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OBJECTIVE: We aimed at reviewing the currently available guidelines and scientific recommendations regarding the neonatal in-hospital management and feeding in the light of the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: We systematically searched the guideline databases, Medline, Embase, and nationale/international neonatal societies websites as of June 19, 2020, for guidelines on neonatal management and feeding during the COVID-19 pandemic, at the same time assessing the methodological quality using the Appraisal of Guidelines for Research and Evaluation II tool. RESULTS: Eleven guidelines were included. The Chinese and American recommendations suggest separation of the mother and her neonate, whereas in French, Italian, UK, Canadian, and World Health Organization consensus documents the rooming-in is suggested, with Centers for Disease Control and Prevention guidelines suggesting to decide on a case-by-case basis. All the guidelines recommend breastfeeding or feeding with expressed maternal milk; the only exception is the Chinese recommendations, these last suggesting to avoid breastfeeding. CONCLUSION: This review may provide a useful tool for clinicians and organizers, highlighting differences and similarities of the existing guidelines on the management and feeding strategies in the light of the COVID-19 pandemic. KEY POINTS: · This study compares guidelines on management and nutrition of a newborn born to a mother with SARS-CoV-2 infection.. · Existing guidelines on neonatal management and nutrition during the SARS-CoV-2 pandemic show many differences.. · The majority of recommendations are mainly based on experts' opinion and are not evidence-based..
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Lactancia Materna/estadística & datos numéricos , Infecciones por Coronavirus/epidemiología , Fenómenos Fisiológicos Nutricionales del Lactante , Neumonía Viral/epidemiología , Guías de Práctica Clínica como Asunto , COVID-19 , Femenino , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Leche Humana , Pandemias , Organización Mundial de la SaludRESUMEN
Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.
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Asfixia/patología , Hipotermia Inducida , Subunidad beta de la Proteína de Unión al Calcio S100/orina , Biomarcadores/orina , Encéfalo/fisiología , Estudios de Casos y Controles , Electroencefalografía , Femenino , Humanos , Hipoxia-Isquemia Encefálica/patología , Inmunoensayo , Recién Nacido , Masculino , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Severe urea cycle defects (UCD), organic acidemias (OA) and maple syrup urine disease (MSUD) are life-threatening disorders presenting in the first days of life. Renal replacement therapy (RRT) is an emergency option in affected newborns, mostly performed as ultima ratio. We report our 10-year experience using emergency RRT in newborns with UCD, OA and MSUD. Twelve newborns (eight with UCD, two with methylmalonic acidemia and two with MSUD) underwent emergency RRT. The overall survival rate to RRT was 58.3%. Hyperammonemic newborns required earlier RRT with respect to MSUD patients (75 (65-102) vs 301 (192-410) h of life, P < 0.01). Hyperammonemic neonates surviving (n = 5) and non-surviving (n = 5) the acute neonatal decompensation showed similar birth weight (P = 0.690), duration of intubation (P = 0.917), ammonia at onset (P = 0.916) and at the start of RRT (P = 0.426), age at RRT (P = 0.999) and duration of coma before RRT (P = 0.691). Remarkably, all survivors quickly responded to RRT, with ammonia concentration less than 300 µmol/L after 8 h of treatment. One patient with UCD successfully treated by neonatal RRT died at 4 months of life because of sepsis. All patients with MSUD had normalized leucine levels after 12 h of RRT, surviving the acute neonatal decompenstation. All long-term survivors (five liver transplanted, one waiting for liver transplantation) currently show normal or near-normal neurological development (48 ± 39 months of age). Early response to RRT was associated with survival irrespective of pre-treatment picture. RRT can be considered even in huge neonatal metabolic decompensations. Early liver transplantation may be an option for select patients.
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Errores Innatos del Metabolismo de los Aminoácidos/terapia , Enfermedad de la Orina de Jarabe de Arce/terapia , Terapia de Reemplazo Renal/métodos , Trastornos Innatos del Ciclo de la Urea/terapia , Factores de Edad , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/mortalidad , Errores Innatos del Metabolismo de los Aminoácidos/fisiopatología , Desarrollo Infantil , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Trasplante de Hígado , Masculino , Enfermedad de la Orina de Jarabe de Arce/diagnóstico , Enfermedad de la Orina de Jarabe de Arce/mortalidad , Enfermedad de la Orina de Jarabe de Arce/fisiopatología , Recuperación de la Función , Terapia de Reemplazo Renal/efectos adversos , Terapia de Reemplazo Renal/mortalidad , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Trastornos Innatos del Ciclo de la Urea/diagnóstico , Trastornos Innatos del Ciclo de la Urea/mortalidad , Trastornos Innatos del Ciclo de la Urea/fisiopatologíaRESUMEN
We report the management of refractory status epilepticus (SE) by using continuous intravenous infusions of lidocaine in a previously healthy 15-year-old girl with a "catastrophic encephalopathy" in whom a diagnosis of febrile infection-related epilepsy syndrome was supposed. One week after a banal pharyngitis and fever, the patient presented confusion and intractable clusters of seizures. Although she underwent multiple examinations investigating all possible etiologies (intracranial infection, autoimmune disease, or toxic and metabolic illness), all results were negative except a feeble positivity to Mycoplasma pneumoniae serum antibodies. SE was initially treated with benzodiazepine followed by administration of barbiturates and subsequent induction of coma because of refractory SE; different antiepileptic drugs (AEDs) were given at different times in a period of 6 weeks but clinical and electroencephalographic improvements were achieved only after continuous infusion of lidocaine. When she recovered from SE, the patient developed severe psychomotor and cognitive impairment associated with cerebral atrophy. Treatment with lidocaine or other alternative drugs in cases of prolonged SE should be taken into account as soon as it becomes clear that the clinical condition is refractory to common AEDs included in available guidelines for SE treatment, to improve the bad outcome of this severe condition, at least limiting the negative effects of prolonged high metabolic demand due to continuous epileptiform activity and/or the possible negative effects of prolonged burst-suppression coma.
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Anestésicos Locales/uso terapéutico , Encefalitis Viral/complicaciones , Lidocaína/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/etiología , Adolescente , Electroencefalografía , Femenino , Estudios de Seguimiento , HumanosRESUMEN
The ACO2 gene encodes the mitochondrial protein aconitate hydratase, which is responsible for catalyzing the interconversion of citrate into isocitrate in the tricarboxylic acid (TCA) cycle. Mitochondrial aconitase is expressed ubiquitously, and deficiencies in TCA-cycle enzymes have been reported to cause various neurodegenerative diseases due to disruption of cellular energy metabolism and development of oxidative stress. We investigated a severe early infantile-onset neurometabolic syndrome due to a homozygous novel variant in exon 13 of the ACO2 gene. The in vitro pathogenicity of this variant of unknown significance was demonstrated by the loss of both protein expression and its enzymatic activity on muscle tissue sample taken from the patient. The patient presented with progressive encephalopathy soon after birth, characterized by hypotonia, progressive severe muscle atrophy, and respiratory failure. Serial brain magnetic resonance imaging showed progressive abnormalities compatible with a metabolic disorder, possibly mitochondrial. Muscle biopsy disclosed moderate myopathic alterations and features consistent with a mitochondriopathy albeit nonspecific. The course was characterized by progressive worsening of the clinical and neurological picture, and the patient died at 5 months of age. This study provides the first report on the validation in muscle from human subjects regarding in vitro analysis for mitochondrial aconitase activity. To our knowledge, no prior reports have demonstrated a correlation of phenotypic and diagnostic characteristics with in vitro muscle enzymatic activity of mitochondrial aconitase in humans. In conclusion, this case further expands the genetic spectrum of ACO2 variants and defines a complex case of severe neonatal neurometabolic disorder.
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We aim to develop evidence-based recommendations for intensivists caring for children admitted to intensive care units and requiring analgesia and sedation. A panel of national paediatric intensivists expert in the field of analgesia and sedation and other specialists (a paediatrician, a neuropsychiatrist, a psychologist, a neurologist, a pharmacologist, an anaesthesiologist, two critical care nurses, a methodologist) started in 2018, a 2-year process. Three meetings and one electronic-based discussion were dedicated to the development of the recommendations (presentation of the project, selection of research questions, overview of text related to the research questions, discussion of recommendations). A telematic anonymous consultation was adopted to reach the final agreement on recommendations. A formal conflict-of-interest declaration was obtained from all the authors. Eight areas of direct interest and one additional topic were considered to identify the best available evidence and to develop the recommendations using the Evidence-to-Decision framework according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. For each recommendation, the level of evidence, the strength of the recommendation, the benefits, the harms and the risks, the benefit/harm balance, the intentional vagueness, the values judgement, the exclusions, the difference of the opinions, the knowledge gaps, and the research opportunities were reported. The panel produced 17 recommendations. Nine were evaluated as strong, 3 as moderate, and 5 as weak. Conclusion: a panel of national experts achieved consensus regarding recommendations for the best care in terms of analgesia and sedation in critically ill children.
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OBJECTIVE: To discuss the results of the KETASER01 trial and the reasons for its failure, particularly in view of future studies. METHODS: KETASER01 is a multicenter, randomized, controlled, open-label, sequentially designed, non-profit Italian study that aimed to assess the efficacy of ketamine compared with conventional anesthetics in the treatment of refractory convulsive status epilepticus (RCSE) in children. RESULTS: During the 5-year recruitment phase, a total of 76 RCSEs treated with third-line therapy were observed in five of the 10 participating Centers; only 10 individuals (five for each study arm; five females, mean age 6.5 ± 6.3 years) were enrolled in the KETASER01 study. Two of the five patients (40%) in the experimental arm were successfully treated with ketamine and two of the five (40%) children in the control arm, where successfully treated with thiopental. In the remaining six (60%) enrolled patients, RCSE was not controlled by the randomized anesthetic(s). SIGNIFICANCE: The KETASER01 study was prematurely halted due to low eligibility of patients and no successful recruitment. No conclusions can be drawn regarding the objectives of the study. Here, we discuss the KETASER01 results and critically analyze the reasons for its failure in view of future trials.
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Anestésicos , Ketamina , Estado Epiléptico , Niño , Preescolar , Protocolos Clínicos , Femenino , Humanos , Lactante , Ketamina/uso terapéutico , Masculino , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Estado Epiléptico/tratamiento farmacológico , TiopentalRESUMEN
BACKGROUND: This prospective surveillance study was designed to estimate the incidence of healthcare-associated infections (HAIs) and to analyze the risk factors for their development in a pediatric neurosurgical unit. METHODS: The study was performed in an Italian teaching hospital from October 2008 through March 2010. All children (0-18 years) undergoing neurosurgery were included and monitored daily for the development of HAIs. RESULTS: The study included 260 patients, with a mean age of 4.3 ± 4.7 years. Thirty-six HAIs were detected in 25 patients; catheter-related infections were the most frequent. Etiological identification was available in 22 cases; Gram-negative bacteria were the most commonly isolated pathogens. The incidence density was 11.0/1,000 patient days, and the incidence rate was 13.8/100 patients. The crude mortality was 0%. The risk of developing HAIs was related to the length of hospital stay, while the higher the age of the patients, the lower the risk of developing HAIs. CONCLUSION: To our knowledge, this survey is the first study to evaluate the overall incidence of HAIs and to explore the risk factors implicated in their development in neurosurgical pediatric patients. The most effective strategies to prevent these infections are reduction of the length of the hospital stay and improvement in device management.
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Infección Hospitalaria/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Neurocirugia/métodos , Adolescente , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/etiología , Infecciones Relacionadas con Catéteres/microbiología , Niño , Preescolar , Infección Hospitalaria/microbiología , Femenino , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/etiología , Hospitales , Humanos , Incidencia , Lactante , Recién Nacido , Italia , Tiempo de Internación , Masculino , Pediatría , Estudios Prospectivos , Factores de RiesgoRESUMEN
Previous studies have shown that human liver stem-like cells (HLSCs) may undergo differentiation in vitro into urea producing hepatocytes and in vivo may sustain liver function in models of experimentally induced acute liver injury. The aim of this study was to assess the safety of HLSCs intrahepatic administration in inherited neonatal-onset hyperammonemia. The study was approved by the Agenzia Italiana del Farmaco on favorable opinion of the Italian Institute of Health as an open-label, prospective, uncontrolled, monocentric Phase I study (HLSC 01-11, EudraCT-No. 2012-002120-33). Three patients affected by argininosuccinic aciduria (patient 1) and methylmalonic acidemia (patients 2 and 3) and included in the liver transplantation list were enrolled. In all patients, HLSCs were administered by percutaneous intrahepatic injections (once a week for two consecutive weeks) within the first months of life. The first patient received 125,000 HLSCs x gram of liver/dose while the other two patients received twice this dose. No immunosuppression was administered since HLSCs possess immunomodulatory activities. None of the patients experienced infections, hyperammonemia decompensation, or other adverse events during the whole observation period. No donor specific antibodies (DSA) against HLSCs were detected. Patients were metabolic stable despite an increase (~30%) in protein intake. Two patients underwent liver transplantation after 19 and 11 months respectively, and after explantation, the native livers showed no histological alterations. In conclusion, percutaneous intrahepatic administration of HLSCs was safe in newborn with inherited neonatal-onset hyperammonemia. These data pave the way for Phase II studies in selected inherited and acquired liver disorders.
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Hiperamonemia/terapia , Trasplante de Hígado , Hígado/metabolismo , Errores Innatos del Metabolismo/terapia , Trasplante de Células Madre , Edad de Inicio , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/patología , Errores Innatos del Metabolismo de los Aminoácidos/terapia , Amoníaco/metabolismo , Aciduria Argininosuccínica/metabolismo , Aciduria Argininosuccínica/patología , Aciduria Argininosuccínica/terapia , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Hiperamonemia/metabolismo , Hiperamonemia/patología , Recién Nacido , Hígado/crecimiento & desarrollo , Hígado/patología , Masculino , Errores Innatos del Metabolismo/genética , Errores Innatos del Metabolismo/metabolismo , Células Madre/metabolismo , Urea/metabolismoAsunto(s)
Anestesia de Conducción/efectos adversos , Bloqueo Nervioso/efectos adversos , Manejo del Dolor/métodos , Amputación Quirúrgica , Cuidados Críticos , Pie/irrigación sanguínea , Pie/patología , Humanos , Lactante , Pierna/irrigación sanguínea , Masculino , Necrosis , Miembro Fantasma/tratamiento farmacológico , Flujo Sanguíneo Regional , Respiración Artificial , Sepsis/complicaciones , Ultrasonografía Doppler en Color , Síndrome de Waterhouse-Friderichsen/complicaciones , Síndrome de Waterhouse-Friderichsen/tratamiento farmacológico , Síndrome de Waterhouse-Friderichsen/terapiaRESUMEN
INTRODUCTION: Status epilepticus (SE) is a life-threatening neurological emergency. SE lasting longer than 120â min and not responding to first-line and second-line antiepileptic drugs is defined as 'refractory' (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-d-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. METHODS AND ANALYSIS: A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/hospitals are involved in enrolling 57 patients aged 1â month to 18â years with RCSE. Primary outcome is the resolution of SE up to 24â hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. ETHICS AND DISSEMINATION: The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT02431663; Pre-results.
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Anticonvulsivantes/administración & dosificación , Ketamina/administración & dosificación , Estado Epiléptico/tratamiento farmacológico , Administración Intravenosa , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Italia , Masculino , Proyectos de Investigación , Resultado del TratamientoRESUMEN
BACKGROUND: Perinatal asphyxia (PA) is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury. METHODS: We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth. RESULTS: S100B salivary levels were significantly (P<0.001) higher in newborns with PA than in normal infants. When asphyxiated infants were subdivided according to a good (Group A; n = 15) or poor (Group B; n = 33) neurological outcome at 12-months, S100B was significantly higher at all monitoring time-points in Group B than in Group A or controls (P<0.001, for all). A cut-off >3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%) and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0). CONCLUSIONS: S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae.
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Asfixia Neonatal/diagnóstico , Lesiones Encefálicas/diagnóstico , Proteínas S100/análisis , Área Bajo la Curva , Asfixia Neonatal/complicaciones , Biomarcadores/análisis , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/diagnóstico por imagen , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Inmunoensayo , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Pronóstico , Curva ROC , Radiografía , Saliva/metabolismo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND OBJECTIVES: To compare ropivacaine, levo-bupivacaine, and racemic bupivacaine for caudal blockade in children. METHODS: Using a prospective observer blinded design, 60 sevoflurane anesthetized children (1 to 7 years) undergoing minor subumbilical surgery, were randomized to receive a caudal block (1 mL/kg) with either ropivacaine 0.2%, racemic bupivacaine 0.25%, or levo-bupivacaine 0.25%. Postoperative analgesia (number of patients needing supplemental analgesia as defined by an objective pain score [OPS] score of > or = 5; time to first analgesic demand) during the first 24 postoperative hours was chosen as the primary end-point. Early postoperative motor block (3-point scale) was assessed as a secondary end-point. RESULTS: All blocks were judged to be clinically successful based on the presence of adequate intraoperative and early postoperative analgesia. An OPS score > or = 5 was found in 5/20 patients in each study group. No difference regarding the time to first analgesic demand was found between the study groups. The use of ropivacaine (P =.02), but not levo-bupivacaine (P =.18), was found to be associated with less motor block during the first postoperative hour compared with racemic bupivacaine. CONCLUSION: All 3 investigated local anesthetics were found to be clinically comparable despite the slight reduction of early postoperative motor block associated with the use of ropivacaine.