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Background/Purpose To implement resident curriculum in France based on theoretical teaching and bed side training, the national council known as the “College Hospitalier et Universitaire de Chirurgie Pediatrique” examined the relevance and feasibility of systematically introducing simulation program in the pediatric surgery resident training. Material and methods A national simulation training program was developed and took place in a 2-day session organized in 7 simulation centers in France. The program included technical (laparoscopic/suturing technique on low-fidelity models) and nontechnical (6 scenarios for standardized consultation, and a team work scenario based on errors prevention in the operative room) skills. Evaluation of the program (Likert scale from 1 (bad) to 5 (excellent) and notation on 20 points) concerned trainees and trainers. Results 40 residents (95% of all pediatric surgery French residents) attended with a ratio of trainees/trainer of ½. The training objectives earned a score of 4.46/5. The pedagogical value of the seminar scored 4.7/5, teaching quality 17.95/20, and the overall seminar score was 17.35/20. Conclusion This program, unique nationally, was assessed very favorably by the participating residents and by the involved trainers. To our knowledge, it represents the first mandatory national simulation training program included within a surgical training model. Level of evidence Level IV.

Resume Propos L'augmentation du nombre de cancers et la generalisation de la pose des chambres implantables pour leur traitement favorisent l'augmentation de frequence des thromboses sur catheter central longue duree. Ces thromboses veineuses de catheter central (TVKTC) chez les patients cancereux ont des consequences medicales : dysfonctionnement du catheter et risque d'embolie pulmonaire. Elles ont egalement des consequences economiques : duree d'hospitalisation superieure a celles des thromboses profondes des membres inferieurs (+6 jours) et superieurs (+4 jours), cout de remplacement de chambre implantable estime a 4500 €. Actualites et points forts Le principal facteur de risque de TVKTC est l'agression de la paroi veineuse lors de la pose du catheter a l'origine du thrombus qui le plus souvent va disparaitre spontanement, mais peut aussi s'organiser sous l'influence de facteurs thrombogenes locaux ou generaux. Ainsi, les TVKTC asymptomatiques sont depistees par phlebographie dans 30 a 60 % des insertions de catheter, mais ne sont symptomatiques que dans 5 % cas. Leur traduction clinique est non specifique associant a des degres divers, douleur et œdeme du membre superieur ou du cou, circulation collaterale et dysfonctionnement du catheter. Actuellement, le diagnostic des TVKTC de longue duree symptomatique repose en premiere intention sur l'echographie couplee au doppler objectivant une incompressibilite de la veine et la presence d'un thrombus adherant a la paroi veineuse et non limite a l'extremite distale du catheter. La place de l'angioscanner ou de l'IRM n'est pas precisee. La phlebographie est reservee aux cas difficiles. Le traitement curatif fait appel, soit aux heparines de bas poids moleculaire (HBPM) avec relais precoce par les antivitamines K pour une duree d'au moins trois a six mois, soit plutot aux HBPM au long cours par analogie aux thromboses veineuses des membres inferieurs chez le patient cancereux, cela avec ou sans ablation du catheter central. Perspectives et projets La prophylaxie primaire des TVKTC par HBPM ou AVK n'est plus indiquee au vu d'etudes methodologiquement bien menees n'ayant pas demontre de benefice. Cependant, la mise sur le marche des nouveaux antithrombotiques et la definition d'une population a risque de thrombose de catheter pourraient deboucher sur une prophylaxie ciblee efficace.

Resume Nous rapportons le cas d’un homme de 49 ans, victime d’un accident de la voie publique avec incarceration et polytraumatisme, pour lequel l’equipe medicale a ete confrontee au piege classique de la prise en charge des traumatismes thoracique severe : a savoir, releguer au second plan l’atteinte thoracique en la presence d’autres points d’appel. Dans notre cas, ce fut une atteinte neurologique : un syndrome de Dandy-Walker, veritable piege iconographique car pouvant etre confondu avec une lesion cerebrale hemorragique. Par cette observation, nous reaffirmons la necessite d’une prise en charge systematique de tout traumatisme thoracique severe en effectuant un electrocardiogramme, un dosage de la troponine T et une echocardiographie transœsophagienne.

Bone lesions above a critical size become scarred rather than regenerated, leading to nonunion. We have attempted to obtain a greater degree of regeneration by using a resorbable scaffold with regeneration-competent cells to recreate an embryonic environment in injured adult tissues, and thus improve clinical outcome. We have used a combination of a coral scaffold with in vitro-expanded marrow stromal cells (MSC) to increase osteogenesis more than that obtained with the scaffold alone or the scaffold plus fresh bone marrow. The efficiency of the various combinations was assessed in a large segmental defect model in sheep. The tissue-engineered artificial bone underwent morphogenesis leading to complete recorticalization and the formation of a medullary canal with mature lamellar cortical bone in the most favorable cases. Clinical union never occurred when the defects were left empty or filled with the scaffold alone. In contrast, clinical union was obtained in three out of seven operated limbs when the defects were filled with the tissue-engineered bone.

OBJECTIVE:Midstream clean-catch urine is an accepted method to diagnose urinary tract infection but is impracticable in infants before potty training. We tested the bladder stimulation technique to obtain a clean-catch urine sample in infants. MATERIALS AND METHODS:We included 142 infants under walking age who required a urine sample in a cross-sectional study carried out during a 3-months period, from September to November 2014, in the emergency department of the University Children's Hospital of Nice (France). A technique based on bladder stimulation and lumbar stimulation maneuvers, with at least two attempts, was tested by four trained physicians. The success rate and time to obtain urine sample within 3 minutes were evaluated. Discomfort (EVENDOL score ≥4/15) was measured. We estimated the risk factors in the failure of the technique. Chi-square test or Fisher's exact test were used to compare frequencies. T-test and Wilcoxon test were used to compare quantitative data according to the normality of the distribution. Risk factors for failure of the technique were evaluated using a multivariate logistic regression model. RESULTS:We obtained midstream clean-catch urine in 55.6% of infants with a median time of 52.0 s (10.0; 110.0). The success rate decreased with age from 88.9% (newborn) to 28.6% (>1 y) (p = 0.0001) and with weight, from 85.7% (10 kg) (p = 0.0004). The success rate was 60.8% for infants without discomfort (p

Two unusual but similar cases of very high serum iron, extremely high transferrin concentrations (5.4 to 6.5 g/L), and increased transferrin saturation are reported. No anemia or microcytosis was observed. The ferritin concentration remained within the normal range, and no iron overload was observed. In one case, the in vivo half-life of 59Fe-labeled transferrin was shown to be prolonged (206 minutes versus 75 minutes for controls). In both patients, a monoclonal IgG was observed in the serum. The association between serum transferrin and monoclonal IgG was demonstrated by Western blot analysis and affinity chromatography. We suggest that the transferrin bound to the monoclonal IgG molecule has a prolonged half-life in the circulation, leading to high transferrin concentrations, and that the increased serum iron values prevent the onset of anemia. The antitransferrin activity of monoclonal antibody should be added to the list of situations accounting for elevated serum iron with elevated transferrin saturation.

Large bone defects are still a challenge to orthopedic surgeons. In this study, a massive bone defect with a clinically relevant volume was efficiently reconstructed by transplanting an engineered bone in which mesenchymal stem cells (MSCs) expanded in autologous serum (AS) were combined with a porous scaffold. In the first step, we established that the way in which the MSCs are distributed over the scaffold affects the ultimate bone-forming ability of the transplant: constructs consisting of a natural coral scaffold and a pseudo-periosteal layer of MSCs surrounding the implant (coral-MSC3D) formed significantly more bone than constructs in which the MSCs were distributed throughout the implant (p = 0.01). However, bone healing occurred in only one sheep, owing to the high resorption rate of natural coral scaffold. To overcome this problem, constructs in which MSCs were combined with a porous coralline-based hydroxyapatite (CHA) scaffold having the same architecture as natural coral but a lower resorption rate were prepared. After their implantation, these constructs were found to have the same osteogenic potential as autologous bone grafts in terms of the amount of newly formed bone present at 4 months (p = 0.89) and to have been completely replaced by newly formed, structurally competent bone within 14 months. Nevertheless, although the rate of bone healing was strikingly improved when CHA-MSC3D constructs were used (five of seven animals healed) as compared with the coral-MSC3D construct (one of seven healed), it was still less satisfactory than that obtained with autografts (five of five healed).

Objective—To develop a technique for use in investigation of healing of long-bone defects by creation of a critical-size defect in the left metarsal III and IV bone (metatarsus) of sheep. Animals—18 healthy adult sheep. Procedure—Sheep were allocated to 4 groups (3, 3, 5, and 7 sheep in groups 1 to 4, respectively). An ostectomy with various segmental length-to-diaphyseal diameter ratios (0.5, 1.0, 2.0, and 2.0 for groups 1 to 4, respectively) was performed on the left metatarsus of each sheep. The defect was left empty in sheep of groups 1, 2, and 3, whereas the defect was filled with a massive corticocancellous bone autograft in sheep of group 4. Results—All sheep tolerated the surgical procedure well and were able to use the affected limb the day after surgery. Radiographic and histologic examinations conducted 16 weeks after surgery revealed nonunion in all sheep of groups 1, 2, and 3, whereas consistent bone healing with abundant bone formation was observed in all sheep of group 4. Conclusions and Clinical Relevance—Analysis of these findings suggests that the sheep metatarsal model is a critical-size defect model with low morbidity. It should allow the assessment of new technologies for bone regeneration in conditions closely mimicking the clinical setting. Impact for Human Medicine—Use of this technique in sheep should be of benefit for the preclinical study of osteoconductive, osteoinductive, or osteogenic biomaterials for use in humans. (Am J Vet Res 2004;65:1653–1657)

A potential therapy to enhance healing of bone tissue is to deliver isolated mesenchymal stem cells (MSCs) to the site of a lesion to promote bone formation. A key issue within this technology is the development of an injectable system for the delivery of MSCs. Fibrin gel exploits the final stage of the coagulation cascade in which fibrinogen molecules are cleaved by thrombin, convert into fibrin monomers and assembled into fibrils, eventually forming fibers in a three-dimensional network. This gel could have many advantages as a cell delivery vehicle in terms of biocompatibility, biodegradation and hemostasis. The objective of this study was to explore the possibility of using fibrin gel as a delivery system for human MSCs (HMSCs). To this end we have determined the optimal fibrinogen concentrations and thrombin activity for loading HMSCs in vitro into the resultant fibrin gels to obtain cell proliferation. We found that a concentration of 18 mg/ml of fibrinogen and a thrombin activity of 100 IU/ml was optimal for producing fibrin scaffolds that would allow good HMSCs spreading and proliferation. In these conditions, cells were able to proliferate and expressed alkaline phosphatase, a bone marker, in vitro. When implanted in vivo, HMSCs were able to migrate out of the fibrin gel and invade a calcium carbonate based ceramic scaffold suggesting that fibrin gel could serve as a delivery system for HMSCs.

We have previously shown that basic fibroblast growth factor (bFGF) inhibits the FSH-induced differentiation of cultured rat granulosa cells, as manifested by prominent reduction of the LH receptor expression. We now investigate the possible sites and mechanism of action of bFGF. Whereas bFGF decreased the cAMP formation induced by FSH, it enhanced the cAMP production caused by cholera toxin and forskolin, suggesting that bFGF exerted its inhibitory action on cell differentiation at a step to cAMP production. Photoaffinity labeling with 8-azido-[32P]cAMP revealed that bFGF markedly reduced the FSH-induced increase in the level of regulatory subunit RII beta of the cAMP-dependent protein kinase (PKA) type II. In contrast to its striking effect on RII beta expression (70-80% inhibition), bFGF decreased PKA enzymatic activity by only 30%. On the other hand, transforming growth factor-beta (TGF beta) slightly amplified the stimulatory action of FSH and antagonized the bFGF inhibitory effect on both LH receptor expression and RII beta synthesis. We report that the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA), which impaired granulosa cell differentiation, also abolished the RII beta synthesis induced by FSH. The activation of PKC by bFGF in granulosa cells was supported by the following findings: (i) bFGF markedly enhanced the production of diacylglycerol (2.3-fold stimulation at 5 min), the intracellular activator of PKC; (ii) bFGF promoted tight association of PKC to cellular membranes, a process that is believed to correlate with the enzyme activation; (iii) bFGF induced the phosphorylation of an endogenous M(r) 78,000/pI 4.7 protein that appears as a specific PKC substrate; (iv) bFGF mimicked the TPA-induced transmodulation of the epidermal growth factor (EGF) receptor, reducing by 36% the 125I-EGF binding on granulosa cells. We conclude that bFGF may exert its repressive action on RII beta synthesis, PKA activity, and granulosa cell differentiation by primarily targeting PKC activation.

AR4-2J, a rat pancreatic acinar-tumor cell line, was used to investigate long-term effects of basic fibroblast growth factor (bFGF) and somatostatin on pancreatic cancer cells. We observed that bFGF stimulated cell proliferation when cells were cultured in serum-free medium. The effect was dose-dependent with half-maximal and maximal effects at 25 pM and I nM bFGF, respectively. The somatostatin analog SMS 201-995 (SMS) decreased the growth-promoting effect of bFGF. The maximal effect was observed at I nM SMS and the half-maximal effect at 20 pM SMS. Characterization of bFGF receptor-binding properties with [125I]bFGF revealed that AR4-2J cells exhibited 2 classes of bFGF binding site with respective KD values of 47 pM and 3 nM and binding capacities of 14 fmol and 0.9 pmol/10(6) cells. High-affinity receptors correlated with bFGF stimulation of AR4-2J cell growth, suggesting that the effects of bFGF are receptor-mediated.

Background: Congenital chylothorax (CC) is the leading cause of prenatal and neonatal pleural effusion but its etiology remains unknown. Some cases are associated with hydrops fetalis, chromosomal anomalies and congenital heart disease. Aim: To study the prenatal diagnosis, associated anomalies and chromosomal abnormalities, clinical evolution, management and final outcome and long-term follow-up of CC. Methods: Prenatal and postnatal follow-up of 32 fetuses with CC detected antenatally from 1990 to 2006, reviewed retrospectively. Follow-up ranged from 5 to 14 years. Results: Mean gestational age at diagnosis was 30 weeks (range, 30–40). Eighteen infants (18/32, 56.2%) presented with hydrops fetalis. Bilateral pleural effusion was observed in 26 cases (26/32, 81.2%). Eleven infants required intrauterine drainages (11/32, 34.4%) consisting on 5 thoracocentesis and 6 pleuro-amniotic shunting. In 8 cases there were associated congenital anomalies (25%) being congenital heart defects the most common findings (6/8,). In three cases (3/32, 9.4%) a trisomy 21 was diagnosed. Mean gestational age at birth was 34 weeks (range 30 to 40) with 24 (75.0%) preterm deliveries. Three patients died antenatally an eleven in the postnatal period; 11 associated non inmune hydrops. The overall rate of survivors beyond neonatal period was 56.2% (18/32). Of the 18 survivors, 14 were asymptomatic whereas 4 developed asthma, 2 of them with normal chest x ray. Conclusions: CC is the most common cause of pleural effusion in the perinatal period. Most of the cases of CC are diagnosed prenatally. Pleural effusion is bilateral in most cases. In absence of hydrops fetalis or associated anomalies, we can expect a good long-term prognosis.

Publisher Summary This chapter describes the direct reconstruction of intrathoracic great vessels. The knowledge of arterial pathology is important as it governs the type of reconstructive procedure to be used. Most occlusive lesions are atherosclerotic in origin. They are usually much localized, although sometimes multiple. Atherosclerotic involvement of the aortic arch, leading to ostial stenosis, is the most frequently encountered lesion. Each of the three intrathoracic great vessels, the innominate artery, the left common carotid artery, and the left subclavian artery (LSCA), may be involved. Different combinations of these lesions are possible but when all three are involved, it is called the aortic arch syndrome. The lesions of the middle part of the innominate artery or the LSCA, not involving the aortic origin of these vessels, are much rarer, as are the localized lesions of the bifurcation of the innominate artery, extending in various degrees to the right subclavian artery and/or to the right common carotid artery. The congenital lesions of the intrathoracic great vessels may be associated with the left or right aortic arch. A retroesophageal subclavian artery is present in 0.5% of the normal population but surgery is only indicated in the occasional symptomatic case. The isolation of the innominate or left subclavian artery is much less common.