Publications by authors named "George B Mychaliska"

81 Publications

Switching to centrifugal pumps may decrease hemolysis rates among pediatric ECMO patients.

Perfusion 2021 Jan 18:267659120982572. Epub 2021 Jan 18.

Division of Pediatric Surgery, Mott Children's Hospital, Ann Arbor, MI, USA.

Recent advances in ECLS technology have led to the adoption of centrifugal pumps for the majority of patients worldwide. Despite several advantages of centrifugal pumps, they remain controversial because a number of studies have shown increased rates of hemolysis. The aim of this study was to assess the impact of transitioning from roller to centrifugal pumps on hemolysis rates at our center. A retrospective analysis of all pediatric ECMO patients at a single center between 2005 and 2017 was undertaken. Hemolysis was defined as a plasma free hemoglobin >50 mg/dL. Multivariable logistic regression was performed correcting for several factors to determine risk factors for hemolysis and analyze outcomes among patients with hemolysis. Significant findings were those with  < 0.05. A total of 590 patients were identified during the study period. Multivariable logistic regression for risk factors for hemolysis showed roller pumps (OR 1.92, CI 1.11-3.33) and ECMO duration (OR 1.002 per hour, CI 1.00-1.01) to be significant factors. Rates of hemolysis significantly improved following conversion from roller to centrifugal pumps, with significantly lower rates of hemolysis in 2012, 2015, 2016, and 2017 when compared to the historical average with roller pumps from 2005 to 2009 (34.7%). Additionally, hemolysis was associated with an increased risk of death (OR 3.59, CI 2.05-6.29) when correcting for other factors. These data suggest decreasing rates of hemolysis with centrifugal pumps compared to roller pumps. Since hemolysis was also associated with increased risk of death, these data support the switch from roller to centrifugal pumps at ECMO centers.
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http://dx.doi.org/10.1177/0267659120982572DOI Listing
January 2021

Fetal Surgery in the Primate 4.0: A New Technique 30 Years Later.

Fetal Diagn Ther 2021 27;48(1):43-49. Epub 2020 Oct 27.

Department of Surgery, UC Davis Children's Hospital, University of California, Davis, Sacramento, California, USA.

Introduction: Open fetal surgery requires a hemostatic hysterotomy that minimizes membrane separation. For over 30 years, the standard of care for hysterotomy in the gravid uterus has been the AutoSuture Premium Poly CS*-57 stapler.

Objective: In this study, we sought to test the feasibility of hysterotomy in a rhesus monkey model with the Harmonic ACE®+7 Shears.

Methods: A gravid rhesus monkey underwent midgestation hysterotomy at approximately 90 days of gestation (2nd trimester; term = 165 ± 10 days) using the Harmonic ACE®+7 Shears. A two-layer uterine closure was completed and the dam was monitored by ultrasound intermittently throughout the pregnancy. At 58 days after hysterotomy (near term), a final surgery was performed to evaluate the uterus and hysterotomy site.

Results: A 3.5-cm hysterotomy was completed in 2 min 7 s. The opening was hemostatic and the membranes were sealed. Immediately after closure and throughout the pregnancy, ultrasound revealed intact membranes without separation and normal amniotic fluid levels. At term, the scar was well healed without signs of thinning or dehiscence.

Conclusions: The Harmonic ACE®+7 Shears produced a hemostatic midgestation hysterotomy with membrane sealing in the rhesus monkey model. Importantly, healing was acceptable.
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http://dx.doi.org/10.1159/000511355DOI Listing
October 2020

Predicting lethal pulmonary hypoplasia in congenital diaphragmatic hernia (CDH): Institutional experience combined with CDH registry outcomes.

J Pediatr Surg 2020 Dec 15;55(12):2618-2624. Epub 2020 Aug 15.

University of Michigan, Department of Surgery, Section of Pediatric Surgery, C.S. Mott Children's Hospital, Pediatric Surgery, 1540 E. Hospital Dr., Ann Arbor, MI 48109-4211, USA. Electronic address:

Background: The Severe Pulmonary Hypoplasia and Evaluation for Resuscitative Efforts (SPHERE) protocol was developed to attempt to identify CDH patients with likely lethal pulmonary hypoplasia. We present our experience with this protocol and utilize the CDH Registry to critically assess the protocol.

Methods: SPHERE patients identified based on prenatal imaging (10/2009-1/2018) were offered ECMO if meeting postnatal physiologic criteria, while others received comfort measures. Within the CDH Registry, patients with suspected severe CDH were identified and separated into "passed" (lowest pCO2 ≤100) versus "failed" (lowest pCO2 >100) groups.

Results: Of 23 SPHERE patients, 57% (13/23) passed criteria for ECMO and survival was 46% (6/13) in that cohort. Of 4912 patients in the CDH Registry, 265 met criteria. There was no difference in survival rates between those that "passed" (122/227; 54%) versus "failed" (18/38; 47%). However, the latter had longer ECMO runs and more required ventilator/ECMO support at 30 days. Amongst survivors, the "failed" group had longer hospital stays and more frequently required tube feeds at discharge.

Conclusions: The SPHERE protocol did not predict mortality in the CDH Registry. However, our data suggest resource utilization is significant when unable to reach pCO2 ≤100 despite resuscitation. Morbidity remains high in this group.

Level Of Evidence: Level III ANNOTATION OF CHANGES: Institutional Review Board Approval at University of Michigan (HUM00031524 and HUM00044010) TYPE OF STUDY: Retrospective Review.
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http://dx.doi.org/10.1016/j.jpedsurg.2020.08.010DOI Listing
December 2020

Likely damaging de novo variants in congenital diaphragmatic hernia patients are associated with worse clinical outcomes.

Genet Med 2020 12 28;22(12):2020-2028. Epub 2020 Jul 28.

Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.

Purpose: Congenital diaphragmatic hernia (CDH) is associated with significant mortality and long-term morbidity in some but not all individuals. We hypothesize monogenic factors that cause CDH are likely to have pleiotropic effects and be associated with worse clinical outcomes.

Methods: We enrolled and prospectively followed 647 newborns with CDH and performed genomic sequencing on 462 trios to identify de novo variants. We grouped cases into those with and without likely damaging (LD) variants and systematically assessed CDH clinical outcomes between the genetic groups.

Results: Complex cases with additional congenital anomalies had higher mortality than isolated cases (P = 8 × 10). Isolated cases with LD variants had similar mortality to complex cases and much higher mortality than isolated cases without LD (P = 3 × 10). The trend was similar with pulmonary hypertension at 1 month. Cases with LD variants had an estimated 12-17 points lower scores on neurodevelopmental assessments at 2 years compared with cases without LD variants, and this difference is similar in isolated and complex cases.

Conclusion: We found that the LD genetic variants are associated with higher mortality, worse pulmonary hypertension, and worse neurodevelopment outcomes compared with non-LD variants. Our results have important implications for prognosis, potential intervention and long-term follow up for children with CDH.
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http://dx.doi.org/10.1038/s41436-020-0908-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710626PMC
December 2020

Comparing mortality risk models in VLBW and preterm infants: systematic review and meta-analysis.

J Perinatol 2020 05 18;40(5):695-703. Epub 2020 Mar 18.

Department of Surgery, Section of Pediatric Surgery, University of Michigan, Michigan Medicine, Ann Arbor, MI, 48109, USA.

Objective: To compare the prognostic accuracy of six neonatal illness severity scores (CRIB, CRIB II, SNAP, SNAP II, SNAP-PE, and SNAP-PE II), birthweight (BW), and gestational age (GA) for predicting pre-discharge mortality among very low birth weight (VLBW) infants (<1500 g) and very preterm infants (<32 weeks' gestational age).

Study Design: PubMed, EMBASE, and Scopus were the data sources searched for studies published before January 2019. Data were extracted, pooled, and analyzed using random-effects models and reported as AUC with 95% confidence intervals (CI).

Results: Of 1659 screened studies, 24 met inclusion criteria. CRIB was the most discriminate for predicting pre-discharge mortality [AUC 0.88 (0.86-0.90)]. GA was the least discriminate [AUC 0.76 (0.72-0.80)].

Conclusions: Although the original CRIB score was the most accurate predictor of pre-discharge mortality, significant heterogeneity between studies lowers confidence in this pooled estimate. A more precise illness severity score to predict pre-discharge mortality is still needed.
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http://dx.doi.org/10.1038/s41372-020-0650-0DOI Listing
May 2020

Recurrent endobronchial inflammatory myofibroblastic tumors: Novel treatment options.

Pediatr Pulmonol 2020 03 27;55(3):788-790. Epub 2020 Jan 27.

Division of Pediatric Pulmonology, Department of Pediatrics, CS Mott Children's Hospital, University of Michigan Medical Center, Ann Arbor, Michigan.

Endobronchial inflammatory myofibroblastic tumors (IMTs) rarely occur in children younger than 10 years of age and have intermediate malignant potential. A 7-year-old girl initially presented with pneumonia. After failing outpatient treatment, she re-presented in status asthmaticus. Computed tomography showed a left mainstem endobronchial mass which was resected bronchoscopically. Pathology was consistent with IMT. Surveillance bronchoscopy identified a recurrence. Despite a left upper lobectomy, recurrence led to further treatment with celecoxib and argon plasma coagulation. Follow-up bronchoscopy revealed complete resolution. She remains disease and symptom-free at her six-year follow-up.
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http://dx.doi.org/10.1002/ppul.24666DOI Listing
March 2020

Calculating Observed-to-Expected Total Fetal Lung Volume in CDH Fetuses in Twin Gestation: Is There a Better Way?

Fetal Diagn Ther 2020 20;47(7):545-553. Epub 2019 Dec 20.

Department of Surgery, Section of Pediatric Surgery, University of Michigan, Michigan Medicine, Ann Arbor, Michigan, USA,

Background: Congenital diaphragmatic hernia (CDH) is a potentially lethal birth defect, and identifying prenatal predictors of outcome is important. Observed-to-expected total fetal lung volume (o/e TFLV) has been shown to be a predictor of severity and useful in risk stratification but is variable due to different TFLV formulas.

Objectives: To calculate o/e TFLV for CDH patients part of a twin gestation using the unaffected sibling as an internal control and comparing these values to those calculated using published formulas for TFLV.

Methods: Seven twin gestations with one fetus affected by CDH were identified between 2006 and 2017. The lung volume for each twin was calculated using magnetic resonance imaging (MRI), and o/e TFLV was calculated using the unaffected twin's TFLV. This percentage was then compared to the o/e TFLV calculated using published formulas.

Results: Lung volumes in the unaffected twins were within normal ranges at the lower end of the spectrum. No single TFLV formula was found to correlate perfectly. Intraclass correlation coefficient estimate was most consistent for o/e TFLV calculated with the Meyers formula and supported by Bland-Altman plots.

Conclusions: O/e TFLV measured in CDH/non-CDH twin gestations using the unaffected sibling demonstrated agreement with o/e TFLV calculated using the Meyers formula. We urge the fetal community to standardize the method, use, and interpretation of fetal MRI in the prenatal evaluation of CDH.
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http://dx.doi.org/10.1159/000504510DOI Listing
December 2019

Discordant prenatal ultrasound and fetal MRI in CDH: wherein lies the truth?

J Pediatr Surg 2020 Sep 26;55(9):1879-1884. Epub 2019 Nov 26.

Department of Surgery, Section of Pediatric Surgery, University of Michigan, Michigan Medicine; Fetal Diagnosis and Treatment Center, University of Michigan, Michigan Medicine. Electronic address:

Purpose: Prenatal risk assessment of congenital diaphragmatic hernia (CDH) relies on prenatal ultrasound (U/S) and fetal magnetic resonance imaging (MRI). When the modalities differ in prognosis, it is unclear which is more reliable.

Methods: Retrospective chart review identified cases of prenatally diagnosed CDH from 4/2010-6/2018 meeting inclusion criteria. Demographic, radiologic, and postnatal outcomes data were collected. Ultrasound- versus MRI-based prognosis (mild, moderate, and severe) was compared with clinical outcomes. Kappa measures compared congruency in disease severity scaling between imaging modalities, while logistic regression and receiver operating characteristics curves compared the ability of each modality to predict outcomes.

Results: Forty-two patients met criteria. Both U/S- and MRI-based prognosis categories differentiated for survival. MRI categories differentiated for ECMO use, surgical repair, and defect type. O/e TFLV better discriminated for survivors and defect type than o/e LHR. Seventeen (40.5%) had discordant prenatal prognostic categories. In 13/17 (76.5%), o/e TFLV predicted higher severity when compared to o/e LHR, but sample size was insufficient to compare accuracy in cases of discordance.

Conclusions: Clinical outcomes suggest fetal MRI may more accurately predict severe pulmonary hypoplasia compared to prenatal ultrasound. Our analysis suggests fetal MRI is a valuable adjunct in the prenatal evaluation of CDH.

Level Of Evidence: Level III.

Type Of Study: Retrospective Review.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.11.007DOI Listing
September 2020

Comparative outcomes of right versus left congenital diaphragmatic hernia: A multicenter analysis.

J Pediatr Surg 2020 Jan 26;55(1):33-38. Epub 2019 Oct 26.

Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA.

Background: Congenital diaphragmatic hernia (CDH) occurs in 1 out of 2500-3000 live births. Right-sided CDHs (R-CDHs) comprise 25% of all CDH cases, and data are conflicting on outcomes of these patients. The aim of our study was to compare outcomes in patients with right versus left CDH (L-CDH).

Methods: We analyzed a multicenter prospectively enrolled database to compare baseline characteristics and outcomes of neonates enrolled from January 2005 to January 2019 with R-CDH vs. L-CDH.

Results: A total of 588, 495 L-CDH, and 93 R-CDH patients with CDH were analyzed. L-CDHs were more frequently diagnosed prenatally (p=0.011). Lung-to-head ratio was similar in both cohorts. R-CDHs had a lower frequency of primary repair (p=0.022) and a higher frequency of need for oxygen at discharge (p=0.013). However, in a multivariate analysis, need for oxygen at discharge was no longer significantly different. There were no differences in long-term neurodevelopmental outcomes assessed at two year follow up. There was no difference in mortality, need for ECMO, pulmonary hypertension, or hernia recurrence.

Conclusion: In this large series comparing R to L-CDH patients, we found no significant difference in mortality, use of ECMO, or pulmonary complications. Our study supports prior studies that R-CDHs are relatively larger and more often require a patch or muscle flap for repair.

Type Of Study: Prognosis study LEVEL OF EVIDENCE: Level II.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.09.046DOI Listing
January 2020

Safety of delayed decannulation of venoarterial cannulas in patients with congenital diaphragmatic hernia.

J Pediatr Surg 2020 Jan 25;55(1):29-32. Epub 2019 Oct 25.

Section of Pediatric Surgery, Department of Surgery, Michigan Medicine, University of Michigan, Ann Arbor, MI. Electronic address:

Background: The practice of "cutting-away" from venoarterial extracorporeal life support (ECLS) and leaving indwelling heparinized cannulas prior to decannulation is controversial. This study aims to determine the safety and efficacy of this strategy in patients with congenital diaphragmatic hernia (CDH) who require ECLS.

Methods: A single-center retrospective review of electronic health records was performed on all patients with CDH who underwent elective ECLS decannulation between January 2014 and September 2018. Descriptive statistics are presented as medians with interquartile range.

Results: Seventy-three percent (19/26) of patients who underwent venoarterial ECLS for CDH were electively decannulated. After a median ECLS run of 10.7 days [6.1-19.5], patients were "cut-away" for a median of 26 h [19.8-43] prior to decannulation. One patient required re-initiation at 36 h for a pulmonary hypertensive crisis (5%). There were no major bleeding or embolic events while "cut-away", and four (21%) patients had clots removed from the cannulas without clinical sequelae. One patient was recannulated 16 days following initial decannulation.

Conclusions: Our data suggests that "cutting-away" from ECLS in patients with congenital diaphragmatic hernia is safe and allows a period of observation without significant complications. This strategy may be particularly helpful in patients at risk for recannulation, but better prognostic criteria are needed.

Level Of Evidence: Level IV.

Type Of Study: Treatment Study.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.09.070DOI Listing
January 2020

Tidal Flow Perfusion for the Artificial Placenta: A Paradigm Shift.

ASAIO J 2020 07;66(7):796-802

From the Department of Surgery, ECLS Laboratory, University of Michigan, Ann Arbor, Michigan.

The modalities of vascular access for the extracorporeal artificial placenta (AP) have undergone many iterations over the past decade. We hypothesized that single lumen cannulation (SLC) of the jugular vein using tidal flow extracorporeal life (ECLS) support is a feasible alternative to venovenous (VV) umbilical-jugular cannulation and double lumen cannulation (DLC) and can maintain fetal circulation, stable hemodynamics, and adequate gas exchange for 24 hours. After in vitro evaluation of the tidal flow system, six preterm lambs at estimated gestational age 118-124 days (term 145 days) were delivered and underwent VV-ECLS. Three were supported using DLC and three with SLC utilizing tidal flow AP support. Hemodynamics, circuit flow, and gas exchange were monitored. Target fetal parameters were as follows: mean arterial pressure 40-60 mmHg, heart rate 140-240 beats per minute (bpm), SatO2% 60-80%, PaO2 25-50 mmHg, PaCO2 30-55 mmHg, oxygen delivery >5 ml O2/dl/kg/min, and circuit flow 100 ± 25 ml/kg/min. All animals survived 24 hours and maintained fetal circulation with stable hemodynamics and adequate gas exchange. Parameters of the tidal flow group were comparable with those of DLC. Single lumen jugular cannulation using tidal flow is a promising vascular access strategy for AP support. Successful miniaturization holds great potential for clinical translation to support extremely premature infants.
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http://dx.doi.org/10.1097/MAT.0000000000001077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103518PMC
July 2020

Prenatal Dilated Rectum: Do We Need to Worry?

J Surg Res 2019 12 11;244:291-295. Epub 2019 Jul 11.

Department of Surgery, Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan, Michigan Medicine, Ann Arbor, Michigan; University of Michigan, Michigan Medicine, Fetal Diagnosis and Treatment Center, Ann Arbor, Michigan. Electronic address:

Background: Advances in prenatal imaging is increasing detection of abnormally dilated bowel. There is no literature to date defining the criteria for a dilated rectum or its association with postnatal pathology. The aim of this study is to investigate the clinical significance of a prenatally identified dilated rectum.

Methods: A retrospective review was performed of all cases of "dilated bowel" on prenatal ultrasound between January 2000 and December 2017 at a single institution. We excluded ventral wall defects from review and sought to include only cases of a prominent or dilated rectum. Collected data included prenatal bowel measurements, postnatal diagnoses, need for surgical intervention, and outcomes. Descriptive statistics were applied.

Results: One hundred and ninety-three cases of prenatal "dilated bowel" were identified in which 12 (6.2%) had specifically visualized a prominent or dilated rectum. Nine of these (75.0%) had no rectal or intestinal abnormality on postnatal evaluation and were discharged feeding and defecating normally. The remaining three cases exhibited clinical pathology necessitating additional management: (1) meconium plug, (2) jejunal atresia with cecal perforation, and (3) rectal perforation with retroperitoneal abscess. All three had rectal biopsies with identification of ganglionated submucosa.

Conclusions: Although a prenatal dilated rectum is a normal variant in the vast majority of cases, it may be associated with a gastrointestinal abnormality requiring surgical intervention. Interestingly, there were no cases of Hirschsprung's disease or anorectal malformations in this cohort. These results, in conjunction with continued efforts to identify and define rectal dilation, are useful for prenatal counseling and postnatal evaluation.
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http://dx.doi.org/10.1016/j.jss.2019.06.066DOI Listing
December 2019

Splenic development and injury in premature lambs supported by the artificial placenta.

J Pediatr Surg 2019 Jun 1;54(6):1147-1152. Epub 2019 Mar 1.

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, MI; Fetal Diagnosis and Treatment Center, C.S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI.

Introduction: The purpose of this study is to evaluate splenic effects during artificial placenta (AP) support.

Methods: AP lambs (118-121 d, n = 14) were delivered and placed on the AP support for a goal of 10-14 days. Cannulation used right jugular drainage and umbilical vein reinfusion. Early (ETC; 115-120 d; n = 7) and late (LTC; 125-131 d; n = 7) tissue controls were delivered and immediately sacrificed. Spleens were formalin fixed, H&E stained, and graded for injury, response to inflammation, and extramedullary hematopoiesis (EMH). CD68 and CD163 stains were used to assess for macrophage activation and density. Clinical variables were correlated with splenic scores. Groups were compared using Fisher's Exact Test and descriptive statistics. p < 0.05 indicated significance.

Results: Mean survival for AP lambs was 12 ± 5 d. There was no necrosis found in any of the groups. Vascular congestion and sinusoidal histiocytosis did not significantly differ between AP and control groups (p = 0.72; p = 0.311). There were significantly more pigmented macrophages (p = 0.008), CD163 (p = <0.001), and CD68 (p = <0.001) stained cells in the AP group. ETC and LTC demonstrated more EMH than AP spleens (p = <0.001).

Conclusions: During AP support, spleens appear to develop normally and exhibit an appropriate inflammatory response. After initiation of AP support, EMH transitions away from the spleen.

Study Type: Research Paper/Therapeutic Potential.

Level Of Evidence: N/A.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.02.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545267PMC
June 2019

An Artificial Placenta Protects Against Lung Injury and Promotes Continued Lung Development in Extremely Premature Lambs.

ASAIO J 2019 Sep/Oct;65(7):690-697

From the Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, Michigan.

An artificial placenta (AP) utilizing extracorporeal life support (ECLS) could protect premature lungs from injury and promote continued development. Preterm lambs at estimated gestational age (EGA) 114-128 days (term = 145) were delivered by Caesarian section and managed in one of three groups: AP, mechanical ventilation (MV), or tissue control (TC). Artificial placenta lambs (114 days EGA, n = 3; 121 days, n = 5) underwent venovenous (VV)-ECLS with jugular drainage and umbilical vein reinfusion for 7 days, with a fluid-filled, occluded airway. Mechanical ventilation lambs (121 days, n = 5; 128 days, n = 5) underwent conventional MV until failure or maximum 48 hours. Tissue control lambs (114 days, n = 3; 121 days, n = 5; 128 days, n = 5) were sacrificed at delivery. At the conclusion of each experiment, lungs were procured and sectioned. Hematoxylin and eosin (H&E) slides were scored 0-4 in seven injury categories, which were summed for a total injury score. Slides were also immunostained for platelet-derived growth factor receptor (PDGFR)-α and α-actin; lung development was quantified by the area fraction of double-positive tips of secondary alveolar septa. Support duration of AP lambs was 163 ± 9 (mean ± SD) hours, 4 ± 3 for early MV lambs, and 40 ± 6 for late MV lambs. Total injury scores at 121 days were 1.7 ± 2.1 for AP vs. 5.5 ± 1.6 for MV (p = 0.02). Using immunofluorescence, double-positive tip area fraction at 121 days was 0.017 ± 0.011 in AP lungs compared with 0.003 ± 0.003 in MV lungs (p < 0.001) and 0.009 ± 0.005 in TC lungs. At 128 days, double-positive tip area fraction was 0.012 ± 0.007 in AP lungs compared with 0.004 ± 0.004 in MV lungs (p < 0.001) and 0.016 ± 0.009 in TC lungs. The AP is protective against lung injury and promotes lung development compared with mechanical ventilation in premature lambs.
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http://dx.doi.org/10.1097/MAT.0000000000000939DOI Listing
June 2020

De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders.

PLoS Genet 2018 12 10;14(12):e1007822. Epub 2018 Dec 10.

Department of Systems Biology, Columbia University Medical Center, New York, New York, United States of America.

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is often accompanied by other congenital anomalies. Previous exome sequencing studies for CDH have supported a role of de novo damaging variants but did not identify any recurrently mutated genes. To investigate further the genetics of CDH, we analyzed de novo coding variants in 362 proband-parent trios including 271 new trios reported in this study. We identified four unrelated individuals with damaging de novo variants in MYRF (P = 5.3x10(-8)), including one likely gene-disrupting (LGD) and three deleterious missense (D-mis) variants. Eight additional individuals with de novo LGD or missense variants were identified from our other genetic studies or from the literature. Common phenotypes of MYRF de novo variant carriers include CDH, congenital heart disease and genitourinary abnormalities, suggesting that it represents a novel syndrome. MYRF is a membrane associated transcriptional factor highly expressed in developing diaphragm and is depleted of LGD variants in the general population. All de novo missense variants aggregated in two functional protein domains. Analyzing the transcriptome of patient-derived diaphragm fibroblast cells suggest that disease associated variants abolish the transcription factor activity. Furthermore, we showed that the remaining genes with damaging variants in CDH significantly overlap with genes implicated in other developmental disorders. Gene expression patterns and patient phenotypes support pleiotropic effects of damaging variants in these genes on CDH and other developmental disorders. Finally, functional enrichment analysis implicates the disruption of regulation of gene expression, kinase activities, intra-cellular signaling, and cytoskeleton organization as pathogenic mechanisms in CDH.
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http://dx.doi.org/10.1371/journal.pgen.1007822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301721PMC
December 2018

Reply to Letter to the Editor: The Artificial Womb: What is the Next Step?

J Pediatr Surg 2019 02 6;54(2):363. Epub 2018 Nov 6.

University of Michigan, Department of Surgery, 2110 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109.

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http://dx.doi.org/10.1016/j.jpedsurg.2018.10.069DOI Listing
February 2019

An Early Investigation into Possible Alternatives to Stapled Hysterotomy in Open Fetal Surgery.

Am J Perinatol 2019 06 29;36(7):742-750. Epub 2018 Oct 29.

Department of Surgery, Fetal Diagnosis and Treatment Center, Michigan Medicine, University of Michigan, Ann Arbor, Michigan.

Purpose: We hypothesized that surgical energy could be used to create hysterotomies in open fetal surgery.

Study Design: Initial studies compared the LigaSure Impact and Harmonic ACE + 7 Shears in the efficiency of hysterotomy and thermal damage. Pregnant ewes at an estimated gestational age (EGA) of 116 to 120 days (term = 145;  = 7) underwent hysterotomy using either device. Hysterotomy edges were resected, and thermal injury extent was determined by histopathological assessment. Upon determining a superior device, subsequent studies compared this to the AutoSuture Premium Poly CS*-57 Stapler in uterine healing. Pregnant ewes ( = 6) at an EGA of 87 to 93 days underwent 6-cm hysterotomy in each gravid horn with either the stapler ( = 5) or Harmonic ( = 5) followed by closure and animal recovery. After 37 to 42 days, uterine healing was assessed by evaluating tensile strength and histopathology.

Results: Thermal damage was more extensive with the LigaSure ( = 11 hysterotomies) than with the Harmonic ( = 11; 5.6 ± 1 vs. 3.1 ± 0.6 mm;  < 0.0001);therefore, the Harmonic was selected for healing studies. Gross scar appearance and tensile strength were the same between the Harmonic and stapler. The stapler caused more fibrosis (4/7 samples with "moderate" fibrosis vs. 0/8 with the Harmonic;  = 0.02).

Conclusion: The Harmonic ACE + 7 caused less thermal injury than the LigaSure Impact and performed similar to the CS*-57 Stapler in uterine healing with continued gestation.
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http://dx.doi.org/10.1055/s-0038-1673664DOI Listing
June 2019

Diagnostic accuracy of imaging studies in congenital lung malformations.

Arch Dis Child Fetal Neonatal Ed 2019 Jul 26;104(4):F372-F377. Epub 2018 Jul 26.

Department of Surgery, Section of Pediatric Surgery, C.S. Mott Children's and Von Voigtlander Women's Hospital, Michigan Medicine, Ann Arbor, Michigan, USA.

Background: Although fetal ultrasound, fetal MRI and postnatal CT are now widely used in the evaluation of congenital lung malformations (CLM), their diagnostic accuracy remains undefined.

Objective: To correlate prenatal and postnatal imaging studies with pathological data after CLM resection.

Design: Retrospective, descriptive case series study.

Setting: A North American tertiary care centre.

Patients: One hundred and three consecutive lung resections for a suspected CLM between 1 January 2005 and 31 December 2015.

Main Outcome Measures: Diagnostic accuracy of imaging diagnosis compared with pathological evaluation.

Results: Pathological diagnoses included congenital pulmonary airway malformation ((CPAM) n=45, 44%), bronchopulmonary sequestration (BPS; n=25, 24%), CPAM/BPS hybrid lesions (n=22, 21%) and pleuropulmonary blastoma (n=2, 2%). Fetal ultrasound detected 85 (82.5%) lesions and correctly diagnosed whether or not a lesion was a CPAM in 75% of cases (sensitivity 93%, specificity 32%). Fetal MRI had a similar concordance rate (73%) but was superior in correctly determining whether a systemic feeding vessel was present in 80% of cases (sensitivity 71%, specificity 88%) compared with an ultrasound accuracy rate of 72% (sensitivity 49%, specificity 93%). By comparison, postnatal CT correctly diagnosed whether a CPAM was present in 84% of cases (sensitivity 86%, specificity 77%) and whether a systemic feeding vessel was present in 90% of cases (sensitivity 92%, specificity 88%).

Conclusions: Fetal ultrasound remains an important tool in the detection and evaluation of congenital lung malformations. However, it does not correctly predict histology in approximately 25% of prenatally detected CLMs and remains limited by relatively poor sensitivity for systemic feeding vessels pathognomic for a bronchopulmonary sequestration. These data suggest the importance of obtaining additional cross-sectional imaging, preferably a postnatal CT scan, in all patients to help counsel families and to guide in the optimal management of these lesions.
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http://dx.doi.org/10.1136/archdischild-2018-314979DOI Listing
July 2019

The artificial placenta: Continued lung development during extracorporeal support in a preterm lamb model.

J Pediatr Surg 2018 Oct 8;53(10):1896-1903. Epub 2018 Jun 8.

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, B560 MSRB II/SPC 5686, 1150 W. Medical Center Dr., Ann Arbor, MI, USA; Fetal Diagnosis and Treatment Center, C.S. Mott Children's Hospital, Michigan Medicine, 1540 E. Medical Center Dr., Ann Arbor, MI.

Purpose: An artificial placenta (AP) utilizing extracorporeal life support (ECLS) could avoid the harm of mechanical ventilation (MV) while allowing the lungs to develop.

Methods: AP lambs (n = 5) were delivered at 118 days gestational age (GA; term = 145 days) and placed on venovenous ECLS (VV-ECLS) with jugular drainage and umbilical vein reinfusion. Lungs remained fluid-filled. After 10 days, lambs were ventilated. MV control lambs were delivered at 118 ("early MV"; n = 5) or 128 days ("late MV"; n = 5), and ventilated. Compliance and oxygenation index (OI) were calculated. After sacrifice, lungs were procured and H&E-stained slides scored for lung injury. Slides were also immunostained for PDGFR-α and α-actin; alveolar development was quantified by the area fraction of alveolar septal tips staining double-positive for both markers.

Results: Compliance of AP lambs was 2.79 ± 0.81 C compared to 0.83 ± 0.19 and 3.04 ± 0.99 for early and late MV, respectively. OI in AP lambs was lower than early MV lambs (6.20 ± 2.10 vs. 36.8 ± 16.8) and lung injury lower as well (1.8 ± 1.6 vs. 6.0 ± 1.2). Double-positive area fractions were higher in AP lambs (0.012 ± 0.003) than early (0.003 ± 0.0005) and late (0.004 ± 0.002) MV controls.

Conclusions: Lung development continues and lungs are protected from injury during AP support relative to mechanical ventilation.

Level Of Evidence: n/a (basic/translational science).
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http://dx.doi.org/10.1016/j.jpedsurg.2018.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151273PMC
October 2018

Effects of an artificial placenta on brain development and injury in premature lambs.

J Pediatr Surg 2018 Jun 8;53(6):1234-1239. Epub 2018 Mar 8.

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, MI.

Purpose: We evaluated whether brain development continues and brain injury is prevented during Artificial Placenta (AP) support utilizing extracorporeal life support (ECLS).

Methods: Lambs at EGA 118days (term=145; n=4) were placed on AP support (venovenous ECLS with jugular drainage and umbilical vein reinfusion) for 7days and sacrificed. Early (EGA 118; n=4) and late (EGA 127; n=4) mechanical ventilation (MV) lambs underwent conventional MV for up to 48h and were sacrificed, and early (n=5) and late (n=5) tissue control (TC) lambs were sacrificed at delivery. Brains were harvested, formalin-fixed, rehydrated, and studied by magnetic resonance imaging (MRI). The gyrification index (GI), a measure of cerebral folding complexity, was calculated for each brain. Diffusion-weighted imaging was used to determine fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in multiple structures to assess white matter (WM) integrity.

Results: No intracranial hemorrhage was observed. GI was similar between AP and TC groups. ADC and FA did not differ between AP and late TC groups in any structure. Compared to late MV brains, AP brains demonstrated significantly higher ADC (0.45±0.08 vs. 0.27±0.11, p=0.02) and FA (0.61±0.04 vs. 0.44±0.05; p=0.006) in the cerebral peduncles.

Conclusions: After 7days of AP support, WM integrity is preserved relative to mechanical ventilation.

Type Of Study: Research study.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.02.091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994355PMC
June 2018

Gastrointestinal mucosal development and injury in premature lambs supported by the artificial placenta.

J Pediatr Surg 2018 Jun 8;53(6):1240-1245. Epub 2018 Mar 8.

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, MI; Fetal Diagnosis and Treatment Center, C.S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI.

Background: An Artificial Placenta (AP) utilizing extracorporeal life support (ECLS) could revolutionize care of extremely premature newborns, but its effects on gastrointestinal morphology and injury need investigation.

Methods: Lambs (116-121days GA, term=145; n=5) were delivered by C-section, cannulated for ECLS, had total parenteral nutrition (TPN) provided, and were supported for 7days before euthanasia. Early and Late Tissue Controls (ETC, n=5 and LTC, n=5) delivered at 115-121days and 125-131days, respectively, were immediately sacrificed. Standardized jejunal samples were formalin-fixed for histology. Crypt depth (CD), villus height (VH), and VH:CD ratios were measured. Measurements also included enterocyte proliferation (Ki-67), Paneth cell count (Lysozyme), and injury scores (H&E). ANOVA and Chi Square were used with p<0.05 considered significant.

Results: CD, VH, and VH:CD were similar between groups (p>0.05). AP demonstrated more enterocyte proliferation (95.7±21.8) than ETC (49.4±23.4; p=0.003) and LTC (66.1+11.8; p=0.04), and more Paneth cells (81.7±17.5) than ETC (41.6±7.0; p=0.0005) and LTC (40.7±8.2, p=0.0004). Presence of epithelial injury and congestion in the bowel of all groups were not statistically different. No villus atrophy or inflammation was present in any group.

Conclusions: This suggests preserved small bowel mucosal architecture, high cellular turnover, and minimal evidence of injury.

Study Type: Research paper/therapeutic potential.

Level Of Evidence: N/A.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.02.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994371PMC
June 2018

Neurodevelopmental outcomes in CDH survivors: A single institution's experience.

J Pediatr Surg 2018 Jun 5;53(6):1087-1091. Epub 2018 Mar 5.

Section of Pediatric Surgery, Department of Surgery, Michigan Medicine, Ann Arbor, MI.

Purpose: Survivors of congenital diaphragmatic hernia (CDH) face high morbidity. We studied the neurodevelopmental outcomes of CDH survivors at a single institution.

Methods: CDH survivors born July 2006-March 2016 at a free-standing children's hospital were reviewed. Neurodevelopment was assessed using the Peabody Developmental Motor Scales (PDMS-2) broken into gross, fine, and total motor quotients. Data collected included prenatal variables (liver herniation, defect laterality, observed:expected total fetal lung volume (o:eTFLV) on MRI), birth demographics (sex, race, estimated gestational age (EGA), birth weight (BtWt), 5 min APGAR, associated anomalies), and therapies/hospital course (HFOV/HFJV, ECMO, timing of repair, pulmonary hypertension (PHTN) severity, length of stay, ventilator days). Variables were analyzed using mixed linear modeling.

Results: Sixty-eight children were included. Most patients had left-sided CDH (55/68, 81%) without liver herniation (42/68, 62%). ECMO utilization was 25/68 (37%). The mean [95% confidence interval] gross motor quotient for the entire cohort was 87 [84-91], fine motor quotient was 92 [88-96], and total motor quotient was 88 [84-93], representing below average, average, and below average functioning, respectively. o:eTFLV predicted fine motor quotient among prenatal variables. Associated anomalies and ECMO use predicted all quotients in the final model.

Conclusions: Associated anomalies and ECMO use predict neurodevelopmental delay in CDH survivors.

Type Of Study: Retrospective observational study; Prognostic.

Level Of Evidence: II.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.02.064DOI Listing
June 2018

Perfluorocarbons Prevent Lung Injury and Promote Development during Artificial Placenta Support in Extremely Premature Lambs.

Neonatology 2018 23;113(4):313-321. Epub 2018 Feb 23.

Background: Extremely premature neonates suffer high morbidity and mortality. An artificial placenta (AP) using extracorporeal life support (ECLS) is a promising therapy.

Objectives: We hypothesized that intratracheal perfluorocarbon (PFC) instillation during AP support would reduce lung injury and promote lung development relative to intratracheal amniotic fluid or crystalloid.

Methods: Lambs at an estimated gestational age (EGA) 116-121 days (term 145 days) were placed on venovenous ECLS with jugular drainage and umbilical vein reinfusion and intubated. Airways were managed by the instillation of amniotic fluid and tracheal occlusion (TO; n = 4), or lactated Ringer's (LR; n = 4) or perfluorodecalin (a PFC) without occlusion (n = 4). After 7 days, the animals were sacrificed. Early (EGA 116-121 days) and late (EGA 125-131 days) tissue control lambs were delivered and sacrificed. Lungs were formalin-inflated to 30 cm H2O and sectioned for histology. Injury was scored by an unbiased pathologist. Slides were immunostained for PDGFR-α and α-actin; development was quantified by the area fraction of double-positive tips. Surfactant protein-C (SP-C) concentration in bronchoalveolar lavage fluid was quantified using ELISA.

Results: Total injury scores were lower in PFC lungs (1.8 ± 1.7) than in TO (6.5 ± 2.1; p = 0.01) and LR lungs (5.5 ± 2.4; p = 0.01). The area fraction of double-positive alveolar tips appeared higher in PFC lungs than in TO lungs (0.18 ± 0.007 vs. 0.008 ± 0.004; p = 0.07). SP-C concentration was higher in PFC lungs than in TO lungs (37.9 ± 7.6 vs. 20.0 ± 5.4 pg/mL; p = 0.005), and both early (12.4 ± 1.7 g/mL; p = 0.007) and late tissue control lungs (15.1 ± 5.0 pg/mL; p = 0.0008).

Conclusion: During AP support, intratracheal PFC prevents lung injury and promotes normal lung development better than crystalloid or amniotic fluid with TO.
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http://dx.doi.org/10.1159/000486387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980738PMC
September 2019

Is there a best approach for extracorporeal life support cannulation: a review of the extracorporeal life support organization.

J Pediatr Surg 2018 Jul 31;53(7):1301-1304. Epub 2018 Jan 31.

Division of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, United States.

Background: Neurologic complications are common, and amongst the most devastating complications in pediatric patients undergoing extracorporeal life support (ECLS). Carotid artery cannulation (CAN) has been associated with an increase in these complications, thereby shaping practices to avoid this approach in most pediatric patients in which other cannulation approaches are viable.

Methods: A retrospective review of children (0-18years) in the ELSO database was undertaken from 1989 through 2013. Multivariate logistic regression analysis of rates of stroke and other neurologic complications based on cannulation technique was undertaken, adjusting for patient factors including age, underlying disease process, and severity of illness.

Results: A total of 30,282 ECLS runs were found in the database. CAN was associated with higher rates of stroke (5.15% vs 3.74%) and overall neurologic complications. However, when correcting for patient factors, including age, underlying disease process, and support type, CAN was not associated with an increased rate of neurologic complications or stroke (p>0.05 for both).

Conclusion: When correcting for patient related factors CAN is not associated with an increase in stroke or neurologic compilcations. CAN should be re-examined as a cannulation technique for older pediatric patients.

Level Of Evidence: III.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.01.015DOI Listing
July 2018

Outcomes of fetuses with primary hydrothorax that undergo prenatal intervention (prenatal intervention for hydrothorax).

J Surg Res 2018 01 18;221:121-127. Epub 2017 Sep 18.

Section of Pediatric Surgery, Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan; University of Michigan Health System, Fetal Diagnosis and Treatment Center, Ann Arbor, Michigan. Electronic address:

Background: Primary hydrothorax is a congenital anomaly affecting 1 in 10,000-15,000 pregnancies. The natural history of this condition is variable with some fetuses having spontaneous resolution and others showing progression. The associated pulmonary hypoplasia leads to increased perinatal morbidity and mortality. Optimal prenatal intervention remains controversial.

Methods: After obtaining the Institutional Review Board approval, a retrospective review of all patients evaluated for a fetal pleural effusion in the Fetal Diagnosis and Treatment Center at The University of Michigan, between 2006 and 2016 was performed. Cases with secondary etiologies for an effusion or when families decided to pursue elective termination were excluded.

Results: Pleural effusions were identified in 175 patients. Primary hydrothorax was diagnosed in 15 patients (8%). The effusions were bilateral in 13/15 cases (86%) and 10/15 (66%) had hydrops at presentation. All 15 patients with primary hydrothorax underwent prenatal intervention. Thoracentesis was performed in 14/15 cases (93%). Shunt placement was performed in 10/15 cases (66%). Shunt migration was seen in four patients (40%) and all of these underwent prenatal shunt replacement. Overall survival was 76%. The rates of prematurity and preterm premature rupture of membranes were 69% and 35%, respectively.

Conclusions: Fetal intervention for the treatment of primary hydrothorax is effective, and it appears to confer a survival advantage. Both the fetuses and the mothers tolerated the procedures well. Preterm labor and preterm premature rupture of membranes remain an unsolved problem. Further studies are needed to understand the mechanisms behind the development of fetal hydrothorax.
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http://dx.doi.org/10.1016/j.jss.2017.08.034DOI Listing
January 2018

Comparison of early versus delayed strategies for repair of congenital diaphragmatic hernia on extracorporeal membrane oxygenation.

J Pediatr Surg 2018 Apr 22;53(4):629-634. Epub 2017 Nov 22.

Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan, 1540 E. Hospital Dr., Ann Arbor, MI. Electronic address:

Purpose: For the last seven years, our institution has repaired infants with CDH that require ECMO early after cannulation. Prior to that, we attempted to decannulate before repair, but repaired on ECMO if we were unable to wean after two weeks. This study compares those strategies.

Methods: From 2002 to 2016, 65 infants with CDH required ECMO. 67.7% were repaired on ECMO, and 27.7% were repaired after decannulation. Data were compared between patients repaired ≤5days after cannulation ("early protocol", n=30) and >5days after cannulation or after de-cannulation ("late protocol", n=35). We used Cox regression to assess differences in outcomes between groups.

Results: Survival for the early and late protocol groups was 43.3% and 68.8%, respectively (p=0.0485). For patients that were successfully decannulated before repair, survival was 94.4%. Moreover, the early repair protocol was associated with prolongation of ECMO (16.8±7.4 vs. 12.6±6.8days, p=0.0216). After multivariate regression, the early repair protocol was an independent predictor of both mortality (HR=3.48, 95% CI=1.28-9.45, p=0.015) and days on ECMO (IRR=1.39, 95% CI=1.07-1.79, p=0.012). All bleeding occurred in patients repaired on ECMO (29.5%, 13/44).

Conclusions: Our data suggest that protocolized CDH repair early after ECMO cannulation may be associated with increased mortality and prolongation of ECMO. However, early repair is not necessarily harmful for those patients who would otherwise be unable to wean from ECMO before repair. Further work is needed to better move towards individualized patient care.

Type Of Study: Treatment Study.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2017.10.056DOI Listing
April 2018

Avalon catheters in pediatric patients requiring ECMO: Placement and migration problems.

J Pediatr Surg 2017 Oct 12. Epub 2017 Oct 12.

Pediatric Surgery, Department of Surgery, C.S. Mott Children's and Von Voigtlander Women's Hospital, University of Michigan, Ann Arbor, MI, USA.

Purpose: The Avalon dual-lumen venovenous catheter has several advantages, but placement techniques and management have not been adequately addressed in the pediatric population. We assessed our institutional outcomes and complications using the Avalon catheter in children.

Methods: We reviewed all pediatric patients who had Avalon catheters placed for respiratory failure at our institution, excluding congenital heart disease patients, from April 2009 to March 2016. All patients were managed using our standard ECMO protocol, and cannula position was followed by daily chest x-ray and intermittent echocardiography (ECHO). Data included demographics, diagnosis, PRISM3 predicted mortality, ECMO duration, complications, and survival. The primary outcome was the need for catheter repositioning.

Results: Twenty-five patients were included, with mean age 8.3±6.9years and 15±22days of ECMO support. Overall survival was 68% (17/25). Fourteen patients (56%) underwent placement with fluoroscopy in addition to ultrasound and ECHO, primarily after 2013. Overall, thirteen patients (52%) had problems with cannula malposition. 9 of these (69%) required cannula repositioning. Three of 14 (21%) cannulas placed with fluoroscopy required repositioning, compared to 7/11 (64%) placed without fluoroscopy (p=0.05).

Conclusions: Complications are common with the Avalon catheter in children. Safe percutaneous access requires ultrasound guidance, and use of intraoperative fluoroscopy in addition to echocardiography decreases malposition rates.

Level Of Evidence: IV (Prognosis study).
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http://dx.doi.org/10.1016/j.jpedsurg.2017.10.036DOI Listing
October 2017

Pulmonary Hypertension in Patients with Congenital Diaphragmatic Hernia: Does Lung Size Matter?

Eur J Pediatr Surg 2018 Dec 16;28(6):508-514. Epub 2017 Oct 16.

Section of Pediatric Surgery, Department of Surgery, University of Michigan Medical School and C.S. Mott Children's Hospital, Ann Arbor, Michigan, United States.

Purpose:  The relationship between pulmonary hypoplasia and pulmonary arterial hypertension (PHTN) in patients with congenital diaphragmatic hernia (CDH) remains ill-defined. We hypothesized that prenatal estimates of lung size would directly correlate with PHTN severity.

Methods:  Infants with isolated CDH (born 2004-2015) at a single institution were included. Estimates of lung size included observed-to-expected LHR (o:eLHR) and %-predicted lung volumes (PPLV = observed/predicted volumes). The primary outcome was severity of PHTN (grade 0-3) on echocardiography performed between day of life 3 and 30.

Results:  Among 62 patients included, there was 32% mortality and 65% ECMO utilization. PPLV (odds ratio [OR] = 0.94 per 1 grade in PHTN severity, 95% confidence interval [CI] = 0.89-0.98,  < 0.01) and o:eLHR (OR = 0.97, 95% CI = 0.94-0.99,  < 0.01) were significantly associated with PHTN grade. Among patients on ECMO, PPLV (OR = 0.92, 95% CI = 0.84-0.99,  = 0.03) and o:eLHR (OR = 0.95, 95% CI = 0.92-0.99,  = 0.01) were more strongly associated with PHTN grade. PPLV and o:eLHR were significantly associated with the use of inhaled nitric oxide (iNO) (OR = 0.90, 95% CI = 0.83-0.98,  = 0.01 and OR = 0.94, 95% CI = 0.91-0.98,  < 0.01, respectively) and epoprostenol (OR = 0.91, 95% CI = 0.84-0.99,  = 0.02 and OR = 0.93, 95% CI = 0.89-0.98,  < 0.01, respectively).

Conclusion:  Among infants with isolated CDH, PPLV, and o:eLHR were significantly associated with PHTN severity, especially among patients requiring ECMO. Prenatal lung size may help predict postnatal PHTN and associated therapies.
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http://dx.doi.org/10.1055/s-0037-1607291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183369PMC
December 2018

Cerebral Oxygenation of Premature Lambs Supported by an Artificial Placenta.

ASAIO J 2018 Jul/Aug;64(4):552-556

From the Extracorporeal Life Support Laboratory, Department of Surgery, University of Michigan, Ann Arbor, Michigan.

An artificial placenta (AP) using venovenous extracorporeal life support (VV-ECLS) could represent a paradigm shift in the treatment of extremely premature infants. However, AP support could potentially alter cerebral oxygen delivery. We assessed cerebral perfusion in fetal lambs on AP support using near-infrared spectroscopy (NIRS) and carotid arterial flow (CAF). Fourteen premature lambs at estimated gestational age (EGA) 130 days (term = 145) underwent cannulation of the right jugular vein and umbilical vein with initiation of VV-ECLS. An ultrasonic flow probe was placed around the right carotid artery (CA), and a NIRS sensor was placed on the scalp. Lambs were not ventilated. CAF, percentage of regional oxygen saturation (rSO2) as measured by NIRS, hemodynamic data, and blood gases were collected at baseline (native placental support) and regularly during AP support. Fetal lambs were maintained on AP support for a mean of 55 ± 27 hours. Baseline rSO2 on native placental support was 40% ± 3%, compared with a mean rSO2 during AP support of 50% ± 11% (p = 0.027). Baseline CAF was 27.4 ± 5.4 ml/kg/min compared with an average CAF of 23.7 ± 7.7 ml/kg/min during AP support. Cerebral fractional tissue oxygen extraction (FTOE) correlated negatively with CAF (r = -0.382; p < 0.001) and mean arterial pressure (r = -0.425; p < 0.001). FTOE weakly correlated with systemic O2 saturation (r = 0.091; p = 0.017). Cerebral oxygenation and blood flow in premature lambs are maintained during support with an AP. Cerebral O2 extraction is inversely related to carotid flow and is weakly correlated with systemic O2 saturation.
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http://dx.doi.org/10.1097/MAT.0000000000000676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860928PMC
March 2019

Hepatoduodenal ligament teratoma with immature elements.

Pediatr Surg Int 2017 Sep 6;33(9):1023-1026. Epub 2017 Jul 6.

Section of Pediatric Surgery, Department of Surgery, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA.

Pediatric germ cell tumors comprise 1-3% of all malignant pediatric tumors and are found in variable locations. We present the case of a term 3.7 kg neonate who was found to have a giant liver mass at birth, later determined to be an immature teratoma arising from the hepatoduodenal ligament. This case report and images add to the limited literature a very rare presentation of a teratoma.
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http://dx.doi.org/10.1007/s00383-017-4123-2DOI Listing
September 2017