Congenital diaphragmatic hernia: current status and review of the literature

Treatment of congenital diaphragmatic hernia (CDH) challenges obstetricians, pediatric surgeons, and neonatologists. Persistent pulmonary hypertension (PPHT) associated with lung hypoplasia in CDH leads to a high mortality rate at birth. PPHT is principally due to an increased muscularization of the arterioles. Management of CDH has been greatly improved by the introduction of prenatal surgical intervention with tracheal obstruction (TO) and by more appropriate postnatal care. TO appears to accelerate fetal lung growth and to increase the number of capillary vessels and alveoli. Improvement of postnatal care over the last years is mainly due to the avoidance of lung injury by applying low peak inflation pressure during ventilation. The benefits of other drugs or technical improvements such as the use of inhaled nitric oxide or extracorporeal membrane oxygenation (ECMO) are still being debated and no single strategy is accepted worldwide. Despite intensive clinical and experimental research, the treatment of newborn with CDH remains difficul

Infected epidermal cyst of the clitoris in an infant

Clitoral enlargement in the pediatric population is a rare condition, usually related to problems of sexual differentiation, but malignant and benign clitoral lesions have also been described. We report the case of a newborn infant, investigated at birth for an intersex disorder because of clitoromegaly. Hormonal screening was normal and ultrasound (US) did not show a pelvic or abdominal mass. Three weeks later, the lesion was larger, tense and erythematous. An abscess was suspected. A drainage was then performed, and the bacteriological culture revealed the presence of Staphylococci aurei. A magnetic resonance imaging (MRI) performed to exclude a tumor of the soft tissue was normal. A diagnosis of infected epidermal cyst was confirmed by the pathology. Two months later, the external genital aspect was normal and the child asymptomatic

Predictive factors at birth of the severity of gastroschisis.

To establish children born with gastroschisis (GS). We performed a retrospective study covering the period from January 2000 to December 2007. The following variables were analyzed for each child: Weight, sex, apgar, perforations, atresia, volvulus, bowel lenght, subjective description of perivisceritis, duration of parenteral nutrition, first nasogastric milk feeding, total milk feeding, necrotizing enterocolitis, average period of hospitalization and mortality. For statistical analysis, descriptive data are reported as mean ± standard deviation and median (range). The non parametric test of Mann-Whitney was used. The threshold for statistical significance was P < 0.05 (Two-Tailed). Sixty-eight cases of GS were studied. We found nine cases of perforations, eight of volvulus, 12 of atresia and 49 children with subjective description of perivisceritis (72%). The mortality rate was 12% (eight deaths). Average duration of total parenteral nutrition was 56.7 d (8-950; median: 22), with five cases of necrotizing enterocolitis. Average length of hospitalization for 60 of our patients was 54.7 d (2-370; median: 25.5). The presence of intestinal atresia was the only factor correlated with prolonged parenteral nutrition, delayed total oral milk feeding and longer hospitalization. In our study, intestinal atresia was our predictive factor of the severity of GS

Evolution of Biological Bandages as First Cover for Burn Patients.

Significance: Cutaneous wound regeneration is vital to keep skin functions and for large wounds, to maintain human survival. In a deep burn, the ability of the skin to heal is compromised due to the damage of vasculature and resident cells, hindering a coordinated response in the regeneration process. Temporal skin substitutes used as first cover can play a major role in skin regeneration as they allow a rapid wound covering that, in turn, can significantly reduce infection risk, rate of secondary corrective surgeries, and indirectly hospitalization time and costs. Recent Advances: Skin was one of the first tissues to be bioengineered providing thus a skin equivalent; however, what is the current status subsequent to 40 years of tissue engineering? We review the classic paradigms of biological skin substitutes used as first cover and evaluate recent discoveries and clinical approaches adapted for burn injuries cover, with an emphasis on innovative cell-based approaches. Critical Issues: Cell-based first covers offer promising perspectives as they can have an active function in wound healing, such as faster healing minimizing scar formation and prepared wound bed for subsequent grafting. However, cell-based therapies encounter some limitations due to regulatory hurdles, as they are considered as "Advanced Therapy Medicinal Products," which imposes the same industry-destined good manufacturing practices as for pharmaceutical products and biological drug development. Future Directions: Further improvements in clinical outcome can be expected principally with the use of cell-based therapies; however, hospital exemptions are necessary to assure accessibility to the patient and safety without hindering advances in therapies

Burn patient care lost in good manufacturing practices?

Application of cell therapies in burn care started in the early 80s in specialized hospital centers world-wide. Since 2007, cell therapies have been considered as "Advanced Therapy Medicinal Products" (ATMP), so classified by European Directives along with associated Regulations by the European Parliament. Consequently, regulatory changes have transformed the standard linear clinical care pathway into a more complex one. It is important to ensure the safety of cellular therapies used for burn patients and to standardize as much as possible the cell sources and products developed using cell culture procedures. However, we can definitely affirm that concentrating the bulk of energy and resources on the implementation of Good Manufacturing Practice (GMP) alone will have a major negative impact on the care of severely burned patients world-wide. Developing fully accredited infrastructures and training personnel (required by the new directives), along with obtaining approval for clinical trials to go ahead, can be a lengthy process.We discuss whether or not these patients could benefit from cell therapies provided by standard in-hospital laboratories, thus avoiding having to meet rigid regulations concerning the use of industrial pharmaceutical products. "Hospital Exemption" could be a preferred means to offer burn patients a customized and safe product, as many adaptations may be required throughout their treatment pathway. Patients who are in need of rapid treatment will be the ones to suffer the most from regulations intended to help them

Success and Failure for Children Born with Facial Clefts in Africa: A 15-Year Follow-up

Background: This study reviews the 15year program of our Department of Pediatric Surgery for the treatment and follow-up of children born with a cleft in Benin and Togo. Methods: We analyzed files of children born in Africa with a cleft. They were referred to us through a nongovernmental organization (NGO) between 1993 and 2008 and assessed in Africa by local pediatricians before and after surgery. Operations were performed by our team. Results: Two hundred files were reviewed: 60 cases of unilateral cleft lip, seven of bilateral cleft lip, 44 of unilateral cleft lip palate (UCLP), 29 of bilateral cleft lip palate (BCLP), 53 of cleft palate (CP), three of bilateral oro-ocular cleft, one of unilateral and two of median clefts (Binder), and one of commissural cleft. Sixty-nine (35%) of these cases were not operated in Africa: 25 (12.5%) had not shown up, 28 (15%) were considered unfit for surgery (Down's syndrome, HIV-positive, malnutrition, cardiac malformation), and 16 (7.5%) were transferred to Switzerland. Palatal fistula occurred in 20% of UCLP, 30% of BCLP, and 16% of CP. Evaluation of speech after palate surgery gave less than 50% of socially acceptable speech. Conclusions: Our partnership with a NGO and a local team makes it possible to treat and subsequently follow children born with a cleft in West Africa. Surgery is performed under good conditions. If aesthetic results are a success, functional results after palate surgery need further improvement to promote integration in school and social lif

Human muscular fetal cells: a potential cell source for muscular therapies

Myoblast transfer therapy has been extensively studied for a wide range of clinical applications, such as tissue engineering for muscular loss, cardiac surgery or Duchenne Muscular Dystrophy treatment. However, this approach has been hindered by numerous limitations, including early myoblast death after injection and specific immune response after transplantation with allogenic cells. Different cell sources have been analyzed to overcome some of these limitations. The object of our study was to investigate the growth potential, characterization and integration in vivo of human primary fetal skeletal muscle cells. These data together show the potential for the creation of a cell bank to be used as a cell source for muscle cell therapy and tissue engineering. For this purpose, we developed primary muscular cell cultures from biopsies of human male thigh muscle from a 16-week-old fetus and from donors of 13 and 30years old. We show that fetal myogenic cells can be successfully isolated and expanded in vitro from human fetal muscle biopsies, and that fetal cells have higher growth capacities when compared to young and adult cells. We confirm lineage specificity by comparing fetal muscle cells to fetal skin and bone cells in vitro by immunohistochemistry with desmin and 5.1H11 antibodies. For the feasibility of the cell bank, we ensured that fetal muscle cells retained intrinsic characteristics after 5years cryopreservation. Finally, human fetal muscle cells marked with PKH26 were injected in normal C57BL/6 mice and were found to be present up to 4days. In conclusion we estimate that a human fetal skeletal muscle cell bank can be created for potential muscle cell therapy and tissue engineerin

Development, characterization, and use of a fetal skin cell bank for tissue engineering in wound healing.

Wound healing in fetal skin is characterized by the absence of scar tissue formation, which is not dependent on the intrauterine environment and amniotic fluid. Fetal cells have the capacity of extraordinary expansion and we describe herein the development of a fetal skin cell bank where from one organ donation (2-4 cm2) it is possible to produce several hundred million fetal skin constructs of 9 x 12 cm2. Fetal cells grow three to four times more rapidly than older skin cells cultured in the same manner and these banked fetal cells are very resistant against physical and oxidative stress when compared to adult skin cells under the same culture conditions. They are up to three times more resistant to UVA radiation and two times more resistant towards hydrogen peroxide treatment. This mechanism may be of major importance for fetal cells when they are delivered to hostile wound environments. For fetal cell delivery to patients, cells were associated with a collagen matrix to form a three-dimensional construct in order to analyze the capacity of these cells for treating various wounds. We have seen that fetal cells can modify the repair response of skin wounds by accelerating the repair process and reducing scarring in severe bums and wounds of various nature in children. Hundreds of thousands of patients could potentially be treated for acute and chronic wounds from one standardized and controlled cell bank

Biologicals and Fetal Cell Therapy for Wound and Scar Management

Few biopharmaceutical preparations developed from biologicals are available for tissue regeneration and scar management. When developing biological treatments with cellular therapy, selection of cell types and establishment of consistent cell banks are crucial steps in whole-cell bioprocessing. Various cell types have been used in treatment of wounds to reduce scar to date including autolog and allogenic skin cells, platelets, placenta, and amniotic extracts. Experience with fetal cells show that they may provide an interesting cell choice due to facility of outscaling and known properties for wound healing without scar. Differential gene profiling has helped to point to potential indicators of repair which include cell adhesion, extracellular matrix, cytokines, growth factors, and development. Safety has been evidenced in Phase I and II clinical fetal cell use for burn and wound treatments with different cell delivery systems. We present herein that fetal cells present technical and therapeutic advantages compared to other cell types for effective cell-based therapy for wound and scar management