Core outcome set for perinatal interventions for congenital diaphragmatic hernia.

OBJECTIVE: To develop a core set of prenatal and neonatal outcomes for clinical studies evaluating perinatal interventions for congenital diaphragmatic hernia, using a validated consensus-building method. METHODS: An international steering group comprising 13 leading maternal-fetal medicine specialists, neonatologists, pediatric surgeons, patient representatives, researchers and methodologists guided the development of this core outcome set. Potential outcomes were collected through a systematic review of the literature and entered into a two-round online Delphi survey. A call was made for stakeholders with experience of congenital diaphragmatic hernia to review the list and score outcomes based on their perceived relevance. Outcomes that fulfilled the consensus criteria defined a priori were discussed subsequently in online breakout meetings. Results were reviewed in a consensus meeting, during which the core outcome set was defined. Finally, the definitions, measurement methods and aspirational outcomes were defined in online and in-person definition meetings by a selection of 45 stakeholders. RESULTS: Overall, 221 stakeholders participated in the Delphi survey and 198 completed both rounds. Fifty outcomes met the consensus criteria and were discussed and rescored by 78 stakeholders in the breakout meetings. During the consensus meeting, 93 stakeholders agreed eventually on eight outcomes, which constituted the core outcome set. Maternal and obstetric outcomes included maternal morbidity related to the intervention and gestational age at delivery. Fetal outcomes included intrauterine demise, interval between intervention and delivery and change in lung size in utero around the time of the intervention. Neonatal outcomes included neonatal mortality, pulmonary hypertension and use of extracorporeal membrane oxygenation. Definitions and measurement methods were formulated by 45 stakeholders, who also added three aspirational outcomes: duration of invasive ventilation, duration of oxygen supplementation and use of pulmonary vasodilators at discharge. CONCLUSIONS: We developed with relevant stakeholders a core outcome set for studies evaluating perinatal interventions in congenital diaphragmatic hernia. Its implementation should facilitate the comparison and combination of trial results, enabling future research to better guide clinical practice. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Learning curves of open and endoscopic fetal spina bifida closure: systematic review and meta-analysis.

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). RESULTS: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. CONCLUSIONS: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Curvas de aprendizaje del cierre de la espina bífida fetal mediante cirugía abierta y endoscópica: revisión sistemática y metaanálisis OBJETIVO: El ensayo del Estudio sobre la Gestión del Mielomeningocele (MOMS, por sus siglas en inglés) demostró la seguridad y eficacia de la cirugía fetal abierta para la espina bífida aperta (EBA). Las técnicas alternativas recientemente desarrolladas pueden reducir los riesgos de la madre sin comprometer los efectos neuroprotectores del feto. El objetivo de esta revisión sistemática fue evaluar la curva de aprendizaje (CA) de diferentes técnicas de cierre de la EBA fetal. MÉTODOS: Se realizaron búsquedas en las bases de datos de MEDLINE, Web of Science, EMBASE, Scopus y Cochrane, así como en la literatura gris, para identificar artículos relevantes sobre cirugía fetal para la EBA, sin restricción de idioma, publicados entre enero de 1980 y octubre de 2018. Se examinaron sistemáticamente los estudios identificados y se seleccionaron los que informaban de todos los procedimientos consecutivos y con seguimiento postnatal ≥12 meses. Los estudios se incluyeron sólo si informaban sobre las variables de resultado necesarias para medir la CA, definidas por la seguridad y la eficacia para el feto. Dos autores recuperaron los datos de forma independiente, evaluaron la calidad de los estudios y clasificaron las observaciones en bloques de 30 pacientes. Para el metaanálisis, los datos se agruparon mediante un modelo de efectos aleatorios cuando fueron heterogéneos. Para medir la CA, se usaron dos métodos complementarios. En el método de división de grupos, la competencia se definió cuando el procedimiento proporcionó resultados comparables a los del ensayo MOMS para 12 variables de resultados que representaban el resultado quirúrgico inmediato, la neuroprotección neonatal a corto plazo y la neuroprotección a largo plazo a ≥12 meses de edad. Luego, cuando se dispuso de los datos brutos de los pacientes, se realizó un análisis de suma acumulada basado en un resultado binario compuesto que definió el éxito de la cirugía. El resultado compuesto combinó cuatro variables clínicamente relevantes en cuanto a la seguridad (ausencia de parto pretérmino extremo <30 semanas; ausencia de muerte fetal a ≤7 días después de la cirugía) y eficacia (reducción de la hernia del rombencéfalo y ausencia de cualquier tratamiento neonatal de dehiscencia o derrame de líquido cefalorraquídeo en el lugar del cierre). RESULTADOS: De los 6024 resultados de la búsqueda, se incluyeron 17 (0,3%) estudios, todos ellos con un riesgo de sesgo bajo, moderado o incierto. El cierre de la EBA fetal se realizó mediante histerotomía estándar (11 estudios), mini histerotomía (un estudio) o fetoscopia, ya fuera mediante el cierre exteriorizado del útero de una sola capa (un estudio), el cierre percutáneo de una sola capa (tres estudios) o el cierre percutáneo de dos capas (un estudio). Sólo se pudieron metaanalizar los resultados de la histerotomía estándar. En general, los resultados mejoraron significativamente con la experiencia. Se alcanzó la competencia después de 35 casos consecutivos para la histerotomía estándar y se predijo que se alcanzaría después de ≥57 casos para la mini histerotomía y ≥56 para la fetoscopia percutánea de dos capas. En el caso de las fetoscopias percutánea y exteriorizada del útero de una sola capa, no se alcanzó la competencia en los 81 y 28 casos disponibles para el análisis, respectivamente, y no se pudo realizar el análisis de predicción de la CA. CONCLUSIONES: El número de casos operados está correlacionado con el resultado del cierre de la EBA fetal, y el número de casos operados necesarios para alcanzar la competencia estuvo entre 35 para la histerotomía estándar y ≥56-57 para las operaciones con mínima agresividad. Las observaciones realizadas proporcionan información importante para las instituciones que buscan establecer un nuevo centro fetal, desarrollar una nueva técnica de cirugía fetal o entrenar a su equipo, e informar a los médicos que remiten a especialistas a los posibles pacientes y a terceros. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The multi-disciplinary management of complex congenital and acquired tracheo-oesophageal fistulae.

AIM OF THE STUDY: Complex tracheo-oesophageal fistulae (TOF) are rare congenital or acquired conditions in children. We discuss here a multidisciplinary (MDT) approach adopted over the past 5 years. METHODS: We retrospectively collected data on all patients with recurrent or acquired TOF managed at a single institution. All cases were investigated with neck and thorax CT scan. Other investigations included flexible bronchoscopy and bronchogram (B&B), microlaryngobronchoscopy (MLB) and oesophagoscopy. All cases were subsequently discussed in an MDT meeting on an emergent basis if necessary. MAIN RESULTS: 14 patients were referred during this study period of which half had a congenital aetiology and the other half were acquired. The latter included button battery ingestions (5/7) and iatrogenic injuries during oesophageal atresia (OA) repair. Surgical repair was performed on cardiac bypass in 3/7 cases of recurrent congenital fistulae and all cases of acquired fistulae. Post-operatively, 9/14 (64%) patients suffered complications including anastomotic leak (1), bilateral vocal cord paresis (1), further recurrence (1), and mortality (1). Ten patients continue to receive surgical input encompassing tracheal/oesophageal stents and dilatations. CONCLUSIONS: MDT approach to complex cases is becoming increasingly common across all specialties and is important in making decisions in these difficult cases. The benefits include shared experience of rare cases and full access to multidisciplinary expertise.

Thalamonal, droperidol and fentanyl in induced hypovolaemic shock in the conscious dog.

Previous studies had shown that Thalamonal exerts a protective activity against hypovolaemic shock in experimental animals as well as in patients. The purpose of the present study was to make a long-term evaluation of the value of single doses of Thalamonal fentanyl and droperidol as shock-protecting agents in conscious dogs which received no replacement of blood loss. The study was conducted in 20 animals in which devices were implanted for measuring heart rate, arterial and venous blood pressure, left ventricular and left atrial blood pressure. The dogs were divided into 4 groups, receiving 20 ml of an i.v. injection containing either 0.025 mg/kg fentanyl, 0.625 mg/kg droperidol, 0.25 ml/kg Thalamonal (0.625 mg/kg droperidol + 0.0125 mg/kg fentanyl), or saline. Thalamonal allowed a 100 per cent survival of the dogs, one of the 5 animals survived in the droperidol group, whereas fentanyl and saline were completely ineffective. As a possible mechanism of action the interruption of the vicious sequence of blood loss, vasoconstriction and circulatory arrest at a peripheral and/or central level is discussed. The hypothesis of intracorporeal blood volume correction under the influence of Thalamonal as an anti-vasoconstrictor seems to be logical but needs further investigation.