Role of innate T cells in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a destructive gastrointestinal disease primarily affecting preterm babies. Despite advancements in neonatal care, NEC remains a significant cause of morbidity and mortality in neonatal intensive care units worldwide and the etiology of NEC is still unclear. Risk factors for NEC include prematurity, very low birth weight, feeding with formula, intestinal dysbiosis and bacterial infection. A review of the literature would suggest that supplementation of prebiotics and probiotics prevents NEC by altering the immune responses. Innate T cells, a highly conserved subpopulation of T cells that responds quickly to stimulation, develops differently from conventional T cells in neonates. This review aims to provide a succinct overview of innate T cells in neonates, encompassing their phenotypic characteristics, functional roles, likely involvement in the pathogenesis of NEC, and potential therapeutic implications.

Core Outcome Set for Necrotizing Enterocolitis Treatment Trials.

BACKGROUND AND OBJECTIVES: Variability in outcome reporting in necrotizing enterocolitis (NEC) treatment trials hinders conducting meta-analyses and implementing novel treatments. We aimed to develop a core outcome set (COS) for NEC treatment trials including outcome measures most relevant to patients and physicians, from NEC diagnosis to adulthood. METHODS: Clinicians and/or researchers from low-middle- and high-income countries were approached based on their scientific contributions to NEC literature, and patients and parents through local organizations. We presented participants with 45 outcomes used in NEC research, identified through a systematic review. To achieve consensus, outcomes were rated on a scale of 1 to 9 in 3 online Delphi rounds, and discussed at a final consensus meeting. RESULTS: Seventy-one participants from 25 countries completed all Delphi rounds, including 15 patients and family representatives. Thirteen outcomes reached consensus in one of the stakeholder groups and were included in the consensus meeting, 6 outcomes reached consensus in both groups. Twenty-seven participants from both high- and low-middle-income countries attended the online consensus meeting, including family representatives and NEC patients. After discussion and a final vote, 5 outcomes reached consensus to be included: mortality, NEC-related mortality, short bowel syndrome, quality of life, and neurodevelopmental impairment. CONCLUSIONS: This NEC COS includes 5 predominantly long-term outcomes agreed upon by clinicians, patients, and family representatives. Use of this international COS will help standardize outcome selection in clinical trials, ensure these are relevant to those most affected by NEC care, and, ultimately, improve the care of infants with NEC.

The entwined circles of quality improvement & advocacy.

Health policy and quality improvement initiatives exist symbiotically. Quality projects can be spurred by policy decisions, such as the creation of financial incentives for high-value care. Then, advocacy can streamline high-value care, offering opportunities for quality improvement scholars to create projects consistent with evidenced-based care. Thirdly, as pediatrics and neonatology reconcile with value-based payment structures, successful quality initiatives may serve as demonstration projects, illustrating to policy-makers how best to allocate and incentivize resources that optimize newborn health. And finally, quality improvement (QI) can provide an essential link between broad reaching advocacy principles and boots-on-the-ground local or regional efforts to implement good ideas in ways that work practically in particular environments. In this paper, we provide examples of how national legislation elevated the importance of QI, by penalizing hospitals for low quality care. Using Medicaid coverage of pasteurized human donor milk as an example, we discuss how advocacy improved cost-effectiveness of treatments used as tools for quality projects related to reduction of necrotizing enterocolitis and improved growth. We discuss how the future of QI work will assist in informing the agenda as neonatology transitions to value-based care. Finally, we consider how important local and regional QI work is in bringing good ideas to the bedside and the community.

Neonatal Necrotizing Enterocolitis: An Update on Pathophysiology, Treatment, and Prevention.

Necrotizing enterocolitis (NEC) is a life-threatening disease predominantly affecting premature and very low birth weight infants resulting in inflammation and necrosis of the small bowel and colon and potentially leading to sepsis, peritonitis, perforation, and death. Numerous research efforts have been made to better understand, treat, and prevent NEC. This review explores a variety of factors involved in the pathogenesis of NEC (prematurity, low birth weight, lack of human breast milk exposure, alterations to the microbiota, maternal and environmental factors, and intestinal ischemia) and reports treatment modalities surrounding NEC, including pain medications and common antibiotic combinations, the rationale for these combinations, and recent antibiotic stewardship approaches surrounding NEC treatment. This review also highlights the effect of early antibiotic exposure, infections, proton pump inhibitors (PPIs), and H2 receptor antagonists on the microbiota and how these risk factors can increase the chances of NEC. Finally, modern prevention strategies including the use of human breast milk and standardized feeding regimens are discussed, as well as promising new preventative and treatment options for NEC including probiotics and stem cell therapy.

Fecal virus-like particles are sufficient to reduce necrotizing enterocolitis.

Fecal filtrate transfer (FFT) is emerging as a safer alternative to traditional fecal microbiota transplantation (FMT) - particularly in the context of necrotizing enterocolitis (NEC), a severe gastrointestinal condition affecting preterm infants. Using a preterm piglet model, FFT has demonstrated superiority over FMT in safety and NEC prevention. Since FFT is virtually devoid of bacteria, prokaryotic viruses (bacteriophages) are assumed to mediate the beneficial effects. However, this assumption remains unproven. To address this gap, we separated virus-like particles (30 kDa to 0.45 µm) of donor feces from the residual postbiotic fluid. We then compared clinical and gut microbiota responses to these fractions with the parent FFT solution after transferring them to NEC-susceptible preterm piglets. Virome transfer was equally effective as FFT in reducing the severity of NEC-like pathology. The bacterial compositional data corroborated clinical findings as virome transfer reduced the relative abundance of several NEC-associated pathogens e.g. Klebsiella pneumoniae and Clostridium perfringens. Virome transfer diversified gut viral communities with concomitant constraining effects on the bacterial composition. Unexpectedly, virome transfer, but not residual postbiotic fluid, led to earlier diarrhea. While diarrhea may be a minor concern in human infants, future work should identify ways of eliminating this side effect without losing treatment efficacy.

Prevención, diagnóstico y tratamiento de la enterocolitis necrosante en recién nacidos menores de 32 semanas al nacimiento en España / Prevention, diagnosis and treatment of necrotising enterocolitis in newborns less than 32 weeks at birth in Spain

OBJETIVO: Describir la prevención, diagnóstico y tratamiento de la enterocolitis necrosante en hospitales españoles e identificar puntos fuertes, áreas de mejora y líneas de investigación pendientes. MÉTODOS: Se realizaron 2 encuestas sobre manejo de pacientes en riesgo o diagnóstico de enterocolitis necrosante en recién nacidos pretérmino menores de 32 semanas, distribuidas entre representantes de los cirujanos pediátricos y neonatólogos de los centros participantes en la red española SEN 1500 con Servicio de Cirugía Pediátrica. RESULTADOS: El porcentaje de respuestas fue del 77,1% y del 88,6% entre los cirujanos y neonatólogos contactados, respectivamente. El 52% de los hospitales dispone de un protocolo de diagnóstico y manejo médico de la enterocolitis y el 33% uno sobre tratamiento quirúrgico. El acceso a leche de banco y disponer de personal dedicado a la promoción de la lactancia materna es común (87%), por el contrario, la ligadura tardía de cordón solo se realiza en el 52% de los centros y en un 23% se administran probióticos. La ecografía abdominal está cada vez más extendida. No hay grandes diferencias en cuanto a la duración de los antibióticos y del reposo intestinal, pero sí en cuanto a los antibióticos seleccionados, la indicación quirúrgica y el tipo de intervención. CONCLUSIONES: La implementación de la ligadura tardía de cordón y la extensión del acceso a leche de banco son áreas de mejora en el aspecto preventivo. En cuanto al diagnóstico y tratamiento existe una gran división que afecta precisamente a las áreas donde la evidencia en la literatura es menor

OBJECTIVES: To describe preventive, diagnostic and therapeutic strategies regarding necrotising enterocolitis in Spain and to identify the strengths, areas of further improvement, and future research lines. METHODS: Two questionnaires on the management of preterm infants less than 32 weeks, at risk of, or with diagnosed necrotising enterocolitis, were distributed among selected representatives of the surgeons and neonatologists of the Spanish Neonatal Network (SEN1500) participant hospitals with a Paediatric Surgery Department. RESULTS: Percentage of response was 77.1% of contacted surgeons and 88.6% of neonatologists. There is a written protocol on the diagnosis and medical management of necrotising enterocolitis in 52% of the hospitals, and as regards surgical treatment in 33%. There is wide access to donor bank milk and to staff dedicated to breastfeeding promotion (87%). On the contrary, only 52% of the centres perform delayed cord clamping, and probiotics are used in just 23%. The use of abdominal ultrasound is increasing. There are no large differences as regards duration of antibiotic use and bowel rest, whereas there was as regards antibiotic selection, surgical indication, and type of intervention. CONCLUSIONS: As regards prevention, delayed cord clamping and extended access to donor milk are two possible aspects of further improvement. The observed discrepancies noted in diagnostic and therapeutic aspects are common in precisely the areas where evidence in the literature is weakest

Ecografía a pie de cama en el diagnóstico precoz de la enterocolitis necrosante: una estrategia para mejorar el pronóstico / Bedside ultrasound in the early diagnosis of necrotising enterocolitis: A strategy to improve the prognosis

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Anomalías colorrectales / Colorectal anomalies

Las anomalías colorrectales constituyen un grupo de patologías muy variadas. el objetivo de este artículo es repasar su diagnóstico y manejo inicial hasta llegar al tratamiento quirúrgico

Colorrectal diseases are very different entities. The aim of this paper is reviewing the diagnosis and initial management of them to reach the appropriate surgical treatment

Microbiota y enfermedades gastrointestinales / Microbiota and gastrointestinal diseases

La colonización bacteriana se establece inmediatamente después del nacimiento, por contacto directo con la microbiota materna, y puede modificarse durante la lactancia. Están apareciendo datos indicativos de que modificaciones cuantitativas y cualitativas de la microbiota intestinal son capaces de estimular cambios en la activación del sistema inmune que pueden conducir a la aparición de enfermedades gastrointestinales o extraintestinales. El equilibrio entre la microbiota patógena y beneficiosa durante la niñez y la adolescencia es importante para la salud gastrointestinal, incluyendo la protección frente a patógenos, la inhibición de patógenos, el procesamiento de nutrientes (síntesis de vitamina K), el estímulo de la angiogénesis y la regulación del almacenamiento de la grasa corporal. También los probióticos pueden modular la microbiota intestinal para favorecer la salud del huésped. Este artículo es una revisión sobre la acción moduladora de la microbiota intestinal en la prevención y el tratamiento coadyuvante de las enfermedades gastrointestinales pediátricas

The bacterial colonisation is established immediately after birth, through direct contact with maternal microbiota, and may be influenced during lactation. There is emerging evidence indicating that quantitative and qualitative changes on gut microbiota contribute to alterations in the mucosal activation of the immune system, leading to intra- or extra-intestinal diseases. A balance between pathogenic and beneficial microbiota throughout childhood and adolescence is important to gastrointestinal health, including protection against pathogens, inhibition of pathogens, nutrient processing (synthesis of vitamin K), stimulation of angiogenesis, and regulation of host fat storage. Probiotics can promote an intentional modulation of intestinal microbiota favouring the health of the host. A review is presented on the modulation of intestinal microbiota on prevention, and adjuvant treatment of some paediatric gastrointestinal diseases

Enterocolitis necrotizante fulminante en un bebé colodión: caso clínico / Fulminant necrotizing enterocolitis in a collodion baby: a case report

Introducción: El bebé colodión es una ictiosis neonatal muy poco frecuente. La piel apergaminada, amarilla y dura que recubre el cuerpo resulta ser una barrera ineficaz, que predispone a la deshidratación, pérdida de calor e infecciones. El mejor manejo de estos pacientes ha permitido aumentar su supervivencia, pero su comorbi-lidad requiere de un seguimiento estricto y cauteloso. Objetivo: Describir un caso de enterocolitis fulminante desarrollada en un bebé colodión, con el fin de ayudar a la identificación más precoz de esta patología. Caso clínico: Recién nacido de 34 semanas, con membrana colodión, que ingresa en la unidad de cuidados intensivo con dificultad respiratoria severa. Se mantiene en una incubadora con humedad, aplicando emolientes y lubricación cutánea y oftalmológica. Se inició tratamiento antibiótico de amplio espectro. El quinto día de vida, comenzó con intolerancia a la alimentación, desarrollándose una enterocolitis fulminante que le ocasionó el fallecimiento. Conclusiones: La asociación con enterocolitis necrosante en un bebé colodión no ha sido descrita en la literatura, por lo que, ocasiona una demora diagnóstica y esto contribuye a una evolución fulminante que puede ocasionar la muerte. El tener presente esta infrecuente comorbilidad podrá favorecer su pesquisa para el manejo oportuno.

Introduction: Collodion baby is a rare neonatal ichthyosis. The leathery, hard and yellow skin that covers the body is an ineffective barrier that predisposes to dehydration, heat loss and infections. A better management of these patients has been shown to increase survival, but the comorbidity requires strict and cautious monitoring. Objective: To describe a case of fulminant enterocolitis in a collodion infant in order to help to identify early this pathology. Case report: A 34-week newborn with collodion membrane was admitted to the intensive care unit with severe respiratory distress. The baby was maintained in an incubator with humidity, applying emollients and skin and eye lubrication. Broad-spectrum antibiotic treatment was initiated. The patient presented feeding intolerance on the fifth day of life, developing a fulminant enterocolitis resulting in death. Conclusion: The necrotizing enterocolitis associated with a collodion baby has not been described in the literature, causing a delay in diagnosis and contributing to a fulminant course that can lead to death. Keeping in mind this rare comorbidity may facilitate a timely management.

Avanços em enterocolite necrosante / Advances in necrotizing enterocolitis

OBJETIVO: Avaliar relatos recentes sobre a enterocolite necrosante, com especial interesse na etiopatogenia, manejo e prevenção. FONTE DOS DADOS: Os artigos utilizados nessa revisão consistem em ensaios randomizados ou semi-randomizados, estudos de caso-controle, metanálises e artigos de revisão recentemente publicados. Alguns outros artigos foram selecionados devido à sua importância para o tema. RESULTADOS: A enterocolite necrosante é uma importante causa de morbimortalidade neonatal em prematuros. Entre esses, os nascidos com retardo de crescimento intra-uterino apresentam um risco mais elevado. O processo fisiopatológico inicia-se intra-útero e continua após o nascimento. Entre outros fatores envolvidos na fisiopatologia, estão a ação da arginina na produção do óxido nítrico intestinal e a ação do fator de crescimento epidérmico na regeneração celular. A perfuração intestinal ainda é um problema cirúrgico, e evidências melhores quanto à sua abordagem precisam ser avaliadas. Após a cirurgia, a extensão da alça intestinal remanescente, a preservação da válvula ileocecal, assim como a utilização precoce de leite materno ou solução de aminoácidos, são determinantes na duração da nutrição parenteral e no sucesso da readaptação intestinal. Estratégias preventivas estão centradas nas práticas alimentares e, recentemente, na suplementação de aminoácidos. CONCLUSAO: Com um melhor entendimento do processo fisiopatológico, do manejo clínico e cirúrgico, assim como das medidas de prevenção, importantes resultados serão alcançados em termos de redução da morbimortalidade conseqüente à enterocolite necrosante.

Enterocolitis necrotizante: experiencia de 15 años / Necrotizing enterocolitis: 15 years experience

El objetivo fue determinar las características clínicas, exámenes de laboratorio, radiografía de abdomen, evolución, tratamiento y sobrevida de los RN con ECN. Se analizaron las historias clínicas de 157 RN que desarrollaron ECN en un período de 15 años. En cada RN se evaluaron parámetros biomédicos, manifestaciones clínicas, exámenes complementarios, tratamiento efectuado y sobrevida. La incidencia de ECN fue de 1,8 por 1 000 RN de pretérmino fue de 12,1 días y de 4,4 días en los RN de término. Las manifestaciones clínicas más frecuentes fueron: distensión abdominal en el 94,3 por ciento, residuo gástrico en el 77,7 por ciento y sangre en deposiciones en el 36,9 por ciento. La radiografía de abdomen reveló dilatación asimétrica de asas intestinales en el 63 por ciento, neumatosis en el 45,9 por ciento y neumoperitoneo en el 14,6 por ciento. El tratamiento fue médico en el 62,4 por ciento y además quirúrgico en el 37,6 por ciento. La sobrevida fue de 60,5 por ciento. Se concluye que la ECN afecta principalmente a RN prematuros, cuyo inicio se presenta habitualmente a fines de la segunda semana de vida, en relación posiblemente a infección de predominio bacteriano

Estado actual de las imágenes en enterocolitis necrotizante: radiografía simple y ultrasonido / Current state of the images in necrotizing enterocolitis: ultrasound and radiography

La enterocolitis necrotizante (ECN) es la causa más común de abdomen agudo durante el período neonatal. La radiografía (Rx) de abdomen simple ha sido la modalidad de elección para la evaluación y seguimiento de los pacientes. Con alguna frecuencia, los hallazgos no son específicos o muestran signos discordantes, por lo que no contribuyen a realizar cambios precoces en el manejo médico o quirúrgico. Estudios recientes han reportado la utilidad del ultrasonido (US) en la evaluación complementaria del paciente con ECN, permitiendo evaluar engrosamiento parietal, estado de perfusión de las asas intestinales y presencia de líquido peritoneal. El objetivo de este artículo es actualizar las indicaciones de la Rx simple y del US en el diagnóstico y seguimiento de los recién nacidos con ECN.

Necrotizing enterocolitis is the most common cause of acute abdomen during the neonatal period. Plain film of abdomen has been the modality of choice for the evaluation and follow up of this patients. Sometimes, radiographic findings are not specific or do not help to make early changes of medical or surgical management. Recent papers have reported the utility of the ultrasound in the complementary evaluation of the patient with necrotizing enterocolitis, showing parietal thickening and perfusion of the intestinal wall and peritoneal fluid, as additional findings. In this article images of both techniques and applications are commented.

Enterocolitis necrotizante neonatal / Neonatal necrotizing enterocolitis

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Enterocolitis necrosante y traslocación bacteriana: papel de la nutrición enteral mínima / Necrotizing enterocolitis and bacterial translocation: role of minimal enteral nutrition

Introducción. La enterocolitis necrosante (ECN) y la translocación bacteriana (TB) presentan varias características comunes como son el sobrecrecimiento bacteriano, el déficit inmune y el daño de la mucosa intestinal, los cuales provocan un fallo en la función barrera intestinal. Los principales objetivos de su tratamiento son reducir la mortalidad por sepsis y lograr la tolerancia digestiva los pacientes. En este sentido, la nutrición enteral mínima (NEM) (menos del 25% de las calorías suministradas por ruta enteral), es una técnica usada con frecuencia en neonatos que reciben nutrición parenteral total (NPT), con el objeto de frenar la atrofia de las vellosidades asociadas al ayuno y atenuar sus consecuencias. Objetivo. El objetivo de este trabajo ha sido validar la hipótesis de que la NEM disminuye la incidencia de la TB en un modelo experimental de NPT. Material y métodos. Veinticuatro ratas Wistar adultas fueron sometidas durante 10 días a un régimen de infusión continua de NPT a través de un catéter yugular. Se distribuyeron aleatoriamente en dos grupos: • Grupo Control (n=11): animales en ayunas con infusión de NPT estándar (300 ml/24 h, 280 kcal/kg/24 h), sin acceso a comida y agua. • Grupo NEM (n=13): NPT estándar y dieta oral (hasta 15 g/24 h de pienso, 3,1 kcal/g) y acceso libre a agua. Al final del experimento, los animales fueron sacrificados y se obtuvieron muestras de ganglios linfáticos mesentéricos (GGLL), sangre portal y sangre periférica para su posterior cultivo y diagnóstico de TB, que se definió como la presencia de enterobacterias en cualquiera de los campos observados. Resultados. En el grupo NEM la curva de peso presentó una mejor evolución y la incidencia de la TB disminuyó significativamente, un 8%, frente al 45% del grupo CTRL (p < 0,05). El riesgo relativo (RR) fue de 5,9 (IC 95% 0,81-43,71) y el número necesario a tratar (NNT) fue de 3 (IC 95% 2-20). Conclusiones. La NEM reduce la incidencia de la TB en un modelo experimental de nutrición parenteral, abriéndose como vía de investigación la suposición de que la reducción de la TB puede disminuir el riesgo de sepsis que pueden estar asociadas a la ECN (AU)

Introduction. Both necrotizing enterocolitis (NEC) and bacterial translocation (BT) have in common that bacterial overgrowth, a decrease in immunity and intestinal mucosal damage, followed by a barrier failure, can act as trigger factors. The main objectives in NEC treatment are to reduce mortality due to sepsis and to promote feeding tolerance. To achieve that, Minimal Enteral Nutrition (MEN) (less than 25% of the calories provided by enteral route) is a more and more used technique in newborns who receive Parenteral Nutrition (PN) to slow down fasting related villi atrophy and to attenuate its consequences. Aim. To test the hypothesis that MEN decreases BT in an experimental model of PN. Methods. Twenty-four adult Wistar male rats received a continuous infusion of all-in-one PN solution through a jugular vein catheter. The animals were randomly divided in two groups and maintained in individual metabolic cages for ten days. • Control group (N=11): fasting rats receiving, standard PN (300 mL/kg/24 h, 280 kcal/ kg/24 h). • MEN group (N=13): standard PN and rat chow (15 g /24 h, 3,1 kcal/g). At the end of the experiment animals were sacrificed and mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered and cultured. Bacterial identification in blood was carried out by conventional methods and MLN culture was considered positive with a growth over 100 Colony Forming Units/g. Results. Weight curve was better in MEN group and BT was also significantly reduced. Translocation was found in 45% of control group and 8% of MEN group (p < 0,05). The relative risk (RR) was 5,9 (IC 95% 0,81-43,71) and the number needed to treat (NNT) was 3 (95% CI 2-20). Conclusions. 1. MEN reduces the incidence of BT in an experimental model of parenteral nutrition. 2. BT reduction could decrease NEC-related sepsis risk (AU)

Enterocolitis necrotizante en el período neonatal / Neonatal necrotizing enterocolitis

La E.N. es un cuadro grave y potencialmente fatal. Actualmente se piensa que intervienen en su patogenia: la isquemia intestinal, el exceso de alimentación y la colonización por bacterias patógenas. Se destacan como factores de riesgo la prematurez, la progresión rápida de alimentación, la poliglobulia y la asfixia. El cuadro clínico se caracteriza por distensión abdominal, retención gástrica, sangre en deposiciones y neumatosis intestinal. Sus complicaciones son: perforación intestinal, peritonitis y choque. El diagnóstico oportuno permite un tratamiento médico inicial, que consiste en reposo digestivo, descompresión con sonda, control seriado y antibióticos de amplio espectro. La cirugía se reserva para las complicaciones. Se sugiere la aplicación de un esquema preventivo basado en: uso de leche humana para prematuros, progreso lento de la alimentación, ayuno inicial en niños con asfixia y observación cuidadosa de los recién nacidos de riesgo

Necrotising enterocolitis: a management protocol for developing countries

28 cases of necrotising enterocolitis (NEC) comprising 11 term and 17 preterm patients were diagnosed between January 1990 and December 1995 at the University Hospital of the West Indies (UHWI). Treatment was in accordance with a management protocol which emphasised aggressive screening of potential cases, early laparotomy for bowel perforation and primary anastomosis after small bowel resection. There were three deaths among the 13 cases of bowel perforation. Centres in developing countries can achieve rates of survival comparable to those in the developed world in babies with NEC weighing over 1000 grams by adopting the UHWI management protocol.