¿Cuál es la nutrición que administramos a nuestros recién nacidos de muy bajo peso en las unidades neonatales?: Una encuesta nacional

Background: Significant efforts have been made to improve the nutritional support of very preterm infants. Large surveys may help to know the nutritional practices for preterm infants in neonatal units and identify if they are in line with the current guidelines. Methods: A multicentre nationwide web-based survey on clinical feeding practices in very low birth weight (VLBW) infants was conducted in tertiary neonatal hospitals that admit infants with a birth weight < 1,500 g and/or a gestational age of < 32 weeks. Results: The questionnaire was completed by 53 units (response rate, 59%). Over 90% of the units surveyed start amino-acid administration immediately after birth and more than half use novel intravenous fish oil-based lipid emulsions. Enteral nutrition is started within 24 hours of birth in 65% of units and 86% of these are medium-sized or large. Feeding volumes are increased at a rate of 10-30 ml/kg/day in > 90% of units. Monitoring of serum phosphorus was measured more frequently than albumin (p = 0.009) or triglycerides (p = 0.037), but only 28% of centres regularly measure pre-albumin as a nutritional biomarker. Human milk fortification and iron supplementation, starting at four weeks of age, are almost universal. However, only 30% of units administer 800 IU/day of vitamin D. Nearly 50% of the units discharge infants on preterm formula. Conclusion: Most Spanish neonatology units use early amino-acid supplementation and over half use novel fish oil-based lipid emulsions. Post-discharge nutrition practices and vitamin administration vary greatlyAntecedentes: se han realizado esfuerzos significativos para mejorar la nutrición en los recién nacidos muy prematuros. Las grandes encuestas pueden ayudar a conocer cuál es la nutrición que reciben los recién nacidos prematuros en las unidades neonatales e identificar si están en línea con las directrices actuales. Métodos: se llevó a cabo una encuesta multicéntrica a nivel nacional sobre las prácticas clínicas empleadas en la alimentación en los recién nacidos de muy bajo peso en hospitales de nivel III que ingresan recién nacidos con un peso al nacer < 1.500 g y/o una edad gestacional < 32 semanas. Resultados: el cuestionario fue completado por 53 unidades neonatales (tasa de respuesta del 59%). Más del 90% de las unidades estudiadas inician la administración de aminoácidos inmediatamente después del nacimiento y más de la mitad utilizan nuevas emulsiones lipídicas intravenosas que contienen aceite de pescado. La nutrición enteral se inicia en las primeras 24 horas de nacimiento en el 65% de las unidades y el 86% de ellas son medianas o grandes. El volumen de alimentación aumenta a una velocidad de 10-30 ml/kg/día en > 90% de las unidades. El fósforo sérico se monitoriza con mayor frecuencia que la albúmina (p = 0,009) o los triglicéridos (p = 0,037), pero solo el 28% de los centros miden regularmente la prealbúmina como biomarcador nutricional. La fortificación de la leche humana y la suplementación con hierro, a partir de las cuatro semanas de edad, es casi universal. Sin embargo, solo el 30% de las unidades administran 800 UI/día de vitamina D. Casi el 50% de las unidades utilizan leche de fórmula del prematuro al alta de las unidades. Conclusión: la mayoría de las unidades neonatales españolas administran precozmente los suplementos de aminoácidos y más de la mitad emplean emulsiones de lípidos a base de aceite. Hay una importante variación en las prácticas nutricionales posteriores al alta y en la administración de vitamina

Una emulsión lipídica basada exclusivamente en aceite de pescado revierte la colestasis

Prolonged parenteral nutrition (PN) leads to liver damage. Recent interest has focused on the lipid component of PN. A lipid emulsion based on w-3 fatty acids decrease conjugated bilirubin. A mixed lipid emulsion derived from soybean, coconut, olive, and fish oils reverses jaundice. Here we report the reversal of cholestasis and the improvement of enteral feeding tolerance in 1 infant with intestinal failure-associated liver disease. Treatment involved the substitution of a mixed lipid emulsion with one containing primarily omega-3 fatty acids during 37 days. Growth and biochemical tests of liver function improved significantly. This suggests that fat emulsions made from fish oils may be more effective means of treating this condition compared with an intravenous lipid emulsion containing soybean oil, medium -chain triglycerides, olive oil, and fish oilLa nutrición parenteral prolongada produce daño hepático. Recientemente se ha comunicado el efecto de las emulsiones lipídicas intravenosas basadas exclusivamente en ácidos grasos omega-3 en la resolución de la colestasis. Lo mismo se ha observado con el uso de emulsiones lipídicas mixta derivadas del aceite de soja, coco, oliva y pescado. Comunicamos la desaparición de colestasis y mejoría de la tolerancia enteral en un niño con enfermedad hepática asociada a nutrición parenteral. El tratamiento consistió en sustituir una emulsión lipídica mixta por otra que contenía de forma exclusiva aceite de pescado durante 37 días. El crecimiento y los datos bioquímicos de función hepática mejoraron de forma significativa. Este caso sugiere que emulsiones lipídicas intravenosas a partir de aceite de pescado pueden ser mas eficaces para tratar la colestasis si se comparan con emulsiones mixta

Breakthrough invasive fungal infection among patients with haematologic malignancies: A national, prospective, and multicentre study

Objectives: We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies.Methods: BtIFI in patients with & GE; 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions.Results: 121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)-mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most fre-quent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 10 0-day mor-tality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases.Conclusions: BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceed-ingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used.& COPY; 2023 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000-2015

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy

MixInYeast: A Multicenter Study on Mixed Yeast Infections

Invasive candidiasis remains one of the most prevalent systemic mycoses, and several studies have documented the presence of mixed yeast (MY) infections. Here, we describe the epidemiology, clinical, and microbiological characteristics of MY infections causing invasive candidiasis in a multicenter prospective study. Thirty-four centers from 14 countries participated. Samples were collected in each center between April to September 2018, and they were sent to a reference center to confirm identification by sequencing methods and to perform antifungal susceptibility testing, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A total of 6895 yeast cultures were identified and MY occurred in 150 cases (2.2%). Europe accounted for the highest number of centers, with an overall MY rate of 4.2% (118 out of 2840 yeast cultures). Of 122 MY cases, the most frequent combinations were Candida albicans/C. glabrata (42, 34.4%), C. albicans/C. parapsilosis (17, 14%), and C. glabrata/C. tropicalis (8, 6.5%). All Candida isolates were susceptible to amphotericin B, 6.4% were fluconazole-resistant, and two isolates (1.6%) were echinocandin-resistant. Accurate identification of the species involved in MY infections is essential to guide treatment decisions

Regulación por hormona tiroidea de la expresión del gen NGFI-A en encéfalo durante el desarrollo. Papel de NGFI-A en la diferenciación neuronal

Tesis doctoral inédita leída en laUniversidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 10-07-1995La falta de hormona tiroidea durante el período perinatal provoca daños muy graves e irreversibles en el sistema nervioso central. Estos efectos dependen en última instancia de la regulación de la expresión génica, ya que la hormona tiroidea actúa a través de su unión a receptores nucleares específicos que son factores de transcripción dependientes de ligando. En el presente estudio demostramos que la expresión en el encéfalo de un gen temprano conocido como NGFI-Alegr-1 es dependiente del estado tiroideo durante el desarrollo. Los niveles de mensajero para NGFI-A en el encéfalo no se modifican, sin embargo, cuando el hipotiroidismo es inducido en el animal adulto. La respuesta de este gen a la administración de T3 es muy rápida y tan sólo 1 hora después de la administración de T3 a animales hipotiroideos los niveles de expresión de este gen se incrementan significativamente, lo cual sugiere un efecto directo de esta hormona sobre los niveles de transcripción de NGFI-A. El efecto de T3 sobre la expresión del gen NGFI-A es diferente según el área encefálica estudiada y la edad del animal: el estriado es sensible al estado tiroideo en todas las edades estudiadas, incluso en edades tan tempranas como el mismo día del nacimiento. Otras regiones como el giro dentado son insensibles a la hormona o bien van perdiendo progresivamente su respuesta a T3 a medida que avanza el desarrollo, como es el caso de las zonas CA 1, CA2 y CA3 del hipocampo y la corteza piriforme. El clonaje y posterior secuenciación de 1'3 kb de la zona 5' promotora del gen NGFI-A, ha mostrado varios motivos similares a elementos consenso de respuesta a hormona tiroidea (TRE). Sin embargo, estudios de transfección en células de neuroblastoma N2A no indican regulación por T3 y sólo se observa una inducción moderada por dos isoformas del receptor de T3, a 1 y P1, pero independiente de la unión del ligando. Debido a la presencia en este fragmento de TRES potencialmente funcionales, la falta de respuesta a T3 se podría deber a la presencia de secuencias atenuadoras de la acción de esta hormona. Estudios realizados con oligonucleótidos complementarios del mRNA-NGFI-A demuestran que la adición de éstos a células de neuroblastoma impide el proceso de neuritogénesis y la redistribución de la proteína asociada a microtúbulos MAPlB que tiene lugar durante este proceso. Estos datos sugieren que el gen NGFI-A es parte esencial de las rutas que conducen a la diferenciación neural y que por tanto podría ser un mediador de la acción de la hormona tiroidea en el control que ésta ejerce en los procesos de diferenciación durante el desarrollo encefálico in vivo. Ya que NGFI-A codifica un factor de transcripción, el conocimiento de los efectos desencadenados por T3 en el encéfalo requerirá la identificación y caracterización de genes regulados por NGFI-A.Thyroid hormone (T3) has profound effects on the development of the central nervous systern. These effects are rnediated via specific nuclear thyroid hormone receptors, which act as ligand-activated transcription factors. Thus, the control by T3 of developmental processes is ultirnately rnediated by the control of gene expression. In the present study we dernonstrate that the expression of an early-growth response gene, NGFI-Alegr- 1, is under the control of thyroid hormone in the developing rat brain. When hypothyroidism was induced in adult life, no changes were obsemed in the content of NGFI-A transcripts. T3 administration to hypothyroid animals caused a significant increase in NGFI-A-mRNA levels as early as 1 hour after T3 injection, suggesting a direct effect of T3 on this gene. T3 differentially regulates the expression of NGFI-A in the brain depending on the developmental stage and the brain region being studied. At birth, the expression of NGFI-A is high in the striatum of control animals while hypothyroid rats show reduced levels of NGFI-A transcripts at al1 ages studied in this region. However, other brain regions, such as the dentate gynis, are not sensitive to the thyroidal state, and others lose their response to T3 through development (piriform cortex and fields CAl, CA2 and CA3 of the hippocarnpus). Cloning and sequencing of a 1.3 kb fragrnent of the 5'-upstream region of the NGFI-A gene, revealed several potential thyroid hormone response elements. However, transfection experirnents using this fragment have not shown regulation by T3. On the contrary, cotransfection studies with thyroid hormone receptors al or p l , show a T3-independent increase in the expression of the reporter gene. The observed lack of effect of T3 on this promoter could be attributable to the presence of a neighboring silencer element. Treatment of neuro2A cells with an antisense oligodeoxynucleotide for the NGFI-A-mRNA, blocks both neuritogenesis and redistribution of the microtubule-associated protein MAPlB which takes place during the extension of the neurites. These results suggest that NGFI-A gene expression is necessary for neurona1 differentiation and, therefore, this gene could be a mediator of the effects of T3 on the rnaturation of the brain. Since the NGFI-A gene codes for a transcription factor, the elucidation of the regulatory cascade of events triggered by T3 in the brain will then pass for the identification of NGFI-A-regulated genes

How should we define postnatal growth restriction in preterm infants?

Postnatal growth restriction is very common among preterm infants. Growth restriction might be associated with neurodevelopment impairment. The definition of postnatal growth restriction varies among studies. It has often been based on statistical parameters, but we lack biological data to support this definition. Objectives: The aim here was to study the association between neurodevelopment and postnatal growth restriction defined applying 2 different strategies. Methods: Bayley Scales of Infant Development-II was performed at 2 years corrected age in 168 preterm infants. Postnatal growth restriction was defined as a weight z-score at 36 weeks <–1.5 or treated as a continuous variable (fall in weight z-scores from birth to 36 weeks postmenstrual age). Results: Weight z-scores fell in almost all patients (98.8%), and 44.1% had z-scores <–1.5 at 36 weeks. After adjusting for gestational age and small for gestational age at birth, every 1-point fall in weight z-score was associated with a 5.6 point (95% CI 1.7 to 9.4) decrease in the Mental Developmental Index. A weight z-score <–1.5 at 36 weeks was not associated with a worse mental or psychomotor result. Conclusion: A fall in the weight z-score from birth to 36 weeks is a more rational definition of postnatal growth restriction, and it could predict neurodevelopmen

Induction of chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI ) gene expression is mediated by ETS factor binding sites

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Fludarabine resistance mediated by aminoglycoside-3′-phosphotransferase-IIa and the structurally related eukaryotic cAMP-dependent protein kinase

While working with G418-resistant stably transfected cells, we realized the neomycin resistance (NeoR) gene, which encodes the aminoglycoside-3′-phosphotransferase-IIa [APH(3′)-IIa], also confers resistance to the nucleoside analog fludarabine. Fludarabine is a cytostatic drug widely used in the treatment of hematologic and solid tumors, as well as in the conditioning of patients before transplantation of hematopoietic progenitors. We present evidence that NeoR-transfected cells do not incorporate fludarabine, thus avoiding DNA damage caused by the drug, evidenced by a lack of FANCD2 monoubiquitination and impaired apoptosis. A screening of other nucleoside analogs revealed that APH(3′)-IIa only protects against ATP purine analogs. Moreover, APH(3′)-IIa ATPase activity is inhibited by fludarabine monophosphate, suggesting that APH(3′)-IIa blocks fludarabine incorporation into DNA by dephosphorylating its active fludarabine triphosphate form. Furthermore, overexpression of the catalytic subunit of the eukaryotic kinase PKA, which is structurally related to APHs, also provides resistance to fludarabine, anticipating its putative utility as a response marker to the drug. Our results preclude the use of Neo marker plasmids in the study of purine analogs and unveils a new resistance mechanism against these chemotherapeuticals.This work was supported by the Hematology Service of the Hospital Marques de Valdecilla and Spanish Ministerio de Economía y Competitividad (Grant BFU2011-22874 to E.C and I.A).Peer Reviewe