Timing of magnetic resonance imaging in pregnancy for outcome prediction in congenital diaphragmatic hernia.

PURPOSE: To evaluate the impact of the timing of MRI on the prediction of survival and morbidity in patients with CDH, and whether serial measurements have a beneficial value. METHODS: This retrospective cohort study was conducted in two perinatal centers, in Germany and Italy. It included 354 patients with isolated CDH having at least one fetal MRI. The severity was assessed with the observed-to-expected total fetal lung volume (o/e TFLV) measured by two experienced double-blinded operators. The cohort was divided into three groups according to the gestational age (GA) at which the MRI was performed (< 27, 27-32, and > 32 weeks' gestation [WG]). The accuracy for the prediction of survival at discharge and morbidity was analyzed with receiver operating characteristic (ROC) curves. Multiple logistic regression analyses and propensity score matching examined the population for balance. The effect of repeated MRI was evaluated in ninety-seven cases. RESULTS: There were no significant differences in the prediction of survival when the o/e TFLV was measured before 27, between 27 and 32, and after 32 WG (area under the curve [AUC]: 0.77, 0.79, and 0.77, respectively). After adjustment for confounding factors, it was seen, that GA at MRI was not associated with survival at discharge, but the risk of mortality was higher with an intrathoracic liver position (adjusted odds ratio [aOR]: 0.30, 95% confidence interval [95%CI] 0.12-0.78), lower GA at birth (aOR 1.48, 95%CI 1.24-1.78) and lower o/e TFLV (aOR 1.13, 95%CI 1.06-1.20). ROC curves showed comparable prediction accuracy for the different timepoints in pregnancy for pulmonary hypertension, the need of extracorporeal membrane oxygenation, and feeding aids. Serial measurements revealed no difference in change rate of the o/e TFLV according to survival. CONCLUSION: The timing of MRI does not affect the prediction of survival rate or morbidity as the o/e TFLV does not change during pregnancy. Clinicians could choose any gestational age starting mid second trimester for the assessment of severity and counseling.

Multicentre, randomised controlled trial of physiological-based cord clamping versus immediate cord clamping in infants with a congenital diaphragmatic hernia (PinC): statistical analysis plan.

BACKGROUND: Infants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial). DESIGN: The PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4-8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved. TRIAL REGISTRATION: ClinicalTrials.gov NCT04373902 (registered April 2020).

Long-Term Evaluation of the Shape of the Reconstructed Diaphragm in Patients with Left-Sided Congenital Diaphragmatic Hernia Using Serial Chest Radiographs and Correlation to Further Complications.

Background: Defining risk factors for long-term comorbidities in patients after neonatal repair of congenital diaphragmatic hernia (CDH) is an important cornerstone of the implementation of targeted longitudinal follow-up programs. Methods: This study systematically assessed serial chest radiographs of 89 patients with left-sided CDH throughout a mean follow-up of 8.2 years. These geometrical variables for the left and right side were recorded: diaphragmatic angle (LDA, RDA), diaphragmatic diameter (LDD, RDD), diaphragmatic height (LDH, RDH), diaphragmatic curvature index (LDCI, RDCI), lower lung diameter (LLLD, RLLD) and thoracic area (LTA, RTA). Results: It was demonstrated that the shape of the diaphragm in patients with large defects systematically differs from that of patients with small defects. Characteristically, patients with large defects present with a smaller LDCI (5.1 vs. 8.4, p < 0.001) at 6 months of age, which increases over time (11.4 vs. 7.0 at the age of 15.5 years, p = 0.727), representing a flattening of the patch and the attached rudimentary diaphragm as the child grows. Conclusions: Multiple variables during early follow-up were significantly associated with comorbidities such as recurrence, scoliotic curves of the spine and a reduced thoracic area. Some geometrical variables may serve as surrogate parameters for disease severity, which is associated with long-term comorbidities.

Fetoscopic endoluminal tracheal occlusion vs expectant management for fetuses with severe left-sided congenital diaphragmatic hernia.

BACKGROUND: The treatment of fetuses with a congenital diaphragmatic hernia is challenging, but there is evidence that fetoscopic endoluminal tracheal occlusion has a benefit over expectant care. In addition, standardization and expertism have a great impact on survival and are probably crucial in centers that rely on expectant management with extracorporeal membrane oxygenation after birth. OBJECTIVE: This study aimed to examine the survival and morbidity rates of fetuses with a severe isolated left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion vs expectant management in high-volume centers. STUDY DESIGN: This was a multicenter, retrospective study that included all consecutive fetuses with severe isolated left-sided congenital diaphragmatic hernia who were expectantly managed in a German center or who underwent fetoscopic endoluminal tracheal occlusion in 3 other European centers (Belgium, France, and Italy). Severe congenital diaphragmatic hernia was defined as having an observed to expected total fetal lung volume ≤35% with intrathoracic position of the liver diagnosed with magnetic resonance imaging. All magnetic resonance images were centralized, and lung volumes were measured by 2 experienced operators who were blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect of the management strategy in the 2 groups on the short- and long-term outcomes. RESULTS: A total of 147 patients who were managed expectantly and 47 patients who underwent fetoscopic endoluminal tracheal occlusion were analyzed. Fetuses who were managed expectantly had lower observed to expected total fetal lung volumes (20.6%±7.5% vs 23.7%±6.8%; P=.013), higher gestational age at delivery (median weeks of gestation, 37.4; interquartile range, 36.6-38.00 vs 35.1; interquartile range, 33.1-37.2; P<.001), and more frequent use of extracorporeal membrane oxygenation (55.8% vs 4.3%; P<.001) than the fetuses who underwent fetoscopic endoluminal tracheal occlusion. The survival rates at discharge and at 2 years of age in the expectant management group were higher than the survival rates of the fetoscopic endoluminal tracheal occlusion group (74.3% vs 44.7%; P=.001 and 72.8% vs 42.5%; P=.001, respectively). After adjustment for maternal age, gestational age at birth, observed to expected total fetal lung volume, and birth weight Z-score, the odds ratios were 4.65 (95% confidence interval, 1.9-11.9; P=.001) and 4.37 (95% confidence interval, 1.8-11.0; P=.001), respectively. CONCLUSION: Fetuses with a severe isolated left-sided congenital diaphragmatic hernia had a higher survival rate when treated in an experienced center in Germany with antenatal expectant management and frequent use of extracorporeal membrane oxygenation during the postnatal period than fetuses who were treated with fetoscopic endoluminal tracheal occlusion in 3 centers in Belgium, France, and Italy.

Case Report: Fetoscopic Laparoschisis (FETO-LAP)-A New Therapeutic Route to Explore for Fetuses with Severe Diaphragmatic Hernias.

BACKGROUND: The purpose of this report is to describe the seminal case of a near-term human fetus with a life-threatening left diaphragmatic hernia that underwent fetoscopic tracheal occlusion (FETO) combined with fetoscopic partial removal of herniated bowel from the fetal chest by fetoscopic laparoschisis (FETO-LAP). CASE SUMMARY: A life-threatening left diaphragmatic hernia (liver-up; o/e LHR of ≤25%; MRI lung volume ≤ 20%) was observed in a human fetus at 34 weeks of gestation. After counselling the mother about the high risks of postnatal demise if left untreated, the expected limitations of fetoscopic tracheal occlusion (FETO), and the previously untested option of combining FETO with fetoscopic laparoschisis, i.e., partial removal of the herniated bowel from the fetal chest (FETO-LAP), she consented to the latter novel treatment approach. FETO-LAP was performed at 36 + 5 weeks of gestation under general maternofetal anesthesia. Mother and fetus tolerated the procedure well. The neonate was delivered and the balloon removed on placental support at 37 + 2 weeks of gestation. On ECMO, a rapid increase in tidal volume was seen over the next eight days. Unfortunately, after this period, blood clots obstructed the ECMO circuit and the neonate passed away. DISCUSSION: This seminal case shows that in a fetus with severe left diaphragmatic hernia, partial removal of the herniated organs from the fetal chest is not only possible by minimally invasive fetoscopic techniques but also well tolerated. As the effect of FETO alone is limited in saving severely affected fetuses, combining FETO with fetoscopic laparoschisis (FETO-LAP) offers a new therapeutic route with multiple, potentially life-saving implications.

Survival in very preterm infants with congenital diaphragmatic hernia and association with prenatal imaging markers: A retrospective cohort study.

OBJECTIVES: To describe the outcomes of preterm born infants with congenital diaphragmatic hernia (CDH; ≤32.0 weeks of gestation) and the associations between prenatal imaging markers and survival. DESIGN: Retrospective cohort study. SETTING: Multicentre study in large referral centres. POPULATION: Infants with an isolated unilateral CDH, live born at 32.0 weeks or less of gestation, between January 2009 and January 2020. METHODS: Neonatal outcomes were evaluated for infants that were expectantly managed during pregnancy and infants that underwent fetoscopic endoluminal tracheal occlusion (FETO) therapy, separately. We evaluated the association between prenatal imaging markers and survival to discharge. Prenatal imaging markers included observed to expected lung-to-head ratio (o/e LHR), side of the defect, liver position, stomach position grade, and observed to expected total fetal lung volume (o/e TFLV). MAIN OUTCOME MEASURE: Survival to discharge. RESULTS: We included 53 infants born at 30+4 (interquartile range 29+1 -31+2 ) weeks. Survival in fetuses expectantly managed during pregnancy was 48% (13/27) in left-sided CDH and 33% (2/6) in right-sided CDH. Survival in fetuses that underwent FETO therapy was 50% (6/12) in left-sided CDH and 25% (2/8) in right-sided CDH. The o/e LHR at baseline was positively associated with survival in cases expectantly managed during pregnancy (odds ratio [OR] 1.20, 95% CI 1.07-1.42, p < 0.01), but not in cases that received FETO therapy (OR 1.01, 95% CI 0.88-1.15, p = 0.87). Stomach position grade (p = 0.03) and o/e TFLV were associated with survival (p = 0.02); liver position was not (p = 0.13). CONCLUSIONS: In infants with CDH born at or before 32 weeks of gestation, prenatal imaging markers of disease severity were associated with postnatal survival.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

Spontaneous breathing approach in mild congenital diaphragmatic hernia: A resuscitation algorithm.

Background: Infants with a congenital diaphragmatic hernia (CDH) and expected mild pulmonary hypoplasia have an estimated survival rate of 90%. Current guidelines for delivery room management do not consider the individual patient's disease severity, but an individualized approach with spontaneous breathing instead of routine mechanical ventilation could be beneficial for the mildest cases. We developed a resuscitation algorithm for this individualized approach serving two purposes: improving the success rate by structuring the approach and providing a guideline for other centers. Methods: An initial algorithm was discussed with all local stakeholders. Afterwards, the resulting algorithm was refined using input from international experts. Results: Eligible CDH infants: left-sided defect, observed to expected lung-to-head ratio ≥50%, gestational age at birth ≥37.0 weeks, and no major associated structural or genetic abnormalities. To facilitate fetal-to-neonatal transition, we propose to start stabilization with non-invasive respiratory support and to adjust this individually. Conclusions: Infants with mild CDH might benefit from an individualized approach for neonatal resuscitation. Herein, we present an algorithm that could serve as guidance for centers implementing this.

Impact of Time Point of Extracorporeal Membrane Oxygenation on Mortality and Morbidity in Congenital Diaphragmatic Hernia: A Single-Center Case Series.

Since there are no data available on the influence of the time point of ECMO initiation on morbidity and mortality in patients with congenital diaphragmatic hernia (CDH), we investigated whether early initiation of ECMO after birth is associated with a beneficial outcome in severe forms of CDH. All neonates with CDH admitted to our institution between 2010 until 2020 and undergoing ECMO treatment were included in this study and divided into four different groups: (1) ECMO initiation < 12 h after birth (n = 143), (2) ECMO initiation between 12−24 h after birth (n = 31), (3) ECMO initiation between 24−120 h after birth (n = 48) and (4) ECMO initiation > 120 h after birth (n = 14). The mortality rate in the first (34%) and fourth group (43%) was high and in the second group (23%) and third group (12%) rather low. The morbidity, characterized by chronic lung disease (CLD), did not differ significantly in the three groups; only patients in which ECMO was initiated >120 h after birth had an increased rate of severe CLD. Our data, although not randomized and limited due to small study groups, suggest that very early need for ECMO and ECMO initiation > 120 h after birth is associated with increased mortality.

Chronic Lung Disease Following Neonatal Extracorporeal Membrane Oxygenation: A Single-Center Experience.

Objective: To assess the incidence and severity of chronic lung disease (CLD) after neonatal extracorporeal membrane oxygenation (ECMO) and to identify factors associated with its development. Methods: A retrospective observational study in a neonatal ECMO center was conducted. All neonates who received support with ECMO in our institution between January 2019 and October 2021 were included and their pulmonary outcome was investigated. Results: A total of 91 patients [60 with congenital diaphragmatic hernia (CDH), 26 with meconium aspiration syndrome, and 5 with other diagnoses] were included in this study. Sixty-eight (75%) neonates survived. Fifty-two (76%) ECMO survivors developed CLD. There was no statistical difference between patients with and without CLD with regard to gender or gestational age. Patients with CLD had lower birth weight, were younger at the initiation of ECMO, and required longer ECMO runs. Patients with CDH developed CLD more often than infants with other underlying diseases (94 vs. 60%). Seventeen ECMO survivors (25%) developed severe CLD. Conclusion: The incidence of CLD after neonatal ECMO is substantial. Risk factors for its development include CDH as an underlying condition, the necessity for early initiation of ECMO, and the need for ECMO over 7 days.

Small Bowel Obstruction After Neonatal Repair of Congenital Diaphragmatic Hernia-Incidence and Risk-Factors Identified in a Large Longitudinal Cohort-Study.

Objective: In patients with a congenital diaphragmatic hernia (CDH), postoperative small bowel obstruction (SBO) is a life-threatening event. Literature reports an incidence of SBO of 20% and an association with patch repair and ECMO treatment. Adhesions develop due to peritoneal damage and underly various biochemical and cellular processes. This longitudinal cohort study is aimed at identifying the incidence of SBO and the risk factors of surgical, pre-, and postoperative treatment. Methods: We evaluated all consecutive CDH survivors born between January 2009 and December 2017 participating in our prospective long-term follow-up program with a standardized protocol. Results: A total of 337 patients were included, with a median follow-up of 4 years. SBO with various underlying causes was observed in 38 patients (11.3%) and significantly more often after open surgery (OS). The majority of SBOs required surgical intervention (92%). Adhesive SBO (ASBO) was detected as the leading cause in 17 of 28 patients, in whom surgical reports were available. Duration of chest tube insertion [odds ratio (OR) 1.22; 95% CI 1.01-1.46, p = 0.04] was identified as an independent predictor for ASBO in multivariate analysis. Beyond the cut-off value of 16 days, the incidence of serous effusion and chylothorax was higher in patients with ASBO (ASBO/non-SBO: 2/10 vs. 3/139 serous effusion, p = 0.04; 2/10 vs. 13/139 chylothorax, p = 0.27). Type of diaphragmatic reconstruction, abdominal wall closure, or ECMO treatment showed no significant association with ASBO. A protective effect of one or more re-operations has been detected (RR 0.16; 95% CI 0.02-1.17; p = 0.049). Conclusion: Thoracoscopic CDH repair significantly lowers the risk of SBO; however, not every patient is suitable for this approach. GoreTex®-patches do not seem to affect the development of ASBO, while median laparotomy might be more favorable than a subcostal incision. Neonates produce more proinflammatory cytokines and have a reduced anti-inflammatory capacity, which may contribute to the higher incidence of ASBO in patients with a longer duration of chest tube insertion, serous effusion, chylothorax, and to the protective effect of re-operations. In the future, novel therapeutic strategies based on a better understanding of the biochemical and cellular processes involved in the pathophysiology of adhesion formation might contribute to a reduction of peritoneal adhesions and their associated morbidity and mortality.

Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trial.

INTRODUCTION: Pulmonary hypertension is a major determinant of postnatal survival in infants with a congenital diaphragmatic hernia (CDH). The current care during the perinatal stabilisation period in these infants might contribute to the development of pulmonary hypertension after birth-in particular umbilical cord clamping before lung aeration. An ovine model of diaphragmatic hernia demonstrated that cord clamping after lung aeration, called physiological-based cord clamping (PBCC), avoided the initial high pressures in the lung vasculature while maintaining adequate blood flow, thereby avoiding vascular remodelling and aggravation of pulmonary hypertension. We aim to investigate if the implementation of PBCC in the perinatal stabilisation period of infants born with a CDH could reduce the incidence of pulmonary hypertension in the first 24 hours after birth. METHODS AND ANALYSIS: We will perform a multicentre, randomised controlled trial in infants with an isolated left-sided CDH, born at ≥35.0 weeks. Before birth, infants will be randomised to either PBCC or immediate cord clamping, stratified by treatment centre and severity of pulmonary hypoplasia on antenatal ultrasound. PBCC will be performed using a purpose-built resuscitation trolley. Cord clamping will be performed when the infant is considered respiratory stable, defined as a heart rate >100 bpm, preductal oxygen saturation >85%, while using a fraction of inspired oxygen of <0.5. The primary outcome is pulmonary hypertension diagnosed in the first 24 hours after birth, based on clinical and echocardiographic parameters. Secondary outcomes include neonatal as well as maternal outcomes. ETHICS AND DISSEMINATION: Central ethical approval was obtained from the Medical Ethical Committee of the Erasmus MC, Rotterdam, The Netherlands (METC 2019-0414). Local ethical approval will be obtained by submitting the protocol to the regulatory bodies and local institutional review boards. TRIAL REGISTRATION NUMBER: NCT04373902.

MR lung perfusion measurements in adolescents after congenital diaphragmatic hernia: correlation with spirometric lung function tests.

OBJECTIVES: To evaluate whether lung perfusion continues to be reduced in 10-year-old children after congenital diaphragmatic hernia (CDH) and whether lung perfusion values correlate with spirometric lung function measurements. METHODS: Fifty-four patients after CDH repair received dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI)-based lung perfusion measurements at the age of 10 years (10.2 ± 1.0 years). Additionally, a control group of 10 children has been examined according to the same protocol. Lung spirometry was additionally available in 43 patients of the CDH group. A comparison of ipsilateral and contralateral parameters was performed. RESULTS: Pulmonary blood flow (PBF) was reduced on the ipsilateral side in CDH patients (60.4 ± 23.8 vs. 93.3 ± 16.09 mL/100 mL/min; p < 0.0001). In comparison to the control group, especially the ratio of ipsilateral to contralateral, PBF was reduced in CDH patients (0.669 ± 0.152 vs. 0.975 ± 0.091; p < 0.0001). There is a positive correlation between ipsilateral pulmonary blood flow, and spirometric forced 1-s volume (r = 0.45; p = 0.0024). CONCLUSIONS: Pulmonary blood flow impairment persists during childhood and correlates with spirometric measurements. Without the need for ionizing radiation, MRI measurements seem promising as follow-up parameters after CDH. KEY POINTS: • Ten-year-old children after congenital diaphragmatic hernia continue to show reduced perfusion of ipsilateral lung. • Lung perfusion values correlate with lung function tests after congenital diaphragmatic hernia.

Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure -A clinical practice Guideline Level 3.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements. Conclusions This first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated.

Assessing Anticoagulation in Neonates With Congenital Diaphragmatic Hernia During Extracorporeal Membrane Oxygenation: Does Anti-Factor Xa or Thromboelastometry Provide Additional Benefit?

Objective: The optimal management of anticoagulation in neonatal/pediatric patients during extracorporeal membrane oxygenation (ECMO) has not been established yet and varies greatly among ECMO centers worldwide. Therefore, we aimed to assess whether the use of anti-factor Xa assay and/or thromboelastometry correlate better than activated clotting time with heparin dose in newborns with congenital diaphragmatic hernia during ECMO. We also examined whether these coagulation assays correlate with thrombotic and/or hemorrhagic complications, when the management of anticoagulation is based only on activated clotting time values. Methods: A prospective observational study in a neonatal ECMO center was conducted. We included all neonates with congenital diaphragmatic hernia born in our institution between March 2018 and January 2019 and requiring support with venoarterial ECMO. A total of 26 ECMO runs were analyzed. During the study, the heparin dose was still adjusted according to activated clotting time values. Measurements of anti-factor Xa assay, activated partial thromboplastin time, and a thromboelastometry from the same blood specimen were performed twice a day. Results: Anti-factor Xa levels showed a moderate correlation with heparin dose, whereas the other tests showed a weak correlation. Four patients (17.4%) had thrombotic complications, 2 patients (8.7%) experienced life-threatening bleeding, and in 11 patients (47.8%) disseminated intravascular coagulation (DIC) occurred. Anti-factor Xa levels were lower in the group with thrombotic complications (0.23 vs. 0.27 IU/ml; p = 0.002), while activated partial thromboplastin time was higher in the group with hemorrhagic complications (69.4 s vs. 59.8 s; p = 0.01). In patients experiencing DIC, heparin dose and anti-factor Xa levels were lower, while no difference in activated clotting time and clotting time in INTEM and INTEM-HEPTEM were shown. Conclusions: Anti-factor Xa levels correlate better to heparin dose than activated clotting time. The use of anti-factor Xa assay instead of activated clotting time for dosing of unfractionated heparin could reduce thrombotic complications in neonates with congenital diaphragmatic hernia on ECMO support. The thromboelastometry showed no additional benefit for this purpose.

Genetics of diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a life-threatening malformation characterised by failure of diaphragmatic development with lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). The incidence is 1:2000 corresponding to 8% of all major congenital malformations. Morbidity and mortality in affected newborns are very high and at present, there is no precise prenatal or early postnatal prognostication parameter to predict clinical outcome in CDH patients. Most cases occur sporadically, however, genetic causes have long been discussed to explain a proportion of cases. These range from aneuploidy to complex chromosomal aberrations and specific mutations often causing a complex phenotype exhibiting multiple malformations along with CDH. This review summarises the genetic variations which have been observed in syndromic and isolated cases of congenital diaphragmatic hernia.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.