RESUMEN
INTRODUCTION: Eating, drinking and swallowing difficulties are commonly reported morbidities for individuals born with OA/TOF. This study aimed to determine the nature and prevalence of eating, drinking and oro-pharyngeal swallowing difficulties reported in this population. METHOD: A systematic review and meta-proportional analysis were conducted (PROSPERO: CRD42020207263). MEDLINE, EMBASE, CINAHL, Pubmed, Scopus, Web of Science databases and grey literature were searched. Quantitative and qualitative data were extracted relating to swallow impairment, use of mealtime adaptations and eating and drinking-related quality of life. Quantitative data were summarised using narrative and meta-proportional analysis methods. Qualitative data were synthesised using a meta-aggregation approach. Where quantitative and qualitative data described the same phenomenon, a convergent segregated approach was used to synthesise data. RESULTS: Sixty-five studies were included. Six oro-pharyngeal swallow characteristics were identified, and pooled prevalence calculated: aspiration (24%), laryngeal penetration (6%), oral stage dysfunction (11%), pharyngeal residue (13%), nasal regurgitation (7%), delayed swallow initiation (31%). Four patient-reported eating/drinking difficulties were identified, and pooled prevalence calculated: difficulty swallowing solids (45%), difficulty swallowing liquids (6%), odynophagia (30%), coughing when eating (38%). Three patient-reported mealtime adaptations were identified, and pooled prevalence calculated: need for water when eating (49%), eating slowly (37%), modifying textures (28%). Mixed methods synthesis of psychosocial impacts identified 34% of parents experienced mealtime anxiety and 25% report challenging mealtime behaviours reflected in five qualitative themes: fear and trauma associated with eating and drinking, isolation and a lack of support, being aware and grateful, support to cope and loss. CONCLUSIONS: Eating and drinking difficulties are common in adults and children with repaired OA/TOF. Oro-pharyngeal swallowing difficulties may be more prevalent than previously reported. Eating, drinking and swallowing difficulties can impact on psychological well-being and quality of life, for the individual and parents/family members. Long-term, multi-disciplinary follow-up is warranted.
Asunto(s)
Trastornos de Deglución , Atresia Esofágica , Humanos , Trastornos de Deglución/etiología , Atresia Esofágica/cirugía , Fístula Traqueoesofágica/cirugía , Calidad de Vida , Ingestión de Alimentos/fisiología , Ingestión de Líquidos/fisiologíaRESUMEN
PURPOSE: Previous studies have shown a higher recurrence rate and longer operative times for thoracoscopic repair (TR) of congenital diaphragmatic hernia (CDH) compared to open repair (OR). An updated meta-analysis was conducted to re-evaluate the surgical outcomes of TR. METHODS: A comprehensive literature search comparing TR and OR in neonates was performed in accordance with the PRISMA statement (PROSPERO: CRD42020166588). RESULTS: Fourteen studies were selected for quantitative analysis, including a total of 709 patients (TR: 308 cases, OR: 401 cases). The recurrence rate was higher [Odds ratio: 4.03, 95% CI (2.21, 7.36), p < 0.001] and operative times (minutes) were longer [Mean Difference (MD): 43.96, 95% CI (24.70, 63.22), p < 0.001] for TR compared to OR. A significant reduction in the occurrence of postoperative bowel obstruction was observed in TR (5.0%) compared to OR (14.8%) [Odds ratio: 0.42, 95% CI (0.20, 0.89), p = 0.02]. CONCLUSIONS: TR remains associated with higher recurrence rates and longer operative times. However, the reduced risk of postoperative bowel obstruction suggests potential long-term benefits. This study emphasizes the importance of meticulous patient selection for TR to mitigate detrimental effects on patients with severe disease.
Asunto(s)
Hernias Diafragmáticas Congénitas , Herniorrafia , Toracoscopía , Humanos , Hernias Diafragmáticas Congénitas/cirugía , Toracoscopía/métodos , Herniorrafia/métodos , Recién Nacido , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , RecurrenciaRESUMEN
Medium-chain fatty acids (MCFAs), particularly decanoic acid (C10) and octanoic acid (C8), have garnered attention in recent years for their potential antiepileptic properties. A previous study from our laboratory demonstrated that C10 targets the PPARγ nuclear receptor, increasing the activity of the antioxidant enzyme catalase and thereby possibly modulating peroxisomal content. Here, we examined markers of peroxisomal content and activity in response to C10 and C8 exposure in neuronal-like SH-SY5Y cells. SH-SY5Y were treated with 250 mM C10 or C8 for a period of 6 days. Following this, biochemical markers of peroxisomal content and function were assessed, including acyl-coA oxidase activity, peroxisomal gene expression and peroxisomal VLCFA ß-oxidation. Our findings revealed that C10 treatment augments acyl-CoA oxidase 1 (ACOx1) activity by 129% in comparison to control cells. An exploration into genes related to peroxisomal biosynthesis showed 23% increased expression of PEX11α upon C10 exposure, implying peroxisomal proliferation. Furthermore, it was observed that C10 exposure not only elevated ACOx1 activity but also enhanced peroxisomal ß-oxidation of docosanoic acid (C22). Our findings bolster the premise that C10 functions as a peroxisome proliferator, influencing peroxisomal content and function. Further investigations are required to fully understand the mechanistic details as to how this may be beneficial in epilepsy and the potential implications with regards to peroxisomal disease.
RESUMEN
Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.
Asunto(s)
Inositol , Defectos del Tubo Neural , Inositol/metabolismo , Inositol/farmacología , Defectos del Tubo Neural/metabolismo , Defectos del Tubo Neural/prevención & control , Animales , Femenino , Ratones , Embarazo , Embrión de Mamíferos/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos , Metaboloma , Ácido Fólico/metabolismoRESUMEN
BACKGROUND: The long-term effects of Hirschsprung disease are clinically variable. An improved understanding of challenges patients may face as adults can help inform transitional care management. OBJECTIVE: To explore the outcomes and transitional care experiences in adult patients with Hirschsprung. DESIGN: Cohort study. SETTING: Single center. PATIENTS: All patients treated for Hirschsprung between 1977 and 2001 (aged older than 18 years at the time of survey distribution in July 2018-2019). Eligible patients were sent validated multidomain surveys and qualitative questions regarding their transitional care. MAIN OUTCOME MEASURES: Status of transitional care, bowel function, and quality-of-life assessment. Qualitative analysis of transitional care experience. RESULTS: Of 139 patients, 20 had received transition care (10 had at least 1 visit but had been discharged and 10 were receiving ongoing follow-up). These patients had inferior bowel function and quality-of-life scores at follow-up. Twenty-three patients (17%) had issues with soiling at the time of discharge, and 7 patients received transitional care. Of these 23 patients, 9 (39%) had a normal Bowel Function Score (17 or more), 5 (22%) had a poor score (less than 12), and 1 had since had a stoma formation. Eighteen patients (13%) had active moderate-severe issues related to bowel function, only 5 had been transitioned, and just 2 remained under ongoing care. Importantly, when these patients were discharged from our pediatric center, at a median age of 14 (interquartile range, 12-16) years, 10 of 17 patients had no perceptible bowel issues, suggesting a worsening of function after discharge. LIMITATIONS: The retrospective design and reliance on clinical notes to gather information on discharge status as well as patient recall of events. CONCLUSIONS: There remains a small but significant proportion of Hirschsprung patients for whom bowel function either remains or becomes a major burden. These results support a need to better stratify patients requiring transitional care and ensure a clear route to care if their status changes after discharge. See Video Abstract . ATENCIN DE TRANSICIN EN PACIENTES CON ENFERMEDAD DE HIRSCHSPRUNG, LOS QUE SE QUEDAN ATRS: ANTECEDENTES:Los efectos a largo plazo de la enfermedad de Hirschsprung son clínicamente variables. Una mejor comprensión de los desafíos que los pacientes pueden enfrentar cuando sean adultos puede ayudar a informar la gestión de la atención de transición.OBJETIVO:Explorar los resultados y las experiencias de atención de transición en pacientes adultos con Hirschsprung.DISEÑO:Estudio de cohorte.AJUSTE:Unico centro.PACIENTES:Todos los pacientes tratados por Hirschsprung 1977-2001 (edad >18 años en el momento de la encuesta, Julio de 2018-2019). A los pacientes elegibles se les enviaron encuestas multidominio validadas, así como preguntas cualitativas sobre su atención de transición.PRINCIPALES MEDIDAS DE RESULTADOS:Estado de la atención de transición, función intestinal y evaluación de la calidad de vida. Análisis cualitativo de la experiencia de cuidados transicionales.RESULTADOS:De 139 pacientes, 20 habían recibido atención de transición (10 tuvieron al menos una visita pero habían sido dados de alta y 10 estaban recibiendo seguimiento continuo). Estos pacientes tenían puntuaciones inferiores de función intestinal y calidad de vida en el seguimiento. Veintitrés (17%) pacientes tuvieron problemas para ensuciarse en el momento del alta y 7 recibieron atención de transición. De estos, 9/23 (39%) tenían una puntuación de función intestinal normal (≥17), 5/23 (22%) tenían una puntuación baja (<12) y un paciente había tenido desde entonces una formación de estoma. Dieciocho (13%) pacientes tenían problemas activos de moderados a graves relacionados con la función intestinal, solo cinco habían realizado la transición y solo 2 permanecían bajo atención continua. Es importante destacar que cuando estos pacientes fueron dados de alta de nuestro centro pediátrico, a una edad promedio de 14 [RIQ 12-16] años, 10/17 no tenían problemas intestinales perceptibles, lo que sugiere un empeoramiento de la función después del alta.LIMITACIONES:El diseño retrospectivo y la dependencia de notas clínicas para recopilar información sobre el estado del alta, así como el recuerdo de los eventos por parte del paciente.CONCLUSIÓN:Sigue existiendo una proporción pequeña pero significativa de pacientes con Hirschsprung para quienes la función intestinal permanece o se convierte en una carga importante. Estos resultados respaldan la necesidad de estratificar mejor a los pacientes que requieren atención de transición y garantizar una ruta clara hacia la atención si su estado cambia después del alta. ( Traducción-Dr. Yesenia Rojas-Khalil ).
Asunto(s)
Enfermedad de Hirschsprung , Calidad de Vida , Humanos , Enfermedad de Hirschsprung/terapia , Enfermedad de Hirschsprung/cirugía , Masculino , Femenino , Adulto , Adolescente , Cuidado de Transición/organización & administración , Adulto Joven , Incontinencia Fecal/terapia , Incontinencia Fecal/etiología , Transición a la Atención de Adultos , Estudios Retrospectivos , Estudios de Cohortes , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Microbioma Gastrointestinal , Cirrosis Hepática , Humanos , Animales , Cirrosis Hepática/complicaciones , Ratones , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Método Doble Ciego , Ratas , Modelos Animales de Enfermedad , Femenino , Persona de Mediana Edad , Traslocación Bacteriana/efectos de los fármacos , Carbono/uso terapéutico , Carbono/farmacologíaRESUMEN
BACKGROUND: The Clavien-Madadi classification is a novel instrument for the assessment and grading of unexpected events in pediatric surgery, based on the Clavien-Dindo classification. The system has been adjusted to better fit the pediatric population in a prospective single-center study. There is a need now to validate the Clavien-Madadi classification within an international expert network. METHODS: A pediatric surgical working group created 19 case scenarios with unexpected events in a multi-staged process. Those were circulated within the European Reference Network of Inherited and Congenital Anomalies (ERNICA) and surgeons were instructed to rate the scenarios according to the Clavien-Madadi vs. Clavien-Dindo classification. RESULTS: 59 surgeons from 12 European countries completed the questionnaire. Based on ratings of the case scenarios, the Clavien-Madadi classification showed significantly superior agreement rates of the respondents (85.9% vs 76.2%; p < 0.05) and was less frequently considered inaccurate for rating the pediatric population compared to Clavien-Dindo (2.1% vs 11.1%; p = 0.05). Fleiss' kappa analysis showed slightly higher strength of agreement using the Clavien-Madadi classification (0.74 vs 0.69). Additionally, intraclass correlation coefficient was slightly higher for the Clavien-Madadi compared to the Clavien-Dindo classification (ICCjust 0.93 vs 0.89; ICCunjust 0.93 vs 0.89). More pediatric surgeons preferred the Clavien-Madadi classification for the case scenarios (43.0% vs 11.8%; p = 0.002) and advantages of the Clavien-Madadi were confirmed by 81.4% of the surgeons. CONCLUSION: The Clavien-Madadi classification is an accurate and reliable instrument for the grading of unexpected events in pediatric surgery. We therefore recommend its application in clinical and academic pediatric surgical practice. LEVEL OF EVIDENCE: III.
Asunto(s)
Pediatría , Humanos , Niño , Estudios Prospectivos , Europa (Continente) , Encuestas y Cuestionarios , Complicaciones Posoperatorias/epidemiología , Complicaciones Intraoperatorias/clasificación , Complicaciones Intraoperatorias/epidemiología , Procedimientos Quirúrgicos OperativosRESUMEN
Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous. Amniotic fluid (AF) is a source of cells from multiple developing organs. Using single-cell analysis, we characterized the cellular identities present in human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modeling, we derived lung organoids from AF and tracheal fluid cells of congenital diaphragmatic hernia fetuses, recapitulating some features of the disease. AF organoids are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalized to the fetus at clinically relevant developmental stages.
Asunto(s)
Hernias Diafragmáticas Congénitas , Embarazo , Femenino , Humanos , Hernias Diafragmáticas Congénitas/metabolismo , Líquido Amniótico/metabolismo , Atención Prenatal , Pulmón/metabolismo , Organoides/metabolismoRESUMEN
BACKGROUND: The European Reference Network for rare Inherited Congenital Anomalies, ERNICA, guidelines for gastroschisis cover perinatal period to help teams to improve care. METHOD: A systematic literature search including 136 publications was conducted. Research findings were assessed following the GRADE methodology. The evidence to decision framework was used to determine the strength and direction of recommendations. RESULTS: The mode or timing of delivery do not impact neonatal mortality, risk of NEC or time on parenteral nutrition (PN). Intra or extra abdominal bowel dilatation predict complex gastroschisis and longer length of hospital stay but not increased perinatal mortality. Outcomes after Bianchi procedure and primary fascia closure under anesthesia are similar. Sutureless closure decreases the rate of surgical site infections and duration of ventilation compared to surgical closure. Silo-staged closure with or without intubation results in similar outcomes. Outcomes of complex gastroschisis (CG) undergoing early or delayed surgical repair are similar. Early enteral feeds starting within 14 days is associated with lower risk of surgical site infection. RECOMMENDATIONS: The panel suggests vaginal birth between 37 and 39 w in cases of uncomplicated gastroschisis. Bianchi's approach is an option in simple gastroschisis. Sutureless closure is suggested when general anesthesia can be avoided, sutured closure. If anesthesia is required. Silo treatment without ventilation and general anesthesia can be considered. In CG with atresia primary intestinal repair can be attempted if the condition of patient and intestine allows. Enteral feeds for simple gastroschisis should start within 14 days.
Asunto(s)
Gastrosquisis , Gastrosquisis/cirugía , Humanos , Recién Nacido , Europa (Continente) , Enfermedades Raras , FemeninoRESUMEN
The urea cycle enzyme argininosuccinate lyase (ASL) enables the clearance of neurotoxic ammonia and the biosynthesis of arginine. Patients with ASL deficiency present with argininosuccinic aciduria, an inherited metabolic disease with hyperammonemia and a systemic phenotype coinciding with neurocognitive impairment and chronic liver disease. Here, we describe the dysregulation of glutathione biosynthesis and upstream cysteine utilization in ASL-deficient patients and mice using targeted metabolomics and in vivo positron emission tomography (PET) imaging using (S)-4-(3-18F-fluoropropyl)-l-glutamate ([18F]FSPG). Up-regulation of cysteine metabolism contrasted with glutathione depletion and down-regulated antioxidant pathways. To assess hepatic glutathione dysregulation and liver disease, we present [18F]FSPG PET as a noninvasive diagnostic tool to monitor therapeutic response in argininosuccinic aciduria. Human hASL mRNA encapsulated in lipid nanoparticles improved glutathione metabolism and chronic liver disease. In addition, hASL mRNA therapy corrected and rescued the neonatal and adult Asl-deficient mouse phenotypes, respectively, enhancing ureagenesis. These findings provide mechanistic insights in liver glutathione metabolism and support clinical translation of mRNA therapy for argininosuccinic aciduria.
Asunto(s)
Aciduria Argininosuccínica , Hepatopatías , Adulto , Humanos , Animales , Ratones , Aciduria Argininosuccínica/genética , Aciduria Argininosuccínica/terapia , Cisteína , Glutatión , MetabolómicaRESUMEN
BACKGROUND: Optimising postnatal growth facilitates better long-term neonatal neurodevelopmental outcomes. Early postnatal growth is often hindered by a variety of factors unique to the extrauterine environment and digestive immaturity both contributing to reduced enteral feed tolerance during the first few days and weeks after birth. Preterm infants display varying levels of pancreatic insufficiency that are related to gestational age and providing digestive enzyme supplementation, may be one way in which to improve postnatal growth in enterally fed preterm babies. SUMMARY: In this review, we explore which exocrine pancreatic enzymes are deficient in preterm babies, the methods by which exocrine pancreatic function is measured, potential avenues by which digestive enzyme replacement might improve postnatal growth failure, and which babies might benefit most from this intervention. KEY MESSAGES: Pancreatic exocrine function exhibits developmental immaturity in extremely preterm infants and may contribute to postnatal growth failure. Stool elastase is a simple, non-invasive method of assessing pancreatic function in preterm infants. Available evidence does not currently support routine use of digestive enzyme supplementation in preterm infants.
Asunto(s)
Suplementos Dietéticos , Insuficiencia Pancreática Exocrina , Recien Nacido Prematuro , Humanos , Recién Nacido , Insuficiencia Pancreática Exocrina/tratamiento farmacológico , Recien Nacido Prematuro/crecimiento & desarrollo , Elastasa Pancreática , Nutrición Enteral , Terapia de Reemplazo Enzimático , Edad Gestacional , Desarrollo InfantilRESUMEN
BACKGROUND: Tissue hypoxia remains a leading cause of morbidity and mortality in preterm infants. Current biomarkers often detect irreversible hypoxic cellular injury (i.e. lactate) and are non-specific. A new biomarker is needed which detects tissue hypoxia before irreversible damage occurs. AIMS: To investigate the relation between serum ischemia modified albumin (IMA), a marker of hypoxia; and analytic variables, patient related variables and conditions associated with hypoxia, in preterm infants. STUDY DESIGN: Retrospective cohort study. SUBJECTS: Infants with a gestational age < 30 weeks and/or birth weight < 1000 g. OUTCOME MEASURES: We collected two remnant blood samples in the first week after birth and measured IMA. IMA/albumin ratio (IMAR) was used to adjust for albumin. We assessed correlations between IMA(R) and analytic variables (albumin, lipemia- and haemolysis index); mean-2 h SpO2; mean-2 h variability of regional splanchnic oxygen saturation (rsSO2), measured using near-infrared spectroscopy; and patent ductus arteriosus (PDA). RESULTS: Sixty-five infants were included. Albumin, the lipemia- and haemolysis index correlated negatively with IMA (r:-0.620, P<0.001; r:-0.458, P<0.001; and r:-0.337, P=0.002). IMAR correlated negatively with SpO2 (rho:-0.614, P<0.001). Lower rsSO2 variability correlated with higher IMAR values (rho:-0.785, n=14, P=0.001 and rho:-0.773, n=11, P=0.005). Infants with a hemodynamic significant PDA (hsPDA) had higher IMAR values than infants without PDA (0.13 [0.11-0.28], n=16 vs. 0.11 [0.08-0.20], n=29, P=0.005 and 0.11 [0.09-0.18], n=13 vs. 0.09 [0.06-0.17], n=37, P=0.026). CONCLUSIONS: When adjusted for albumin, the lipemia- and haemolysis index, IMAR has potential value as a marker for systemic hypoxia in preterm infants, considering the associations with SpO2, variability of rsSO2, and hsPDA.
Asunto(s)
Conducto Arterioso Permeable , Hiperlipidemias , Humanos , Recién Nacido , Lactante , Recien Nacido Prematuro , Biomarcadores , Estudios Retrospectivos , Hemólisis , Albúmina Sérica , Hipoxia , IsquemiaRESUMEN
AIM OF THE STUDY: Neonatal enterostomy is a known risk for growth failure. We hypothesized that episodes of inflammation may drive a catabolic state, exploring this by assessing serum biochemistry alongside growth trajectory in enterostomy patients. METHODS: A retrospective analysis of infants with histologically confirmed NEC from 01/2012-07/2021 in a tertiary neonatal surgical centre was performed. Change in weight-for-age Z-score (ΔZ) between stoma formation and closure was calculated. Serum CRP (C-reactive protein), urea, and creatinine levels were recorded and duration of elevated levels calculated as Area Under Curve (AUC). We examined for trends of serum levels rising together using intersecting moving averages. Spearman's correlation analysis was performed, while multivariable linear regression examined factors associated with ΔZ. RESULTS: 79 neonates were included. At stoma formation, median Z-score was -1.42 [range -4.73, +1.3]. Sixty-two patients (78 %) had a fall in Z-score during their time with a stoma, 16 (20 %) had a ΔZ less than -2. Urea AUC was significantly univariably correlated with ΔZ and remained statistically significant in a multivariable model (Exp(B) x 100 = -0.57[-1, -0.09]; p = 0.022). The number of biomarker peaks correlated significantly with ΔZ for urea (r = -0.25; p = 0.025) and CRP (r = -0.35; p = 0.0017) but not Creatinine (r = -0.21; p = 0.066). Analysing the number of peaks of any combination of variables coinciding was consistently significantly correlated negatively with ΔZ (r = -0.29 to -0.27; p ≤ 0.016 for all). CONCLUSION: Our data shows that infants who were more severely affected by growth failure had more frequent and severe uremia while they had a stoma (suggesting a catabolic state). Disturbances in urea were commonly associated with CRP, suggesting that inflammation is a significant factor in growth failure in these infants. These findings promote aggressive management of sepsis in these infants, as well as suggesting an earlier closure of stoma to minimise their "at-risk"' period.
Asunto(s)
Enterocolitis Necrotizante , Enterostomía , Estomas Quirúrgicos , Recién Nacido , Lactante , Humanos , Estudios Retrospectivos , Insuficiencia de Crecimiento/etiología , Inflamación , Urea , Enterocolitis Necrotizante/cirugíaRESUMEN
The role of a basic scientist working with paediatric surgeons is not an obvious one. However, there are several levels at which science can contribute to the speciality, and also ways that scientists can learn useful lessons from paediatric surgery. As most conditions treated by paediatric surgeons have low case numbers, we need to find ways of defining optimal treatment and developing novel therapies within a challenging number of patients.
Asunto(s)
Investigación Biomédica , Especialidades Quirúrgicas , Cirujanos , Niño , HumanosRESUMEN
AIM OF THE STUDY: We describe the short- and medium-term outcomes following open and laparoscopic assisted oesophageal replacement surgery in a single tertiary paediatric surgical centre. METHODS: A retrospective review (institutional audit approval no. 3213) on patients who underwent open or laparoscopic-assisted oesophageal replacement (OAR vs. LAR) at our centre between 2002 and 2021 was completed. Data collected (demographics, early complications, stricture formation, need for oesophageal dilatations, and mortality) were analysed using GraphPad Prism v 9.50 and are presented as median (IQR). RESULTS: 71 children (37 male) had oesophageal replacement surgery at a median age of 2.3 years (IQR 4.7 years). 51 were LAR (6 conversions). Replacement conduit was stomach (n = 67), colon (n = 3), or jejunum (n = 1). Most gastric transpositions had a pyloroplasty (46/67) or pyloromyotomy (14/67). Most common pathology was oesophageal atresia (n = 50 including 2 failed transpositions), caustic injury (n = 19 including 3 due to button battery), stricture of unknown cause (n = 1), and megaoesophagus (n = 1). There were 2 (2.8 %) early postoperative deaths at 2 days (major vessel thrombosis), 1 month (systemic sepsis), and one death at 5 years in the community. The rate of postoperative complications were comparable across LAR and OAR including anastomotic leak, pleural effusions, or early strictures. More patients with caustic pathology needed dilatations (60 % vs 30 % in OA, p = 0.05). CONCLUSIONS: Outcomes of open and laparoscopic-assisted oesophageal replacement procedures are comparable in the short and medium term. Anastomotic stricture is higher in those with caustic injury. LEVEL OF EVIDENCE: IV.
Asunto(s)
Cáusticos , Atresia Esofágica , Estenosis Esofágica , Laparoscopía , Niño , Humanos , Masculino , Preescolar , Estenosis Esofágica/epidemiología , Estenosis Esofágica/etiología , Estenosis Esofágica/cirugía , Constricción Patológica/cirugía , Atresia Esofágica/cirugía , Atresia Esofágica/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Laparoscopía/métodos , Estudios RetrospectivosRESUMEN
Argininosuccinate lyase (ASL) is integral to the urea cycle detoxifying neurotoxic ammonia and the nitric oxide (NO) biosynthesis cycle. Inherited ASL deficiency causes argininosuccinic aciduria (ASA), a rare disease with hyperammonemia and NO deficiency. Patients present with developmental delay, epilepsy and movement disorder, associated with NO-mediated downregulation of central catecholamine biosynthesis. A neurodegenerative phenotype has been proposed in ASA. To better characterise this neurodegenerative phenotype in ASA, we conducted a retrospective study in six paediatric and adult metabolic centres in the UK in 2022. We identified 60 patients and specifically looked for neurodegeneration-related symptoms: movement disorder such as ataxia, tremor and dystonia, hypotonia/fatigue and abnormal behaviour. We analysed neuroimaging with diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) in an individual with ASA with movement disorders. We assessed conventional and DTI MRI alongside single photon emission computer tomography (SPECT) with dopamine analogue radionuclide 123 I-ioflupane, in Asl-deficient mice treated by hASL mRNA with normalised ureagenesis. Movement disorders in ASA appear in the second and third decades of life, becoming more prevalent with ageing and independent from the age of onset of hyperammonemia. Neuroimaging can show abnormal DTI features affecting both grey and white matter, preferentially basal ganglia. ASA mouse model with normalised ureagenesis did not recapitulate these DTI findings and showed normal 123 I-ioflupane SPECT and cerebral dopamine metabolomics. Altogether these findings support the pathophysiology of a late-onset movement disorder with cell-autonomous functional central catecholamine dysregulation but without or limited neurodegeneration of dopaminergic neurons, making these symptoms amenable to targeted therapy.
RESUMEN
AIM: To review our experience of laparoscopic inguinal hernia repair (LIHR) regarding complication rates, the practice of closing the asymptomatic patent processes vaginalis (PPV), and comparison of complication rates between pre-term (< 37 week gestation) and term infants. METHODS: Retrospective review of LIHR performed between 2009 and 2021. Repair was performed by intracorporal single or double purse string/purse string + Z-stitch using a non-absorbable suture. Data were analyzed using Chi-squared/Mann-Whitney and are quoted as median (range). RESULTS: 1855 inguinal rings were closed in 1195 patients (943 (79%) male). 1378 rings (74%) were symptomatic. 492 (41%) patients were pre-term. Corrected gestational age at surgery was 55 weeks (31 weeks-14.6 years) and weight 5.9 kg (1-65.5). Closure of contralateral PPV was higher in the premature group (210/397 [53%] vs. 265/613 [43%] p = 0.003). There were 23 recurrences in 20 patients, of whom 10 had been born prematurely. The only factor significantly associated with a lower recurrence was use of a second stitch (p = 0.011). CONCLUSION: This is the largest single-center reported series of LIHR. LIHR is safe at any age, the risk of recurrence is low, and can be corrected by re-laparoscopy. Use of a Z-stitch or second purse string is associated with a significantly lower rate of recurrence.
Asunto(s)
Hernia Inguinal , Laparoscopía , Hidrocele Testicular , Lactante , Femenino , Humanos , Masculino , Hernia Inguinal/cirugía , Resultado del Tratamiento , Herniorrafia , Recurrencia , Hidrocele Testicular/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVE: Survival of neonates with esophageal atresia (EA) is relatively high and stable, resulting in increased attention to optimizing care and longer-term morbidity. This study aimed to reach consensus on a quality indicator set for benchmarking EA care between hospitals, regions, or countries in a European clinical audit. METHODS: Using an online Delphi method, a panel of EA health care professionals and patient representatives rated potential outcome, structure, and process indicators for EA care identified through systematic literature and guideline review on a nine-point Likert scale in three questionnaires. Items were included based on predefined criteria. In rounds 2 and 3, participants were asked to select the five to ten most essential of the included indicators. RESULTS: An international panel of 14 patient representatives and 71 multidisciplinary health care professionals representing 41 European hospitals completed all questionnaires (response rate: 81%), eventually including 22 baseline characteristics and 32 indicators. After ranking, 10 indicators were prioritized by both stakeholder groups. In addition, each stakeholder group highly prioritized one additional indicator. Following an additional online vote by the other group, these were both added to the final set. CONCLUSION: This study established a core indicator set of twenty-two baseline characteristics, eight outcome indicators, one structure indicator, and three process indicators for evaluating (quality of) EA care in Europe. These indicators, covering various aspects of EA care, will be implemented in the European Pediatric Surgical Audit to enable recognition of practice variation and focus EA care improvement initiatives.
RESUMEN
Bioenergetic failure caused by impaired utilisation of glucose and fatty acids contributes to organ dysfunction across multiple tissues in critical illness. Ketone bodies may form an alternative substrate source, but the feasibility and safety of inducing a ketogenic state in physiologically unstable patients is not known. Twenty-nine mechanically ventilated adults with multi-organ failure managed on intensive care units were randomised (Ketogenic n = 14, Control n = 15) into a two-centre pilot open-label trial of ketogenic versus standard enteral feeding. The primary endpoints were assessment of feasibility and safety, recruitment and retention rates and achievement of ketosis and glucose control. Ketogenic feeding was feasible, safe, well tolerated and resulted in ketosis in all patients in the intervention group, with a refusal rate of 4.1% and 82.8% retention. Patients who received ketogenic feeding had fewer hypoglycaemic events (0.0% vs. 1.6%), required less exogenous international units of insulin (0 (Interquartile range 0-16) vs.78 (Interquartile range 0-412) but had slightly more daily episodes of diarrhoea (53.5% vs. 42.9%) over the trial period. Ketogenic feeding was feasible and may be an intervention for addressing bioenergetic failure in critically ill patients. Clinical Trials.gov registration: NCT04101071.