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The prognosis of giant cervical teratomas is determined by the severity of the associated airway obstruction. Ex-utero intrapartum treatment (EXIT) is a technique to establish a patent airway before completion of birth, while the infant remains on placental support. We present two cases of newborns with cervical teratomas treated with the EXIT procedure. In the first, this technique allowed a tracheotomy to be performed, and in the second, correction of tracheal displacement and subsequent nasotracheal intubation was achieved. [ABSTRACT FROM AUTHOR]

Objectives: The failure of a fetus to develop to its full potential due to maternal or placental factors is known as intrauterine growth restriction (IUGR). Fetal head growth is usually preserved in that situation producing a potential discordance between head and body size. Our goal is to discover if IUGR has an impact on the prenatal ultrasound measurements taken to assess pulmonary development in congenital diaphragmatic hernia (CDH)., Methods: A retrospective chart review (IRB#2017-6361) was performed on all prenatally diagnosed CDH patients from 2007 to 2016. Patient demographics, fetal and neonatal anthropometric measurements, and fetal lung parameters were the main subjects of the data that were gathered. Fetal growth was assessed by the curves based on US data by Olsen et al. and by Peleg et al. Of 147 CDH patients, 19 (12.9 %) patients were diagnosed with IUGR before the 30th gestational week while there were 20 (13.6 %) patients after the 30th gestational week., Results: Patients with IUGR and the observed-to-expected lung-to-head ratio (O/E LHR) less than 25 % had better survival rates both to discharge and date compared to non IUGR group (p=0.226, OR 2.25 95 % CI 0.60-1.08 and p=0.175, OR 2.40 95 % CI 0.66-1.17, respectively). Moreover, the ECMO need of the patients who had IUGR and O/E LHR less than 25 % was significantly less than the patients without IUGR (38.5 vs. 80.0 %, p=0.005)., Conclusions: This study confirms that the intrauterine measurements to predict pulmonary hypoplasia in CDH patients are misleading in the presence of IUGR and cause an overestimation., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Skeletal muscle injuries represent a major concern in sports medicine. Cell therapy has emerged as a promising therapeutic strategy for muscle injuries, although the preclinical data are still inconclusive and the potential clinical use of cell therapy has not yet been established., Purpose: To evaluate the effects of muscle precursor cells (MPCs) on muscle healing in a small animal model., Study Design: Controlled laboratory study., Methods: A total of 27 rats were used in the study. MPCs were isolated from rat (n = 3) medial gastrocnemius muscles and expanded in primary culture. Skeletal muscle injury was induced in 24 rats, and the animals were assigned to 3 groups. At 36 hours after injury, animals received treatment based on a single ultrasound-guided MPC (10 5 cells) injection (Cells group) or MPC injection in combination with 2 weeks of daily exercise training (Cells+Exercise group). Animals receiving intramuscular vehicle injection were used as controls (Vehicle group). Muscle force was determined 2 weeks after muscle injury, and muscles were collected for histological and immunofluorescence evaluation., Results: Red fluorescence-labeled MPCs were successfully transplanted in the site of the injury by ultrasound-guided injection and were localized in the injured area after 2 weeks. Transplanted MPCs participated in the formation of regenerating muscle fibers as corroborated by the co-localization of red fluorescence with developmental myosin heavy chain (dMHC)-positive myofibers by immunofluorescence analysis. A strong beneficial effect on muscle force recovery was detected in the Cells and Cells+Exercise groups (102.6% ± 4.0% and 101.5% ± 8.5% of maximum tetanus force of the injured vs healthy contralateral muscle, respectively) compared with the Vehicle group (78.2% ± 5.1%). Both Cells and Cells+Exercise treatments stimulated the growth of newly formed regenerating muscles fibers, as determined by the increase in myofiber cross-sectional area (612.3 ± 21.4 µm 2 and 686.0 ± 11.6 µm 2 , respectively) compared with the Vehicle group (247.5 ± 10.7 µm 2 ), which was accompanied by a significant reduction of intramuscular fibrosis in Cells and Cells+Exercise treated animals (24.2% ± 1.3% and 26.0% ± 1.9% of collagen type I deposition, respectively) with respect to control animals (40.9% ± 4.1% in the Vehicle group). MPC treatment induced a robust acceleration of the muscle healing process as demonstrated by the decreased number of dMHC-positive regenerating myofibers (enhanced replacement of developmental myosin isoform by mature myosin isoforms) (4.3% ± 2.6% and 4.1% ± 1.5% in the Cells and Cells+Exercise groups, respectively) compared with the Vehicle group (14.8% ± 13.9%)., Conclusion: Single intramuscular administration of MPCs improved histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries. Cell therapy showed a synergistic effect when combined with an early active rehabilitation protocol in rats, which suggests that a combination of treatments can generate novel therapeutic strategies for the treatment of human skeletal muscle injuries., Clinical Relevance: Our study demonstrates the strong beneficial effect of MPC transplant and the synergistic effect when the cell therapy is combined with an early active rehabilitation protocol for muscle recovery in rats; this finding opens new avenues for the development of effective therapeutic strategies for muscle healing and clinical trials in athletes undergoing MPC transplant and rehabilitation protocols.

Purpose: Primary closure is often inadequate for large congenital diaphragmatic hernia (CDH) and necessitates repair by prosthetic patch or autologous muscle flap. Our aim was to evaluate outcomes of open patch versus flap repair, specifically diaphragmatic reherniation., Methods: A retrospective review (IRB #2017-6361) was performed on all CDH patients repaired from 2005 to 2016 at a single academic children's hospital. Patients were excluded from final analysis if they had primary or minimally invasive repair, expired, or were lost to follow-up., Results: Of 171 patients, 151 (88.3%) survived to discharge, 9 expired after discharge and 11 were lost to follow up, leaving 131 (86.8%) long-term survivors. Median follow-up was 5 years. Open repair was performed in 119 (90.8%) of which 28 (23.5%) underwent primary repair, 34 (28.6%) patch repair, and 57 (47.9%) flap repair. Overall, 6/119 (5%) patients reherniated, 1/28 (3.6%) in the primary group, 3/34 (8.8%) in the patch group, and 2/57 (3.5%) in the flap group. Comparing prosthetic patch to muscle flap repair, there was no significant difference in the number of patients who recurred nor time to reherniation (3 vs. 2, p = 0.295; 5.5 ± 0.00 months vs. 53.75 ± 71.06 months, p = 0.288). One patient in the patch group recurred twice., Conclusions: Both muscle flap and patch repair of large CDH are feasible and durable with a relatively low risk of recurrence.

Aim: With the advancement in the treatment strategies of congenital diaphragmatic hernia (CDH), there is an increase in the survival rates. This fact leads to an increase in the morbidity and extrapulmonary complications in the long term such as failure to thrive, hernia recurrence, neurodevelopmental delay, gastrointestinal problems, and musculoskeletal anomalies. Herein, we aim to investigate the association between the long-term musculoskeletal complications in CDH patients regarding the defect size, repair type, and perinatal parameters., Methods: After Institutional Review Board approval was obtained (2017-6361), a retrospective chart review was performed on CDH patients from 2003 to 2016. Patients who were operated due to left-sided isolated congenital diaphragmatic hernia and survived to date were included in the study. Data were collected on demographics, preoperative characteristics, operative interventions, and postoperative outcomes. Statistical analysis was performed with IBM SPSS Statistics 20.0.0 (Chicago, IL)., Results: There were 98 patients with left CDH of whom 33 (33.7%) had primary repair, 25 (25.5%) had patch repair, and 40 (40.8%) had muscle flap repair. The median age of the patients was 6.00 ± 3.83 years. 45 patients (45.9%) had large diaphragmatic defects, 28 patients (28.6%) had at least one type of musculoskeletal deformities, 2 of which were pectus carinatum, 16 were pectus excavatum, and 18 were scoliosis. CDH patients who had small diaphragmatic defects and repaired with a patch were less likely develop musculoskeletal deformities while who had primary abdominal closure after ventral hernia significantly have more pectus excavatum., Conclusion: Although there was a trend towards an increased risk of the pectus deformity and scoliosis in patients repaired with muscle flap, it did not reach statistical significance. There is a correlation between musculoskeletal deformities and the severity of the CDH.

Objective: To assess the reliability of the interpretation of a new technique for the ultrasound evaluation of the level of neurological lesion in fetuses with myelomeningocele., Methods: Observational study including myelomeningocele fetuses, referred to our center for the sonographic assessment of the fetal lower-limb movements, made and recorded by an expert in Maternal-fetal medicine and a specialist in Rehabilitation. Two observers, with different levels of expertise and blinded to each other's results, interpreted each recorded scan two different times. The agreement for the segmental levels assigned between the observers and the gold standard, the inter-observer and intra-observer reproducibility were tested using the weighed Kappa (wκ) index., Results: Twenty-eight scans were recorded and evaluated. The agreement between the observers and the gold standard remained constant for the expert observer (wκ = 0.82) and increased (wκ = 0.66-wκ = 0.72) for the other one. The inter-observer and the intra-observer variability for the expert observer were wκ = 0.72 and wκ = 0.94, respectively., Discussion: The agreement for the prenatal evaluation of the segmental neurological level was excellent, after a short training period, for observers with different degrees of expertise. The interpretation of this technique is reproducible enough and this supports its value for the prediction of postnatal motor function in myelomeningocele fetuses.

Despite benefits of prenatal in utero repair of myelomeningocele, a severe type of spina bifida aperta, many of these patients will still suffer mild to severe impairment. One potential source of stem cells for new regenerative medicine-based therapeutic approaches for spinal cord injury repair is neural progenitor cells (NPCs) in cerebrospinal fluid (CSF). To this aim, we extracted CSF from the cyst surrounding the exposed neural placode during the surgical repair of myelomeningocele in 6 fetuses (20 to 26weeks of gestation). In primary cultured CSF-derived cells, neurogenic properties were confirmed by in vitro differentiation into various neural lineage cell types, and NPC markers expression (TBR2, CD15, SOX2) were detected by immunofluorescence and RT-PCR analysis. Differentiation into three neural lineages was corroborated by arbitrary differentiation (depletion of growths factors) or explicit differentiation as neuronal, astrocyte, or oligodendrocyte cell types using specific induction mediums. Differentiated cells showed the specific expression of neural differentiation markers (βIII-tubulin, GFAP, CNPase, oligo-O1). In myelomeningocele patients, CSF-derived cells could become a potential source of NPCs with neurogenic capacity. Our findings support the development of innovative stem-cell-based therapeutics by autologous transplantation of CSF-derived NPCs in damaged spinal cords, such as myelomeningocele, thus promoting neural tissue regeneration in fetuses., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Skeletal muscle injuries are the most common sports-related injury and a major concern in sports medicine. The effect of platelet-rich plasma (PRP) injections on muscle healing is still poorly understood, and current data are inconclusive., Purpose: To evaluate the effects of an ultrasound-guided intramuscular PRP injection, administered 24 hours after injury, and/or posttraumatic daily exercise training for 2 weeks on skeletal muscle healing in a recently established rat model of skeletal muscle injury that highly mimics the muscle trauma seen in human athletes., Study Design: Controlled laboratory study., Methods: A total of 40 rats were assigned to 5 groups. Injured rats (medial gastrocnemius injury) received a single PRP injection (PRP group), daily exercise training (Exer group), or a combination of a single PRP injection and daily exercise training (PRP-Exer group). Untreated and intramuscular saline-injected animals were used as controls. Muscle force was determined 2 weeks after muscle injury, and muscles were harvested and evaluated by means of histological assessment and immunofluorescence microscopy., Results: Both PRP (exhibiting 4.8-fold higher platelet concentration than whole blood) and exercise training improved muscle strength (maximum tetanus force, TetF) in approximately 18%, 20%, and 30% of rats in the PRP, PRP-Exer, and Exer groups, respectively. Specific markers of muscle regeneration (developmental myosin heavy chain, dMHC) and scar formation (collagen I) demonstrated the beneficial effect of the tested therapies in accelerating the muscle healing process in rats. PRP and exercise treatments stimulated the growth of newly formed regenerating muscle fibers (1.5-, 2-, and 2.5-fold increase in myofiber cross-sectional area in PRP, PRP-Exer, and Exer groups, respectively) and reduced scar formation in injured skeletal muscle (20%, 34%, and 41% of reduction in PRP, PRP-Exer, and Exer groups, respectively). Exercise-treated muscles (PRP-Exer and Exer groups) had significantly reduced percentage of dMHC-positive regenerating fibers (35% and 47% decrease in dMHC expression, respectively), indicating that exercise therapies accelerated the muscle healing process witnessed by the more rapid replacement of the embryonic-developmental myosin isoform by mature muscle myosin isoforms., Conclusion: Intramuscular PRP injection and, especially, treadmill exercise improve histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries in athletes. However, there was not a synergistic effect when both treatments were combined, suggesting that PRP does not add any beneficial effect to exercise-based therapy in the treatment of injured skeletal muscle., Clinical Relevance: This study demonstrates the efficacy of an early active rehabilitation protocol or single intramuscular PRP injection on muscle recovery. The data also reveal that the outcome of the early active rehabilitation is adversely affected by the PRP injection when the two therapies are combined, and this could explain why PRP therapies have failed in randomized clinical trials where the athletes have adhered to postinjection rehabilitation protocols based on the principle of early, active mobilization.

Objectives: Necrotizing enterocolitis is a severe multifactorial intestinal disorder that primarily affects preterm newborns, causing 20-40% mortality and morbidity. Intestinal fatty acid-binding protein has been reported to be a biomarker for the detection of intestinal injuries. Our aim was to assess intestinal tissue injury and the molecular expression of intestinal fatty acid-binding protein over time in a necrotizing enterocolitis model., Methods: A total of 144 Newborn rats were divided into two groups: 1) Control, which received breastfeeding (n=72) and 2) Necrotizing Enterocolitis, which received formula feeding and underwent hypoxia and hypothermia (n=72). A total of six time points of ischemia (2 times a day for 3 days; 12 pups for each time point) were examined. Samples were collected for analysis of body weight, morphological and histological characteristics, intestinal weight, intestinal weight/body weight ratio, injury grade, and intestinal fatty acid-binding protein levels., Results: Body and intestinal weights were lower in the Necrotizing Enterocolitis group than in the Control group (p<0.005 and p<0.0005, respectively). The intestinal weight/body weight ratio was higher in the Necrotizing Enterocolitis group than in the Control group (p<0.005) only at the sixth ischemia time point. The Necrotizing Enterocolitis group displayed higher expression of intestinal fatty acid-binding protein (p<0.0005) and showed greater tissue damage than the Control group., Conclusion: Intestinal fatty acid-binding protein was an efficient marker of ischemic injury to the intestine and a good correlation was demonstrated between the time of ischemic injury and the grade of intestinal injury.

Fetal teratomas are the most common tumors diagnosed prenatally. The majority of these tumors are benign and cured by complete resection of the mass during the neonatal period. Prenatal diagnosis has improved the perinatal management of these lesions and especially for the teratomas that might benefit from fetal intervention. A comprehensive prenatal evaluation including conventional ultrasounds, Doppler, echocardiography and fetal MRI, is essential for an effective counseling and perinatal management. Antenatal counseling helps the parents to better understand the natural history, fetal intervention, and perinatal management of these tumors, which differ dramatically depending on their size and location. Fetal surgical debulking improves survival in cases of sacrococcygeal teratoma with cardiac decompensation. Additionally, the use of an EXIT procedure reduces the morbidity and mortality if a complicated delivery in cases of cervical and mediastinal teratomas. Here, we offer an overview of all fetal teratomas and their recommended management, with emphasis on in utero treatment options.

Background: Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and pulmonary hypertension. Tracheal occlusion (TO) stimulates fetal lung growth and maturation and reverse vascular changes responsible for pulmonary hypertension, which are related to mechanisms involving nitric oxide (NO) in CDH. We aim to evaluate the effect of TO and ventilation on NO pathways., Methods: Eight groups were created: (1) control; (2) control ventilated (CV); (3) CDH (CDH); (4) CDH ventilated (CDHV); (5) TO control; (6) TO ventilated; (7) TO + CDH; and (8) TO + CDH ventilated (CDHTOV). Fetuses were weighed, and volume ventilated for 30 min after harvested. Total lung weight and the ratio of total lung weight to body weight, thickness of the middle layer of the pulmonary arteriole, and the air space diameter were measured. The NO synthase inducible and NO synthase inducible were performed by immunohistochemistry and Western blotting., Results: The total lung weight and the ratio of total lung weight to body weight decreased in animals with nitrofen and also after ventilation for all groups (P < 0.05). The thickness of the middle layer of the pulmonary arteriole decreased in all groups with TO when compared with controls (P < 0.001). The air space diameter decreased after ventilation in the CDHTOV compared to the TO + nitrofen-induced CDH (P < 0.001). Compared to nonventilated cohorts, NO synthase inducible increased in CV and TO ventilated (P < 0.001) and decreased in CDHV and CDHTOV (P < 0.001). NO synthase inducible increased in CV and CDHV (P < 0.001) and decreased in the TO control and CDHTOV (P < 0.001)., Conclusions: TO and ventilation alter the NO pathway with possible implications in reducing the pulmonary hypertension in CDH., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To investigate the effect of combined prenatal treatment with retinoic acid (RA) and tracheal occlusion (TO) on the pulmonary vascular morphology and expression of vascular endothelial growth factors (VEGF) and its receptors in a rat model of congenital diaphragmatic hernia (CDH)., Material and Methods: Rats were given nitrofen at 9 days of gestation followed by no treatment (CDH), RA (CDH + RA), TO (CDH + TO), or both (CDH + RA + TO) (n = 16). We measured the median wall thickness of the pulmonary arterioles (MWT) and analyzed the expression of VEGF and its receptors (VEGFR1 and VEGFR2)., Results: Compared to control animals, CDH had increased MWT (44 ± 15 vs. 58 ± 7; p < 0.05) and decreased expression of VEGF, VEGFR1, and VEGFR2 (p < 0.05). Treatment with RA or TO alone, and RA + TO reduced the MWT (46 ± 9, 42 ± 11, 46 ± 8, respectively) and improved the expression of VEGF, VEGFR1, and VEGFR2 compared to CDH (p < 0.05). However, the combination of RA + TO did not confer additional benefit in the reduction of the MWT or in increasing the VEGF and its receptors compared to either treatment alone., Conclusion: Antenatal treatment with either RA or TO improved the MWT and expression of VEGF and its receptors in a CDH rat model. However, combined treatment with RA + TO was not superior to either treatment alone.

Introduction: Fetal endoscopic tracheal occlusion in congenital diaphragmatic hernia (CDH) may reduce pulmonary hypertension and ameliorate postnatal cardiac output. The effects of sustained early (ETO) and late (LTO) tracheal occlusion on left ventricular (LV) cells in the lamb model have not been described., Materials and Methods: CDH was created in lambs at 70 days' gestation (term = 145 days). ETO (85 days) or LTO (105 days) was sustained till term. After cesarean section (140 days) fetuses were euthanized and hearts harvested. LV myocardial cells were studied by histological and immunofluorescence (TGF-beta 1, endothelin-1) assays in CDH, ETO, LTO, and the control group (two subjects per group). Small intramyocardial arteries were evaluated by traditional histology., Results: LV myocardial histology in CDH and LTO was similar. ETO-induced LV myocardial cell enlargement and increased endothelin-1 and TGF-beta 1 staining; a weaker immunofluorescence signal was observed in LTO compared with ETO. Myocardial vascular wall thickness was greater in CDH than in controls. ETO was associated with a vascular wall thickness within the range of controls., Conclusion: With only two fetuses in each group, only an explorative evaluation was possible. The time point at which TO is performed seems to have an effect on cardiac morphology. Functional studies as well as confirmation in clinical samples are mandatory., (© 2016 John Wiley & Sons, Ltd.)

Introduction: The lung-to-head ratio (LHR) is routinely used to select the best candidates for prenatal surgery and to follow-up the fetuses with congenital diaphragmatic hernia (CDH). Since this index is gestation-dependent, the quantitative lung index (QLI) was proposed as an alternative parameter that stays constant throughout pregnancy. Our objective was to study the performance of QLI to predict survival in fetuses with CDH., Materials and Methods: Observational retrospective study of fetuses with isolated CDH, referred to our center. LHR was originally used for the prenatal surgery evaluation. We calculated the QLI and compared the performance of both indexes (QLI and LHR) to predict survival., Results: From January-2009 to February-2015 we followed 31 fetuses with isolated CDH. The mean QLI was 0.66 (95% CI: 0.57-0.75) for survivors and 0.41 (95% CI: 0.25-0.58) for non-survivors (p<0.01) and the mean LHR was 1.38 (95% CI: 1.17-1.60) for survivors and 0.91 (95% CI: 0.57-1.25) for non-survivors (p<0.02). All operated fetuses (n=12) had a LHR <1 and a QLI <0.5 and none of them survived when the QLI was <0.32. When separately considering the prenatal surgery status, the mean values of the QLI (but not those of the LHR) were still significantly different between survivors and non-survivors. The comparative ROC curves showed a better performance of the QLI with respect to the LHR for the prediction of survival, especially in the group of operated fetuses, although differences were not statistically significant., Comment: The QLI seems to be a better predictor for survival than the LHR, especially for the group of fetuses undergoing prenatal surgery., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Skeletal muscle injuries are the most common sports-related injuries in sports medicine. In this work, we have generated a new surgically-induced skeletal muscle injury in rats, by using a biopsy needle, which could be easily reproduced and highly mimics skeletal muscle lesions detected in human athletes. By means of histology, immunofluorescence and MRI imaging, we corroborated that our model reproduced the necrosis, inflammation and regeneration processes observed in dystrophic mdx-mice, a model of spontaneous muscle injury, and realistically mimicked the muscle lesions observed in professional athletes. Surgically-injured rat skeletal muscles demonstrated the longitudinal process of muscle regeneration and fibrogenesis as stated by Myosin Heavy Chain developmental (MHCd) and collagen-I protein expression. MRI imaging analysis demonstrated that our muscle injury model reproduces the grade I-II type lesions detected in professional soccer players, including edema around the central tendon and the typically high signal feather shape along muscle fibers. A significant reduction of 30% in maximum tetanus force was also registered after 2 weeks of muscle injury. This new model represents an excellent approach to the study of the mechanisms of muscle injury and repair, and could open new avenues for developing innovative therapeutic approaches to skeletal muscle regeneration in sports medicine., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: To report our preliminary experience in the use of prenatal ultrasound examination to assess lower-limb movements in fetuses with myelomeningocele. We aimed to determine the accuracy of this method to establish the segmental level of neurological lesion, as this is the best known predictor of the future ability to walk., Methods: This was a preliminary, observational study including fetuses with myelomeningocele operated on prenatally. The patterns of movements present and absent in the affected fetuses' lower limbs were evaluated systematically by ultrasound examination. According to the known nerve function associated with each muscle group, the segmental level of neurological lesion was established before birth. The agreement for the segmental levels assigned, between the prenatal ultrasound technique and the classical neurological clinical examination after birth (gold standard), was tested using the weighed kappa (wκ) index., Results: Seventy-one fetuses with myelomeningocele were evaluated at the Hospital Universitari Vall d'Hebron. After counseling, the parents opted for prenatal surgery (26 cases), termination of pregnancy (43 cases) or postnatal repair (two cases). Five patients did not fulfil the inclusion criteria for prenatal surgery and three were excluded after birth. In the 18 fetuses that underwent surgery and were analyzed, the agreement between prenatal and postnatal segmental levels assigned was 91.7% for the right limb (wκ = 0.80) and 88.9% for the left limb (wκ = 0.73)., Conclusions: The agreement found between prenatal and postnatal assignment of level of lesion in this preliminary study suggests that neurological sonographic evaluation is feasible before birth. This may provide accurate individualized information about the motor function and future ambulation prognosis of fetuses with myelomeningocele., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Purpose: The use of dexamethasone (Dx) stimulates growth, fetal lung maturation and can improve pulmonary hypertension in congenital diaphragmatic hernia (CDH). Our aim was to evaluate the effect of Dx on the lung after fetal pulmonary ventilation in the CDH rat model., Methods: Some groups underwent prenatal treatment with dexamethasone (0.4 mg/kg) that was given at 18.5 gestational day (GD). Sprague-Dawley rat fetuses were divided into groups: control (C); ventilated control (CV); control exposed to dexamethasone (CDx); ventilated control exposed to dexamethasone (CVDx); congenital diaphragmatic hernia (CDH), ventilated CDH (CDHV), CDH exposed to dexamethasone (CDHDx) and ventilated CDH exposed to dexamethasone (CDHVDx). At 21.5 GD fetuses were delivered by C-section, weighed and ventilated for 30 min. We analyzed the lung morphometry by Masson's Trichrome stain, and VEGF, VEGFR1, VEGFR2 and NOS3 expression by immunohistochemistry., Results: All fetuses with CDH, with or without prenatal dexamethasone showed lung and body weight lower than control fetuses (p < 0.05). All groups that received dexamethasone showed a decrease in the medial muscular layer of arterioles, the internal diameter of the air spaces (Lma) and length of parenchymal transection/airspace ratio (p < 0.05). In the immunohistochemistry, VEGF decreased more in CDHDV group (p < 0.05). VEGFR1 showed no difference, whereas VEGFR2 decreased significantly in the CDHDV group (p < 0.05). NOS3 increased in the group CDHDV (p < 0.05)., Conclusion: The use of prenatal dexamethasone added to ventilation alters the VEGF and NO pathways.

Objective: To assess the presence of early bladder abnormalities in a prenatally corrected and uncorrected animal model of Myelomeningocele (MMC)., Method: A MMC-like lesion was surgically created in 18 fetal lambs between the 60th and the 80th day of gestation. Eight of them did not undergo fetal repair (group A), three were repaired with an open two-layer closure (group B), three using BioGlue® (groupC) and four fetoscopically (group D). At term, bladders were examined macroscopically and histopathological changes were assessed using H-E and Masson Trichrome., Results: Five animals in group A (5/8, 62%), two in group B (2/3, 66%), one in group C (1/3, 33%) and one in group D (1/4, 25%) survived. Macroscopically bladders in group A were severely dilated and showed thinner walls. Microscopically they showed a thin layer of colagenous tissue (Blue layer. BL) lying immediately subjacent to the urothelium. The muscular layers were thinner. Non compliant pattern with thick wall and low capacity was also found in the non corrected model. Group B and the control showed preservation of muscular layers and absence of BL. Groups C and D presented BL but also preservation of muscular layers., Conclusion: Bladder changes in a surgically-induced model of MMC can be described using histopathological data. Both extremes of bladder changes can be observed in the model. These changes were completely prevented with open fetal surgery and partially with other coverage modalities., (Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.)

Background: Fetuses with severe congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia may benefit from fetal endoluminal tracheal occlusion (FETO). Enlargement of the main bronchi and trachea appears to be a common complication of FETO., Objective: To retrospectively evaluate the trachea and main bronchi of infants who underwent FETO for CDH and compare diameters with age-matched references., Material and Methods: Postnatal and follow-up chest radiographs were performed in seven children with unilateral CDH treated by FETO. Additional CT was performed in six of these (one neonate died before CT could be performed). Images were acquired from 3 days to 23 months of age. For each child, radiographs and CT images with optimal visualisation of the airways were selected for retrospective analysis. Tracheal and bronchial morphology was assessed by two experienced paediatric radiologists, and the diameters of these structures measured and compared with age-matched references., Results: Mean diameters of the trachea and main bronchi were above the age-matched normal range in all patients, regardless of the side of the hernia or the degree of lung hypoplasia., Conclusion: Enlargement of the trachea and main bronchi appears following FETO and persists at least to the age of 5 years.

Purpose: The purpose of this study is to describe the malformations of cortical development detected in a model of cerebrospinal fluid (CSF) leakage and the influence of surgical closure technique on developmental outcome., Methods: Using a surgically induced model of myelomeningocele (MMC) in sheep, we studied the effects of different repair methods upon the development of hydrocephalus, the presence of the Arnold-Chiari II (AC-II) hindbrain malformation, and cerebral cortex developmental anomalies using gross and histologic (hematoxylin and eosin and Nissl staining) study techniques., Results: A malformed cerebral cortex, including 2 anomalous cortical folding patterns, and lower brain weights were observed in the untreated animals. Hydrocephalus and AC-II malformations were also found in this group. These malformations were mostly prevented with prenatal 2-layer closure., Conclusions: Cerebral cortical malformations and hydrocephalus, in addition to the AC-II hindbrain malformation, are disorders caused by fetal CSF leakage. These malformations were prevented with the technique of MMC closure currently used in humans. Both observations magnify the importance of the second hit associated with chronic CSF leakage, in addition to the primary defect causing the MMC, in the development of the malformation complex., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Cervical lymphangiomas can not only cause severe sequelae (aesthetic, phonatory or deglutory) but can also be life thereatening due to airway compresion or massive bleeding. This paper analyzes our surgical results, the value of prenatal diagnosis and the use of new techniques such as the EXIT procedure for airway control in sereve cases., Patients and Methods: We retrospectively reviewed the medical record of patients with cervical lymphangiomas treated in our center between 1986 and 2009, according to our Clinical Documentation Database. Data referred to prenatal diagnosis, intrapartum airway management, surgical procedures and morbidity, sclerosing substance infiltration and long term sequelae was analyzed., Results: Thirteen cases were identified. 53.8% of the patients were diagnosed by prenatal ultrasound, and MRI was performed in 46.1%. The tongue was affected in 30.7%, parotid glands in 38.4% and airway in 38.4%. Four EXIT procedures were carried out (nasotracheal intubation) and one emergency tracheotomy was needed. Five patients required more than one surgical prodedures, including partial glossectomy, with severe intraoperatory complications in 23% (bleeding, pharyngeal damage). In eight patients primary or adyuvant sclerotherapy was used. Three children with giant masses died, two due to intracystic bleeding and one from sepsis. Among the survivors, 50% have no sequelae., Conclusions: Cervical lymphangiomas are a very sereve condition, not only due to possible airway compresion or massive bleeding but also becose of the severe secualaes they may cause. Tongue or parotid gland infiltration are difficult to treat. In severe cases diagnosed prenatally a close follow up in selected centers, with multidisciplinary teams consisting of obstetricians and pediatric surgeons, trained in the EXIT procedure is warranted. Despite therapeutic efforts the prognosis of large masses is still poor.

Purpose: To describe the presence of bladder malformations in a surgically induced model of myelomeningocele (MMC)., Methods: A MMC like defect was created in the mid gestation using the previously described model in sheep. Bladders were examined macroscopically and histopathological changes were assessed using H-E., Results: Non prenatally corrected animals presented dilated bladders and separation between muscle bundles. Those malformations were not found in corrected animals or controls., Conclusions: Some bladder changes can be described in a surgically-induced model of MMC. These changes could be prevented using open fetal surgery.

We evaluated the clinical presentation and prognosis of three children with acute glomerulonephritis (AGN) associated with pneumonia. The patient database of Niño Jesús Children's Hospital was analyzed retrospectively (1996-2007) for patients diagnosed at discharge with both pneumonia and AGN. Those with recent pharyngeal or cutaneous infection were excluded. Three patients (1.67, 4.25, and 5 years old, respectively) were selected. All of them had lobar pneumonia, developing both macrohematuria and proteinuria within 24 h after admission. Decreased glomerular filtration rate was found in one patient. Two children developed arterial hypertension and one a slight pleural effusion. Two children had low C3 levels, and one had both low C3 and C4 levels. A Streptococcus pneumoniae serotype 17F was isolated from the blood culture of one patient. On follow-up, all patients had normal blood pressure and renal function with microhematuria persisting long term. Our patients with pneumonia-associated AGN had a good prognosis for both pulmonary and renal involvement.

Aim: To describe central nervous system malformations in the surgically induced model of Myelomeningocele (MMC) and their prevention using different prenatal treatments., Methods: MMC was surgically created in 33 fetal lambs. Fifteen did not undergo fetal repair (group A). Of the lambs that did undergo repair, 10 were repaired with open two layer surgical closure (group B), 5 with fetoscopic coverage using bioglue (group C) and 3 fetoscopically using a patch (group D). All procedures were recorded and lamb brains and spinal cords were examined grossly and microscopically in coronal sections for structural organization anomalies. Histopathological changes were assessed using HE and S-100 neural marker., Results: Hydrocephalus, Arnold-Chiari type II (AC-II) malformation and some neuronal migration disorders were observed in group A. Brains from group B and D were not hydrocephalic and had neither cell migration disorders nor hindbrain herniation. Group C presents mild degrees of hydrocephalus and AC-II. In group C lumbar lesion was covered by fibrous tissue., Conclusions: Some of the central nervous system abnormalities observed in human disease are present in the surgically induced model of MMC. In this model avoidance of fluid drainage using open fetal surgery limits malformation severity.

Background: Prenatal ultrasound study allows the detection of fetal malformations. Intrauterine interventions are now contemplated to correct, or interfere with, the natural history of these anomalies. Minimally invasive techniques, such as the so-called "Fetendo" (fetal endoscopy), are now therapeutic possibilities., Methods: From 2002 to 2007, 205 fetoscopies were performed in our hospital's fetal surgery program. Fetoscopic interventions were carried out under epidural anesthesia, accessing the uterine cavity with a fetoscope containing a 1.2-mm telescope. Following ultrasound-guided needle puncture of the amniotic cavity, the fetoscope was inserted through a 3-mm sheath by the Seldinger technique. Visibility was maintained with an amnioinfusion system. This procedure offers access to the placental surface, umbilical cord, and fetus., Results: Fetoscopy was used to perform laser coagulation of communicant placental vessels in 148 biamniotic monochorionic gestations with twin-to-twin transfusion syndrome (TTTS) and to occlude the umbilical cord in 32 cases of discordant monochorionic twins with a severe or lethal anomaly in one of the fetuses, and 5 cases of reversed arterial perfusion (TRAP) sequence. In addition, fetoscopy was performed in 18 cases to treat severe congenital diaphragmatic hernia by tracheal occlusion with an endotracheal balloon. Finally, in 2 cases, fetoscopic release of amniotic bands was performed to rescue extremities and the umbilical cord. The most common complications (10%) were preterm rupture of membranes, which resulted in preterm delivery. Other indications for fetoscopy, which we are currently using in experimental animal models, include low urinary tract obstruction, sacrococcygeal teratoma, and repair of myelomeningocele defects., Conclusions: Fetoscopy can lower the incidence of preterm labor that occurs in response to the aggression of open surgery. At present, fetoscopy is effective for treating several fetal anomalies. Preterm rupture of membranes remains the weak link of fetoscopy. Refinement of the technique and technologic advances will help this problem and allow the use of fetoscopy for other pathologies in the future.

Umbilical cord amniotic bands occur in approximately 10% of cases of amniotic band syndrome and are a well-known cause of fetal death. An unexpected amniotic band encircling the umbilical cord was diagnosed during a fetoscopic procedure to release a leg constriction. Both bands were released fetoscopically using a YAG laser. We report the first case of an amniotic band involving the umbilical cord diagnosed and released prenatally.

Purpose: To examine if brain malformations, similar to those which account for cognitive disorders seen in human disease, are present in an ovine model of myelomeningocele (MMC)., Methods: An MMC-like lesion was surgically created in 16 fetal lambs between 60 and 80 days of gestation. Ten did not undergo fetal repair (group A), 2 were repaired with an open two-layer closure (group B), 2 with open bioglue coverage (group C) and 2 with fetoscopic coverage (group D). Lambs were killed and their brains were examined. Two brains from normal unoperated lambs served as controls., Results: Thirteen lambs died in utero (81%). Two lambs in group A and 1 in group B were delivered at term. Group A brains showed hydrocephalus and extensive areas of polymicrogyria. There was also an extensive denudation of the ependymal lining under the polymicrogyric areas and the corpus callosum was thinner than normal. No hindbrain herniation was observed. Brains from group B and the control did not show any of these abnormalities., Conclusions: Some of the central nervous system abnormalities associated to MMC in human patients are also found in the uncorrected fetal lamb model of MMC but not in the only survivor to intrauterine coverage. Further studies are necessary to ascertain if these abnormalities can be prevented by coverage of the defect.

The ex-utero intrapartum treatment (EXIT) procedure is a technique designed to allow partial foetal delivery via caesarean section with establishment of a safe foetal airway by either intubation, bronchoscopy, or tracheostomy while foetal oxygenation is maintained through utero-placental circulation. The most common indication for the EXIT procedure is the presence of foetal airway obstruction, which is usually caused by a prenatal diagnosed neck mass. We report three cases of head and neck tumours with airway obstruction treated by means of EXIT and with different solutions in the management of the airway. With the involvement of Paediatric Otolaryngologists in EXIT, new indications and select variations from the standard EXIT protocol should be considered.

Damage of neural elements (spinal cord and encephalus) in myelomeningocele (MMC) seems to be progressive during gestation because of amniotic fluid chemical contact and continuous leakage of CSF. We studied the effect of preterm delivery and steroid treatment in a model of MMC in the rabbit foetus. Twelve New Zealand White rabbits underwent laparotomy and hysterotomy at 23 days of gestation. Fifty-nine out of 107 foetuses underwent lumbar laminectomy (three to four levels). Dura was opened to expose the neural elements to the amniotic fluid. Six rabbits underwent caesarean section on gestational day 31 for fetal harvest; three of them had no treatment (group T) and three received corticosteroid treatment (group TC). The other six rabbits underwent caesarean section on gestational day 29 for fetal harvest (preterm delivery); three of them had no treatment (group P) and three received corticosteroid treatment (group PC). Alive newborns were clinically, neurophysiologically and histologically analysed. None of mothers died during the procedure. After birth, animals in group preterm showed statistically significant less deformity than animals in group at term. Lower kyphosis was observed in group PC (preterm and steroids). Pain related and spontaneous mobility of lower extremities was higher in groups treated with corticosteroids (TC and PC). Only newborns at term (T and TC groups) showed response to evoked potentials (CMEPs). The response was earlier and higher in group treated with steroids (TC). Histologically, we observed progressive lesion of the spinal cord. Groups treated with steroids (TC and PC) show less inflammatory response. Arnold-Chiari malformation was present in all groups. Animals in group preterm with steroids show statistically significant less herniation than those group at term. Preterm delivery and prenatal steroid therapy seem to be an effective treatment to get less neural injury (spinal cord and encephalus) in myelomeningocele foetuses.

Objective: The objective of the study was to reproduce severe forms of extremity amniotic bands, which result in amputation or severe lesions., Study Design: Right limbs of 5 60-day gestational age pregnant sheep were ligated with silk suture at the infracondylar level. Left limbs were used for paired comparison. The limbs obtained from term fetuses were analyzed morphologically, radiologically, and histologically., Results: The ligated limbs showed an amputation or quasiamputation. Four extremities showed a necrotic pattern and 4 an edema pattern., Conclusion: A model of severe extremity amniotic bands that reproduces the effect of the extremity amniotic bands in the human fetus was developed. Future applications of this new model could be an experimental study of in utero salvage of limbs affected with severe extremity amniotic bands in the ovine fetus.

Introduction: Gastroschisis (GS) is a congenital abdominal wall defect that permits bowel exposure to amniotic fluid (AF). Intestinal damage is related to the chemical action of AF and constriction. After birth at term, a thickened intestinal wall with inflammation and, in some cases, intestinal atresias were observed. Surgical repair and intestinal reubication may be difficult, and thus staged silo repair could be necessary. These patients require a long hospital stay owing to bowel damage causing severe intestinal hypoperistalsis and poor absorptive capacity. Total parenteral nutrition (TPN) is required for a long period., Objective: The aim of this prospective study is to evaluate the benefits of a preterm delivery to avoid bowel damage and its post-natal consequences., Patients and Methods: Six cases of prenatally-diagnosed GS have been treated following a new strategy since July 2002. A preterm Cesarean section (c-section) delivery was programmed at 34-35 weeks of gestational age (GA). Some hours after birth, at bedside in the NICU, bowel reduction through the defect hole was performed under general anesthesia. This preterm group (PT) was compared the past 6 cases at term (AT) from January 1998 to July 2002. Macroscopic appearance, atresia existence, surgical technique, silo requirement, neonatal outcome, TPN and hospital stay were analyzed., Results: All six cases AT (mean GA: 36.3 weeks) presented bowel inflammation and thickened wall. Only 2/6 cases allowed the intestine to be housed in a primary closure after laparotomy. 4/6 cases required staged silo repair. 1 patient presented intestinal atresia and other had perforations who died at 17 days of life from intestinal sepsis. Mean postoperative intubation period was 16.2 days. Mean TPN was 41.2 days and mean hospital stay 69.8 days. PT group was monitored by prenatal sonography seeking bowel sonolucency. After programmed PT c-section delivery (mean GA: 34.8 weeks) in all 6 cases, bowel loops presented normal appearance and intestinal thickening was absent, except in one case. No prematurity-related respiratory complications were observed. Easy bowel reduction without abdominal compression was performed in all cases. 1/6 cases required surgical release of occlusive intestinal adherence. Mean postoperative intubation period was 0.4 days (9.6 hours). Oral feeding was started at 6 days. Mean TPN was 13.4 days and mean hospital stay 28.6 days., Conclusions: The third trimester is a critical period for fetal bowel development. Intestinal damage rises with increasing exposure time to amniotic fluid. This strategy of preterm delivery for the treatment of GS avoids intestinal damage, prevents "peel" and intestinal atresia, renders surgical reduction easier, reduces the hypoperistalsis, need for TPN and hospital stay. Multidisciplinary coordination between obstetricians, neonatologists and pediatric surgeons is required.

Since 1998 we have operated 5 patients with gastroesophageal reflux (GER) by laparoscopic procedure, aged between 6 and 16 years. In the 3 smaller patients we have done the Boix-Ochoa antireflux technique. In the other 2 patients we have done the Nissen fundoplicature. At 3 months of postoperative course, the 24 hours-pHmetry is normal in all the patients. They also refer the absence of symptomatology of vomiting and/or pyrosis. In 3 patients we could do a postoperative manometry of the distal esophagic sphincter, with normal values. The postoperative dysphagia of the first seems to be lesser in the group treated with the Boix-Ochoa technique.

Hypertensive cardiomyopathy is nowadays the most precious, prevalent and fatal condition of all cerebral, renal and arterial complications that leads to arterial hypertension. Left ventricular hypertrophy is the basis of the macroscopic structural damage that belongs to this entity. Basically, this complication produces, in the daily practice, alterations in the systolic and dyastolic functions, myocardial ischemia and arrhythmias. At present, it is obvious that we need to take better advantage of resources to diagnose hypertensive cardiopathy, and that the cost of explorations are lower must imply an agreement between cardiologists and general practitioners. In this article, we review the resources available at general practice level for the efficient diagnosis of the complications produced by hypertensive cardiopathy.

Since 1988, we have performed the Passerini-Glazel technique, in 5 patients, between 7 months and 3 years old. All showed female pseudohermaphroditism with severe signs of masculinization, and consequently, high outlet of the vagina in the urethra, secondary to Congenital Adrenal Hyperplasia (CAH). The technique use is to get a functional and esthetically acceptable vagina at the expense of a urethral flap and two flaps of skin, coming from the hypertrophic clitoris. The results were excellent in all the patients. In one occasion it was necessary to insert a cylinder of vesical mucous to get a suture without tension of both hemivaginas. In one case there appeared a late vaginal stenosis that was solved with dilations. The present technique is indicated in those cases of CAH, with great testosterone impregnation, in which the vagina ends very high and her primary descent is difficult. It is also indicate in those cases in which there exists the risk of hurting the external sphincter, which would damage the urinary continence mechanism.

We have studied a girl seven and a half years old with a renal disease manifested by proteinuria and nephrotic syndrome combined with initial macroscopic hematuria normal blood pressure and persistent depression of the complement C3 levels with the complement activating gamma globulin (C3 Nef) present in serum. The anatomopathological study showed findings of membranoproliferative glomerulonephritis type II with intramembranous deposit (dense deposit disease). An unusual association with partial lipodystrophy was present in this case. A follow-up of five years, and a few considerations about etiopathogenic theories were presented.