Postgraduate training in surgery: From theory to practice.

INTRODUCTION: Postgraduate training is a time-honored entity, the goal of which was to develop and ensure the acquisition of new medical knowledge for the medical profession. MATERIAL AND METHODS: The main goal of this retrospective study is to analyze the current situation of postgraduate training in surgical disciplines within the framework of the French Universities. We studied the legal texts found in the LéxisNéxis® and Légifrance® sites up until December 1, 2018; references were sought from the Web of Science repository. RESULTS: Postgraduate training in France is mandatory from the legal point of view. Currently there are two possibilities for validation of postgraduate training: either through a recognized continuing professional development (CPD) organization controlled by the National Agency of Continuing Professional Development (NACPD), or by asking for certification through an official accreditation council (AC) (one exists for each surgical specialty), controlled by the High Health Authority that can automatically provide the equivalence of passing through the NACPD organization. DISCUSSION: The continuing education process remains complex. It could well be modified in the near future by the creation of a new certification procedure. With regard to surgical education, whether it concerns the CPD or the accreditation process, the goal is to decrease patient risk and to be an integral part of the overall policy to decrease health care costs. The role of professional national counsels will be more and more important; this is an advantage for each of the surgical specialties. Nonetheless, from the regulatory viewpoint, the decree concerning the role of National Professional Councils has not yet been published in the Journal Officiel de la République Française (French Republic official journal) at the time of writing. CONCLUSIONS: Currently two systems are available for surgeons to comply with the 2016 legislative obligation of continuing education: CPD which is run by the NACPD, and the accreditation process, run by an AC and controlled by the HAS; in the first instance, surgeons can ask for reimbursement from the NACPD and in the second, request that the National Health Insurance Fund for Salaried Employees cover a portion of the litigation insurance premium. LEVEL OF EVIDENCE: Retrospective study: level of evidence IV.

No-go decision: A newly identified adverse event in orthopaedic surgery - causes and medico-legal implications.

BACKGROUND: No-go designates a decision not to perform surgery when it becomes apparent that safety and/or feasibility requirements are not met. No-go decisions can occur at any time between patient admission to a hospital department and immediately before the first incision. The primary objective of this study was to assess the causes of no-go decisions reported as healthcare-associated adverse events (HAAEs). HYPOTHESIS: Most no-go decisions in orthopaedic surgery are related to problems with medical devices. MATERIAL AND METHODS: A preliminary retrospective study assessed HAAEs reported over the 1-year period from 1st October 2014 to 30th September 2015, using the risk-management tool ALARM. A prospective survey was then performed by emailing a 15-item questionnaire to the 1828 members of Orthorisq (the French orthopaedic surgeon accreditation agency). Responses were either yes/no or open. Statistical comparisons were performed, using the paired Wilcoxon signed-rank test to estimate p values. RESULTS: Among reported HAAEs, 5.6% were no-go decisions. Of the 101 reported no-go decisions, 43.5% and 45.2% were due to problems with managing implantable medical devices in the retrospective and prospective assessments, respectively. In over 85% of cases, surgery was cancelled or postponed. Over half the no-go decisions were associated with unnecessary anaesthesia. Checklist completion was performed in only half the cases and was not associated with no-go decisions (p>0.8). DISCUSSION: This study provides descriptive data on no-go decisions in orthopaedic surgery. Healthcare professionals use many methods to enhance patient safety by preventing adverse events or diminishing their impact. Errors in managing implantable medical devices are the leading cause of no-go decisions. The current checklist is not appropriate for managing implantable medical devices in orthopaedic surgery, in part because it does not include checking devices upon receipt. Before surgery, patients should be informed of the risk of a no-go decision, since unnecessary anaesthesia occurs in over half the cases. LEVEL OF EVIDENCE: IV, prospective study.

The concept of a waiting period for preoperative patient consent: Prospective study of 51 shoulder arthroscopy cases.

INTRODUCTION: The French Code of Public Health (CSP) does not explicitly require that patients should be given a certain amount of time to think about a procedure, except for cosmetic surgery, where 15 days is required (Art. L 6322-2 CSP). We hypothesized that patients require a waiting period during their decision-making process for scheduled shoulder arthroscopy procedure. MATERIALS AND METHODS: This prospective observational study of 51 patients analysed the concept of a waiting period based on a 10-item questionnaire. A comparative statistical approach was used and the P values were calculated using a paired Wilcoxon rank-sum test. RESULTS: Of the 51 patients, 42 (82%) rejected the concept of a waiting period before the procedure and 37 patients (73%) did not want a mandatory waiting period imposed by law. DISCUSSION: This study looked at the decision-making process during scheduled orthopaedic surgery and differentiated between the conscious and unconscious approach corresponding to an active and passive waiting period. A waiting period does not allow patients to make a conceptually deliberative decision that conforms to the criteria defined by the French Health Authority. This study rejects the need for a mandatory waiting period imposed on surgeons and patients as it does not integrate itself into the informative model of ethical decision-making for scheduled shoulder arthroscopy. TYPE OF STUDY: Prospective, observational; level of evidence IV.

Specialist nurse in Europe: education, regulation and role.

BACKGROUND: The concept of a 'specialist nurse' has existed for many years and related education programmes are proliferating. However, while literature clearly outlines the roles and practice of registered nurses and advanced practice nurses, those of specialist nurses remain unclear and nursing specializations across Europe need clarifying. AIM: This pilot study aimed to explore the competencies, education requirements and regulation of specialist nurses in Europe. DESIGN: A descriptive cross-sectional survey. METHODS: An online questionnaire named 'Specialist nurse and specialization in Europe' was sent to 550 members of the European Federation of Nurse Educators and ten members of the European Specialist Nurses Organizations. Snowball sampling was then used to build a convenience sample of nurse educators, clinical nurses and specialist nurses, national nursing association members, and chief nursing officers from all European countries. Besides quantitative aspects, responses to open-ended questions were analysed using a qualitative content analysis process. RESULTS: A total of 77 experts from 29 European countries responded to the questionnaire. Findings highlighted variations in titles, levels and length of education, certification, regulation and scope of practice for specialized nurses in Europe. Analysis of the promoted competencies revealed dominant clinical and technical aspects of the role with a high level of knowledge. CONCLUSIONS: The study emphasized the need to improve standards for education, certification and regulation for specialist nurses. Interpretation of the role and competencies is diverse with a weak presence of health policy that would enhance and develop the specialities. IMPLICATIONS FOR NURSING AND HEALTH POLICY: To address the current lack of provisions for automatic recognition of specialist nurses, common training frameworks corresponding to the relevant level of the European Qualifications Framework should promote lifelong learning and mobility, and enhance levels of health care and patient safety.

Impact of free on-site vaccine and/or healthcare workers training on hepatitis B vaccination acceptability in high-risk subjects: a pre-post cluster randomized study.

Despite recommendations for adults at high-risk of hepatitis B virus (HBV) infection, HBV vaccine uptake remains low in this population. A pre-post randomized cluster study was conducted to evaluate the impact of on-site free HBV vaccine availability and/or healthcare worker training on HBV vaccination acceptability in high-risk adults consulting in 12 free and anonymous HIV and hepatitis B/C testing centres (FATC). The FATC were randomly allocated into three groups receiving a different intervention: training on HBV epidemiology, risk factors and vaccination (Group A), free vaccination in the FATC (Group B), both interventions (Group C). The main outcomes were the increase in HBV vaccination acceptability (receipt of at least one dose of vaccine) and vaccine coverage (receipt of at least two doses of vaccine) after intervention. Respectively, 872 and 809 HBV-seronegative adults at high-risk for HBV infection were included in the pre- and post-intervention assessments. HBV vaccination acceptability increased from 14.0% to 75.6% (p <0.001) in Group B and from 17.1% to 85.8% (p <0.001) in Group C and HBV vaccine coverage increased from 9.4% to 48.8% (p <0.001) in Group B and from 11.2% to 41.0% (p <0.001) in Group C. The association of training and free on-site vaccine availability was more effective than free on-site vaccine availability alone to increase vaccination acceptability (ratio 1.14; from 1.02 to 1.26; p 0.017). No effect of training alone was observed. These results support the policy of making HBV vaccine available in health structures attended by high-risk individuals. Updating healthcare workers' knowledge on HBV virus and its prevention brings an additional benefit to vaccination acceptability.

Expression and localization of alpha-fetoprotein mRNA and protein in human early villous trophoblasts.

Alpha-fetoprotein (AFP) is a major plasma protein produced during human fetal life. It is a good marker for several possible disorders affecting gestation. We previously reported that afp gene expression, which takes place mainly in yolk sac and fetal liver, also occurs in normal human placenta, specifically in early pregnancy. The aim of the present study was to determine the precise location of AFP synthesis sites within the placental villi. In situ hybridization and immunohistochemical experiments were performed on sections obtained from placentas of first-trimester and full-term pregnancies. We found that the pattern of afp gene expression was restricted to specific villous trophoblastic areas in early placentas. Both afp transcripts and AFP protein were mainly located in discontinuous regions, at junctions between two villi and at budding sites. In contrast, no AFP expression was detected in the cytotrophoblastic extravillous proliferative zone or in other placental cell types. According to the earlier studies, no AFP synthesis was detected in placental villous tissue from full-term pregnancies, using in situ hybridization and immunohistochemistry.

Alpha-fetoprotein gene expression in early and full-term human trophoblast.

Alpha-fetoprotein (AFP) is a major serum glycoprotein synthesized during fetal life mainly by the yolk sac and the fetal liver. At term, it reaches high concentrations in the maternal intervillous blood, which is in direct contact with the placental trophoblastic microvillous membrane, and this suggests the placental origin of the AFP at the fetal-maternal interface. We used several experimental approaches to investigate the expression of AFP gene and fetal protein production in early gestation and term placentas. RT-PCR and immunological studies clearly identified AFP messenger RNA and AFP protein in the placental villi from first trimester of pregnancy. The AFP gene was also expressed in highly purified cytotrophoblasts from early placentas, and enzymo-immunoassay showed that AFP protein was synthesized and secreted by early cytotrophoblasts. AFP was also detected in the cytoplasm of these cells by immuno-cytochemistry. However, none of these methods detected any expression of the AFP gene in full-term placental villi or in cultured trophoblasts. These findings demonstrate that both AFP mRNA and protein are present in trophoblastic cells early in pregnancy. The absence of AFP gene expression in term placental villi also suggests, that the AFP at the fetal-maternal interface is attributable to a notable transplacental passage of AFP from fetal blood in late pregnancy.

Outcome of severe diabetic foot ulcers after standardised management in a specialised unit.

OBJECTIVE: The primary objective was to evaluate the efficacy in terms of limb salvage and healing time of standardised multidisciplinary management for high-grade diabetic foot ulcers. The secondary objective was to retrospectively identify the factors that influenced time to healing. STUDY DESIGN AND METHODS: Over a 2-year period, 157 patients with diabetic foot ulcers were managed in our specialised unit using a standard treatment strategy; 118 were followed until healing or for at least 7 months (range, 7-29) after hospital discharge and form the basis for this study. Predetermined criteria were used to diagnose and manage the lesions. The number of major amputations and the time to healing were the main outcome measures. Univariable and multivariable analyses were done retrospectively to look for factors associated with time to healing. RESULTS: The limb salvage rate was 97.5% and the healing rate was 50% after 10 months and 70% after 16 months. Factors significantly associated with healing time were arterial disease without bypass surgery (p<0.001) and renal replacement therapy (p<0.05). Osteomyelitis, as managed in this study, did not increase the healing time (p > 0.6). CONCLUSION: In high-grade diabetic foot ulcers, standardised conservative management with second-line bone-sparing surgery, if needed, yields an acceptable limb salvage rate. With combined medical and surgical treatment, osteomyelitis is not a poor prognosis factor.

Severe hypoxia specifically downregulates hepatocyte nuclear factor-4 gene expression in HepG2 human hepatoma cells.

The liver is one of the organs in which hypoxia helps to regulate gene expression under normal physiological conditions and in diseases such as cirrhosis and cancer. We postulated that the expression/activity of some of the 'liver-enriched' transcription factors, which control liver-specific genes, was sensitive to hypoxia. We tested hepatocyte nuclear factor-1 (HNF-1), HNF-3 and HNF-4, which play key roles in differentiation, development and hepatic gene expression, using HepG2 human hepatoma cells cultured under hypoxic conditions. Severe hypoxia/anoxia downregulated HNF-4 DNA-binding activity while DNA-binding activity of HNF-1 and HNF-3 remained unaffected. These hypoxic conditions also strongly and specifically decreased cell contents of HNF-4 protein, indicating that the decrease in HNF-4 DNA-binding activity was due to the lower amount of protein and not to decreased DNA-binding affinity. Northern analysis indicated that the expression of the hnf-4 gene was also downregulated in HepG2 cells cultured under hypoxic conditions. These results provide evidence that hypoxic stress triggers a cascade of events that inhibits the transactivation potential of HNF-4 in HepG2 cells. This step may be crucial in modulating the expression of a subset of liver genes that are targets for this nuclear receptor. This relationship provides a new route for the investigation of the effects of hypoxia on the liver cell.

Modulation of the far-upstream enhancer of the rat alpha-fetoprotein gene by members of the ROR alpha, Rev-erb alpha, and Rev-erb beta groups of monomeric orphan nuclear receptors.

Expression of the oncodevelopmental alpha-fetoprotein (AFP) gene is tightly regulated and occurs in the yolk sac, fetal liver and intestine, and cancerous liver cells. Transcription of the AFP gene is under the control of three enhancers that are very tissue specific. We have shown that the most upstream of these enhancers, located at -6 kb, works through the combined action of liver-enriched factors and nuclear receptors that bind to three regions of this DNA regulatory element. This study showed that orphan nuclear receptors of the ROR alpha, Re-verb alpha, and Rev-erb beta groups can bind as monomers with high affinity and specificity to an evolutionarily conserved AGGTCA motif in the functionally important region 1 of this AFP enhancer. Transient transfection experiments performed with human HepG2 hepatoma cells showed that overproduction of ROR alpha 4 stimulated the activity of the AFP enhancer in a dose-dependent manner, while that of Rev-erb alpha and Rev-erb beta had the opposite effect. These effects were highly specific and required the integrity of the AGGTCA motif. The action of these nuclear receptors also occurred in the context of the entire 7-kb regulatory region of the rat AFP gene. These results suggest that altering the amounts or activities of these orphan receptors in cells of hepatic or endodermal origin could modulate AFP gene expression in response to a variety of developmental or carcinogenic stimuli.

Rat alpha-fetoprotein promoter and proximal enhancer direct expression of the nls-lacZ reporter gene in embryonic yolk sac, gut, and eustachian canal of transgenic mice.

The alpha-fetoprotein (AFP) gene is expressed mainly in the yolk sac, liver and intestine during embryonic and fetal life. We have analyzed the activities of some of the rat AFP regulatory elements in vivo, using transgenic mice bearing the LacZ gene with a nuclear localization signal (nls-lacZ) placed under the control of the rat AFP promoter and the most proximal enhancer regions (from -3,127 to +102). Four of the six transgenic lines, with two genetic backgrounds, had highly specific reproducible patterns of transgene expression on embryonic days E10.5, E12 and E15. Analyses were performed on the whole embryo and histologically. There was nuclear staining in the yolk sac endodermal cells and in the epithelial cells of the intestine, indicating that the proximal enhancer and promoter drive expression in these cells where the AFP gene is actively transcribed. The pharyngo-tympanic canal was also stained in the transgenic embryos. But there was no expression of the lacZ transgene in the embryonic liver, indicating that additional sequences of rat genomic DNA are required for correct expression in the liver.

Regulation of alpha-foetoprotein gene expression by fatty acids and fibrates.

Alpha-foetoprotein (AFP), the major plasma protein in the foetus, is mainly synthesized by yolk sac and foetal liver. It binds polyunsaturated fatty acids and probably controls their metabolism and action. We investigated the effects of fatty acids and fibrates on expression of the AFP gene using two complementary approaches. Treatment with 5-8-11-14 eicosatetraynoic acid (ETYA), an analogue of arachidonic acid, specifically led to lower AFP mRNA levels in cultured rat yolk sac explants whereas treatment with palmitic or oleic acid did not. Clofibric acid and fenofibrate also gave lower AFP mRNA levels. Transient transfection experiments with HepG2 hepatoma cells showed that ETYA and clofibric acid decreased the transcriptional activity of the 7 kb regulatory region of the rat AFP gene. The 330 bp AFP promoter was identified as a target for these down regulating effects.

Rat yolk sac explants as a system for studying the regulation of endodermal genes: down-regulation of the alpha-fetoprotein gene by dexamethasone and phorbol ester.

The visceral yolk sac is a fetal membrane with essential placental functions. It is the major site of synthesis of alpha-fetoprotein (AFP), the most abundant plasma protein in the fetus. We developed a system of rat yolk sac explants in serum-free culture medium to study the regulation of endodermal gene expression in yolk sac. The explanted yolk sac tissues retained their double-sided morphology for up to 48 hours. The epithelial cells of both layers remained tightly joined on a basement membrane as seen by light and electron microscopy. This probably accounts for the continued expression of several endodermal cell-specific markers. The levels of mRNA encoding AFP, vitamin D-binding protein (DBP), hepatocyte nuclear factor 1alpha and beta transcription factors did not change during the 48-hour culture period. This reflects the stability of the differentiation state of the yolk sac endodermal cells. Dexamethasone and phorbol ester (TPA) specifically reduced the AFP mRNA level without affecting that of DBP. This suggests that these transduction pathways are functional in the yolk sac during this period of gestation and could be involved in the physiological down-regulation of AFP gene expression before birth. All these results show that this serum-free culture of rat yolk sac explants is a valuable system for further investigating the action of natural compounds and pharmacological drugs on endodermal gene expression during the embryonic and fetal periods.

Phorbol esters down-regulate alpha-fetoprotein gene expression without affecting growth in fetal hepatocytes in primary culture.

The effects of phorbol esters (phorbol-12,13-dibutyrate, PDB) on alpha-fetoprotein expression and cell growth were assayed by using fetal hepatocytes in primary culture. PDB acts synergistically with epidermal growth factor (EGF) to specifically decrease alpha-fetoprotein (AFP) mRNA levels, without affecting the expression of other genes of the same family, such as albumin and Vitamin D-binding protein (DBP). This effect is PDB-dose dependent, maximal effects being at 10 ng/ml. The implication of protein kinase C (PKC) in this effect seems clear since bisindolylmaleimide (BIS), a specific PKC inhibitor, completely blocks the PDB effect on AFP expression. Nuclear run-on experiments show that the decrease in AFP mRNA levels is mainly due to an inhibition in the transcription rate of the gene. Determination of PKC activities shows that fetal hepatocytes contain mainly Ca(2+)-independent isoenzymes, which patterns of activation was not modified by EGF plus PDB treatment with respect to PDB treatment. We have found that MAPK and JNK activities, c-jun and c-fos mRNA levels and AP-1 binding activity are notably increased when cells are incubated with both EGF and PDB, PDB does not stimulate growth of fetal hepatocytes, measured either as [3H]-thymidine incorporation into DNA or by cell cycle analysis using flow cytometry. All these results suggest that activation of PKC may affect liver gene expression rather than cell growth in fetal hepatocytes.

Chicken ovalbumin upstream promoter-transcription factor, hepatocyte nuclear factor 3, and CCAAT/enhancer binding protein control the far-upstream enhancer of the rat alpha-fetoprotein gene.

We have further characterized the most distal of the three alpha-fetoprotein (AFP) enhancers required for expression of the AFP gene in fetal hepatocytes and yolk sac endodermal cells. Almost total rat AFP enhancer 3 (E3) activity is driven by a 160-bp fragment at -6 kb containing three target regions for nuclear proteins that cooperate to stimulate transcription from the AFP and the thymidine kinase promoters in HepG2 hepatoma cells. Region 1, recently shown to be crucial for correct function of the enhancer in liver of transgenic mice, is recognized by two sets of transcription factors that bind to partly overlapping sites, 1a and 1b, in a noncooperative and nonexclusive manner. Site 1a contains a motif, AGGTCA, which is recognized by chicken ovalbumin upstream promoter transcription factors (COUP-TFs), but not by hepatocyte nuclear factor 4. Hepatocyte nuclear factor 3 (HNF3) and CCAAT/enhancer binding protein (C/EBP), which bind to regions 2 and 3, respectively, are likely responsible for the liver-specific E3 action. They play a key role by acting in synergy. The participation of nuclear receptors such as COUP-TFs, with C/EBP and HNF3, in the tight control of the distal AFP enhancer is a new, and perhaps key, step toward understanding the regulation and function of this enhancer, which may remain active throughout development.

Treatment of osteomyelitis in the diabetic foot. Contribution of conservative surgery.

OBJECTIVE: To compare the duration of healing of foot ulcers with osteomyelitis in diabetic patients treated by medical treatment versus medical treatment associated with conservative orthopedic surgery. RESEARCH DESIGN AND METHODS: We entered into the study 67 diabetic patients who had a foot ulcer with osteomyelitis without ischemia requiring a peripheral arterial reconstruction. Thirty-two diabetic patients were included in a first historic group from 1986 to 1993, treated by antibiotic therapy, offloading, and wound care. Thirty-two patients were included from September 1993 to March 1995, treated by the same medical treatment and conservative orthopedic surgery. RESULTS: The healing rate was 57% in the group treated by the medical treatment alone versus 78% in the surgical group (P < 0.008). The duration of healing was 462 +/- 98 days versus 181 +/- 30 days (P < 0.008). CONCLUSIONS: Conservative surgery contributes to an increase in the healing rate of foot ulcers with osteomyelitis compared with a medical treatment alone.