Russell Jennings | Harvard Medical School (original) (raw)

Papers by Russell Jennings

Research paper thumbnail of Acellular bi-layer silk fibroin scaffolds support functional tissue regeneration in a rat model of onlay esophagoplasty

Biomaterials, 2015

Surgical management of long-gap esophageal defects with autologous gastrointestinal tissues is fr... more Surgical management of long-gap esophageal defects with autologous gastrointestinal tissues is frequently associated with adverse complications including organ dysmotility, dysphagia, and donor site morbidity. In order to develop alternative graft options, bi-layer silk fibroin (SF) scaffolds were investigated for their potential to support functional tissue regeneration in a rodent model of esophageal repair. Onlay esophagoplasty was performed with SF matrices (N = 40) in adult rats for up to 2 m of implantation. Parallel groups consisted of animals implanted with small intestinal submucosa (SIS) scaffolds (N = 22) or sham controls receiving esophagotomy alone (N = 20). Sham controls exhibited a 100% survival rate while rats implanted with SF and SIS scaffolds displayed respective survival rates of 93% and 91% prior to scheduled euthanasia. Animals in each experimental group were capable of solid food consumption following a 3 d post-op liquid diet and demonstrated similar degrees of weight gain throughout the study period. End-point μ-computed tomography at 2 m post-op revealed no evidence of contrast extravasation, fistulas, strictures, or diverticula in any of the implant groups. Ex vivo tissue bath studies demonstrated that reconstructed esophageal conduits supported by both SF and SIS scaffolds displayed contractile responses to carbachol, KCl and electrical field stimulation while isoproterenol produced tissue relaxation. Histological (Masson's trichrome and hematoxylin and eosin) and immunohistochemical (IHC) evaluations demonstrated both implant groups produced de novo formation of skeletal and smooth muscle bundles positive for contractile protein expression [fast myosin heavy chain (MY32) and α-smooth muscle actin (α-SMA)] within the graft site. However, SF matrices promoted a significant 4-fold increase in MY32+ skeletal muscle and a 2-fold gain in α-SMA+ smooth muscle in comparison to the SIS cohort as determined by histomorphometric analyses. A stratified squamous, keratinized epithelium expressing cytokeratin 5 and involucrin proteins was also present at 2 m post-op in all experimental groups. De novo innervation and vascularization were evident in all regenerated tissues indicated by the presence of synaptophysin (SYP38)+ boutons and vessels lined with CD31 expressing endothelial cells. In respect to SIS, the SF group supported a significant 4-fold increase in the density of SYP38+ boutons within the implant region. Evaluation of host tissue responses revealed that SIS matrices elicited chronic inflammatory reactions and severe fibrosis throughout the neotissues, in contrast to SF scaffolds. The results of this study demonstrate that bi-layer SF scaffolds represent promising biomaterials for onlay esophagoplasty, capable of producing superior regenerative outcomes in comparison to conventional SIS scaffolds.

Research paper thumbnail of Thoracoscopic Aortopexy for the Treatment of Pediatric Tracheomalacia: A Right-Sided Approach

Operative Techniques in Thoracic and Cardiovascular Surgery, 2011

Research paper thumbnail of Prune Belly Syndrome

Seminars in Pediatric Surgery

ABSTRACT

Research paper thumbnail of Tracheobronchomalacia in pediatric patients with esophageal atresia: Comparison of diagnostic laryngoscopy/bronchoscopy and dynamic airway multidetector computed tomography

Journal of pediatric surgery, 2015

Diagnostic laryngoscopy and bronchoscopy (DLB) has been the traditional preoperative diagnostic m... more Diagnostic laryngoscopy and bronchoscopy (DLB) has been the traditional preoperative diagnostic modality for evaluating presence and severity of tracheobronchomalacia (TBM), and requires anesthesia. Alternatively, multidetector computed tomography (MDCT) is potentially a noninvasive modality that provides high-resolution, 3-dimensional (3D) imaging of the thorax providing preoperative guidance for pediatric surgeons. This study compares MDCT with intraoperative DLB in the assessment of TBM in symptomatic pediatric patients with esophageal atresia (EA). Following IRB approval all pediatric patients (≤18years) who had EA and who underwent an MDCT study as a preoperative evaluation of TBM prior to aortopexy were retrospectively reviewed. Patients with incomplete reports on intraoperative DLB or MDCT studies were excluded. Two pediatric radiologists independently evaluated all MDCT studies in a blinded fashion. On both DLB and MDCT studies, TBM was scored as present or absent in five an...

Research paper thumbnail of Intermittent single lung ventilation in a 620-gram micropremie during postintubation carinal laceration repair

Pediatric Anesthesia, 2010

Research paper thumbnail of Paravertebral nerve block catheters using chloroprocaine in infants with prolonged mechanical ventilation for treatment of long-gap esophageal atresia

Paediatric anaesthesia, 2015

Infants with long-gap esophageal atresia (LGEA) undergo repeated thoracotomies for staged surgica... more Infants with long-gap esophageal atresia (LGEA) undergo repeated thoracotomies for staged surgical repair known as the Foker process (FP). Associated prolonged mechanical ventilation results in exposure to high doses of opioids and benzodiazepines, and prolonged weaning times and ICU stays. The aim of this study was to determine the effectiveness of short-term paravertebral nerve block (PVNB) catheters in reducing opioid/benzodiazepine exposure and effects on clinical variables. The medical records of seventeen infants were retrospectively reviewed; 11 with PVNB and six without (CG). PVNB were placed using ultrasound-guidance and chloroprocaine infusions implemented in the ICU. Opioids and benzodiazepines were administered via the protocol for 5 days following thoracotomies for Foker-I and Foker-II. Foker-I: Average reduction in morphine and midazolam consumption was 36% (2.18 vs 3.40 mg·kg(-1) ·day(-1) ; P < 0.001) and 31% (2.25 vs 3.25 mg·kg(-1) ·day(-1) ; P = 0.033), respectiv...

Research paper thumbnail of Fetal cardiac bypass alters regional blood flows, arterial blood gases, and hemodynamics in sheep

The American journal of physiology

Successful fetal cardiac bypass might allow prenatal correction of some congenital heart defects.... more Successful fetal cardiac bypass might allow prenatal correction of some congenital heart defects. However, previous studies have shown that fetal cardiac bypass may result in impaired fetal gas exchange after bypass. To investigate the etiology of this impairment, we determined whether fetal cardiac bypass causes a redistribution of fetal regional blood flows and, if so, whether a vasodilator (sodium nitroprusside) can prevent this redistribution. We also determined the effects of fetal cardiac bypass with and without nitroprusside on fetal arterial blood gases and hemodynamics. Eighteen fetal sheep were studied in utero under general anesthesia. Seven fetuses underwent bypass without nitroprusside, six underwent bypass with nitroprusside, and five were no-bypass controls. Blood flows were determined using radionuclide-labeled microspheres. After bypass without nitroprusside, placental blood flow decreased by 25-60%, whereas cardiac output increased by 15-25%. Flow to all other fetal organs increased or remained unchanged. Decreased placental blood flow after bypass was accompanied by a fall in PO2 and a rise in PCO2. Nitroprusside improved placental blood flow, cardiac output, and arterial blood gases after bypass. Thus fetal cardiac bypass causes a redistribution of regional blood flow away from the placenta and toward the other fetal organs. Nitroprusside partially prevents this redistribution. Methods of improving placental blood flow in the postbypass period may prove critical to the success of fetal cardiac bypass.

Research paper thumbnail of Fetal surgery

Journal of Intensive Care Medicine

Fetal surgery has emerged from the realm of medical curiosity into an exciting, multidisciplinary... more Fetal surgery has emerged from the realm of medical curiosity into an exciting, multidisciplinary specialty now capable of improving patient outcomes for a wide variety of diseases. Recent advances allow prenatal providers to both accurately diagnose and treat many fetal anomalies while maintaining maternal safety. As the initial postnatal health care providers to the majority of these newborns, neonatologists need to be familiar with some of the more recent state-of-the-art procedures currently being used. In this review, the authors discuss the prenatal evaluation process and various operative approaches (ie, open hysterotomy, fetoscopy, and percutaneous) to conduct fetal surgery. They then analyze the effectiveness of some of the more established and experimental prenatal therapies that are being performed for a number of fetal anomalies, including twin-twin transfusion syndrome, thoracic malformations, airway obstruction, congenital diaphragmatic hernia, myelomeningocele, and ao...

Research paper thumbnail of Does the EXIT to ECMO Procedure Change Outcomes for High-Risk CDH Patients?

Purpose The care of infants with high-risk congenital diaphragmatic hernia is often very challeng... more Purpose The care of infants with high-risk congenital diaphragmatic hernia is often very challenging. In the most severely affected infants, significant barotrauma or death can occur before advanced therapies such as ECMO can be initiated. We have previously examined the use of the EXIT to ECMO procedure (ex utero intrapartum treatment with placement on extracorporeal membrane oxygenation) in high-risk fetuses to determine if survival would be improved. Our initial experience with a small number of cases seemed to indicate a survival benefit with this approach when compared with historic controls. We report our experience with this technique in a larger cohort of our most severe CDH patients. Methods A comprehensive literature search was performed and our own experience was reviewed. We defined high-risk using our own institution's published method of percent Predicted Lung Volume (PPLV) using fetal MRI. Every fetus with less than fifteen PPLV (severe risk group) during January ...

Research paper thumbnail of Upper Airway Anomalies in Congenital Tracheoesophageal Fistula and Esophageal Atresia Patients

Annals of Otology, Rhinology & Laryngology, 2015

To examine the prevalence of upper airway anomalies in patients diagnosed with congenital tracheo... more To examine the prevalence of upper airway anomalies in patients diagnosed with congenital tracheoesophageal fistula and esophageal atresia (TEF/EA). A retrospective review was conducted of all TEF/EA patients seen at a tertiary pediatric hospital between January 2008 and December 2013. Inclusion criteria included evaluation by the otolaryngology service. Exclusion criteria included age&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;18 years, acquired TEF/EA, subsequent rule out of TEF/EA, and otolaryngology evaluation for reasons not pertaining to the airway. Data collected and analyzed included demographics, comorbidities, presenting symptoms, surgical interventions, laryngoscopic and bronchoscopic examinations, and subsequent medical and surgical management. Four hundred and thirty patients were diagnosed with TEF/EA at our institution. In all, 32.3%, or 139 children, were included in the analysis; 56.1% (n=78) male, 43.9% (n=61) female. Of the analyzed patients, 4.3% (n=6) were diagnosed with laryngomalacia. Eighteen patients (12.9%) were diagnosed with subglottic stenosis. Thirty (21.6%) had vocal fold paresis or immobility. Laryngeal cleft was diagnosed in 25.9% (n=36). Tracheomalacia was the most common airway finding, diagnosed in 37.4% (n=52) patients. Patients diagnosed with congenital TEF/EA have a high rate of secondary upper airway anomalies. Consideration should be given to perform a complete airway evaluation in all of these patients.

Research paper thumbnail of Restoring esophageal continuity following a failed colonic interposition for long-gap esophageal atresia

Journal of surgical case reports, 2015

The Foker process is a method of esophageal lengthening through axial tension-induced growth, all... more The Foker process is a method of esophageal lengthening through axial tension-induced growth, allowing for subsequent primary reconstruction of the esophagus in esophageal atresia (EA). In this unique case, the Foker process was used to grow the remaining esophageal segment long enough to attain esophageal continuity following failed colonic interpositions for long-gap esophageal atresia (LGEA). Initially developed for the treatment of LGEA in neonates, this case demonstrates that (i) an active esophageal lengthening response may still be present beyond the neonate time-period; and, (ii) the Foker process can be used to restore esophageal continuity following a failed colonic interposition if the lower esophageal segment is still present.

Research paper thumbnail of The association between laryngeal cleft and tracheoesophageal fistula: Myth or reality?

The Laryngoscope, 2014

Laryngeal cleft (LC) associated with tracheoesophageal fistula (TEF) with or without esophageal a... more Laryngeal cleft (LC) associated with tracheoesophageal fistula (TEF) with or without esophageal atresia (EA) has rarely been described. The purpose of this study is to review our experience, clinical features, management, delay in diagnosis, and complications in children with these anomalies. Retrospective chart review at pediatric tertiary referral center. Patients diagnosed with LC alone or LC and TEF over a 10-year period were included. Data including demographics, type of TEF and LC, comorbidities, symptoms, management, complications and swallowing outcomes were analyzed. There were 161 pediatric patients diagnosed with LC alone and 22 with LC and TEF. In patients with LC and TEF, aspiration was the most common presenting symptom (n = 11, 50%). Seventeen patients (77%, mean age 4 years 7 months) underwent endoscopic repair and five patients (23%) with type I clefts did not require surgery. Two patients required revision surgery. For patients with LC alone, the mean age at repair was 3.70 years (4 months-19.9 years) compared to 4.69 years (8 months-17.83 years) for patients with LC and TEF (P = 0.0187). The postoperative swallowing studies from 15 patients showed no aspiration. Mean follow-up was 4 years and 6 months. The diagnosis and management of LC in patients with TEF is often delayed. If a child presents with persistent aspiration after TEF repair, a complete airway endoscopy should be performed to evaluate for vocal fold mobility and cleft. Endoscopic repair is the recommended approach for those patients requiring surgical intervention. 4.

Research paper thumbnail of Postnatal outcome of fetuses with the prenatal diagnosis of gastroschisis

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 2013

The purpose of this study was to assess the postnatal outcome and complications that arise in inf... more The purpose of this study was to assess the postnatal outcome and complications that arise in infants with the prenatal diagnosis of gastroschisis. Prenatal sonograms with the diagnosis of gastroschisis were identified. Maternal age, indication for sonography, gestational age at diagnosis, other sonographic abnormalities, and postnatal outcome were recorded. Ninety-eight fetuses at 14.3 to 36 weeks' gestation had the diagnosis of gastroschisis on sonography. In 14 cases (14%), other fetal anomalies were identified, including hydronephrosis, hydrocephalus, coarctation of the aorta, and a limb anomaly. Bowel dilatation developed in 72 of 84 cases (86%) followed prenatally with sonography, and bowel wall thickening developed in 40 of 73 cases (55%). On postnatal follow-up, 57 of 68 infants (84%) had postnatal complications, many with multisystem complications, including 6 deaths, 40 with bowel-related complications, 30 with infectious complications, and 32 with anomalies involving ...

Research paper thumbnail of Neural stem cell delivery to the spinal cord in an ovine model of fetal surgery for spina bifida

Surgery, 2008

Background. We introduce the notion of prenatal neural stem cell (NSC) delivery to the spinal cor... more Background. We introduce the notion of prenatal neural stem cell (NSC) delivery to the spinal cord as an adjuvant to fetal repair of spina bifida. Methods. Fetal lambs with experimental myelomeningocele (MMC; n = 25) were divided in 3 groups: group I, no repair; group II, standard surgical MMC coverage; and group III, MMC coverage plus delivery of a murine NSCs clone into the spinal cord defect. Donor cells constitutively expressed lacZ encoding for Escherichia coli b-galactosidase, yet they were further labeled by exposure to either BrdU and/or to the fluorescent membrane dye PKH-26. Blinded initial clinical evaluations and multiple spinal cord analyses were undertaken soon after birth.

Research paper thumbnail of Factors affecting technical success of fetal aortic valve dilation

Ultrasound in Obstetrics and Gynecology, 2006

Objective We have reported previously that valve dilation enhances growth of cardiac structures a... more Objective We have reported previously that valve dilation enhances growth of cardiac structures and may prevent hypoplastic left heart syndrome (HLHS) in fetuses with critical aortic stenosis. We aimed to investigate maternal/fetal factors which may affect the technical success of fetal valvuloplasty, and to describe perinatal complications of the procedure. Methods This was a descriptive series of 22 fetuses diagnosed with critical aortic stenosis developing into HLHS which underwent intervention by valvuloplasty. Initially this was attempted using a percutaneous approach; reassessment after our first five attempts, only one of which was successful, led to the introduction of the option of laparotomy. Technical success was defined as balloon inflation across the aortic annulus and a broader jet through the aortic valve as assessed by Doppler. Data collected included body mass index, demographic variables, ultrasound findings and postprocedure interventions. Results Technical success increased significantly if maternal laparotomy was an option (83.3% vs. 20.0%, P = 0.017). Laparotomy was performed in 66.6% (12/18) of cases. There was a learning curve that showed an increase in success rate and decrease in need for laparotomy over the 3-year study period. Neither the need for laparotomy nor the chances of technical success were predictable by gestational age, body mass index or placental location. Tocolysis was limited to perioperative prophylaxis; one woman experienced wound infection and fluid overload. Postoperatively, three fetuses died and two delivered prematurely, 2 and 7 weeks after intervention. Conclusion Fetal aortic valvuloplasty can be performed with technical success, with low fetal loss rate and few maternal complications.

Research paper thumbnail of Significance and outcome of left heart hypoplasia in fetal congenital diaphragmatic hernia

Ultrasound in Obstetrics and Gynecology, 2010

K E Y W O R D S: cardiac development; congenital diaphragmatic hernia; fetal cardiac output; left... more K E Y W O R D S: cardiac development; congenital diaphragmatic hernia; fetal cardiac output; left heart hypoplasia ABSTRACT Objective In patients with a left-sided congenital diaphragmatic hernia (CDH), the left ventricle (LV) is often compressed and smaller than normal. The objective of this study was to investigate whether small left heart dimensions prenatally normalize after birth in patients with CDH, or whether prenatal indices of left heart size and flow predict postnatal outcome.

Research paper thumbnail of In-utero intervention for hypoplastic left heart syndrome — a perinatologist's perspective

Ultrasound in Obstetrics and Gynecology, 2005

Research paper thumbnail of Fetal Cartilage Engineering from Amniotic Mesenchymal Progenitor Cells

Stem Cells and Development, 2006

We determined whether cartilage could be engineered from mesenchymal progenitor cells (MPCs) norm... more We determined whether cartilage could be engineered from mesenchymal progenitor cells (MPCs) normally found in amniotic fluid. Mesenchymal amniocytes were isolated from ovine amniotic fluid samples (n = 5) and had their identity confirmed by immunocytochemistry. Cells were expanded and then cultured as micromass pellets (n = 5) in a chondrogenic medium containing transforming growth factor-beta2 (TGF-beta2) and insulin growth factor-1 (IGF-1) for 6-12 weeks. Pellets derived from fetal dermal fibroblasts (n = 4) were cultured under identical conditions. Additionally, expanded mesenchymal amniocytes were seeded onto biodegradable polyglycolic acid scaffolds (n = 5) and maintained in the same chondrogenic medium within a rotating bioreactor for 10-15 weeks. Engineered specimens were analyzed quantitatively and compared with native fetal hyaline cartilage samples (n = 5). Statistical analysis was by the unpaired Student&amp;amp;#39;s t-test (p &amp;amp;lt; 0.05). The isolated cells stained positively for vimentin and cytokeratins-8 and -18, but negatively for CD31. Micromass pellets derived from mesenchymal amniocytes exhibited chondrogenic differentiation by both standard and matrix-specific staining. In contrast, these findings could not be replicated in dermal fibroblast-based pellets. The engineered constructs derived from mesenchymal amniocytes similarly displayed histological evidence of chondrogenic differentiation and maintained their original size and three-dimensional architecture. Quantitative assays of the engineered constructs revealed lower concentrations of collagen type II, but similar amounts of glycosaminoglycans, elastin, and DNA, when compared to native fetal hyaline cartilage. We conclude that mesenchymal amniocytes can be used for the engineering of cartilaginous tissue in vitro. Cartilage engineering from the amniotic fluid may become a practical approach for the surgical treatment of select congenital anomalies.

Research paper thumbnail of Fetal neurenteric cyst causing hydrops: case report and review of the literature

Prenatal Diagnosis, 1999

Routine prenatal ultrasound revealed a unilocular cystic mass associated with upper thoracic hemi... more Routine prenatal ultrasound revealed a unilocular cystic mass associated with upper thoracic hemivertebrae that grew to 6 cm at 28 weeks and was associated with hydrops. A thoraco-amniotic shunt decompressed the cyst and resolved the hydrops, but the shunt occluded 17 days later. Preterm labour led to vaginal delivery at 31 2/7 weeks. Postnatally, the cyst was decompressed by thoracentesis due to respiratory distress. It was resected on day four of life. Severe tracheobronchomalacia was present post-operatively, presumably due to prenatal mass effect of the cyst. At one year of age, the child has recovered completely without adverse respiratory or neurological sequelae.

Research paper thumbnail of Reversal of Parenteral Nutrition-Associated Liver Disease in Two Infants With Short Bowel Syndrome Using Parenteral Fish Oil: Implications for Future Management

PEDIATRICS, 2006

Here we report the reversal of cholestasis in 2 infants with intestinal failure and parenteral nu... more Here we report the reversal of cholestasis in 2 infants with intestinal failure and parenteral nutrition-associated liver disease. Treatment involved the substitution of a conventional intravenous fat emulsion with one containing primarily omega-3 fatty acids. Biochemical tests of liver function improved significantly. One child was removed from the liver transplantation list because of improved hepatic function, and the second child had complete resolution of cholestasis while solely on parenteral nutrition. This suggests that fat emulsions made from fish oils may be an effective means of treating and preventing this often-fatal condition. A randomized, controlled trial is necessary to study the efficacy of this new approach to parenteral nutrition-associated liver disease.

Research paper thumbnail of Acellular bi-layer silk fibroin scaffolds support functional tissue regeneration in a rat model of onlay esophagoplasty

Biomaterials, 2015

Surgical management of long-gap esophageal defects with autologous gastrointestinal tissues is fr... more Surgical management of long-gap esophageal defects with autologous gastrointestinal tissues is frequently associated with adverse complications including organ dysmotility, dysphagia, and donor site morbidity. In order to develop alternative graft options, bi-layer silk fibroin (SF) scaffolds were investigated for their potential to support functional tissue regeneration in a rodent model of esophageal repair. Onlay esophagoplasty was performed with SF matrices (N = 40) in adult rats for up to 2 m of implantation. Parallel groups consisted of animals implanted with small intestinal submucosa (SIS) scaffolds (N = 22) or sham controls receiving esophagotomy alone (N = 20). Sham controls exhibited a 100% survival rate while rats implanted with SF and SIS scaffolds displayed respective survival rates of 93% and 91% prior to scheduled euthanasia. Animals in each experimental group were capable of solid food consumption following a 3 d post-op liquid diet and demonstrated similar degrees of weight gain throughout the study period. End-point μ-computed tomography at 2 m post-op revealed no evidence of contrast extravasation, fistulas, strictures, or diverticula in any of the implant groups. Ex vivo tissue bath studies demonstrated that reconstructed esophageal conduits supported by both SF and SIS scaffolds displayed contractile responses to carbachol, KCl and electrical field stimulation while isoproterenol produced tissue relaxation. Histological (Masson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s trichrome and hematoxylin and eosin) and immunohistochemical (IHC) evaluations demonstrated both implant groups produced de novo formation of skeletal and smooth muscle bundles positive for contractile protein expression [fast myosin heavy chain (MY32) and α-smooth muscle actin (α-SMA)] within the graft site. However, SF matrices promoted a significant 4-fold increase in MY32+ skeletal muscle and a 2-fold gain in α-SMA+ smooth muscle in comparison to the SIS cohort as determined by histomorphometric analyses. A stratified squamous, keratinized epithelium expressing cytokeratin 5 and involucrin proteins was also present at 2 m post-op in all experimental groups. De novo innervation and vascularization were evident in all regenerated tissues indicated by the presence of synaptophysin (SYP38)+ boutons and vessels lined with CD31 expressing endothelial cells. In respect to SIS, the SF group supported a significant 4-fold increase in the density of SYP38+ boutons within the implant region. Evaluation of host tissue responses revealed that SIS matrices elicited chronic inflammatory reactions and severe fibrosis throughout the neotissues, in contrast to SF scaffolds. The results of this study demonstrate that bi-layer SF scaffolds represent promising biomaterials for onlay esophagoplasty, capable of producing superior regenerative outcomes in comparison to conventional SIS scaffolds.

Research paper thumbnail of Thoracoscopic Aortopexy for the Treatment of Pediatric Tracheomalacia: A Right-Sided Approach

Operative Techniques in Thoracic and Cardiovascular Surgery, 2011

Research paper thumbnail of Prune Belly Syndrome

Seminars in Pediatric Surgery

ABSTRACT

Research paper thumbnail of Tracheobronchomalacia in pediatric patients with esophageal atresia: Comparison of diagnostic laryngoscopy/bronchoscopy and dynamic airway multidetector computed tomography

Journal of pediatric surgery, 2015

Diagnostic laryngoscopy and bronchoscopy (DLB) has been the traditional preoperative diagnostic m... more Diagnostic laryngoscopy and bronchoscopy (DLB) has been the traditional preoperative diagnostic modality for evaluating presence and severity of tracheobronchomalacia (TBM), and requires anesthesia. Alternatively, multidetector computed tomography (MDCT) is potentially a noninvasive modality that provides high-resolution, 3-dimensional (3D) imaging of the thorax providing preoperative guidance for pediatric surgeons. This study compares MDCT with intraoperative DLB in the assessment of TBM in symptomatic pediatric patients with esophageal atresia (EA). Following IRB approval all pediatric patients (≤18years) who had EA and who underwent an MDCT study as a preoperative evaluation of TBM prior to aortopexy were retrospectively reviewed. Patients with incomplete reports on intraoperative DLB or MDCT studies were excluded. Two pediatric radiologists independently evaluated all MDCT studies in a blinded fashion. On both DLB and MDCT studies, TBM was scored as present or absent in five an...

Research paper thumbnail of Intermittent single lung ventilation in a 620-gram micropremie during postintubation carinal laceration repair

Pediatric Anesthesia, 2010

Research paper thumbnail of Paravertebral nerve block catheters using chloroprocaine in infants with prolonged mechanical ventilation for treatment of long-gap esophageal atresia

Paediatric anaesthesia, 2015

Infants with long-gap esophageal atresia (LGEA) undergo repeated thoracotomies for staged surgica... more Infants with long-gap esophageal atresia (LGEA) undergo repeated thoracotomies for staged surgical repair known as the Foker process (FP). Associated prolonged mechanical ventilation results in exposure to high doses of opioids and benzodiazepines, and prolonged weaning times and ICU stays. The aim of this study was to determine the effectiveness of short-term paravertebral nerve block (PVNB) catheters in reducing opioid/benzodiazepine exposure and effects on clinical variables. The medical records of seventeen infants were retrospectively reviewed; 11 with PVNB and six without (CG). PVNB were placed using ultrasound-guidance and chloroprocaine infusions implemented in the ICU. Opioids and benzodiazepines were administered via the protocol for 5 days following thoracotomies for Foker-I and Foker-II. Foker-I: Average reduction in morphine and midazolam consumption was 36% (2.18 vs 3.40 mg·kg(-1) ·day(-1) ; P < 0.001) and 31% (2.25 vs 3.25 mg·kg(-1) ·day(-1) ; P = 0.033), respectiv...

Research paper thumbnail of Fetal cardiac bypass alters regional blood flows, arterial blood gases, and hemodynamics in sheep

The American journal of physiology

Successful fetal cardiac bypass might allow prenatal correction of some congenital heart defects.... more Successful fetal cardiac bypass might allow prenatal correction of some congenital heart defects. However, previous studies have shown that fetal cardiac bypass may result in impaired fetal gas exchange after bypass. To investigate the etiology of this impairment, we determined whether fetal cardiac bypass causes a redistribution of fetal regional blood flows and, if so, whether a vasodilator (sodium nitroprusside) can prevent this redistribution. We also determined the effects of fetal cardiac bypass with and without nitroprusside on fetal arterial blood gases and hemodynamics. Eighteen fetal sheep were studied in utero under general anesthesia. Seven fetuses underwent bypass without nitroprusside, six underwent bypass with nitroprusside, and five were no-bypass controls. Blood flows were determined using radionuclide-labeled microspheres. After bypass without nitroprusside, placental blood flow decreased by 25-60%, whereas cardiac output increased by 15-25%. Flow to all other fetal organs increased or remained unchanged. Decreased placental blood flow after bypass was accompanied by a fall in PO2 and a rise in PCO2. Nitroprusside improved placental blood flow, cardiac output, and arterial blood gases after bypass. Thus fetal cardiac bypass causes a redistribution of regional blood flow away from the placenta and toward the other fetal organs. Nitroprusside partially prevents this redistribution. Methods of improving placental blood flow in the postbypass period may prove critical to the success of fetal cardiac bypass.

Research paper thumbnail of Fetal surgery

Journal of Intensive Care Medicine

Fetal surgery has emerged from the realm of medical curiosity into an exciting, multidisciplinary... more Fetal surgery has emerged from the realm of medical curiosity into an exciting, multidisciplinary specialty now capable of improving patient outcomes for a wide variety of diseases. Recent advances allow prenatal providers to both accurately diagnose and treat many fetal anomalies while maintaining maternal safety. As the initial postnatal health care providers to the majority of these newborns, neonatologists need to be familiar with some of the more recent state-of-the-art procedures currently being used. In this review, the authors discuss the prenatal evaluation process and various operative approaches (ie, open hysterotomy, fetoscopy, and percutaneous) to conduct fetal surgery. They then analyze the effectiveness of some of the more established and experimental prenatal therapies that are being performed for a number of fetal anomalies, including twin-twin transfusion syndrome, thoracic malformations, airway obstruction, congenital diaphragmatic hernia, myelomeningocele, and ao...

Research paper thumbnail of Does the EXIT to ECMO Procedure Change Outcomes for High-Risk CDH Patients?

Purpose The care of infants with high-risk congenital diaphragmatic hernia is often very challeng... more Purpose The care of infants with high-risk congenital diaphragmatic hernia is often very challenging. In the most severely affected infants, significant barotrauma or death can occur before advanced therapies such as ECMO can be initiated. We have previously examined the use of the EXIT to ECMO procedure (ex utero intrapartum treatment with placement on extracorporeal membrane oxygenation) in high-risk fetuses to determine if survival would be improved. Our initial experience with a small number of cases seemed to indicate a survival benefit with this approach when compared with historic controls. We report our experience with this technique in a larger cohort of our most severe CDH patients. Methods A comprehensive literature search was performed and our own experience was reviewed. We defined high-risk using our own institution's published method of percent Predicted Lung Volume (PPLV) using fetal MRI. Every fetus with less than fifteen PPLV (severe risk group) during January ...

Research paper thumbnail of Upper Airway Anomalies in Congenital Tracheoesophageal Fistula and Esophageal Atresia Patients

Annals of Otology, Rhinology & Laryngology, 2015

To examine the prevalence of upper airway anomalies in patients diagnosed with congenital tracheo... more To examine the prevalence of upper airway anomalies in patients diagnosed with congenital tracheoesophageal fistula and esophageal atresia (TEF/EA). A retrospective review was conducted of all TEF/EA patients seen at a tertiary pediatric hospital between January 2008 and December 2013. Inclusion criteria included evaluation by the otolaryngology service. Exclusion criteria included age&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;18 years, acquired TEF/EA, subsequent rule out of TEF/EA, and otolaryngology evaluation for reasons not pertaining to the airway. Data collected and analyzed included demographics, comorbidities, presenting symptoms, surgical interventions, laryngoscopic and bronchoscopic examinations, and subsequent medical and surgical management. Four hundred and thirty patients were diagnosed with TEF/EA at our institution. In all, 32.3%, or 139 children, were included in the analysis; 56.1% (n=78) male, 43.9% (n=61) female. Of the analyzed patients, 4.3% (n=6) were diagnosed with laryngomalacia. Eighteen patients (12.9%) were diagnosed with subglottic stenosis. Thirty (21.6%) had vocal fold paresis or immobility. Laryngeal cleft was diagnosed in 25.9% (n=36). Tracheomalacia was the most common airway finding, diagnosed in 37.4% (n=52) patients. Patients diagnosed with congenital TEF/EA have a high rate of secondary upper airway anomalies. Consideration should be given to perform a complete airway evaluation in all of these patients.

Research paper thumbnail of Restoring esophageal continuity following a failed colonic interposition for long-gap esophageal atresia

Journal of surgical case reports, 2015

The Foker process is a method of esophageal lengthening through axial tension-induced growth, all... more The Foker process is a method of esophageal lengthening through axial tension-induced growth, allowing for subsequent primary reconstruction of the esophagus in esophageal atresia (EA). In this unique case, the Foker process was used to grow the remaining esophageal segment long enough to attain esophageal continuity following failed colonic interpositions for long-gap esophageal atresia (LGEA). Initially developed for the treatment of LGEA in neonates, this case demonstrates that (i) an active esophageal lengthening response may still be present beyond the neonate time-period; and, (ii) the Foker process can be used to restore esophageal continuity following a failed colonic interposition if the lower esophageal segment is still present.

Research paper thumbnail of The association between laryngeal cleft and tracheoesophageal fistula: Myth or reality?

The Laryngoscope, 2014

Laryngeal cleft (LC) associated with tracheoesophageal fistula (TEF) with or without esophageal a... more Laryngeal cleft (LC) associated with tracheoesophageal fistula (TEF) with or without esophageal atresia (EA) has rarely been described. The purpose of this study is to review our experience, clinical features, management, delay in diagnosis, and complications in children with these anomalies. Retrospective chart review at pediatric tertiary referral center. Patients diagnosed with LC alone or LC and TEF over a 10-year period were included. Data including demographics, type of TEF and LC, comorbidities, symptoms, management, complications and swallowing outcomes were analyzed. There were 161 pediatric patients diagnosed with LC alone and 22 with LC and TEF. In patients with LC and TEF, aspiration was the most common presenting symptom (n = 11, 50%). Seventeen patients (77%, mean age 4 years 7 months) underwent endoscopic repair and five patients (23%) with type I clefts did not require surgery. Two patients required revision surgery. For patients with LC alone, the mean age at repair was 3.70 years (4 months-19.9 years) compared to 4.69 years (8 months-17.83 years) for patients with LC and TEF (P = 0.0187). The postoperative swallowing studies from 15 patients showed no aspiration. Mean follow-up was 4 years and 6 months. The diagnosis and management of LC in patients with TEF is often delayed. If a child presents with persistent aspiration after TEF repair, a complete airway endoscopy should be performed to evaluate for vocal fold mobility and cleft. Endoscopic repair is the recommended approach for those patients requiring surgical intervention. 4.

Research paper thumbnail of Postnatal outcome of fetuses with the prenatal diagnosis of gastroschisis

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 2013

The purpose of this study was to assess the postnatal outcome and complications that arise in inf... more The purpose of this study was to assess the postnatal outcome and complications that arise in infants with the prenatal diagnosis of gastroschisis. Prenatal sonograms with the diagnosis of gastroschisis were identified. Maternal age, indication for sonography, gestational age at diagnosis, other sonographic abnormalities, and postnatal outcome were recorded. Ninety-eight fetuses at 14.3 to 36 weeks' gestation had the diagnosis of gastroschisis on sonography. In 14 cases (14%), other fetal anomalies were identified, including hydronephrosis, hydrocephalus, coarctation of the aorta, and a limb anomaly. Bowel dilatation developed in 72 of 84 cases (86%) followed prenatally with sonography, and bowel wall thickening developed in 40 of 73 cases (55%). On postnatal follow-up, 57 of 68 infants (84%) had postnatal complications, many with multisystem complications, including 6 deaths, 40 with bowel-related complications, 30 with infectious complications, and 32 with anomalies involving ...

Research paper thumbnail of Neural stem cell delivery to the spinal cord in an ovine model of fetal surgery for spina bifida

Surgery, 2008

Background. We introduce the notion of prenatal neural stem cell (NSC) delivery to the spinal cor... more Background. We introduce the notion of prenatal neural stem cell (NSC) delivery to the spinal cord as an adjuvant to fetal repair of spina bifida. Methods. Fetal lambs with experimental myelomeningocele (MMC; n = 25) were divided in 3 groups: group I, no repair; group II, standard surgical MMC coverage; and group III, MMC coverage plus delivery of a murine NSCs clone into the spinal cord defect. Donor cells constitutively expressed lacZ encoding for Escherichia coli b-galactosidase, yet they were further labeled by exposure to either BrdU and/or to the fluorescent membrane dye PKH-26. Blinded initial clinical evaluations and multiple spinal cord analyses were undertaken soon after birth.

Research paper thumbnail of Factors affecting technical success of fetal aortic valve dilation

Ultrasound in Obstetrics and Gynecology, 2006

Objective We have reported previously that valve dilation enhances growth of cardiac structures a... more Objective We have reported previously that valve dilation enhances growth of cardiac structures and may prevent hypoplastic left heart syndrome (HLHS) in fetuses with critical aortic stenosis. We aimed to investigate maternal/fetal factors which may affect the technical success of fetal valvuloplasty, and to describe perinatal complications of the procedure. Methods This was a descriptive series of 22 fetuses diagnosed with critical aortic stenosis developing into HLHS which underwent intervention by valvuloplasty. Initially this was attempted using a percutaneous approach; reassessment after our first five attempts, only one of which was successful, led to the introduction of the option of laparotomy. Technical success was defined as balloon inflation across the aortic annulus and a broader jet through the aortic valve as assessed by Doppler. Data collected included body mass index, demographic variables, ultrasound findings and postprocedure interventions. Results Technical success increased significantly if maternal laparotomy was an option (83.3% vs. 20.0%, P = 0.017). Laparotomy was performed in 66.6% (12/18) of cases. There was a learning curve that showed an increase in success rate and decrease in need for laparotomy over the 3-year study period. Neither the need for laparotomy nor the chances of technical success were predictable by gestational age, body mass index or placental location. Tocolysis was limited to perioperative prophylaxis; one woman experienced wound infection and fluid overload. Postoperatively, three fetuses died and two delivered prematurely, 2 and 7 weeks after intervention. Conclusion Fetal aortic valvuloplasty can be performed with technical success, with low fetal loss rate and few maternal complications.

Research paper thumbnail of Significance and outcome of left heart hypoplasia in fetal congenital diaphragmatic hernia

Ultrasound in Obstetrics and Gynecology, 2010

K E Y W O R D S: cardiac development; congenital diaphragmatic hernia; fetal cardiac output; left... more K E Y W O R D S: cardiac development; congenital diaphragmatic hernia; fetal cardiac output; left heart hypoplasia ABSTRACT Objective In patients with a left-sided congenital diaphragmatic hernia (CDH), the left ventricle (LV) is often compressed and smaller than normal. The objective of this study was to investigate whether small left heart dimensions prenatally normalize after birth in patients with CDH, or whether prenatal indices of left heart size and flow predict postnatal outcome.

Research paper thumbnail of In-utero intervention for hypoplastic left heart syndrome — a perinatologist's perspective

Ultrasound in Obstetrics and Gynecology, 2005

Research paper thumbnail of Fetal Cartilage Engineering from Amniotic Mesenchymal Progenitor Cells

Stem Cells and Development, 2006

We determined whether cartilage could be engineered from mesenchymal progenitor cells (MPCs) norm... more We determined whether cartilage could be engineered from mesenchymal progenitor cells (MPCs) normally found in amniotic fluid. Mesenchymal amniocytes were isolated from ovine amniotic fluid samples (n = 5) and had their identity confirmed by immunocytochemistry. Cells were expanded and then cultured as micromass pellets (n = 5) in a chondrogenic medium containing transforming growth factor-beta2 (TGF-beta2) and insulin growth factor-1 (IGF-1) for 6-12 weeks. Pellets derived from fetal dermal fibroblasts (n = 4) were cultured under identical conditions. Additionally, expanded mesenchymal amniocytes were seeded onto biodegradable polyglycolic acid scaffolds (n = 5) and maintained in the same chondrogenic medium within a rotating bioreactor for 10-15 weeks. Engineered specimens were analyzed quantitatively and compared with native fetal hyaline cartilage samples (n = 5). Statistical analysis was by the unpaired Student&amp;amp;#39;s t-test (p &amp;amp;lt; 0.05). The isolated cells stained positively for vimentin and cytokeratins-8 and -18, but negatively for CD31. Micromass pellets derived from mesenchymal amniocytes exhibited chondrogenic differentiation by both standard and matrix-specific staining. In contrast, these findings could not be replicated in dermal fibroblast-based pellets. The engineered constructs derived from mesenchymal amniocytes similarly displayed histological evidence of chondrogenic differentiation and maintained their original size and three-dimensional architecture. Quantitative assays of the engineered constructs revealed lower concentrations of collagen type II, but similar amounts of glycosaminoglycans, elastin, and DNA, when compared to native fetal hyaline cartilage. We conclude that mesenchymal amniocytes can be used for the engineering of cartilaginous tissue in vitro. Cartilage engineering from the amniotic fluid may become a practical approach for the surgical treatment of select congenital anomalies.

Research paper thumbnail of Fetal neurenteric cyst causing hydrops: case report and review of the literature

Prenatal Diagnosis, 1999

Routine prenatal ultrasound revealed a unilocular cystic mass associated with upper thoracic hemi... more Routine prenatal ultrasound revealed a unilocular cystic mass associated with upper thoracic hemivertebrae that grew to 6 cm at 28 weeks and was associated with hydrops. A thoraco-amniotic shunt decompressed the cyst and resolved the hydrops, but the shunt occluded 17 days later. Preterm labour led to vaginal delivery at 31 2/7 weeks. Postnatally, the cyst was decompressed by thoracentesis due to respiratory distress. It was resected on day four of life. Severe tracheobronchomalacia was present post-operatively, presumably due to prenatal mass effect of the cyst. At one year of age, the child has recovered completely without adverse respiratory or neurological sequelae.

Research paper thumbnail of Reversal of Parenteral Nutrition-Associated Liver Disease in Two Infants With Short Bowel Syndrome Using Parenteral Fish Oil: Implications for Future Management

PEDIATRICS, 2006

Here we report the reversal of cholestasis in 2 infants with intestinal failure and parenteral nu... more Here we report the reversal of cholestasis in 2 infants with intestinal failure and parenteral nutrition-associated liver disease. Treatment involved the substitution of a conventional intravenous fat emulsion with one containing primarily omega-3 fatty acids. Biochemical tests of liver function improved significantly. One child was removed from the liver transplantation list because of improved hepatic function, and the second child had complete resolution of cholestasis while solely on parenteral nutrition. This suggests that fat emulsions made from fish oils may be an effective means of treating and preventing this often-fatal condition. A randomized, controlled trial is necessary to study the efficacy of this new approach to parenteral nutrition-associated liver disease.