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1.
Surgery ; 173(3): 774-780, 2023 03.
Article En | MEDLINE | ID: mdl-37534708

BACKGROUND: The Center for Medicaid and Medicare Services predicts the length of stay for pediatric burn patients based on several variables. However, many patients exceed their anticipated length. This study looks to identify aspects of patient presentation, wound characteristics, treatment, and discharge that are associated with a longer-than-predicted length of stay to identify strategies to safely reduce it. METHODS: We conducted a retrospective chart review of 535 pediatric burn patients admitted to our academic hospital from January 2018 to December 2020. 405 patients met inclusion criteria. Data were collected and analyzed. RESULTS: Average patient age was 3.36 years. 72.3% were treated for scald burns. Average length of stay was 13.5 days. 20.5% (n = 83) of patients exceeded their predicted length of stay. In comparing patients who exceeded their predicted length of stay to those who did not, the former had significant differences in burn causes, percent total body surface area burned (12.80% vs 4.24% [P = .000]), and body areas involved. Patients who exceeded length of stay had a higher incidence of endotracheal intubation (15.7% vs 1.3%), surgical intervention (85.5% vs 29.2%), need for tube-feeding (48.2% vs 4.3%), and intensive care unit admissions (22.9% vs 2.2% [P = .00 all]). They also averaged more operations, autografting (31.3% vs 1.6% [P = .00]), total operating room time (250 vs 31 minutes [P = .00]), and time to the first operation (2.32 vs 1.64 days [P = .00]). Tube-feeding averaged 9.52 vs 0.72 days (P = .00) extending patient stay after wound stability (43.9% vs 4.3% [P = .00]). These patients also required more discharge planning, with higher rates of Child Protective Services involvement (39.8% vs 10.9% [P = .00]), services consulted (1.06 vs 0.24 [P = .00]), and discharges to inpatient rehabilitation (8.6% vs 0.6% [P = .00]). 89.6% of all patients followed up in clinic. CONCLUSIONS: Twenty percent of pediatric burn patients had a longer length of stay than predicted by the Center for Medicaid and Medicare Services. Many factors were strongly associated with a longer-than-predicted length of stay. Identifying these early on might help reduce length of stay and meet the targets of the Center for Medicaid and Medicare Services.


Burns , Medicare , Aged , Child , Humans , United States , Child, Preschool , Retrospective Studies , Length of Stay , Burns/therapy , Burns/epidemiology , Hospitalization , Burn Units
2.
Burns ; 49(1): 120-128, 2023 02.
Article En | MEDLINE | ID: mdl-35351355

Treatment for pediatric burns includes fluid resuscitation with formulas estimating fluid requirements based on weight and/or body surface area (BSA) with percent total body surface area burn (%TBSA burn). This study evaluates the risk of complications using weight-based resuscitation in children following burn injuries and compares fluid estimates with those that incorporate BSA. A retrospective review was conducted on 110 children admitted to an ABA-verified urban pediatric burn center over 12 years. Patients had ≥ 15% TBSA burn and were resuscitated with the weight-based Parkland formula. BSA-based Galveston and BSA-incorporated Cincinnati formula predictions were calculated. Complications were collected throughout hospital stay. Patients were classified into weight groups based on percentile. This study included 11 underweight, 60 normal weight, 18 overweight, and 21 obese children. Total fluid administered was higher as percentile increased; however, overweight children received more fluid than the obese (p = 0.023). The Galveston formula underpredicted fluid given over the first 24 h post-injury (p = 0.042); the Parkland and Cincinnati formula predictions did not significantly differ from fluids given. Further research is needed to determine the value of weight-based vs BSA-based or incorporated formulas in reducing risk of complications.


Burns , Fluid Therapy , Child , Humans , Body Surface Area , Burns/therapy , Fluid Therapy/adverse effects , Fluid Therapy/methods , Pediatric Obesity , Retrospective Studies , Body Weight
3.
J Burn Care Res ; 43(2): 483-486, 2022 03 23.
Article En | MEDLINE | ID: mdl-34644382

Pediatric hand friction injuries caused by running treadmills are ever more prevalent due to the increasing presence of home exercise equipment. These and other related injuries have received recent attention in the media, leading to mass product recalls in some cases. These friction injuries are similar to deep thermal burns, and these patients are usually cared for in the pediatric burn unit at our institution. We sought to describe our recent experience managing 22 patients with these injuries. Patients were queried from our urban pediatric burn center database. After Institutional Review Board approval, a retrospective chart review of all patients admitted for a treadmill-related hand injury over a 5-year period was performed. Data collected included patient demographics, initial treatment methods (surgical vs nonoperative), type of dressing used, hospital length of stay (LOS), and compliance with follow-up. We collected patient-centered outcomes included the time to healing and the need for subsequent surgical and/or nonsurgical interventions to treat the sequelae of these injuries. Our center treated 22 hand friction injuries caused by treadmills over the 5-year period. Five patients (23%) underwent early surgical intervention (<30 days from injury), with a median time from injury of 7 days (interquartile range 1.75-13.5). This cohort required additional interventions to treat postoperative sequelae with 2 (40%) requiring additional surgery and 3 (60%) managed nonsurgically. Of the 17 (77%) who were initially treated nonoperatively, 5 (29%) healed completely with dressing changes only and required no further treatment. Eleven (65%) had injury-related sequelae and were managed successfully with nonsurgical interventions. Only 1 patient (6%) required scar modification by Z-plasty. Average LOS was 14 hours and the median number of weekly follow-up visits was 4 until complete healing. Given the excellent outcomes observed in patients treated without acute surgical intervention in this case series, nonoperative management appears to be feasible, safe, and may reduce the need for operative intervention. These injuries, although small, are deep and require a prolonged period of dressing changes and aggressive therapy including posthealing time commitment to scar management in order to achieve best outcomes. Our study supports the need for increased community awareness of this type of injury.


Burns , Hand Injuries , Burns/complications , Burns/therapy , Child , Cicatrix/complications , Friction , Hand Injuries/etiology , Hand Injuries/surgery , Humans , Retrospective Studies
4.
J Burn Care Res ; 43(2): 408-411, 2022 03 23.
Article En | MEDLINE | ID: mdl-34309678

Silver-based topical treatments have seen widespread use for the management of burns due to silver's antimicrobial activity. Recent studies suggest that silver nanoparticles could negatively affect healing time due to their toxic effect on keratinocytes and fibroblasts at higher concentrations. Zinc oxide antimicrobial activity has been demonstrated in vitro, and results from animal studies are promising for burn management. At our ABA-verified pediatric burn center, the use of silver sulfadiazine cream ("Silvadene") has been slowly replaced by a zinc oxide/dimethicone spray-on solution ("Touchless Spray"). The dimethicone allows the spray to be occlusive without interfering with clothing, yet easily removed as opposed to Silvadene cream which requires wound scrubbing to remove and replace; potentially improving patient adherence with at-home treatments. This is the first study of zinc oxide's efficacy as a burn wound management agent in humans. We sought to compare the efficacy of silver sulfadiazine and that of zinc oxide/dimethicone to determine whether zinc oxide/dimethicone, in its easy-to-use form, is a viable alternative to silver sulfadiazine. We conducted a retrospective review of the electronic medical records of all patients treated for perineal, genital, perianal, suprapubic, or buttocks burn wounds at a large pediatric-verified burn center from January 1, 2014 to October 28, 2019. Only patients with superficial second-degree scald burns that arrived at our institution less than 24 hours after injury were included. Of a total 52 patients identified, 27 patients received silver sulfadiazine while 25 received zinc oxide/dimethicone. After initial evaluation and treatment by the burn team, all patients were followed up at our weekly burn clinic until complete healing was achieved. We retrospectively extracted demographic data, wound size, depth, and location, management strategies, time to complete healing, and incidence of infectious and noninfectious complications. The control group contained patients with total body surface area burns significantly greater than the zinc oxide/dimethicone group likely due to selective treatment when zinc oxide/dimethicone was first introduced at our facility. Time to healing was significantly lower in the zinc oxide/dimethicone intervention group (12.16 ± 8.644 days) than the silver sulfadiazine control group (16.89 ± 11.342 days). No infections were observed. Limitations include the relatively small sample sizes and differences in the size of burn wounds that confounded our results and likely negatively affected healing time in the control group. The zinc oxide/dimethicone group had a significantly lower healing time than the silver sulfadiazine group in the treatment of pediatric burns to the perineum, genitalia, suprapubis, and buttocks. Zinc oxide/dimethicone may prove to be a useful tool for treating burn wounds, and further study is needed to determine its efficacy and safety.


Anti-Infective Agents, Local , Anti-Infective Agents , Burns , Metal Nanoparticles , Zinc Oxide , Animals , Anti-Infective Agents, Local/therapeutic use , Burns/drug therapy , Child , Humans , Perineum , Retrospective Studies , Silver , Silver Sulfadiazine/therapeutic use , Zinc Oxide/therapeutic use
5.
Burns ; 46(8): 1875-1879, 2020 12.
Article En | MEDLINE | ID: mdl-32586614

Sink-bathing is common practice among parents. However, this puts infants and young children at unrecognized risk for burn injuries. As the only verified pediatric burn center in a large urban area, we treat burn patients from a large variation in socioeconomic status. This provides us a unique opportunity to examine sink-burn injury patterns, circumstances surrounding these burns, identify areas with high incidence and put in place an injury prevention outreach initiative. This retrospective study included patients treated for sink-bathing burns at our burn center in an 8.5-year period. Analysis of 71 patients revealed infants under one year of age are most commonly afflicted. Additionally, that families of low-socioeconomic means are disproportionately affected. Understanding the different circumstances surrounding sink-bathing burns allows us to be more specific in our community education efforts and efficiently guide our resources.


Baths/adverse effects , Burns/prevention & control , Hot Temperature/adverse effects , Baths/nursing , Baths/statistics & numerical data , Burns/epidemiology , Burns/etiology , Child, Preschool , Female , Humans , Infant , Length of Stay/statistics & numerical data , Male , Program Development/methods , Retrospective Studies , Risk Factors
6.
J Burn Care Res ; 39(1): 65-72, 2018 01 01.
Article En | MEDLINE | ID: mdl-28570306

The purpose of this study was to examine the utility of electrocardiograms (EKGs) for low-risk, low-voltage pediatric electrical burn victims. A retrospective chart review was conducted on 86 pediatric patients who presented to the children's hospital between 2000 and 2015 after sustaining electrical burns. Variables included source and estimated voltage, extent of injuries, length of stay, high risk factors, and EKG results. High risk factors included estimated voltage > 1000 V, lightning, tetany, symptoms, loss of consciousness, or seizures. Statistical analyses were conducted. Average age was 5 years. Of those who sustained burns, 84.5% (n = 71/84) had second-degree burns ≤ 1% TBSA or less. Eleven patients had high risk factors, 12.9% (n = 11/85) and most had length of stay < 3 days (91.8%; n = 78/85). Majority sustained burns from low-voltage (< 300 V) household electrical outlets, cords, or light bulb sockets (90.4%; n = 75/83). Among patients with available EKGs, 12 had arrhythmias on initial EKG (i.e., low right atrial rhythm, t-wave inversions, sinus tachycardia, bundle branch block; 20.7%; n = 12/58). All were transient and nonfatal. The data suggest that low estimated voltage (< 300 V) electrical injuries were associated with negative EKGs; however, due to the low rate of arrhythmias, a Fisher's exact test did not show significance, P = 0.09 (P > 0.05). Preliminary data suggest that most pediatric electrical burns are due to low voltage (< 300 V) household sources. Few have high risk factors or arrhythmias that were transient and nonfatal. These data suggest that low-risk, asymptomatic, low-voltage pediatric electrical burns may not require an initial screening EKG.


Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/epidemiology , Burns, Electric/complications , Burns, Electric/physiopathology , Electrocardiography , Adolescent , Child , Child, Preschool , Female , Humans , Length of Stay , Male , Needs Assessment , Patient Selection , Retrospective Studies , Risk Factors
7.
J Pediatr Surg ; 50(1): 126-30, 2015 Jan.
Article En | MEDLINE | ID: mdl-25598108

BACKGROUND: Air-contrast enema (ACE) is standard treatment for primary ileocolic intussusception. Management of recurrences is less clear. This study aimed to delineate appropriate therapy by quantifying the relationship between recurrence and need for bowel resection, pathologic lead points (PLP), and complication rates. METHODS: After IRB approval, a single institution review of patients with ileocolic intussusception from 1997 to 2013 was performed, noting recurrences, outcomes, and complications. Fisher's exact and t-tests were used. RESULTS: Of 716 intussusceptions, 666 were ileocecal. Forty-four underwent bowel resection, with 29 PLPs and 9 ischemia/perforation. Recurrence after ACE occurred in 96 (14%). Recurrence did not predict PLP (P=0.25). Recurrence (≥3) was associated with higher resection rate (P=0.03), but not ischemia/perforation (P=0.75). ACE-related complications occurred in 4 (0.5%) patients. Successful initial ACE had 98% negative predictive value for resection and PLP (e.g., after successful ACE, 2% had resections, 2% PLP). After failed initial ACE, 36% received resection, and 23% had PLP (P<0.001). CONCLUSIONS: Recurrence is associated with a greater risk of resection but not PLP or ACE-complication. Failed ACE is associated with increased risk for harboring PLP and receiving resection. ACE should be the standard treatment in recurrent intussusception, regardless of number of recurrences.


Enema , Ileal Diseases/surgery , Intussusception/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Recurrence
8.
J Am Coll Surg ; 216(6): 1089-93, 2013 Jun.
Article En | MEDLINE | ID: mdl-23571141

BACKGROUND: Postoperative intussusception (POI) is a sporadic complication whose mechanisms and risk factors remain poorly understood. Its epidemiology in the minimally invasive surgery era has yet to be well described, particularly in children. We sought to examine risk factors, demographics, and anatomic patterns of pediatric POI in recent years. STUDY DESIGN: This was a 13-year retrospective review from a single tertiary pediatric center. Variables analyzed included patient demographics, time of occurrence, type of intussusception, type of anesthesia, and triggering surgical procedure. The latter variable was divided into 2 groups: abdominal and nonabdominal interventions. Statistical analysis was by 2-tailed Fisher's exact test with significance set at p < 0.05. RESULTS: Among 822 cases of intussusception in 718 patients, 22 documented cases of POI were identified. Twelve of them occurred after abdominal procedures; there was a statistically significant difference in the incidence of POI after open surgery (0.091%; 11 of 12,126) when compared with minimally invasive interventions (0.013%; 1 of 7,610; p = 0.036). As expected, ileoileal and jejunojejunal intussusceptions were the most common forms of POI after abdominal operations (12 of 12; 100%); however, ileocolic intussusceptions were common forms of POI after nonabdominal cases (5 of 10; 50%; p = 0.01). Epidural anesthesia did not appear to be a risk factor for POI. CONCLUSIONS: Although rare, postoperative intussusception can occur after a multitude of interventions, including those performed at a distance from the abdomen. Although small bowel intussusception is the predominant variant of this complication after abdominal procedures, ileocolic intussusception is prevalent after other interventions. Minimally invasive abdominal access may protect against postoperative intussusception in children.


Intussusception/epidemiology , Minimally Invasive Surgical Procedures/adverse effects , Postoperative Complications/epidemiology , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Incidence , Infant , Intussusception/etiology , Male , Massachusetts/epidemiology , Minimally Invasive Surgical Procedures/methods , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Time Factors
9.
Stem Cells Dev ; 22(4): 548-53, 2013 Feb 15.
Article En | MEDLINE | ID: mdl-22957979

We sought to determine whether neural stem cells (NSCs) can be isolated from the amniotic fluid in the setting of neural tube defects (NTDs), as a prerequisite for eventual autologous perinatal therapies. Pregnant Sprague-Dawley dams (n=62) were divided into experimental (n=42) and control (n=20) groups, depending on prenatal exposure to retinoic acid for the induction of fetal NTDs. Animals were killed before term for analysis (n=685 fetuses). Amniotic fluid samples from both groups underwent epigenetic selection for NSCs, followed by exposure to neural differentiation media. Representative cell samples underwent multiple morphological and phenotypical analyses at different time points. No control fetus (n=267) had any structural abnormality, whereas at least one type of NTD developed in 52% (217/418) of the experimental fetuses (namely, isolated spina bifida, n=144; isolated exencephaly, n=24; or a combination of the two, n=49). Only amniotic samples from fetuses with a NTD yielded cells with typical neural progenitor morphology and robust expression of both Nestin and Sox-2, primary markers of NSCs. These cells responded to differentiation media by displaying typical morphological changes, along with expression of beta-tubulin III, glial fibrillary acidic protein, and/or O4, markers for immature neurons, astrocytes, and oligodendrocytes, respectively. This was concurrent with downregulation of Nestin and Sox-2. We conclude that the amniotic fluid can harbor disease-specific stem cells, for example, NSCs in the setting of experimental NTDs. The amniotic fluid may be a practical source of autologous NSCs applicable to novel forms of therapies for spina bifida.


Amniotic Fluid , Neural Stem Cells , Spinal Dysraphism , Amniotic Fluid/cytology , Amniotic Fluid/metabolism , Animals , Antigens, Differentiation/biosynthesis , Cell Differentiation , Disease Models, Animal , Female , Fetus/cytology , Fetus/metabolism , Gene Expression Regulation, Developmental , Humans , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Neural Stem Cells/transplantation , Pregnancy , Rats , Rats, Sprague-Dawley , Spinal Dysraphism/embryology , Spinal Dysraphism/pathology , Spinal Dysraphism/therapy , Transplantation, Autologous , Transplantation, Homologous
10.
J Surg Res ; 178(2): 785-90, 2012 Dec.
Article En | MEDLINE | ID: mdl-22656041

BACKGROUND: Ethically acceptable applications of fetal tissue engineering as a perinatal therapy can be expanded beyond life-threatening anomalies by amniotic fluid cell-based methods, in which cell procurement poses no additional risk to the mother. We sought to start to determine whether osseous grafts engineered from amniotic mesenchymal stem cells (aMSCs) could be an adjunct to craniofacial repair. METHODS: New Zealand rabbits (n = 12) underwent creation of a full-thickness diploic nasal bone defect. We then equally divided animals into two groups based on how the defect was repaired: namely, size-matched implants of electrospun biodegradable nanofibers with or without nuclear labeled, allogeneic aMSCs maintained in osteogenic medium. We killed animals 8 wk post-implantation for multiple analyses. Statistical analysis included analysis of variance, post-hoc Bonferroni adjusted comparisons, and Levene's F-test, as appropriate (P < 0.05), with significance set at P < 0.05. RESULTS: Micro-computed tomography scanning (two- and three-dimensional) showed no significant differences in defect radiodensity between groups. However, extracellular calcium levels were significantly higher in engineered grafts than in acellular implants (P = 0.003). There was significantly greater variability in mineralization in acellular implants than in engineered grafts by both direct calcium (P = 0.008) and micro-computed tomography measurements (P = 0.032). There were no significant differences in alkaline phosphatase activity or variance between groups. We documented labeled cells in the engineered grafts. CONCLUSIONS: Craniofacial repair with osseous grafts engineered from aMSCs lead to enhanced and more consistent mineralization compared with an equivalent acellular prosthetic repair. Amniotic fluid-derived engineered bone may become a practical adjunct to perinatal craniofacial reconstruction.


Amniotic Fluid/cytology , Bone Transplantation , Facial Bones/surgery , Fetal Tissue Transplantation , Mesenchymal Stem Cells/cytology , Skull/surgery , Tissue Engineering/methods , Alkaline Phosphatase/metabolism , Animals , Craniofacial Abnormalities/surgery , Rabbits , Tomography, X-Ray Computed
11.
J Pediatr Surg ; 46(6): 1201-7, 2011 Jun.
Article En | MEDLINE | ID: mdl-21683223

PURPOSE: The purpose of this study was to evaluate recurrence and survival outcomes in pediatric adrenal cortical neoplasms. METHODS: A 90-year retrospective review of children with adrenal cortical neoplasms was performed using multivariate Cox regression analysis to identify factors associated with recurrence and tumor-related mortality. RESULTS: The evaluable cohort included 29 patients. Twenty-seven underwent resection. Twenty-two (81%) had localized disease, and 5 (19%) had locally advanced disease (all received chemotherapy and 2 of 5 were cured). Two patients presenting with metastatic disease died despite treatment. There were 4 recurrences; all patients died. Tumor-related mortality was 24% (7/29). Kaplan-Meier freedom from recurrence was 85% at 1 year (95% confidence interval, 75%-95%). Multivariate Cox regression revealed that older age (P = .01), higher mitotic rate (P = .005), and necrosis (P < .001) were independent predictors of tumor-related death. Higher mitotic rate (P = .007) and larger tumor size (P = .03) were significant predictors of tumor recurrence. CONCLUSION: Risk factors for poor outcomes in patients with adrenocortical tumors include older age, higher mitotic rate, higher percent necrosis, and larger tumor size. Therefore, the presence of these factors may warrant consideration of adjuvant chemotherapy, even in the absence of advanced disease.


Adrenal Cortex Neoplasms/mortality , Adrenal Cortex Neoplasms/pathology , Cause of Death , Neoplasm Recurrence, Local/mortality , Adrenal Cortex Neoplasms/therapy , Chemotherapy, Adjuvant , Child , Child, Preschool , Cohort Studies , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Immunohistochemistry , Infant , Kaplan-Meier Estimate , Male , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Neurosurgical Procedures/methods , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Survival Analysis
12.
J Pediatr Surg ; 46(3): 566-9, 2011 Mar.
Article En | MEDLINE | ID: mdl-21376212

Surgical resections of massive sacrococcygeal teratomas (SCTs) carry significant risk due to baseline hemodynamic instability and the potential for significant hemorrhage. In this case report, a fetus with sacrococcygeal teratoma developed high-output cardiac instability at 32 weeks' gestation. After urgent cesarian delivery, a damage-control operation using Teflon-pledgeted mattress sutures allowed for hemodynamic control of bleeding into the tumor. One week later, after subsequent fluid resuscitation and stabilization, an elective staged resection of the complete mass including the pelvic portion was performed. The patient was discharged home on postoperative day 30 and was doing well at her most recent clinic visit at 30 months of age.


Infant, Premature, Diseases/surgery , Plastic Surgery Procedures/methods , Soft Tissue Neoplasms/surgery , Suture Techniques , Teratoma/surgery , Cardiac Output, High/embryology , Cardiac Output, High/etiology , Cesarean Section , Diseases in Twins , Emergencies , Female , Fertilization in Vitro , Fluid Therapy , Gestational Age , Hemorrhage/embryology , Hemorrhage/etiology , Hemorrhage/surgery , Humans , Infant, Newborn , Infant, Premature , Sacrococcygeal Region , Soft Tissue Neoplasms/blood supply , Soft Tissue Neoplasms/complications , Soft Tissue Neoplasms/embryology , Teratoma/blood supply , Teratoma/complications , Teratoma/embryology , Tumor Burden
13.
Methods Mol Biol ; 698: 75-88, 2011.
Article En | MEDLINE | ID: mdl-21431512

The amniotic fluid and placenta are sources of diverse progenitor cell populations, including -mesenchymal, hematopoietic, trophoblastic, and possibly more primitive stem cells. Given that much of the amniotic cavity and placenta share a common origin, namely the inner cell mass of the morula, perhaps it is not surprising that most types of progenitor cells that can be isolated from these two sources also share many characteristics. This chapter focuses solely on the most abundant and easy to isolate progenitor cell population found therein, the mesenchymal stem cells (MSCs). Unlike some of the other stem cell types, MSCs are present throughout gestation. Methods of isolation, expansion, freezing, and thawing of these cells will be presented with preference given to the simplest methods available for any given procedure.


Amniotic Fluid/cytology , Cell Culture Techniques/methods , Cell Separation/methods , Mesenchymal Stem Cells/cytology , Placenta/cytology , Animals , Cryopreservation , Culture Media , Female , Humans , Pregnancy , Reproducibility of Results , Specimen Handling
14.
J Pediatr Surg ; 46(2): e27-31, 2011 Feb.
Article En | MEDLINE | ID: mdl-21292067

Hybrid lesions are part of a spectrum of rare pulmonary diseases that are characterized as having elements of both congenital pulmonary airway malformation and bronchopulmonary sequestration. Fetal thoracic masses arise from alterations during lung development that are separated by timing of the inciting event and are often associated with an underlying degree of bronchial atresia. There are a handful of documented reports of sequestrations occurring in siblings, but no known reports of prenatally diagnosed lesions occurring in families. We present a case of 2 siblings diagnosed prenatally with fetal thoracic lesions who underwent postnatal resection revealing hybrid lesions on pathologic examination. Newer radiologic techniques have increased our ability to detect these masses prenatally, as well as follow them throughout pregnancy to determine their natural history. Ongoing laboratory investigation into the etiology of congenital lung lesions has brought forth more questions and suggested a familial component at a cellular level that has not yet been fully discovered. We reviewed the current literature of factors contributing to the development of congenital lung lesions and suggest that there is a familial link in certain patient populations where screening may be indicated.


Bronchopulmonary Sequestration/diagnosis , Cystic Adenomatoid Malformation of Lung, Congenital/diagnosis , Prenatal Diagnosis , Adult , Bronchopulmonary Sequestration/genetics , Bronchopulmonary Sequestration/surgery , Cystic Adenomatoid Malformation of Lung, Congenital/genetics , Cystic Adenomatoid Malformation of Lung, Congenital/surgery , Female , Fetal Development/physiology , Genetic Predisposition to Disease , Humans , Magnetic Resonance Imaging , Pregnancy , Risk Factors , Ultrasonography, Prenatal
15.
J Pediatr Surg ; 46(1): 57-61, 2011 Jan.
Article En | MEDLINE | ID: mdl-21238640

PURPOSE: Under a Food and Drug Administration directive, we examined definite long-term safety and efficacy aspects of an engineered diaphragmatic tendon graft as a regulatory prerequisite for clinical trials. METHODS: Newborn lambs (N = 27) underwent partial diaphragmatic replacement with a Teflon patch, a composite acellular bioprosthesis, or the same bioprosthesis seeded with autologous amniotic mesenchymal stem cells processed under Good Manufacturing Practice guidelines. Multiple safety and efficacy analyses were performed at different time points up to 14 months of age (ovine adulthood). RESULTS: There was no mortality. None of the blood tests or full body autopsy specimens showed any abnormality. There was a significantly higher failure rate in animals that received an acellular bioprosthetic graft vs an engineered graft, with no significant differences between Teflon and acellular bioprosthetic implants. Tensile strength and total collagen levels were significantly higher in engineered grafts than in acellular bioprosthetic grafts. On histology, lysozyme and myeloperoxidase stainings were unremarkable in all grafts. CONCLUSIONS: Diaphragmatic repair with a clinically viable autologous tendon engineered with amniotic mesenchymal stem cells leads to improved outcomes when compared with an equivalent acellular bioprosthesis, with no local or systemic adverse effects. Clinical trials of engineered diaphragmatic repair appear practicable within regulatory guidelines.


Amniotic Fluid/cytology , Bioprosthesis/standards , Diaphragm/surgery , Mesenchymal Stem Cell Transplantation/methods , Tendons/transplantation , Tissue Engineering/methods , Animals , Disease Models, Animal , Female , Hernia, Diaphragmatic/surgery , Hernias, Diaphragmatic, Congenital , Humans , Mesenchymal Stem Cell Transplantation/standards , Polytetrafluoroethylene , Pregnancy , Sheep , Tissue Engineering/standards , United States , United States Food and Drug Administration
16.
J Pediatr Surg ; 46(1): 67-71, 2011 Jan.
Article En | MEDLINE | ID: mdl-21238642

BACKGROUND/PURPOSE: Severe neonatal pulmonary hypoplasia incurs mortality rates approaching 71% to 95%. We sought to determine the utility of serial amnioinfusions through a subcutaneously implanted intraamniotic catheter to prevent pulmonary hypoplasia in fetal obstructive uropathy. METHODS: Fetal lambs (n = 32) were divided into 3 groups. Group I (n = 12) underwent a sham operation, group II (n = 15) underwent a complete urinary tract obstruction via ligation of the urachus and urethra with a subcutaneous tunneled intraamniotic port-a-cath without amnioinfusions, and group III (n = 5) underwent a creation of a complete urinary tract obstruction with a port-a-cath as described in group II with serial amnioinfusions. Lung tissue was analyzed by lung volume to body weight ratios and stereology. Statistical analysis was performed by analysis of variance and Bonferroni comparisons (P < .05). RESULTS: Obstructed fetuses grossly had smaller lungs than treated and control animals. Lung volume to body weight ratios were statistically significant between groups. Airspace fractions were comparable between groups I and III (average = 0.53 and 0.55, respectively), although both were significantly greater than group II (average = 0.48) (P = .049). CONCLUSIONS: Serial amnioinfusions through an intraamniotic port-a-cath prevented pulmonary hypoplasia in an ovine model of complete obstructive uropathy. The use of an easily accessible device for amnioinfusions may be a viable option to treat oligohydramnios.


Amnion/surgery , Catheterization/methods , Fetal Diseases/prevention & control , Lung/abnormalities , Oligohydramnios/therapy , Amniotic Fluid , Animals , Catheters, Indwelling , Disease Models, Animal , Female , Fetal Diseases/pathology , Fetus/pathology , Fetus/surgery , Follow-Up Studies , Gestational Age , Humans , Lung/embryology , Male , Pregnancy , Pregnancy Outcome , Recurrence , Sheep , Urologic Diseases
17.
J Surg Res ; 171(1): 164-9, 2011 Nov.
Article En | MEDLINE | ID: mdl-20462601

BACKGROUND: Treatment of congenital tracheal stenosis/atresia remains essentially unresolved. Previous models of this disease entity have been restricted to rodents and the chick. We sought to establish the principles of a large, surgical animal model of this spectrum of fetal anomalies. METHODS: Fetal lambs (n = 8) underwent open surgery at 90-112 days gestation. Their cervical tracheas were encircled by a biocompatible polytetrafluoroethylene wrap, so as to extrinsically restrict their external diameter by 25%. Survivors (n = 7) were killed at different time points post-operatively before term. The manipulated tracheal segments were compared with their respective proximal portions (controls). Analyses included morphometry, histology and quantitative extracellular matrix measurements. RESULTS: At necropsy, the typical gross appearance of tracheal stenosis/atresia was present in all manipulated tracheal segments. Histological findings included the virtual disappearance of the membranous portion of the trachea, along with infolding, fragmentation, and/or posterior fusion of cartilaginous rings, often with disappearance of the airway mucosa. There were significant decreases in diameter (P < 0.001) and total collagen levels (P = 0.005) on the manipulated trachea compared with the control portions. No significant differences were observed in overall elastin or glycosaminoglycan contents. A significant time-dependent increase in elastin was noted on the control, but not the experimental side. CONCLUSIONS: In a surgical ovine model, controlled extrinsic compression of the fetal trachea leads to morphological and biochemical findings compatible with the congenital tracheal stenosis/atresia spectrum. This simple and easily reproducible prenatal model can be instrumental in the development of emerging therapies for these congenital anomalies.


Disease Models, Animal , Extracellular Matrix/pathology , Sheep , Trachea/abnormalities , Trachea/pathology , Tracheal Stenosis/pathology , Animals , Biocompatible Materials , Collagen/metabolism , Elastin/metabolism , Extracellular Matrix/metabolism , Female , Fetus/surgery , Fluorocarbon Polymers , Organogenesis , Pregnancy
18.
Stem Cells Dev ; 20(6): 969-76, 2011 Jun.
Article En | MEDLINE | ID: mdl-20979452

Fetal wound healing involves minimal inflammation and limited scarring. Its mechanisms, which remain to be fully elucidated, hold valuable clues for wound healing modulation and the development of regenerative strategies. We sought to determine whether fetal wound healing includes a hitherto unrecognized cellular component. Two sets of fetal lambs underwent consecutive experiments at midgestation. First, fetuses received an intra-amniotic infusion of labeled autologous amniotic mesenchymal stem cells (aMSCs), in parallel to different surgical manipulations. Subsequently, fetuses underwent creation of 2 symmetrical, size-matched skin wounds, both encased by a titanium chamber. One of the chambers was left open and the other covered with a semipermeable membrane that allowed for passage of water and all molecules, but not any cells. Survivors from both experiments had their wounds analyzed at different time points before term. Labeled aMSCs were documented in all concurrent surgical wounds. Covered wounds showed a significantly slower healing rate than open wounds. Paired comparisons indicated significantly lower elastin levels in covered wounds at the mid time points, with no significant differences in collagen levels. No significant changes in hyaluronic acid levels were detected between the wound types. Immunohistochemistry for substance P was positive in both open and covered wounds. We conclude that fetal wound healing encompasses an autologous yet exogenous cellular component in naturally occurring aMSCs. Although seemingly not absolutely essential to the healing process, amniotic cells expedite wound closure and enhance its extracellular matrix profile. Further scrutiny into translational implications of this finding is warranted.


Amnion/cytology , Fetus/pathology , Mesenchymal Stem Cells/cytology , Wound Healing , Animals , Extracellular Matrix/metabolism , Female , Flow Cytometry , Green Fluorescent Proteins/metabolism , Immunophenotyping , Membranes, Artificial , Permeability , Sheep , Staining and Labeling , Time Factors
19.
J Pediatr Surg ; 45(6): 1354-60, 2010 Jun.
Article En | MEDLINE | ID: mdl-20620344

PURPOSE: We sought to compare the efficacy of engineered fetal bone grafts with acellular constructs in an autologous model of chest wall repair. METHODS: Rabbits (n = 10) with a full-thickness sternal defect were equally divided in 2 groups based on how the defect was repaired, namely, either with an autologous bone construct engineered with amniotic mesenchymal stem cells on a nanofibrous scaffold or a size-matched identical scaffold with no cells. Animals were killed at comparable time-points 18 to 20 weeks postimplantation for multiple analyses. RESULTS: Gross evidence of nonunion confirmed by micro-computed tomography scanning was present in 3 (60%) of 5 of the acellular implants but in no engineered grafts. Histology confirmed the presence of bone in both types of repair, albeit seemingly less robust in the acellular grafts. Mineral density in vivo was significantly higher in engineered grafts than in acellular ones, with more variability among the latter. There was no difference in alkaline phosphatase activity between the groups. CONCLUSIONS: Chest wall repair with an autologous osseous graft engineered with amniotic mesenchymal stem cells leads to improved and more consistent outcomes in the midterm when compared with an equivalent acellular prosthetic repair in a leporine model. Amniotic fluid-derived engineered bone may become a practical alternative for perinatal chest wall reconstruction.


Mesenchymal Stem Cell Transplantation/methods , Sternum/embryology , Thoracic Diseases/surgery , Thoracic Wall/abnormalities , Tissue Engineering/methods , Animals , Disease Models, Animal , Graft Survival , Rabbits , Sternum/cytology , Sternum/transplantation , Thoracic Diseases/congenital , Thoracic Wall/surgery , Transplantation, Autologous
20.
Can J Plast Surg ; 14(3): 163-6, 2006.
Article En | MEDLINE | ID: mdl-19554109

Full-thickness burns around the knee joint are usually associated with exposure of bone, tendon or ligaments. Following excision of the deep burns, there is no viable wound bed to which skin grafts can be applied. Although vacuum-assisted closure has been used to encourage granulation tissue, exposure of the tendons and ligaments following excision usually requires muscle flaps or fasciocutaneous flaps.

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