Summary
Over the past decade, amniotic fluid‐derived stem cells have emerged as a novel experimental approach aimed at improving outcomes in children with congenital anomalies, including spina ...bifida, heart defects, and diaphragmatic hernia. Interest in these cells for the treatment of prenatally diagnosed diseases has arisen based on numerous studies demonstrating the relative ease of harvesting an abundant quantity of amniocytes from a small aliquot of fluid, the unique properties of amniocytes themselves, and the beneficial effects of amniotic fluid‐derived stem cells in experimental animal models. This report gives a brief overview of the rationale and current status of amniotic fluid stem cell‐based therapies, focusing on its relevance to birth defects affecting the fetus and neonate. The author proposes a roadmap for further study that would be required prior to clinical application of amniotic fluid stem cell technologies. Stem Cells Translational Medicine 2018;7:767–773
Schematic diagram of autologous fetal stem cells obtained by amniocentesis during the second trimester, followed by ex vivo expansion of amniocytes in parallel with the remainder of gestation, and subsequent seeding of cells within biodegradable scaffolds in preparation for perinatal surgical implantation.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This article reviews the contemporary diagnosis and management of antenatally diagnosed congenital lung lesions. These anomalies, which include congenital pulmonary airway malformation (CPAM) ...(formerly congenital cystic adenomatoid malformation), bronchopulmonary sequestration (BPS), bronchogenic cyst, and congenital lobar emphysema (CLE), are relatively rare but are increasingly encountered by clinicians because of the improved resolution and enhanced sensitivity of fetal ultrasound. Serial assessment of these lesions throughout pregnancy remains the norm rather than the exception. Perinatal management strategies may differ based on initial size and growth patterns of these masses until delivery. Fetal magnetic resonance imaging and other diagnostic testing can sometimes be helpful in providing additional prognostic information. Over the last decade, maternal steroids have become standard of care in the management of larger lesions at risk for nonimmune hydrops. As a result, fetal surgical procedures, including open resection, thoracoamniotic shunting, and ex utero intrapartum treatment (EXIT), are less uncommonly performed. Decisions regarding whether delivery of these fetuses should occur in a tertiary care center with pediatric surgery coverage versus delivery at a local community hospital are now highly relevant in most prenatal counseling discussions with families. Large lung malformations may require urgent surgical removal in the early postnatal period because of respiratory distress. Other complications, such as recurrent pneumonia, pneumothorax, and cancer, are indications for postnatal lung resection on an elective basis. Many children are good candidates for minimally invasive (thoracoscopic) surgical approaches as an alternative to resection by thoracotomy. In the vast majority of cases, the overall prognosis remains excellent.
Objective To test the hypothesis that implementation of a marked reduction in intravenous fat will result in reversal of parenteral nutrition–associated liver disease (PNALD) in infants. Study design ...Prospective study of intravenous fat emulsion reduction in parenteral nutrition to 1 g/kg/d 2 times per week in neonates diagnosed with PNALD. Primary outcome measure was total bilirubin levels compared with gestational age, birth weight, and diagnosis-matched historical controls receiving 3 g/kg/d of intravenous lipids. Results Intravenous fat emulsion reduction resulted in a significant decline in total bilirubin levels compared with controls. Comparison of growth in the 2 groups was similar. Mild essential fatty acid deficiency was detected in 8 of 31 infants and was reversed with additional days of lipid infusion. No significant adverse events were noted. Conclusions An association between intravenous lipid emulsion administration and the development of PNALD seems probable. Use of intravenous fat emulsion reduction is a potential approach to reverse PNALD in young infants. Frequent monitoring of essential fatty acid deficiency is needed with the use of this regimen.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Tissue-engineered small intestine, stomach, large intestine, esophagus, and gastroesophageal (GE) junction have been successfully formed from syngeneic cells, and employed as a rescue ...therapy in a small animal model. The purpose of this study is to determine if engineered intestine and stomach could be generated in an autologous, preclinical large animal model, and to identify if the tissue-engineered intestine retained features of an intact stem cell niche. Methods A short segment of jejunum or stomach was resected from 6-wk-old Yorkshire swine. Organoid units, multicellular clusters with predominantly epithelial content, were generated and loaded onto biodegradable scaffold tubes. The constructs were then implanted intraperitoneally in the autologous host. Seven wk later, all implants were harvested and analyzed using histology and immunohistochemistry techniques. Results Autologous engineered small intestine and stomach formed. Tissue-engineered intestinal architecture replicated that of native intestine. Histology revealed tissue-engineered small intestinal mucosa composed of a columnar epithelium with all differentiated intestinal cell types adjacent to an innervated muscularis mucosae. Intestinal subepithelial myofibroblasts, specialized cells that participate in the stem cell niche formation, were identified. Moreover, cells positive for the putative intestinal stem cell marker, doublecortin and CaM kinase-like-1 (DCAMKL-1) expression were identified at the base of the crypts. Finally, tissue-engineered stomach also formed with antral-type mucosa (mucus cells and surface foveolar cells) and a muscularis. Conclusion We successfully generated tissue-engineered intestine with correct architecture, including features of an intact stem cell niche, in the pig model. To our knowledge, this is the first demonstration in which tissue-engineered intestine was successfully generated in an autologous manner in an animal model, which may better emulate a human host and the intended therapeutic pathway for humans.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The purpose of this study was to evaluate clinical outcomes in children with asymptomatic congenital lung malformations (CLM) who were initially managed nonoperatively.
An IRB-approved retrospective ...review was performed on all CLMs at a single tertiary care referral center (Jan 2006–Dec 2016, n=140). Asymptomatic cases that did not undergo elective resection were evaluated for subsequent CLM-related complications based on clinical records and a telephone quality of life survey.
Out of 39 (27.9%) who were initially managed nonoperatively, 13 (33%) developed CLM-related symptoms and underwent surgical intervention at a median age of 6.8years (range, 0.7–19.8years). The most common indication for conversion to operative management was pneumonia (78%). Larger lesions, as measured by CT scan, were significantly associated with the need for subsequent surgical intervention (mean maximal diameter, 5.7 vs. 2.9cm; p=0.005). Based on survey data with a median follow up of 3.9years (range, 0.2–13.2years), 17% developed chronic pulmonary symptoms, including cough (11%) and asthma requiring bronchodilators (12%).
Although these data support nonoperative management as a viable alternative to surgical resection, at least one-third of CLM children eventually develop pneumonia or other pulmonary symptoms. Larger lesions are correlated with an increased risk for eventual surgical resection.
Level IV.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background Although thoracoscopic lobectomy is a widely accepted surgical procedure in adult thoracic surgery, its role in small children remains controversial. The purpose of this study was to ...evaluate perioperative outcomes after thoracoscopic and open lobectomy in infants and young children with congenital lung malformations at a single academic referral center. Study Design A cohort study of 62 consecutive children who underwent elective pulmonary lobectomy for a congenital lung lesion between 2001 and 2013 was performed. Patient demographics and perioperative outcomes were evaluated in univariate and logistic regression analyses. Results Forty-nine patients underwent thoracoscopy and 13 had a thoracotomy. Six children undergoing thoracoscopy required conversion to thoracotomy (conversion 12.2%). Perioperative outcomes, including median blood loss (2.0 vs 1.1 mL/kg; p = 0.34), chest tube duration (3 vs 3 days; p = 0.33), hospital length of stay (3 vs 3 days; p = 0.42), and morbidity as defined by the Accordion Grading Scale (30.6% vs 30.8%; p = 0.73), were similar between thoracoscopy and thoracotomy, respectively. Although thoracoscopy was associated with increased operative duration compared with thoracotomy (239.9 vs 181.2 minutes, respectively; p = 0.03), thoracoscopy operative times decreased with increasing institutional experience (p = 0.048). Thoracoscopic lobectomy infants younger than 5 months of age had a 2.5-fold higher rate of perioperative adverse outcomes compared with older children (p = 0.048). Conclusions In small children undergoing pulmonary lobectomy, both thoracoscopy and thoracotomy are associated with similar perioperative outcomes. The cosmetic and musculoskeletal benefits of the thoracoscopic approach must be balanced against institutional expertise and a potentially higher risk for complications in younger patients.
Purpose: We sought to evaluate the impact of thoracoscopic repair on perioperative outcomes in infants with esophageal atresia and tracheoesophageal fistula (EA/TEF).
Methods: The American College of ...Surgeons National Surgical Quality Improvement Program pediatric database from 2014 to 2018 was queried for all neonates who underwent operative repair of EA/TEF. Operative approach based on intention to treat was correlated with perioperative outcomes, including 30-day postoperative adverse events, in logistic regression models.
Results: Among 855 neonates, initial thoracoscopic repair was performed in 133 (15.6%) cases. Seventy (53%) of these cases were converted to open. Those who underwent thoracoscopic repair were more likely to be full-term (p = 0.03) when compared to those in the open repair group. There were no significant differences in perioperative outcome measures based on surgical approach except for operative time (thoracoscopic: 217 min vs. open: 180 min, p<0.001). A major cardiac comorbidity (OR 1.6, 95% CI 1.2–2.1; p = 0.003) and preoperative ventilator requirement (OR 1.4, 95% CI 1.0–1.9; p = 0.034) were the only risk factors associated with adverse events.
Conclusions: Thoracoscopic neonatal repair of EA/TEF continues to be used sparingly, is associated with high conversion rates, and has similar perioperative outcomes when compared to open repair.
Level of evidence: III
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We compared early neurodevelopmental morbidity in young children with severe CDH who underwent FETO to those without fetal therapy.
We conducted a prospective study of severe CDH patients undergoing ...FETO (n = 18) at a single North American center from 2015 to 2021 (NCT02710968). Outpatient survivors (n = 12) were evaluated by a multidisciplinary team and compared to expectantly managed CDH patients. Neurodevelopmental outcomes were assessed using the Capute Scales Clinical Linguistic and Auditory Milestone Scales (CLAMS) and Cognitive Adaptive Test (CAT), with a developmental quotient (DQ) < 85 indicative of at-risk for delay.
At one year, 58% (n = 7) of FETO patients underwent evaluation, with notable concern for language delay (CLAMS median DQ, 80.1 interquartile range, 67.6–86.7). FETO scores improved by 24-months, whereas high severity/non-FETO scores declined CLAMS median DQ (Difference in DQ), 92.3 (+12.2) vs. 77.1 (−13.4), respectively; p = 0.049. On the initial CAT, FETO patients had concern for visual motor and problem-solving delays, with a median DQ of 81.3 (62.1–89.4). At 24-months, FETO patients had improving scores Median CAT DQ, 90.8 (+9.5), whereas high severity/non-FETO 87.5 (−3.0), p = 0.28 had declining scores.
These initial data suggest that FETO is associated with favorable neurodevelopmental outcomes at 24-months compared to severe CDH under expectant management.
III.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
PDF
