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06-2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk., Conclusions: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP., Trial Registration: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212., (© 2024. The Author(s).)
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- 2024
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19. Why might cord blood be a better source of platelets for transfusion to neonates?
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Cortesi V, Cavallaro G, Raffaeli G, Ghirardello S, Mosca F, Klei TRL, Fustolo-Gunnink S, Stanworth S, New HV, Deschmann E, and Lopriore E
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- Humans, Infant, Newborn, Infant, Premature, Thrombocytopenia, Neonatal Alloimmune therapy, Female, Hemorrhage therapy, Hemorrhage etiology, Platelet Transfusion methods, Fetal Blood cytology, Blood Platelets cytology, Blood Platelets metabolism
- Abstract
Thrombocytopenia (defined as a platelet count <150×10
9 /L) is a common condition in preterm neonates and may occur in 18-35% of all infants admitted to the Neonatal Intensive Care Unit (NICU). Neonatal platelet functionality in terms of reactivity is often described as reduced compared to adults, even in healthy, term neonates. However, this platelet "hyporeactivity" does not correspond to a global functional impairment of the normal delicately balanced neonatal hemostatic system. The extent to which neonatal thrombocytopenia and platelet hyporeactivity contribute to the bleeding risk in preterm neonates remains unknown. Prophylactic platelet transfusions are often administered to them to reduce the risk of bleeding. However, recent literature indicates that adopting a higher platelet transfusion threshold than a lower one results in significantly higher death rates or major bleeding and can be harmful. Although the mechanism by which this occurs is not entirely clear, a mismatch between adult transfused platelets and the neonatal hemostatic system, as well as volume overload, are speculated to be potentially involved. Therefore, future research should consider novel transfusion products that may be more suitable for premature neonates. Blood products derived from umbilical cord blood (UCB) are promising, as they might perfectly match neonatal blood features. Here, we discuss the current knowledge about UCB-derived products, focusing on UCB-derived platelet concentrates and their potential for future clinical application. We will discuss how they may overcome the potential risks of transfusing adult-derived platelets to premature infants while maintaining efficacy.- Published
- 2024
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20. Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey.
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Arribas C, Decembrino N, Raffaeli G, Amodeo I, González-Caballero JL, Riaza M, Ortiz-Movilla R, Massenzi L, Gizzi C, Araimo G, Cattarelli D, Aversa S, Martinelli S, Frezza S, Orfeo L, Mosca F, Cavallaro G, and Garrido F
- Subjects
- Humans, Italy, Infant, Newborn, Cross-Sectional Studies, Prospective Studies, Spain, Drug Monitoring methods, Drug Monitoring statistics & numerical data, Ibuprofen adverse effects, Sodium Potassium Chloride Symporter Inhibitors adverse effects, Surveys and Questionnaires, Female, Kidney Diseases chemically induced, Kidney Diseases epidemiology, Infant, Premature, Male, Intensive Care Units, Neonatal statistics & numerical data, Aminoglycosides adverse effects, Ototoxicity etiology, Vancomycin adverse effects
- Abstract
Neonates face heightened susceptibility to drug toxicity, often exposed to off-label medications with dosages extrapolated from adult or pediatric studies. Premature infants in Neonatal Intensive Care Units (NICUs) are particularly at risk due to underdeveloped pharmacokinetics and exposure to multiple drugs. The study aimed to survey commonly used medications with a higher risk of ototoxicity and nephrotoxicity in Spanish and Italian neonatal units. A prospective cross-sectional study was conducted in Italian and Spanish neonatal units using a web-based survey with 43 questions. A modified Delphi method involved experts refining the survey through online consensus. Ethical approval was obtained, and responses were collected from January to July 2023. The survey covered various aspects, including drug-related ototoxic and nephrotoxic management, hearing screening, and therapeutic drug monitoring. Responses from 131 participants (35.9% from Spain and 64.1% from Italy) revealed awareness of drug toxicity risks. Varied practices were observed in hearing screening protocols, and a high prevalence of ototoxic and nephrotoxic drug use, including aminoglycosides (100%), vancomycin (70.2%), loop diuretics (63.4%), and ibuprofen (62.6%). Discrepancies existed in guideline availability and adherence, with differences between Italy and Spain in therapeutic drug monitoring practices., Conclusions: The study underscores the need for clinical guidelines and uniform practices in managing ototoxic and nephrotoxic drugs in neonatal units. Awareness is high, but inconsistencies in practices indicate a necessity for standardization, including the implementation of therapeutic drug monitoring and the involvement of clinical pharmacologists. Addressing these issues is crucial for optimizing neonatal care in Southern Europe., What Is Known: • Neonates in intensive care face a high risk of nephrotoxicity and ototoxicity from drugs like aminoglycosides, vancomycin, loop diuretics, and ibuprofen. • Therapeutic drug monitoring is key for managing these risks, optimizing dosing for efficacy and minimizing side effects., What Is New: • NICUs in Spain and Italy show high drug toxicity awareness but differ in ototoxic/nephrotoxic drug management. • Urgent need for standard guidelines and practices to address nephrotoxic risks from aminoglycosides, vancomycin, loop diuretics, and ibuprofen., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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21. Congenital diaphragmatic hernia: automatic lung and liver MRI segmentation with nnU-Net, reproducibility of pyradiomics features, and a machine learning application for the classification of liver herniation.
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Conte L, Amodeo I, De Nunzio G, Raffaeli G, Borzani I, Persico N, Griggio A, Como G, Cascio D, Colnaghi M, Mosca F, and Cavallaro G
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- Humans, Female, Reproducibility of Results, Pregnancy, Deep Learning, Liver Diseases diagnostic imaging, Machine Learning, Hernias, Diaphragmatic, Congenital diagnostic imaging, Magnetic Resonance Imaging methods, Lung diagnostic imaging, Liver diagnostic imaging, Liver pathology, Prenatal Diagnosis methods
- Abstract
Prenatal assessment of lung size and liver position is essential to stratify congenital diaphragmatic hernia (CDH) fetuses in risk categories, guiding counseling, and patient management. Manual segmentation on fetal MRI provides a quantitative estimation of total lung volume and liver herniation. However, it is time-consuming and operator-dependent. In this study, we utilized a publicly available deep learning (DL) segmentation system (nnU-Net) to automatically contour CDH-affected fetal lungs and liver on MRI sections. Concordance between automatic and manual segmentation was assessed by calculating the Jaccard coefficient. Pyradiomics standard features were then extracted from both manually and automatically segmented regions. The reproducibility of features between the two groups was evaluated through the Wilcoxon rank-sum test and intraclass correlation coefficients (ICCs). We finally tested the reliability of the automatic-segmentation approach by building a ML classifier system for the prediction of liver herniation based on support vector machines (SVM) and trained on shape features computed both in the manual and nnU-Net-segmented organs. We compared the area under the classifier receiver operating characteristic curve (AUC) in the two cases. Pyradiomics features calculated in the manual ROIs were partly reproducible by the same features calculated in nnU-Net segmented ROIs and, when used in the ML procedure, to predict liver herniation (both AUC around 0.85). Conclusion: Our results suggest that automatic MRI segmentation is feasible, with good reproducibility of pyradiomics features, and that a ML system for liver herniation prediction offers good reliability. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04609163?term=NCT04609163&draw=2&rank=1 ; Clinical Trial Identification no. NCT04609163. What is Known: • Magnetic resonance imaging (MRI) is crucial for prenatal congenital diaphragmatic hernia (CDH) assessment. It enables the quantification of the total lung volume and the extent of liver herniation, which are essential for stratifying the severity of CDH, guiding counseling, and patient management. • The manual segmentation of MRI scans is a time-consuming process that is heavily reliant upon the skill set of the operator. What is New: • MRI lung and liver automatic segmentation using the deep learning nnU-Net system is feasible, with good Jaccard coefficient values and satisfactory reproducibility of pyradiomics features compared to manual results. • A feasible ML system for predicting liver herniation could improve prenatal assessments and CDH patient management., (© 2024. The Author(s).)
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- 2024
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22. Association between co-sleeping in the first year of life and preschoolers´ sleep patterns.
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Garrido F, González-Caballero JL, García P, Gianni ML, Garrido S, González L, Atance V, Raffaeli G, and Cavallaro G
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- Humans, Male, Female, Child, Preschool, Cross-Sectional Studies, Infant, Surveys and Questionnaires, Sleep Quality, Breast Feeding statistics & numerical data, Parents, Latent Class Analysis, Sleep physiology
- Abstract
This study aimed to investigate the association between co-sleeping practiced during the first year of life and preschoolers' sleep patterns. A cross-sectional study including toddlers was designed to analyze their sleep patterns. The Brief Infant Sleep Questionnaire, validated in Spanish, was used to measure sleep quality. A latent class analysis was performed to identify qualitative subgroups in the sample and explore the effects of co-sleeping. The sleep patterns of 276 children were analyzed. A total of 181 (65%) parents reported having practiced co-sleeping with their children. The latent class analysis identified a two-class solution with two different sleep patterns. One of them showed a worse quality sleep pattern, which had a significant association with having practiced co-sleeping during the first year of life, and with the fact that they were still sleeping in the parents' room, among other characteristics related to co-sleeping and parental concerns. Breastfeeding also showed association with a worse quality sleep pattern. Conclusion: Based on the present findings, co-sleeping during the first year of life appears to be associated with poor sleep patterns in young preschoolers. What is Known: • Co-sleeping shows benefits for infants and parents, mainly facilitating successful breastfeeding. • Literature on the effect of co-sleeping in lately sleep quality in children and their parents is very limited. What is New: • Co-sleeping practiced during the first year of life could be associated with a worse sleep pattern measured with BISQ-E tool. • A balance between the correct practice of co-sleeping and the achievement of a healthy sleep routine in preschool should probably be part of parents' health education., (© 2024. The Author(s).)
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- 2024
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23. Correction to: Association between co-sleeping in the first year of life and preschoolers´ sleep patterns.
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Garrido F, González-Caballero JL, García P, Gianni ML, Garrido S, González L, Atance V, Raffaeli G, and Cavallaro G
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- 2024
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24. Global cross-sectional survey on neonatal pharmacologic sedation and analgesia practices and pain assessment tools: impact of the sociodemographic index (SDI).
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Arribas C, Cavallaro G, Gonzalez JL, Lagares C, Raffaeli G, Smits A, Simons SHP, Villamor E, Allegaert K, and Garrido F
- Abstract
Background: There is variability in the use of sedatives and analgesics in neonatal intensive care units (NICUs). We aimed to investigate the use of analgesics and sedatives and the management of neonatal pain and distress., Methods: This was a global, prospective, cross-sectional study. A survey was distributed May-November 2022. The primary outcome of this research was to compare results between countries depending on their socio-sanitary level using the sociodemographic index (SDI). We organized results based on geographical location., Results: The survey collected 1304 responses, but we analyzed 924 responses after database cleaning. Responses from 98 different countries were analyzed. More than 60% of NICUs reported having an analgosedation guideline, and one-third of respondents used neonatal pain scales in more than 80% of neonates. We found differences in the management of sedation and analgesia between NICUs on different continents, but especially between countries with different SDIs. Countries with a higher SDI had greater availability of and adherence to analgosedation guidelines, as well as higher rates of analgosedation for painful or distressing procedures. Countries with different SDIs reported differences in analgosedation for neonatal intubation, invasive ventilation, and therapeutic hypothermia, among others., Conclusions: Socio-economic status of countries impacts on neonatal analgosedation management., Impact: There is significant variability in the pain management practices in neonates. There is a lack of knowledge related to how neonatal pain management practices differ between regions. Sociodemographic index is a key factor associated with differences in neonatal pain management practices across global regions., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)
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- 2024
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25. Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples.
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Mahoney L, Raffaeli G, Beken S, Ünal S, Kotidis C, Cavallaro G, Garrido F, Bhatt A, Dempsey EM, Allegaert K, Simons SHP, Flint RB, and Smits A
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- Infant, Newborn, Humans, Phenobarbital therapeutic use, Anticonvulsants therapeutic use, Electroencephalography, Midazolam pharmacokinetics, Midazolam therapeutic use, Hypothermia, Induced
- Abstract
Background: Many drugs are used off-label or unlicensed in neonates. This does not mean they are used without evidence or knowledge. We aimed to apply and evaluate the Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies (GAPPS) scoring system for the level of evidence of two commonly used anti-epileptic drugs., Methods: Midazolam and phenobarbital as anti-epileptics were evaluated with a systematic literature search on neonatal pharmacokinetic (PK) and/or pharmacodynamic [PD, (amplitude-integrated) electroencephalography effect] studies. With the GAPPS system, two evaluators graded the current level of evidence. Inter-rater agreement was assessed for dosing evidence score (DES), quality of evidence (QoE), and strength of recommendation (REC)., Results: Seventy-two studies were included. DES scores 4 and 9 were most frequently used for PK, and scores 0 and 1 for PD. Inter-rater agreements on DES, QoE, and REC ranged from moderate to very good. A final REC was provided for all PK studies, but only for 25% (midazolam) and 33% (phenobarbital) of PD studies., Conclusions: There is a reasonable level of evidence concerning midazolam and phenobarbital PK in neonates, although using a predefined target without integrated PK/PD evaluation. Further research is needed on midazolam use in term neonates with therapeutic hypothermia, and phenobarbital treatment in preterms., Impact: There is a reasonable level of evidence concerning pharmacotherapy of midazolam and phenobarbital in neonates. Most evidence is however based on PK studies, using a predefined target level or concentration range without integrated, combined PK/PD evaluation. Using the GAPPS system, final strength of recommendation could be provided for all PK studies, but only for 25% (midazolam) to 33% (phenobarbital) of PD studies. Due to the limited PK observations of midazolam in term neonates with therapeutic hypothermia, and of phenobarbital in preterm neonates these subgroups can be identified for further research., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)
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- 2024
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26. Viscoelastic coagulation testing in Neonatal Intensive Care Units: advantages and pitfalls in clinical practice.
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Manzoni F, Raffaeli G, Cortesi V, Amelio GS, Amodeo I, Gulden S, Cervellini G, Tomaselli A, Colombo M, Artoni A, Ghirardello S, Mosca F, and Cavallaro G
- Subjects
- Infant, Newborn, Humans, Intensive Care Units, Neonatal, Blood Coagulation Tests, Hemostasis, Blood Coagulation, Thrombelastography, Hemostatics therapeutic use, Blood Coagulation Disorders therapy, Blood Coagulation Disorders drug therapy
- Abstract
The expression "developmental hemostasis" indicates the age-related physiological changes occurring during the maturational process of the hemostatic system. Despite the quantitative and qualitative alterations, the neonatal hemostatic system is competent and well-balanced. Conventional coagulation tests do not provide reliable information as they only explore the procoagulants during the neonatal period. In contrast, viscoelastic coagulation tests (VCTs), such as viscoelastic coagulation monitoring (VCM), thromboelastography (TEG or ClotPro), and rotational thromboelastometry (ROTEM), are point-of-care assays that provide a quick, dynamic and global view of the hemostatic process, allowing prompt and individualized therapeutic intervention when necessary. Their use in neonatal care is on the increase and they could help monitor patients at risk of hemostatic derangement. In addition, they are crucial for anticoagulation monitoring during extracorporeal membrane oxygenation. Moreover, implementing VCT-based monitoring could optimize blood product use.
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- 2023
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27. Current pain management practices for preterm infants with necrotizing enterocolitis: a European survey.
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Ten Barge JA, van den Bosch GE, Meesters NJ, Allegaert K, Arribas C, Cavallaro G, Garrido F, Raffaeli G, Vermeulen MJ, and Simons SHP
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- Infant, Infant, Newborn, Humans, Infant, Premature, Pain Management, Intensive Care Units, Neonatal, Analgesics therapeutic use, Pain diagnosis, Pain drug therapy, Enterocolitis, Necrotizing complications, Enterocolitis, Necrotizing diagnosis, Enterocolitis, Necrotizing therapy, Infant, Newborn, Diseases
- Abstract
Background: Necrotizing enterocolitis (NEC) is a highly painful intestinal complication in preterm infants that requires adequate pain management to prevent short- and long-term effects of neonatal pain. There is a lack of international guidelines for pain management in NEC patients. Therefore, this study aims to describe current pain management for NEC patients in European neonatal intensive care units (NICUs)., Methods: An online survey was designed and conducted to assess current practices in pain management for NEC patients in European NICUs. The survey was distributed via neonatal societies, digital platforms, and professional contacts., Results: Out of the 259 responding unique European NICUs from 36 countries, 61% had a standard protocol for analgesic therapy, 73% assessed pain during NEC, and 92% treated NEC patients with intravenous analgosedatives. There was strong heterogeneity in the used pain scales and initial analgesic therapy, which mainly included acetaminophen (70%), fentanyl (56%), and/or morphine (49%). A third of NICU representatives considered their pain assessment adequate, and half considered their analgesic therapy adequate for NEC patients., Conclusions: Various pain scales and analgesics are used to treat NEC patients in European NICUs. Our results provide the first step towards an international guideline to improve pain management for NEC patients., Impact: This study provides an overview of current pain management practices for infants with necrotizing enterocolitis (NEC) in European neonatal intensive care units. Choice of pain assessment tools, analgosedatives, and dosages vary considerably among NICUs and countries. A third of NICU representatives were satisfied with their current pain assessment practices and half of NICU representatives with their analgesic therapy practices in NEC patients in their NICU. The results of this survey may provide a first step towards developing a European pain management consensus guideline for patients with NEC., (© 2023. The Author(s).)
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- 2023
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28. Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner.
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Provitera L, Tomaselli A, Raffaeli G, Crippa S, Arribas C, Amodeo I, Gulden S, Amelio GS, Cortesi V, Manzoni F, Cervellini G, Cerasani J, Menis C, Pesenti N, Tripodi M, Santi L, Maggioni M, Lonati C, Oldoni S, Algieri F, Garrido F, Bernardo ME, Mosca F, and Cavallaro G
- Subjects
- Animals, Mice, Infant, Infant, Newborn, Humans, Bone Marrow, Mice, Inbred C57BL, Intestines, Enterocolitis, Necrotizing, Mesenchymal Stem Cells, Infant, Newborn, Diseases
- Abstract
Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3-6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 10
6 or 1 × 106 ) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls ( p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106 ) inducing a NEC incidence reduction of up to 0% ( p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.- Published
- 2023
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29. Description of the Exposure of the Most-Followed Spanish Instamoms' Children to Social Media.
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Garrido F, Alvarez A, González-Caballero JL, Garcia P, Couso B, Iriso I, Merino M, Raffaeli G, Sanmiguel P, Arribas C, Vacaroaia A, and Cavallaro G
- Subjects
- Child, Preschool, Humans, Child, Female, Cross-Sectional Studies, Marketing, Advertising, Emotions, Social Media
- Abstract
There is evidence of the risk of overexposure of children on social networks by parents working as influencers. A cross-sectional study of the profiles of the sixteen most-followed Instamoms in Spain was carried out. An analysis of these profiles was performed over a full month (April 2022), three times a week, to describe the representation of influencers' children in the posts shared by them, as well as their role in the Instamoms' marketing. A total of 192 evaluations of the profiles were performed in the study period. The average number of children exposed by an Instamom was three, generally preschoolers and schoolchildren. The children appear in a context of the family home and accompanied by their mother. The type of advertising that accompanies the appearance of underage children is usually women or children's clothing, but also food products, leisure, etc. Appearance of children in the posts had a statistically significant influence on followers measured by the number of likes. Results provided the identification of two Instamom clusters with differentiated behaviors in relation to appearance of children in posts. It is important to involve Social Pediatrics in the protection of the privacy and interests of children given the increase in sharenting. The authors believe that there are concerns about their explicit consent to public exposure from early childhood and about the medium and long-term effect that this may have on their future well-being.
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- 2023
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30. BORN study: a multicenter randomized trial investigating cord blood red blood cell transfusions to reduce the severity of retinopathy of prematurity in extremely low gestational age neonates.
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Teofili L, Papacci P, Orlando N, Bianchi M, Pasciuto T, Mozzetta I, Palluzzi F, Giacò L, Giannantonio C, Remaschi G, Santosuosso M, Beccastrini E, Fabbri M, Valentini CG, Bonfini T, Cloclite E, Accorsi P, Dragonetti A, Cresi F, Ansaldi G, Raffaeli G, Villa S, Pucci G, Mondello I, Santodirocco M, Ghirardello S, and Vento G
- Subjects
- Infant, Newborn, Adult, Humans, Infant, Erythrocyte Transfusion adverse effects, Gestational Age, Infant, Low Birth Weight, Infant, Premature, Fetal Blood, Anemia, Neonatal diagnosis, Anemia, Neonatal prevention & control, Retinopathy of Prematurity diagnosis, Retinopathy of Prematurity prevention & control
- Abstract
Background: Extremely low gestational age neonates (ELGANs, i.e., neonates born before 28 weeks of gestation) are at high risk of developing retinopathy of prematurity (ROP), with potential long-life visual impairment. Due to concomitant anemia, ELGANs need repeated red blood cell (RBC) transfusions. These produce a progressive replacement of fetal hemoglobin (HbF) by adult hemoglobin (HbA). Furthermore, a close association exists between low levels of HbF and severe ROP, suggesting that a perturbation of the HbF-mediated oxygen release may derange retinal angiogenesis and promote ROP., Methods/design: BORN (umBilical blOod to tRansfuse preterm Neonates) is a multicenter double-blinded randomized controlled trial in ELGANs, to assess the effect of allogeneic cord blood RBC transfusions (CB-RBCs) on severe ROP development. Recruitment, consent, and randomization take place at 10 neonatology intensive care units (NICUs) of 8 Italian tertiary hospitals. ELGANs with gestational age at birth comprised between 24+0 and 27+6 weeks are randomly allocated into two groups: (1) standard RBC transfusions (adult-RBCs) (control arm) and (2) CB-RBCs (intervention arm). In case of transfusion need, enrolled patients receive transfusions according to the allocation arm, unless an ABO/RhD CB-RBC is unavailable. Nine Italian public CB banks cooperate to make available a suitable amount of CB-RBC units for all participating NICUs. The primary outcome is the incidence of severe ROP (stage 3 or higher) at discharge or 40 weeks of postmenstrual age, which occurs first., Discussion: BORN is a groundbreaking trial, pioneering a new transfusion approach dedicated to ELGANs at high risk for severe ROP. In previous non-randomized trials, this transfusion approach was proven feasible and able to prevent the HbF decrease in patients requiring multiple transfusions. Should the BORN trial confirm the efficacy of CB-RBCs in reducing ROP severity, this transfusion strategy would become the preferential blood product to be used in severely preterm neonates., Trial Registration: ClinicalTrials.gov NCT05100212. Registered on October 29, 2021., (© 2022. The Author(s).)
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- 2022
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31. Endothelial dysfunction in preterm infants: The hidden legacy of uteroplacental pathologies.
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Amelio GS, Provitera L, Raffaeli G, Tripodi M, Amodeo I, Gulden S, Cortesi V, Manzoni F, Cervellini G, Tomaselli A, Pravatà V, Garrido F, Villamor E, Mosca F, and Cavallaro G
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Millions of infants are born prematurely every year worldwide. Prematurity, particularly at lower gestational ages, is associated with high mortality and morbidity and is a significant global health burden. Pregnancy complications and preterm birth syndrome strongly impact neonatal clinical phenotypes and outcomes. The vascular endothelium is a pivotal regulator of fetal growth and development. In recent years, the key role of uteroplacental pathologies impairing endothelial homeostasis is emerging. Conditions leading to very and extremely preterm birth can be classified into two main pathophysiological patterns or endotypes: infection/inflammation and dysfunctional placentation. The first is frequently related to chorioamnionitis, whereas the second is commonly associated with hypertensive disorders of pregnancy and fetal growth restriction. The nature, timing, and extent of prenatal noxa may alter fetal and neonatal endothelial phenotype and functions. Changes in the luminal surface, oxidative stress, growth factors imbalance, and dysregulation of permeability and vascular tone are the leading causes of endothelial dysfunction in preterm infants. However, the available evidence regarding endothelial physiology and damage is limited in neonates compared to adults. Herein, we discuss the current knowledge on endothelial dysfunction in the infectious/inflammatory and dysfunctional placentation endotypes of prematurity, summarizing their molecular features, available biomarkers, and clinical impact. Furthermore, knowledge gaps, shadows, and future research perspectives are highlighted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Amelio, Provitera, Raffaeli, Tripodi, Amodeo, Gulden, Cortesi, Manzoni, Cervellini, Tomaselli, Pravatà, Garrido, Villamor, Mosca and Cavallaro.)
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- 2022
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32. The role of magnetic resonance imaging in the diagnosis and prognostic evaluation of fetuses with congenital diaphragmatic hernia.
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Amodeo I, Borzani I, Raffaeli G, Persico N, Amelio GS, Gulden S, Colnaghi M, Villamor E, Mosca F, and Cavallaro G
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- Female, Fetus pathology, Humans, Lung diagnostic imaging, Lung pathology, Lung Volume Measurements methods, Magnetic Resonance Imaging methods, Pregnancy, Prognosis, Retrospective Studies, Ultrasonography, Prenatal methods, Hernias, Diaphragmatic, Congenital diagnostic imaging
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In recent years, magnetic resonance imaging (MRI) has largely increased our knowledge and predictive accuracy of congenital diaphragmatic hernia (CDH) in the fetus. Thanks to its technical advantages, better anatomical definition, and superiority in fetal lung volume estimation, fetal MRI has been demonstrated to be superior to 2D and 3D ultrasound alone in CDH diagnosis and outcome prediction. This is of crucial importance for prenatal counseling, risk stratification, and decision-making approach. Furthermore, several quantitative and qualitative parameters can be evaluated simultaneously, which have been associated with survival, postnatal course severity, and long-term morbidity., Conclusion: Fetal MRI will further strengthen its role in the near future, but it is necessary to reach a consensus on indications, methodology, and data interpretation. In addition, it is required data integration from different imaging modalities and clinical courses, especially for predicting postnatal pulmonary hypertension. This would lead to a comprehensive prognostic assessment., What Is Known: • MRI plays a key role in evaluating the fetal lung in patients with CDH. • Prognostic assessment of CDH is challenging, and advanced imaging is crucial for a complete prenatal assessment and counseling., What Is New: • Fetal MRI has strengthened its role over ultrasound due to its technical advantages, better anatomical definition, superior fetal lung volume estimation, and outcome prediction. • Imaging and clinical data integration is the most desirable strategy and may provide new MRI applications and future research opportunities., (© 2022. The Author(s).)
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- 2022
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33. Hemostasis in neonatal ECMO.
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Cortesi V, Raffaeli G, Amelio GS, Amodeo I, Gulden S, Manzoni F, Cervellini G, Tomaselli A, Colombo M, Araimo G, Artoni A, Ghirardello S, Mosca F, and Cavallaro G
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Extracorporeal membrane oxygenation (ECMO) is a life-saving support for cardio-respiratory function. Over the last 50 years, the extracorporeal field has faced huge technological progress. However, despite the improvements in technique and materials, coagulation problems are still the main contributor to morbidity and mortality of ECMO patients. Indeed, the incidence and survival rates of the main hemorrhagic and thrombotic complications in neonatal respiratory ECMO are relevant. The main culprit is related to the intrinsic nature of ECMO: the contact phase activation. The exposure of the human blood to the non-endothelial surface triggers a systemic inflammatory response syndrome, which chronically activates the thrombin generation and ultimately leads to coagulative derangements. Pre-existing illness-related hemostatic dysfunction and the peculiarity of the neonatal clotting balance further complicate the picture. Systemic anticoagulation is the management's mainstay, aiming to prevent thrombosis within the circuit and bleeding complications in the patient. Although other agents (i.e., direct thrombin inhibitors) have been recently introduced, unfractionated heparin (UFH) is the standard of care worldwide. Currently, there are multiple tests exploring ECMO-induced coagulopathy. A combination of the parameters mentioned above and the evaluation of the patient's underlying clinical context should be used to provide a goal-directed antithrombotic strategy. However, the ideal algorithm for monitoring anticoagulation is currently unknown, resulting in a large inter-institutional diagnostic variability. In this review, we face the features of the available monitoring tests and approaches, mainly focusing on the role of point-of-care (POC) viscoelastic assays in neonatal ECMO. Current gaps in knowledge and areas that warrant further study will also be addressed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cortesi, Raffaeli, Amelio, Amodeo, Gulden, Manzoni, Cervellini, Tomaselli, Colombo, Araimo, Artoni, Ghirardello, Mosca and Cavallaro.)
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- 2022
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34. Veno-Arterial Extracorporeal Membrane Oxygenation (ECMO) Impairs Bradykinin-Induced Relaxation in Neonatal Porcine Coronary Arteries.
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Provitera L, Amelio GS, Tripodi M, Raffaeli G, Macchini F, Amodeo I, Gulden S, Cortesi V, Manzoni F, Cervellini G, Tomaselli A, Zuanetti G, Lonati C, Battistin M, Kamel S, Parente V, Pravatà V, Villa S, Villamor E, Mosca F, and Cavallaro G
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Extracorporeal membrane oxygenation (ECMO) is a lifesaving support for respiratory and cardiovascular failure. However, ECMO induces a systemic inflammatory response syndrome that can lead to various complications, including endothelial dysfunction in the cerebral circulation. We aimed to investigate whether ECMO-associated endothelial dysfunction also affected coronary circulation. Ten-day-old piglets were randomized to undergo either 8 h of veno-arterial ECMO (n = 5) or no treatment (Control, n = 5). Hearts were harvested and coronary arteries were dissected and mounted as 3 mm rings in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U46619, concentration−response curves to the endothelium-dependent vasodilator bradykinin (BK) and the nitric oxide (NO) donor (endothelium-independent vasodilator) sodium nitroprusside (SNP) were performed. Relaxation to BK was studied in the absence or presence of the NO synthase inhibitor Nω-nitro-L-arginine methyl ester HCl (L-NAME). U46619-induced contraction and SNP-induced relaxation were similar in control and ECMO coronary arteries. However, BK-induced relaxation was significantly impaired in the ECMO group (30.4 ± 2.2% vs. 59.2 ± 2.1%; p < 0.0001). When L-NAME was present, no differences in BK-mediated relaxation were observed between the control and ECMO groups. Taken together, our data suggest that ECMO exposure impairs endothelium-derived NO-mediated coronary relaxation. However, there is a NO-independent component in BK-induced relaxation that remains unaffected by ECMO. In addition, the smooth muscle cell response to exogenous NO is not altered by ECMO exposure.
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- 2022
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35. Proinflammatory Endothelial Phenotype in Very Preterm Infants: A Pilot Study.
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Amelio GS, Provitera L, Raffaeli G, Amodeo I, Gulden S, Cortesi V, Manzoni F, Pesenti N, Tripodi M, Pravatà V, Lonati C, Cervellini G, Mosca F, and Cavallaro G
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Very preterm infants are exposed to prenatal inflammatory processes and early postnatal hemodynamic and respiratory complications, but limited data are available about the endothelial effect of these conditions. The present pilot study investigates the perinatal endothelial phenotype in very preterm infants (VPIs) and explores its predictive value on neonatal mortality and hemodynamic and respiratory complications. Angiopoietin 1 (Ang-1), Ang-2, E-selectin, vascular adhesion molecule 1 (VCAM-1), tissue factor (TF), and endothelin 1 (ET-1) concentrations were tested in first (T1), 3rd (T2), and 7-10th (T3) day of life in 20 VPIs using Luminex technology and compared with 14 healthy full-term infants (FTIs). Compared to FTIs, VPIs had lower Ang-1 at T1 and T2; higher Ang-2 at T1, T2, and T3; higher Ang-2/Ang-1 ratio at T1, T2, and T3; lower E-selectin at T1, T2, and T3; higher VCAM-1 at T1; higher TF at T2. No differences in concentrations were found in neonatal deaths. VPIs with hemodynamic or respiratory complications had higher Ang-2 at T3. Perinatal low Ang-1 and high Ang-2 associated with high VCAM-1 and TF in VPIs suggest a proinflammatory endothelial phenotype, resulting from the synergy of a pathological prenatal inheritance and a premature extrauterine transition.
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- 2022
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36. Hemostatic Evaluation With Viscoelastic Coagulation Monitor: A Nicu Experience.
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Amelio GS, Raffaeli G, Amodeo I, Gulden S, Cortesi V, Manzoni F, Pesenti N, Ghirardello S, Mosca F, and Cavallaro G
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Background: Viscoelastic coagulation tests provide valuable information in neonatal intensive care units (NICUs), but the lack of reference intervals still limits their decision-making power according to gestational age. The aim of the present study is to evaluate the hemostasis of a cohort of full-term (FT) and late-preterm (LP) infants using the viscoelastic coagulation monitor (VCM®) system, a new portable device that uses untreated whole blood., Methods: An observational study was performed to identify non-coagulopathic FT and LP infants admitted to III° level NICU (January 2020 to December 2021) with a VCM test in the first 72 h of life., Results: Forty-five patients were enrolled, 26 FT and 19 LP. No statistical differences in hemostatic parameters were observed between FT and LP nor between stable and unstable neonates. Clotting time (CT) was positive correlated with PT ( p = 0.032), not with aPTT ( p = 0.185). From linear regression, platelet resulted associated with: clot formation time (CTF, p = 0.003), alpha angle (Alpha, p = 0.010), amplitude at 10 (A10, p = 0.001), amplitude at 20 min (A20, p < 0.001), maximum clot firmness (MCF, p < 0.001); and fibrinogen was associated with: A10 ( p = 0.008), A20 ( p = 0.015) and MCF ( p = 0.024). Compared to the adult reference population, neonates showed shorter CT (mean (SD): 5.3 (1.4) vs. 7.0 (0.9) min, p < 0.001), CFT (2.4 (0.7) vs. 2.8 (0.6) minutes, p < 0.001) and higher Alpha (60.8 (6.3) vs. 55 (5)°, p < 0.001). In addition, the neonatal cohort showed an early transient difference in amplitude and fibrinolysis, as follows: A10 (28.0 (5.0) vs. 26 (4) VCM units, p =0.004), A20 (34.8 (5.0) vs. 33 (4) VCM units, p =0.012), and LI30 (99.8 (0.5) vs. 99 (1)%, p <0.001)., Conclusions: The viscoelastic profile of FT and LP infants assessed with VCM showed a hemostatic competence characterized by accelerated coagulation and clot formation time, in line with other viscoelastic techniques. VCM system provides promising applications in the NICU setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Amelio, Raffaeli, Amodeo, Gulden, Cortesi, Manzoni, Pesenti, Ghirardello, Mosca and Cavallaro.)
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- 2022
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37. Optimizing fresh-frozen plasma transfusion in surgical neonates through thromboelastography: a quality improvement study.
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Raffaeli G, Pesenti N, Cavallaro G, Cortesi V, Manzoni F, Amelio GS, Gulden S, Napolitano L, Macchini F, Mosca F, and Ghirardello S
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- Blood Component Transfusion, Fibrinogen, Humans, Infant, Infant, Newborn, Plasma, Quality Improvement, Retrospective Studies, Blood Coagulation Disorders, Thrombelastography methods
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Fresh frozen plasma (FFP) is largely misused in the neonatal setting. The aim of the study is to evaluate the impact of a Thromboelastography (TEG)-based Quality Improvement (QI) project on perioperative FFP use and neonatal outcomes. Retrospective pre-post implementation study in a level-III NICU including all neonates undergoing major non-cardiac surgery before (01-12/2017) and after (01-12/2019) the intervention. In 2018, the intervention included the following: (1) Training on TEG, (2) Implementation of TEG, and (3) Algorithm for TEG-directed FFP administration in surgical neonates. We compared pre- vs post-intervention patient characteristics, hemostasis, and clinical management. Linear and logistic regression models were used to evaluate the impact of the project on main outcomes. We analyzed 139 neonates (pre-intervention: 72/post-intervention: 67) with a mean (± SD) gestational age (GA) 34.9 (± 5) weeks and birthweight 2265 (± 980) grams which were exposed to 184 surgical procedures (pre-intervention: 91/post-intervention: 93). Baseline characteristics were similar between periods. In 2019, prothrombin time (PT) was longer (14.3 vs 13.2 s; p < 0.05) and fibrinogen was lower (229 vs 265 mg/dl; p < 0.05), if compared to 2017. In 2019, the intraoperative exposure to FFP decreased (31% vs 60%, p < 0.001), while the pre-operative FFP use did not change. The reduction of intraoperative FFP did not impact on mortality and morbidity. Intraoperative FFP use was lower in the post-intervention even after controlling for GA, American Society of Anesthesiologists score, PT, and fibrinogen (Odds ratio: 0.167; 95% CI: 0.070, 0.371). Conclusion: The TEG-based QI project for the management of FFP during neonatal surgery reduced intraoperative FFP exposure. What is Known: • PT and aPTT are poor predictors of bleeding risk in acquired neonatal coagulopathy, leading to likely unnecessary fresh frozen plasma (FFP) transfusion in the Neonatal Intensive Care Setting. • As neonatal hemostasis is a delicate balance between the concomitant reduction of pro- and anti-coagulants drivers, thromboelastography (TEG) is a promising alternative for coagulation monitoring. What is New: • The implementation of TEG, training, and shared protocols contributed to reduced intraoperative FFP use, which was not associated with increased mortality or bleeding events. • These findings inform future research showing that there is clinical equipoise to allow for larger studies to confirm the use of TEG in NICUs and to identify TEG cut-offs for transfusion practice., (© 2022. The Author(s).)
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- 2022
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38. Recurrence of Congenital Diaphragmatic Hernia: Risk Factors, Management, and Future Perspectives.
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Macchini F, Raffaeli G, Amodeo I, Ichino M, Encinas JL, Martinez L, Wessel L, and Cavallaro G
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Recurrence is one of the most common surgical complications in Congenital Diaphragmatic Hernia (CDH). It could remain clinically silent for a long time or present as an acute complication week, months, or even years after the primary surgery. Several risk factors have been identified so far. An extended diaphragmatic defect represents one of the leading independent risk factors, together with indirect signs of large defect such as the liver position related to the diaphragm and the use of the prosthetic patch and with the use of a minimally invasive surgical (MIS) approach. However, the exact contribution of each factor and the overall risk of recurrence during the life span still need to be fully understood. This mini-review aims to give an overview of the current knowledge regarding CDH recurrence, focusing on predisposing factors, clinical presentation, management and follow-up of high-risk patients, and future perspectives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Macchini, Raffaeli, Amodeo, Ichino, Encinas, Martinez, Wessel and Cavallaro.)
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- 2022
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39. Red blood cell transfusions in preterm newborns and neurodevelopmental outcomes at 2 and 5 years of age.
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Fontana C, Raffaeli G, Pesenti N, Boggini T, Cortesi V, Manzoni F, Picciolini O, Fumagalli M, Mosca F, and Ghirardello S
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- Child, Child, Preschool, Humans, Infant, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Retrospective Studies, Anemia, Neonatal, Erythrocyte Transfusion adverse effects
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Background: Red blood cell (RBC) transfusion is often considered a life-saving measure in preterm neonates. However, it has been associated with detrimental effects on short-term morbidities and, recently, on brain development. The aim of the present study was to evaluate the association between RBC and long-term neurodevelopmental outcome in a cohort of preterm infants., Materials and Methods: This retrospective cohort study was carried out in the period 2007-2013. Preterm infants with a gestational age (GA) ≤ 32 weeks and birthweight (BW) <1,500 g were included. Infants underwent Griffiths assessment at 24±6 months corrected age (CA) and at 5±1 years of age. We used a multivariate regression model to assess the association of RBC transfusions and long-term neurodevelopment after controlling for GA, being small for GA, major neonatal morbidities, and socio-economic status. We also evaluated the impact of early RBC administration (within the first 28 days of life) compared to those performed after the first month of life., Results: We enrolled 644 preterm infants, among whom 54.3% were transfused during their stay in the neonatal intensive care unit (NICU). In infants with a longitudinal follow-up evaluation (n=360), each RBC transfusion was independently associated with a reduction in the Griffiths General Quotient (GQ) by -0.96 (p=0.002) at 24 months CA. Early RBC administration had the biggest impact, especially in children without brain lesions, where the reduction in Griffiths GQ for each additional transfusion was -2.12 (p=0.001) at 24 months CA and -1.31 (p=0.006) at 5 years of age, respectively., Discussion: In preterm infants, RBC transfusions are associated with long-term neurodevelopmental outcome, with a cumulative effect. Early RBC administration is associated with a greater reduction in Griffiths scores. The impact of RBC transfusion on neurodevelopment is greater at 24 months CA, but persists, although to a lesser degree, at 5 years of age.
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- 2022
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40. Fetal MRI mediastinal shift angle and respiratory and cardiovascular pharmacological support in newborns with congenital diaphragmatic hernia.
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Amodeo I, Borzani I, Corsani G, Pesenti N, Raffaeli G, Macchini F, Condò V, Persico N, Ghirardello S, Colnaghi M, Mosca F, and Cavallaro G
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- Female, Gestational Age, Humans, Infant, Newborn, Lung diagnostic imaging, Lung Volume Measurements, Magnetic Resonance Imaging, Pregnancy, Retrospective Studies, Ultrasonography, Prenatal, Hernias, Diaphragmatic, Congenital diagnostic imaging
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In newborns with congenital diaphragmatic hernia (CDH), the mediastinal shift caused by the herniated organs negatively affects lung development. Assessment of the fetal magnetic resonance imaging (MRI) mediastinal shift angle (MSA) was shown to have an inverse correlation with the total fetal lung volume (TFLV), being associated with neonatal survival. However, a possible association with postnatal morbidity has never been investigated. We hypothesize that the degree of the mediastinal shift could be associated with higher respiratory and cardiocirculatory impairment, requiring intensive treatments and extended hospitalization in survivors. We retrospectively consider a cohort of isolated, left-sided CDH, for whom we calculated the MSA and the observed/expected (O/E) TFLV at fetal MRI. We performed a data collection regarding inotropic or vasoactive support, treatment with pulmonary vasodilators, mechanical ventilation, and length of stay. General linear models were performed. The MSA and O/E TFLV were inversely correlated (Pearson's coefficient - 0.65, p < 0.001), and deceased patients showed higher MSA values then survivors (p = 0.011). Among survivors, an increase in MSA was associated with longer pharmacological treatments (dobutamine: p = 0.016; dopamine: p = 0.049; hydrocortisone: p = 0.003; nitric oxide: p = 0.002; sildenafil: p = 0.039; milrinone: p = 0.039; oxygen: p = 0.066), and mechanical ventilation (p = 0.005), with an increasing trend in the length of hospitalization (p = 0.089).Conclusion: The MSA indirectly reflects lung hypoplasia and is associated with a higher neonatal intensity of cares. However, further studies are needed to consolidate the results.Trial registration: The study is an exploratory post hoc analysis of the registered NeoAPACHE protocol at ClinicalTrials.gov with the identifier NCT04396028. What is Known: • In congenital diaphragmatic hernia, the lung size, liver position, and defect side are the most common prenatal prognostic parameters used in clinical practice for morbidity and mortality prediction. • Lung hypoplasia, strictly associated with lung size, is estimated by observed/expected lung to head ratio and observed/expected total fetal lung volume with prenatal ultrasound and fetal magnetic resonance imaging, respectively. What is New: • A new, faster, more straightforward, and less operator-dependent tool to assess CDH severity could be the mediastinal shift angle calculation with fetal magnetic resonance imaging. • Postnatal clinical severity, considered as a postnatal cardiovascular and respiratory impairment that indirectly reflects lung hypoplasia, is associated with an increased mediastinal shift angle calculation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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41. Selective Bronchial Occlusion for Treatment of a Bronchopleural Fistula in an Extremely Preterm Infant.
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Amelio GS, Colnaghi M, Gulden S, Raffaeli G, Cortesi V, Amodeo I, Cavallaro G, Mosca F, and Ghirardello S
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Neonatal pulmonary air leak commonly occurs as a complication of mechanical ventilation in infants with underlying hyaline membrane disease. They can commonly be managed conservatively or with the application of a chest drain, but some severe cases pose a significant challenge in finding an alternative therapeutic solution. Selective bronchial occlusion represents an unconventional rescue therapy for treating bronchopleural fistula resistant to the standard therapy. A 27-week gestation preterm infant ventilated for respiratory distress syndrome developed tension right-sided pneumothorax. Conventional modalities of treatment were tried and were unsuccessful. Intermittent selective bronchial occlusion with a Fogarty's catheter and high-frequency oscillatory ventilation resulted in considerable improvement in the infant's clinical condition and radiographic findings.
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- 2021
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42. A maChine and deep Learning Approach to predict pulmoNary hyperteNsIon in newbornS with congenital diaphragmatic Hernia (CLANNISH): Protocol for a retrospective study.
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Amodeo I, De Nunzio G, Raffaeli G, Borzani I, Griggio A, Conte L, Macchini F, Condò V, Persico N, Fabietti I, Ghirardello S, Pierro M, Tafuri B, Como G, Cascio D, Colnaghi M, Mosca F, and Cavallaro G
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Introduction: Outcome predictions of patients with congenital diaphragmatic hernia (CDH) still have some limitations in the prenatal estimate of postnatal pulmonary hypertension (PH). We propose applying Machine Learning (ML), and Deep Learning (DL) approaches to fetuses and newborns with CDH to develop forecasting models in prenatal epoch, based on the integrated analysis of clinical data, to provide neonatal PH as the first outcome and, possibly: favorable response to fetal endoscopic tracheal occlusion (FETO), need for Extracorporeal Membrane Oxygenation (ECMO), survival to ECMO, and death. Moreover, we plan to produce a (semi)automatic fetus lung segmentation system in Magnetic Resonance Imaging (MRI), which will be useful during project implementation but will also be an important tool itself to standardize lung volume measures for CDH fetuses., Methods and Analytics: Patients with isolated CDH from singleton pregnancies will be enrolled, whose prenatal checks were performed at the Fetal Surgery Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milan, Italy) from the 30th week of gestation. A retrospective data collection of clinical and radiological variables from newborns' and mothers' clinical records will be performed for eligible patients born between 01/01/2012 and 31/12/2020. The native sequences from fetal magnetic resonance imaging (MRI) will be collected. Data from different sources will be integrated and analyzed using ML and DL, and forecasting algorithms will be developed for each outcome. Methods of data augmentation and dimensionality reduction (feature selection and extraction) will be employed to increase sample size and avoid overfitting. A software system for automatic fetal lung volume segmentation in MRI based on the DL 3D U-NET approach will also be developed., Ethics and Dissemination: This retrospective study received approval from the local ethics committee (Milan Area 2, Italy). The development of predictive models in CDH outcomes will provide a key contribution in disease prediction, early targeted interventions, and personalized management, with an overall improvement in care quality, resource allocation, healthcare, and family savings. Our findings will be validated in a future prospective multicenter cohort study., Registration: The study was registered at ClinicalTrials.gov with the identifier NCT04609163., Competing Interests: The authors have declared that no competing interests exist.
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- 2021
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43. Individualized Bleeding Risk Assessment through Thromboelastography: A Case Report of May-Hegglin Anomaly in Preterm Twin Neonates.
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Amodeo I, Raffaeli G, Vianello F, Cavallaro G, Cortesi V, Manzoni F, Amelio GS, Gulden S, Mosca F, and Ghirardello S
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May-Hegglin anomaly (MHA) is a rare autosomal dominant disorder in the spectrum of myosin heavy chain-related disorders (MYH9-RD), characterized by congenital macrothrombocytopenia and white blood cell inclusions. MHA carries a potential risk of hemorrhagic complications. Bleeding diathesis is usually mild, but sporadic, life-threatening events have been reported. Data regarding the clinical course and outcomes of neonatal MYH9-RD are limited, and specific guidelines on platelet transfusion in asymptomatic patients are lacking. We present monochorionic twins born preterm at 32 weeks of gestation to an MHA mother; both presented with severe thrombocytopenia at birth. Peripheral blood smear demonstrated the presence of macrothrombocytes, and immunofluorescence confirmed the diagnosis of MHA. Close clinical monitoring excluded bleeding complications, and serial hemostatic assessments through a viscoelastic system demonstrated functionally normal primary hemostasis in both patients. Therefore, prophylactic platelet transfusions were avoided. Whole DNA sequencing confirmed the pathogenetic variant of MHA of maternal origin in both twins. Thromboelastography allowed real-time bedside bleeding risk assessment and supported individualized transfusion management in preterm newborns at risk of hemostatic impairment. This report suggests that dynamic and appropriate clotting monitoring may contribute to the more rational use of platelets' transfusions while preserving patients with hemorrhagic complications and potential transfusion-related side effects.
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- 2021
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44. When the unexpected happens: intracardiac extracorporeal membrane oxygenation venous cannula kinking.
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Mayer A, Macchini F, Raffaeli G, Ghirardello S, Schena F, Amodeo I, Mauri L, Baracetti C, Parente V, Carro C, Mosca F, and Cavallaro G
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- Cannula, Catheterization, Heart, Humans, Veins, Extracorporeal Membrane Oxygenation
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- 2021
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45. Variations in Antibiotic Use and Sepsis Management in Neonatal Intensive Care Units: A European Survey.
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Garrido F, Allegaert K, Arribas C, Villamor E, Raffaeli G, Paniagua M, Cavallaro G, and On Behalf Of European Antibiotics Study Group Easg
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Management of neonatal sepsis and the use of antimicrobials have an important impact on morbidity and mortality. However, there is no recent background on which antibiotic regimens are used in different European neonatal intensive care units (NICUs). Our study aimed to describe the use of antibiotics and other aspects of early- and late-onset sepsis (EOS and LOS, respectively) management by European NICUs. We conducted an online survey among NICUs throughout Europe to collect information about antibiotic stewardship, antibiotic regimens, and general aspects of managing neonatal infections. NICUs from up to 38 European countries responded, with 271 valid responses. Most units had written clinical guidelines for EOS (92.2%) and LOS (81.1%) management. For EOS, ampicillin, penicillin, gentamicin, and amikacin were the most commonly used antibiotics. Analysis of the combinations of EOS regimens showed that the most frequently used was ampicillin plus gentamicin (54.6%). For LOS, the most frequently used antibiotics were vancomycin (52.4%), gentamicin (33.9%), cefotaxime (28%), and meropenem (15.5%). Other aspects of the general management of sepsis have also been analyzed. The management of neonatal sepsis in European NICUs is diverse. There was high self-reported adherence to the local clinical guidelines. There was homogeneity in the combination of antibiotics in EOS but less in LOS.
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- 2021
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46. Severe Presentation of Congenital Hemolytic Anemias in the Neonatal Age: Diagnostic and Therapeutic Issues.
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Cortesi V, Manzoni F, Raffaeli G, Cavallaro G, Fattizzo B, Amelio GS, Gulden S, Amodeo I, Giannotta JA, Mosca F, and Ghirardello S
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Congenital hemolytic anemias (CHAs) are a group of diseases characterized by premature destruction of erythrocytes as a consequence of intrinsic red blood cells abnormalities. Suggestive features of CHAs are anemia and hemolysis, with high reticulocyte count, unconjugated hyperbilirubinemia, increased lactate dehydrogenase (LDH), and reduced haptoglobin. The peripheral blood smear can help the differential diagnosis. In this review, we discuss the clinical management of severe CHAs presenting early on in the neonatal period. Appropriate knowledge and a high index of suspicion are crucial for a timely differential diagnosis and management. Here, we provide an overview of the most common conditions, such as glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and hereditary spherocytosis. Although rare, congenital dyserythropoietic anemias are included as they may be suspected in early life, while hemoglobinopathies will not be discussed, as they usually manifest at a later age, when fetal hemoglobin (HbF) is replaced by the adult form (HbA).
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- 2021
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47. NeoAPACHE II. Relationship Between Radiographic Pulmonary Area and Pulmonary Hypertension, Mortality, and Hernia Recurrence in Newborns With CDH.
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Amodeo I, Pesenti N, Raffaeli G, Macchini F, Condò V, Borzani I, Persico N, Fabietti I, Bischetti G, Colli AM, Ghirardello S, Gangi S, Colnaghi M, Mosca F, and Cavallaro G
- Abstract
Congenital diaphragmatic hernia is a rare disease with high mortality and morbidity due to pulmonary hypoplasia and pulmonary hypertension. The aim of the study is to investigate the relationship between radiographic lung area and systolic pulmonary artery pressure (sPAP) on the first day of life, mortality, and hernia recurrence during the first year of life in infants with a congenital diaphragmatic hernia (CDH). A retrospective data collection was performed on 77 CDH newborns. Echocardiographic sPAP value, deaths, and recurrence cases were recorded. Lung area was calculated by tracing the lung's perimeter, excluding mediastinal structures, and herniated organs, on the preoperative chest X-ray performed within 24 h after birth. Logistic and linear regression analyses were performed. Deceased infants showed lower areas and higher sPAP values. One square centimeter of rising in the total, ipsilateral, and contralateral area was associated with a 22, 43, and 24% reduction in mortality risk. sPAP values showed a decreasing trend after birth, with a maximum of 1.84 mmHg reduction per unitary increment in the ipsilateral area at birth. Recurrence patients showed lower areas, with recurrence risk decreasing by 14 and 29% per unit increment of the total and ipsilateral area. In CDH patients, low lung area at birth reflects impaired lung development and defect size, being associated with increased sPAP values, mortality, and recurrence risk. Clinical Trial Registration: The manuscript is an exploratory secondary analysis of the trial registered at ClinicalTrials.gov with identifier NCT04396028., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Amodeo, Pesenti, Raffaeli, Macchini, Condò, Borzani, Persico, Fabietti, Bischetti, Colli, Ghirardello, Gangi, Colnaghi, Mosca and Cavallaro.)
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- 2021
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48. Neonatal respiratory and cardiac ECMO in Europe.
- Author
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Amodeo I, Di Nardo M, Raffaeli G, Kamel S, Macchini F, Amodeo A, Mosca F, and Cavallaro G
- Subjects
- Europe epidemiology, Humans, Infant, Newborn, Survival Rate, Extracorporeal Membrane Oxygenation, Hernias, Diaphragmatic, Congenital therapy, Respiratory Insufficiency etiology, Respiratory Insufficiency therapy
- Abstract
Neonatal extracorporeal membrane oxygenation (ECMO) is a life-saving procedure for critically ill neonates suffering from a potentially reversible disease, causing severe cardiac and/or respiratory failure and refractory to maximal conventional management. Since the 1970s, technology, management, and clinical applications of neonatal ECMO have changed. Pulmonary diseases still represent the principal neonatal diagnosis, with an overall 74% survival rate, and up to one-third of cases are due to congenital diaphragmatic hernia. The overall survival rate in cardiac ECMO is lower, with congenital heart defect representing the main indication. This review provides an overview of the available evidence in the field of neonatal ECMO. We will address the changing epidemiology, basic principles, technologic advances in circuitry, and monitoring, and deliver a current multidisciplinary management framework, focusing on ECMO applications, complications, and long-term morbidities. Lastly, areas for further research will be highlighted.Conclusions: ECMO is a life support with a potential impact on long-term patients' outcomes. In the next years, advances in knowledge, technology, and expertise may push neonatal ECMO boundaries towards more premature and increasingly complex infants, with the final aim to reduce the burden of ECMO-related complications and improve overall patients' outcomes. What is Known: • ECMO is a life-saving option in newborns with refractory respiratory and/or cardiac failure. • The multidisciplinary ECMO management is challenging and may expose neonates to complications with an impact on long-term outcomes. What is New: • Advances in technology and biomaterials will improve neonatal ECMO management and, eventually, the long-term outcome of these complex patients. • Experimental models of artificial placenta and womb technology are under investigation and may provide clinical translation and future research opportunities.
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- 2021
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49. In Reply to: A Risk Score for Predicting the Incidence of Hemorrhage in Critically Ill Neonates: Development and Validation Study.
- Author
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Ghirardello S, Raffaeli G, and Mosca F
- Subjects
- Humans, Incidence, Infant, Newborn, Risk Factors, Critical Illness, Hemorrhage diagnosis, Hemorrhage epidemiology
- Abstract
Competing Interests: None declared.
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- 2021
- Full Text
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50. Plasma Amino Acid Concentrations at Birth and Patent Ductus Arteriosus in Very and Extremely Preterm Infants.
- Author
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Huizing MJ, Borges-Luján M, Cavallaro G, González-Luis GE, Raffaeli G, Bas-Suárez P, Bakker JA, Moonen RM, and Villamor E
- Abstract
Background: Amino acids are increasingly recognized as bioactive molecules in numerous physiological and pathophysiological pathways. The non-essential amino acid glutamate is vasoactive in the rat ductus arteriosus (DA) and a decrease in its levels within the 1st days of life has been associated with the presence of patent DA (PDA) in extremely preterm infants. However, these findings have not been confirmed in other studies. Objective: To investigate the possible association between amino acid concentrations in the 1st day of life and the presence of PDA in a cohort of 121 newborns with gestational age (GA) below 30 weeks and birth weight (BW) below 1,500 g. Methods: Plasma samples were collected 6-12 h after birth and amino acid concentrations were determined by tandem mass spectrometry. Besides PDA, we analyzed the potential association of amino acid concentrations with infant sex, small for GA (SGA, defined as BW < third percentile), antenatal corticosteroids, chorioamnionitis, and preeclampsia. Group differences were analyzed by ANOVA adjusted for GA and BW. A Bonferroni significance threshold of P < 0.0024 was used to correct for multiple testing. Results: PDA was found in 48 of the 121 infants examined. We observed higher mean levels of glutamate in infants with PDA (147.0 μmol/L, SD 84.0) as compared with those without (106.7 μmol/L, SD 49.1, P = 0.0006). None of the other amino acid concentrations in the PDA group reached the level of statistical significance that was pre-set to correct for multiple comparisons. Glutamate levels were not significantly affected by infant sex, being SGA, or by exposure to antenatal corticosteroids, clinical chorioamnionitis, or preeclampsia. Conclusion: Our study not only does not confirm the previous findings of low glutamate levels in preterm infants with PDA, but we have even found elevated glutamate concentrations associated with PDA. Nevertheless, despite the high statistical significance, the difference in glutamate levels may lack clinical significance or may be an epiphenomenon associated with the particular clinical condition of infants with PDA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huizing, Borges-Luján, Cavallaro, González-Luis, Raffaeli, Bas-Suárez, Bakker, Moonen and Villamor.)
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- 2021
- Full Text
- View/download PDF
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