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BACKGROUND: Diaphragm dysfunction is associated with poor outcomes in critically ill patients. Ventilator-induced diaphragmatic dysfunction (VIDD), including diaphragm atrophy (DA), is poorly studied in newborns. We aimed to assess VIDD and its associations in newborns. METHODS: Single-center prospective study. Diaphragm thickness was measured at end-inspiration (TDI) and end-expiration (TDE) on the right midaxillary line. DA was defined as decrease in TDE ≥ 10%. Daily measurements were recorded in preterm newborns on invasive mechanical ventilation (IMV) for ≥2 days. Clinical characteristics of patients and extubation failure were recorded. Univariate analysis, logistic regression, and mixed models were performed to describe VIDD and associated factors. RESULTS: We studied 17 patients (median gestational age 270/7 weeks) and 22 IMV cycles (median duration 9 days). Median TDE decreased from 0.118 cm (interquartile range [IQR] 0.094-0.165) on the first IMV day to 0.104 cm (IQR 0.083-0.120) on the last IMV day (p = .092). DA occurred in 11 IMV cycles (50%) from 10 infants early during IMV (median: second IMV day). Mean airway pressure (MAP) and lung ultrasound score (LUS) on the first IMV day were significantly higher in patients who developed DA. DA was more frequent in patients with extubation failure than in those with extubation success within 7 days (83.3 vs. 33.3%, p = .038). CONCLUSIONS: DA, significantly associated with extubation failure, occurred in 58.8% of the study infants on IMV. Higher MAP and LUS at IMV start were associated with DA. Our results suggest a potential role of diaphragm ultrasound to assess DA and predict extubation failure in clinical practice.
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Respiración Artificial , Desconexión del Ventilador , Lactante , Humanos , Recién Nacido , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Desconexión del Ventilador/métodos , Estudios Prospectivos , Diafragma/diagnóstico por imagen , Extubación Traqueal/efectos adversos , Extubación Traqueal/métodos , Recien Nacido Prematuro , Atrofia/patologíaRESUMEN
OBJECTIVES: To describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy. METHODS: This is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves. RESULTS: Among 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age <37 weeks) was significantly higher in the first and third waves (15.6-12.5%). The risk of intrauterine transmission was always very low, while the risk of postnatal transmission during rooming-in was higher and peaked at 4.5% during the fourth wave. A total of 80% of positive neonates were asymptomatic. CONCLUSION: The risk of adverse maternal and neonatal outcomes was significantly higher during the first and third waves, dominated by unsequenced variants and the Delta variant, respectively. Postnatal transmission accounted for most neonatal infections and was more frequent during the Omicron period. However, the paucity of symptoms in infected neonates should lead us not to separate the dyad.
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COVID-19 , Neonatología , Complicaciones Infecciosas del Embarazo , Recién Nacido , Femenino , Embarazo , Humanos , Lactante , SARS-CoV-2 , COVID-19/epidemiología , Pandemias , Estudios Prospectivos , Estudios de Cohortes , Transmisión Vertical de Enfermedad Infecciosa , Italia/epidemiología , Madres , Complicaciones Infecciosas del Embarazo/epidemiologíaRESUMEN
BACKGROUND: The present study was designed to assess the feasibility and reliability of a Continuous Glucose Monitoring System (CGMS) in a population of asphyxiated neonates during therapeutic hypothermia. METHODS: This non-randomized feasibility study was conducted in the Neonatal Intensive Care Unit (NICU) facilities of Fondazione Policlinico A. Gemelli IRCSS. Infants matching the criteria for hypothermic treatment were included in this study and were connected to the CGMS (Medtronic, Northridge, CA, USA) within the first 12 h of life. Hypoglycemia was defined as a glucose value ≤ 47 mg/dL, and hyperglycemia was defined as a glucose value ≥ 180 mg/dL. Data obtained via the CGMS were compared with those obtained via a point-of-care blood glucometer (GTX). RESULTS: The two measuring techniques were compared using the Modified Clarke Error Grid (MCEG). Sixteen infants were enrolled. The sensor had an average (standard deviation) duration of 93 (38) h. We collected 119 pairs of glycemia values (CGMVs) from the CGMS vs. GTX measurements. The CGMS detected twenty-five episodes of hypoglycemia and three episodes of hyperglycemia. All the CGMVs indicating hyperglycemia matched with the blood sample taken via the point-of-care glucometer. CONCLUSIONS: The use of a CGMS would be useful as it could detect more episodes of disglycemia than standard care. Our data show poor results in terms of the accuracy of the CGMS in this particular setting.
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INTRODUCTION: We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery to evaluate acute and mid-term multidisciplinary outcomes. METHODS: Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48-72 h of life, auxological and ophthalmological assessments, and serologic testing. RESULTS: 791 women and their 791 children (52.3% males) were included. Most placentas (94.9%) had abnormal inflammatory findings. 171 (27.3%) and 36 (13.7%) children respectively had pathological TEOAEs in at least one ear and bilaterally, while only four of the 85 children that underwent ABR had pathological findings (4.7%). 64 children underwent fluorescein angiography, which resulted pathological only in 1 case (1.6%). Anti-SARS-CoV-2 IgGs were found in up to 60% of children tested at six months of age. Our findings showed no association between the maternal vaccination status or the presence of maternal symptoms during pregnancy and neonatal outcomes. CONCLUSIONS: Our study shows that the large majority of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life have optimal outcomes. Our previous report of abnormal ophthalmologic findings was not confirmed on a larger cohort, while further studies are needed to better characterize audiological outcomes. Further prospective, case-controlled studies are still needed.
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BACKGROUND: Artificial intelligence (AI) is a promising field in the neonatal field. We focused on lung ultrasound (LU), a useful tool for the neonatologist. Our aim was to train a neural network to create a model able to interpret LU. METHODS: Our multicentric, prospective study included newborns with gestational age (GA) ≥ 33 + 0 weeks with early tachypnea/dyspnea/oxygen requirements. For each baby, three LU were performed: within 3 h of life (T0), at 4-6 h of life (T1), and in the absence of respiratory support (T2). Each scan was processed to extract the region of interest used to train a neural network to classify it according to the LU score (LUS). We assessed sensitivity, specificity, positive and negative predictive value of the AI model's scores in predicting the need for respiratory assistance with nasal continuous positive airway pressure and for surfactant, compared to an already studied and established LUS. RESULTS: We enrolled 62 newborns (GA = 36 ± 2 weeks). In the prediction of the need for CPAP, we found a cutoff of 6 (at T0) and 5 (at T1) for both the neonatal lung ultrasound score (nLUS) and AI score (AUROC 0.88 for T0 AI model, 0.80 for T1 AI model). For the outcome "need for surfactant therapy", results in terms of area under receiver operator characteristic (AUROC) are 0.84 for T0 AI model and 0.89 for T1 AI model. In the prediction of surfactant therapy, we found a cutoff of 9 for both scores at T0, at T1 the nLUS cutoff was 6, while the AI's one was 5. Classification accuracy was good both at the image and class levels. CONCLUSIONS: This is, to our knowledge, the first attempt to use an AI model to interpret early neonatal LUS and can be extremely useful for neonatologists in the clinical setting.
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Enfermedades del Recién Nacido , Neumonía , Surfactantes Pulmonares , Síndrome de Dificultad Respiratoria del Recién Nacido , Recién Nacido , Humanos , Lactante , Estudios Prospectivos , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Inteligencia Artificial , Pulmón/diagnóstico por imagen , Surfactantes Pulmonares/uso terapéutico , Ultrasonografía , Neumonía/tratamiento farmacológico , TensoactivosAsunto(s)
Neonatología , Surfactantes Pulmonares , Síndrome de Dificultad Respiratoria del Recién Nacido , Humanos , Recién Nacido , Tensoactivos/uso terapéutico , Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Unidades de Cuidado Intensivo NeonatalRESUMEN
Respiratory distress (RD) is one of the most common causes of admission to the neonatal intensive care unit. Correct diagnosis and timely intervention are crucial. Lung ultrasonography (LU) is a useful diagnostic tool for the neonatologist in the diagnosis of RD; the neonatal lung ultrasonography score (nLUS) can be used in the diagnostic process, but some authors hypothesise that it is also useful for the management of some neonatal RD. The aim of this study is to analyse the changes in nLUS score before (T0) and after (T1) the start of respiratory support with nasal CPAP in neonates over 32 weeks of age with RD. Thirty-three newborns were enrolled in this retrospective study. LU was performed before and after the start of CPAP. The median nLUS scores at T0 and T1 were 9 (IQR 7−12) and 7 (IQR 4−10), respectively, and showed a significant difference (p < 0.001). The magnitude of reduction in nLUS score, expressed as a percentage, was inversely related to the need for subsequent administration of exogenous surfactant. The study suggests the usefulness of the nLUS score in assessing the response to CPAP in neonates over 32 weeks gestational age.
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OBJECTIVE: To propose an early lung ultrasound (LUS) score for the prediction of the need for respiratory assistance in newborns of gestational age (GA) ≥ 33 weeks presenting respiratory distress. STUDY DESIGN AND SETTING: Multicenter, prospective observational study in third-level neonatal intensive care units. PATIENT SELECTION: Infants with GA ≥ 33 + 0 weeks with respiratory distress within 3 h of life. METHODS: Three LUS for each patient were collected: within 3 h of life (T0), at 4-6 h of life (T1), and at the resolution of symptoms (T2). The primary aim was to assess the validity of the early LUS score in predicting the need for continuous positive airway pressure (CPAP). We also evaluated the validity of the score in predicting the need for surfactant, the scores' trend in our population, and any correlation with the duration of ventilation and oxygen therapy. RESULTS: Sixty-two patients were enrolled in the study. The mean GA was 36 weeks. The receiver operating characteristic analysis for the LUS T0 and T1 yielded area under the curves of 0.91 and 0.82 in predicting the need for CPAP, respectively. LUS score cut off of 6 (sensitivity 84.8%, specificity 86.2%) and 5 (sensitivity 66.7%, specificity 100%) were calculated at T0 and T1, respectively. We found significant correlations between LUS score and respiratory assistance, surfactant administration, and SpO2 /FiO2 ratio. CONCLUSION: An early LUS score is a good noninvasive predictor of the need for respiratory assistance with CPAP and surfactant administration in newborns with GA ≥ 33 weeks.
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Ventilación no Invasiva , Surfactantes Pulmonares , Síndrome de Dificultad Respiratoria del Recién Nacido , Edad Gestacional , Humanos , Lactante , Recién Nacido , Pulmón/diagnóstico por imagen , Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico por imagen , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Tensoactivos , UltrasonografíaRESUMEN
OBJECTIVE: The extent of vertical transmission (VT) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from mothers their fetuses or neonates is still uncertain. We aimed to determine the incidence of VT. STUDY DESIGN: In this prospective cohort study. All mother diagnosed with SARS-CoV-2 infection at the time of delivery or up to 1 week prior and their neonates, managed in a tertiary referral hospital for pregnancy complicated by coronavirus disease 2019 (COVID-19) in Rome, from April 2 to December 22, 2020, were included. Maternal infection was defined as nasopharyngeal swab test results positive for SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR). Biological samples were collected before, at, and after delivery to test positivity for SARS-CoV-2 RT-PCR and anti-SARS-CoV-2-specific antibodies. RESULTS: The cohort included 95 women and 96 neonates with documented SARS-CoV-2 test results. Four neonates (4.2%) tested positive. The incidence of VT, according to the guidance criteria for diagnosing perinatal SARS-CoV-2 infection, was 5.2%. Neonatal symptoms were due to prematurity or fetal distress: symptomatic infants had lower median (min-max) gestational age, 38.1 (29.3-40.6) versus 39.3 (33.9-41.9) weeks (p = 0.036), and 1-minute and 5-minute Apgar scores, 9 (3-9) versus 9 (7-10) (p = 0.036) and 10 (6-10) versus 10 (8-10) (p = 0.012), respectively, than asymptomatic infants and needed more frequent assistance in the delivery room (22.2 vs 2.5%; p = 0.008). Only six (7.1%) neonates had anti-SARS-CoV-2-specific antibodies, despite the ongoing maternal infection. CONCLUSION: The incidence of VT is low as is the detection of specific anti-SARS-CoV-2 antibodies in cord blood when infection is contracted late in pregnancy. This would suggest poor protection of infants against horizontal transmission of the virus. KEY POINTS: · VT of SARS-CoV-2 from pregnant mothers to fetuses or neonates can be possible.. · In this prospective cohort study, the incidence of VT is found to be 5.2%.. · VT is low but exists..
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BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic emerged in December 2019 and spread rapidly worldwide. So far, evidence regarding the breastfeeding and rooming-in management of mothers with COVID-19 and their newborn infants is scarce. RESEARCH AIMS: 1) To assess the rate of exclusive breastfeeding at discharge among mothers with COVID-19 and their newborn infants managed either using a rooming-in or a separation regimen; and 2) to evaluate different neonatal outcomes, including the need for re-hospitalization related to COVID-19 among newborn infants in the two groups. METHOD: We conducted a retrospective two-group comparative observational study. The sample was participants with COVID-19 and their newborn infants (N = 155 dyads) between March 1, 2020, and April 30, 2021. Two time periods were outlined resulting from the two different clinical practices of mother-infant separation and rooming-in. RESULTS: Within the sample, 145 (93.5%) were asymptomatic. All neonates had documented Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test results, and six tested positive by reverse transcriptase polymerase chain reaction within 48 hr of life. The rate of exclusive breastfeeding was significantly higher (p < .0001) within the rooming-in group. Length of hospital stay was significantly lower (p = .001) within the rooming-in group. CONCLUSIONS: Protected rooming-in practice has proven to be safe and effective in supporting breastfeeding: None of the infants enrolled were hospitalized due to COVID-19 infection and the rate of exclusive breastfeeding at discharge was increased compared to those infants separated from their mothers.
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COVID-19 , Pandemias , Lactancia Materna , COVID-19/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Pandemias/prevención & control , Estudios Retrospectivos , SARS-CoV-2RESUMEN
The long-term outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are still unknown. We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery. Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48-72 h of life, auxological growth and neurological development, serologic testing, and audiological and ophthalmological assessments. One-hundred ninety-eight mothers and 199 newborns were enrolled. Of the 199 newborns, 171 underwent nasopharyngeal swab, four (2.3%) and two (1.15%) children tested positive at birth and 48-72 h of life, respectively. None had SARS-CoV-2 related symptoms. Auxologic and neurologic development were normal in all children during follow-up. Nine out of 59 infants had SARS-CoV-2 IgG at 3 months of life, which was associated with a positive nasopharyngeal swab at birth (P = 0.04). Twenty seven out of 143 (18.8%) newborns had pathologic transitory evoked otoacoustic emissions at birth, although 14/27 repeated after 1 month were normal. Audiological evaluation was completed with Auditory Brainstem Response between the third and sixth month of life in 34 children, showing in all normal hearing threshold. The ophthalmological evaluation found retinal vascular anomalies in 3/20 (15%) children, immature visual acuity in 5/20 (25%) children, and reduced distance attention in 6/20 cases (30%). CONCLUSIONS: Our study showed that the neonatal and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are mostly positive, with the exception of ophthalmologic findings which, in a preliminary cohort, were abnormal in about 15% of cases. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of children exposed to SARS-CoV-2 in utero and in the early postnatal life. WHAT IS KNOWN: ⢠In utero mother-to-child transmission of SARS-CoV-2 has been documented by several independent studies. ⢠Neonatal COVID-19 is a systemic disease that can be severe, although rarely. WHAT IS NEW: ⢠Newborns exposed in utero to SARS-CoV-2 have mostly a normal auxological, audiological, and neurological development during the first months of life. ⢠Fundus fluorescein angiography revealed that up to 5% of newborns exposed in utero to SARS-CoV2 can show retinal and choroidal abnormalities, including peripheral hypofluorescence of the choroid and increased vascular tortuosity.
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COVID-19 , Complicaciones Infecciosas del Embarazo , COVID-19/diagnóstico , COVID-19/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , ARN Viral , SARS-CoV-2RESUMEN
OBJECTIVE: To evaluate the efficacy of a strict glycaemic control protocol using a continuous glucose monitoring (CGM) in infants at high risk of dysglycaemia with the aim of reducing the number of dysglycaemic episodes. DESIGN: Randomised controlled trial. SETTING: Neonatal intensive care unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome. PATIENTS: All infants <1500 g fed on parental nutrition (PN) since birth were eligible. A total of 63 infants were eligible and 48 were randomised. INTERVENTION: All participants wore a CGM sensor and were randomised in two arms with alarms set at different cut-off values (2.61-10 mmol/L (47-180 mg/dL) vs 3.44-7.78 mmol/L (62-140 mg/dL)), representing the operative threshold requiring modulation of glucose infusion rate according to an innovative protocol. MAIN OUTCOME MEASURES: The primary outcome was the number of severe dysglycaemic episodes (<2.61 mmol/L (47 mg/dL) or >10 mmol/L (180 mg/dL)) in the intervention group versus the control group, during the monitoring time. RESULTS: We enrolled 47 infants, with similar characteristics between the two arms. The number of dysglycaemic episodes and of infants with at least one episode of dysglycaemia was significantly lower in the intervention group (strict group): respectively, 1 (IQR 0-2) vs 3 (IQR 1-7); (p=0.005) and 12 (52%) vs 20 (83%); p=0.047. Infants managed using the strict protocol had a higher probability of having normal glycaemic values: relative risk 2.87 (95% CI 1.1 to 7.3). They spent more time in euglycaemia: 100% (IQR 97-100) vs 98% (IQR 94-99), p=0.036. The number needed to treat to avoid dysglycaemia episodes is 3.2 (95% CI 1.8 to 16.6). CONCLUSION: We provide evidence that CGM, combined with a protocol for adjusting glucose infusion, can effectively reduce the episodes of dysglycaemia and increase the percentage of time spent in euglycaemia in very low birthweight infants receiving PN in the first week of life.
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Control Glucémico , Recién Nacido de muy Bajo Peso/sangre , Monitoreo Fisiológico/métodos , Glucosa/administración & dosificación , Humanos , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Recién Nacido , Infusiones Intravenosas , Unidades de Cuidado Intensivo Neonatal , Factores de RiesgoRESUMEN
OBJECTIVE: To assess changes in neonatal lung ultrasonography score (nLUS) after surfactant administration in preterm infants with respiratory distress syndrome (RDS). WORKING HYPOTHESIS: The reduction of nLUS score before (nLUSpre), 2 hours (nLUS2h), and 12 hours (nLUS12h) after surfactant administration to identify patients who will not need a second treatment. STUDY DESIGN AND SETTING: Prospective observational study in the tertiary neonatal intensive care unit. PATIENTS SELECTION: Forty-six preterm neonates with RDS of 32 weeks median gestational age (IQR 30-33) and mean birth weight of 1650 ± 715 g. METHODOLOGY: Lung ultrasonography was performed before, 2 hours, and 12 hours after surfactant administration in preterm infants with RDS needing surfactant treatment. Resulting nLUS was analyzed. RESULTS: The Wilcoxon signed-rank test demonstrated an nLUS lowering after 2 hours (P < .001) and 12 hours (P < .001) from surfactant administration. Sixteen newborns required surfactant retreatment with median gestational age of 32 weeks (IQR 29-33) and mean birth weight of 1519 ± 506 g.The receiver operating characteristic analysis for the nLUS2h yielded an area under the curve of 0.80 (95% confidence interval, 0.76-0.85; P < .001). A nLUS2h ≥7 showed a sensitivity of 94% and a specificity of 60% for needing a second treatment with surfactant. CONCLUSIONS: In preterm infants with RDS requiring surfactant treatment, nLUS evaluated 2 hours after surfactant administration can be used to identify patients who will not need a second treatment.
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Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico por imagen , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Estudios Prospectivos , Curva ROC , UltrasonografíaRESUMEN
BACKGROUND: Continuous glucose monitoring using subcutaneous sensors is useful in the management of glucose control in neonatal intensive care. We evaluated feasibility and reliability of a continuous glucose monitoring system in a population of very low birth weight neonates needing parenteral nutrition. Moreover, we presented percentiles of glycemia of the studied population. METHODS: Very low birth weight neonates were enrolled within 24 h from birth. An ENLITE sensor connected to a continuous glucose monitoring system was inserted and maintained for at least 72 h. Data obtained with the continuous glucose monitoring system and with a glucometer were compared. Calibration was performed every 12 h. RESULTS: Twenty-three patients (9 males) were included. Median gestational age was 28 weeks (range 23-30) and median birth weight was 860 g (range 500-1092). A total of 299 paired glucose values were obtained. Modified Clarke Error Grid criteria for clinical significance were met. 74 and 33 episodes of hypoglycemia and hyperglycemia were detected, respectively. 31,329 values of glycemia were analyzed and the percentiles calculated. CONCLUSIONS: This continuous glucose monitoring system is safe and accurate. It allows increasing the detection of hypo- and hyper-glycaemia episodes and it could be routinely used in the management of glucose infusion in very low birth weight neonates under total parenteral nutrition.
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Glucemia/análisis , Hiperglucemia/diagnóstico , Hipoglucemia/diagnóstico , Monitoreo Fisiológico/instrumentación , Nutrición Parenteral/métodos , Estudios de Cohortes , Bases de Datos Factuales , Estudios de Factibilidad , Femenino , Edad Gestacional , Humanos , Hiperglucemia/mortalidad , Hiperglucemia/terapia , Hipoglucemia/mortalidad , Hipoglucemia/terapia , Recién Nacido , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Masculino , Monitoreo Fisiológico/métodos , Pronóstico , Reproducibilidad de los Resultados , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
Membrane fission is an essential cellular process by which continuous membranes split into separate parts. We have previously identified CtBP1-S/BARS (BARS) as a key component of a protein complex that is required for fission of several endomembranes, including basolateral post-Golgi transport carriers. Assembly of this complex occurs at the Golgi apparatus, where BARS binds to the phosphoinositide kinase PI4KIIIß through a 14-3-3γ dimer, as well as to ARF and the PKD and PAK kinases. We now report that, when incorporated into this complex, BARS binds to and activates a trans-Golgi lysophosphatidic acid (LPA) acyltransferase type δ (LPAATδ) that converts LPA into phosphatidic acid (PA); and that this reaction is essential for fission of the carriers. LPA and PA have unique biophysical properties, and their interconversion might facilitate the fission process either directly or indirectly (via recruitment of proteins that bind to PA, including BARS itself).
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Aciltransferasas/metabolismo , Oxidorreductasas de Alcohol/metabolismo , Citocinesis/fisiología , Proteínas de Unión al ADN/metabolismo , Aparato de Golgi/metabolismo , Membranas Intracelulares/metabolismo , Proteínas 14-3-3/metabolismo , Células HeLa , Humanos , Lisofosfolípidos/metabolismo , Ácidos Fosfatidicos/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Proteína Quinasa C/metabolismo , Quinasas p21 Activadas/metabolismoRESUMEN
PURPOSE: The incidence and management of antitumoral compound extravasation that occurred in our medical day hospital unit were registered in a 10-year period. METHODS: A total of 114 episodes were consecutively recorded out of an estimated number of 211,948 administrations performed (0.05%). Type of compound, localization, timing, symptoms, treatment, resolution, or sequelae were documented. RESULTS: Extravasations after anthracyclines (17/114), platinum compounds (34/114), vinca alkaloids (7/114), and taxanes (34/114) were more frequently associated with edema and erythema ± pain. Five cases of monoclonal antibodies extravasation were observed without sequelae. With the involvement of an interdisciplinary task force and the use of dedicated guidelines, conservative management was successful in all patients. In the great majority of cases, recovery was complete within 48 hours after antidote administration. The support of our pharmacy was crucial. Physiatric evaluation was considered in several cases. No patients required surgery. CONCLUSIONS: We confirm that the adopted standardized approach to this event resulted in a satisfactory outcome and could be suggested as appropriate for managing extravasation in a large clinical context.
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Antídotos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Tratamiento Conservador/métodos , Extravasación de Materiales Terapéuticos y Diagnósticos/complicaciones , Inflamación/inducido químicamente , Inflamación/terapia , Tejido Subcutáneo/efectos de los fármacos , Úlcera/terapia , Adulto , Anciano , Antraciclinas/administración & dosificación , Antraciclinas/efectos adversos , Vesícula/inducido químicamente , Vesícula/terapia , Tratamiento Conservador/normas , Edema/inducido químicamente , Edema/terapia , Eritema/inducido químicamente , Eritema/terapia , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Dolor/inducido químicamente , Manejo del Dolor/métodos , Compuestos de Platino/administración & dosificación , Compuestos de Platino/efectos adversos , Factores de Riesgo , Tejido Subcutáneo/lesiones , Tejido Subcutáneo/patología , Taxoides/administración & dosificación , Taxoides/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Úlcera/inducido químicamente , Alcaloides de la Vinca/administración & dosificación , Alcaloides de la Vinca/efectos adversosRESUMEN
OBJECTIVE: To measure cerebral regional oxygen saturation (CrSO2), renal regional oxygenation saturation (RrSO2) and mesenteric tissue regional oxygen saturation (MrSO2) during immediate transition and continuously for the first 9 hours of age. Fractional tissue oxygen extraction of the brain (CtFOE), kidneys (RtFOE), splanchnic tissue (MtFOE) were also assessed. STUDY DESIGN: Prospective, observational study of 61 term infants, delivered by elective caesarean section. Using near-infrared spectroscopy, changes in CrSO2, RrSO2, MrSO2 and changes in CtFOE, RtFOE and MtFOE were measured all through the first 9 hours of life. All the episodes of feeding during this period were recorded. RESULTS: Mean CrSO2 increased quickly to 7 minutes, with no further changes. On the other hand, mean RrSO2 and mean MrSO2 increased for 10 minutes and thereafter they remained on their newly reached level. RrSO2 and MrSO2 were significantly lower at 3-4-5-6-7 minutes of life compared to the CrSO2 (p<0.05). RtFOE and MtFOE were significantly higher at 3-4-5-6-7 minutes of life compared to the CtFOE (p<0.05). During feeding, CrSO2, RrSO2 and MrSO2 did not significantly change. CONCLUSIONS: During early adaptive period, oxygen delivery is preserved to 'vital' organs, like brain, at the expense of kidneys and splanchnic tissue. Term infants can provide for the increasing metabolic activity of the intestinal tract during feeding periods without compromising oxygenation.
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Encéfalo/metabolismo , Riñón/metabolismo , Mesenterio/metabolismo , Oxígeno/metabolismo , Biomarcadores/metabolismo , Cesárea , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Estudios Prospectivos , Espectroscopía Infrarroja CortaRESUMEN
OBJECTIVE: To investigate the efficacy of a proactive feeding regimen (PFR) in reducing hospital length of stay in a population of moderately preterm small for gestational age (SGA) infants. STUDY DESIGN: SGA infants (z-score <-1.28) of gestational age (GA) 32-36 weeks and birth weight (BW) >1499 g were allocated at random to receive either a PFR, starting with 100 mL/kg/day and gradually increasing to 200 mL/kg/day by day 4, or a standard feeding regimen, starting with 60 mL/kg/day and gradually increasing to 170 mL/kg/day by day 9. All infants received human milk. RESULTS: A total of 72 infants were randomized to the 2 groups, 36 to the PFR group (mean GA, 35.1 ± 0.7 weeks; mean BW, 1761 ± 177 g) and 36 to the standard feeding regimen group (mean GA, 35.5 ± 1.2 weeks; mean BW, 1754 ± 212 g). Infants in the PFR group were discharged significantly earlier (mean, 9.8 ± 3.1 days vs 11.9 ± 4.7 days; P = .029). The need for intravenous fluids (2.8% vs 33.3%; P = .0013) and the incidence of hypoglycemia (0 vs 33.3%; P = .00016) were significantly lower in the PFR group. Feeding intolerance and fecal calprotectin levels did not differ between the 2 groups. CONCLUSION: A PFR in moderately preterm SGA infants is well tolerated and significantly reduces both the length of stay and the risk of neonatal hypoglycemia.
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Nutrición Enteral/métodos , Enfermedades del Prematuro/terapia , Recién Nacido Pequeño para la Edad Gestacional , Retardo del Crecimiento Fetal/terapia , Edad Gestacional , Humanos , Recien Nacido Prematuro , Tiempo de Internación , Leche Humana , Estudios ProspectivosRESUMEN
AIM: Numerous epidemiological studies suggest that exposure to flavonoid-rich fruits has beneficial influence on risk factors for cardiovascular disease. We investigated whether intake of orange juice (OJ) could affect whole blood (WB) procoagulant activity. METHODS: 17 healthy subjects (aged 31 ± 1.5 SEM 10 males) were randomized to receive, according to a cross-over design, either red or blond OJ, enriched or free of anthocyanins, respectively. After one week run-in period on a controlled diet, the subjects were randomly allocated to receive either type of OJ for 4 weeks, with a 4-week wash-out period. Venous blood was collected on citrate before and at the end of each treatment period. WB was incubated with or without an inflammatory stimulus (tumor necrosis factor-α or bacterial endotoxin LPS). Procoagulant activity was evaluated by a one-stage clotting assay. Tissue factor (TF) and TF pathway inhibitor (TFPI) were measured in plasma by ELISA. RESULTS: Intake of either type of OJ caused a prolongation of unstimulated and stimulated WB clotting times, without any difference between the two treatments. Intake of OJ did not modify TF levels. On the contrary, an increase in circulating TFPI antigen was detected following either treatment. CONCLUSIONS: Orange juice intake by healthy volunteers decreases procoagulant activity, possibly through mechanisms independent of its anthocyanin content.