[Comparison of the prognostic value of different clinical, angiographic and scintigraphic scores in stable coronary patients after acute coronary syndrome]. / Étude et comparaison de la valeur pronostique de différents scores clinique, coronarographique et scintigraphique chez le patient coronarien stable après un syndrome coronarien aigu.

INTRODUCTION: To date, there is no consensus regarding the follow-up of asymptomatic coronary patients with an intermediate risk of events. Indeed, most of cardiovascular events (CVE) occur in asymptomatic patients, hence the clinician's interest in establishing risk stratification scores. In asymptomatic patient, the risk assessment after acute coronary syndrome (ACS) can currently be based on 3 types of score: clinical with, for example, the REACH score; angiographic with the residual SYNTAX score; imaging with different scintigraphic scores. These scores differ widely in terms of evaluation criteria and period of analysis. The aim of our study was therefore, in stable and asymptomatic coronary patients after ACS, to compare these different predictive scores; to establish that the combination of these scores makes it possible to optimize the risk assessment during the follow-up. METHODS: Our retrospective study included 236 revascularized patients after ACS. Three different risk scores were collected: 1) the residual SYNTAX score, calculated at the time of revascularization; 2) the scintigraphic risk score described by Sharir et al., performed 3 to 12 months after the event and taking into account the extent of ischemia (SDS) and the poststress left ventricular ejection fraction (LVEF). Patients with LVEF <50% and/or moderate to severe ischemic disease (SDS≥2) were considered with an intermediate or high scintigraphic risk; 3) the REACH clinical score calculated on the day of the scintigraphic examination. After the myocardial scintigraphic exam, patients had a 1-year follow-up and CVE were recorded. Continuous data were analyzed either by Student's t-test or non-parametric Mann-Whitney test. The dichotomous data were compared either by the χ2 test or by Fisher's exact test. RESULTS: Forty-eight patients (20.1%) had a CVE during the 1-year follow-up. Thirty patients (13.8%) had a high residual SYNTAX score (≥8) without any correlation observed between the residual SYNTAX score and CVE (P=0.359). 148 patients (57.7%) had a high REACH clinical score (≥11) with no significant correlation observed with CVE (P=0.079). Lastly, 34 patients (14.4%) had an intermediate or high scintigraphic score, this imaging score being strongly correlated with a greater number of CVE (P<0.001). Multivariate analysis revealed 3 independent factors associated with CVE: a scintigraphic score> 2 (OR [(95% CI): 5.530 [2.426-12.605] P<0.001); Peripheral Arterial Obstructive Disease (PAOD) (OR [95% CI]: 8.531 [2.540-28.660] P<0.001); diabetes (OR [95% CI]: 2.86 [1.262-6.517] P=0,012). CONCLUSION: The combination of the scintigraphic score with two clinical factors, such as PAOD and diabetes, provides optimal prognostic value in the evaluation of asymptomatic and stable patients after ACS. Our study therefore highlights the importance of optimizing evaluation strategies in the follow-up of these patients who remain at risk of post-revascularization CVE.

Microbiology of French military casualties repatriated from overseas for an open traumatic injury.

BACKGROUND: This study aimed to describe the microbiological epidemiology of repatriated French soldiers with an open traumatic injury, and to measure the proportion of multidrug-resistant bacteria (MDRB). METHODS: Retrospective study including all French soldiers repatriated in 2011 and 2012 in Parisian military hospitals for open traumatic injury. Results of clinical samples and MDRB screening were collected. The antibiotic susceptibility was assessed using the agar disk diffusion method. Characterization of resistance mechanisms was performed using PCR. Genotyping of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) isolates was performed using rep-PCR. RESULTS: A total of 139 patients were included; 70% of them were repatriated from Afghanistan. At admission, 24/88 were positive for MDRB (28%), mainly ESBL-E but no carbapenemase-producing Enterobacteriaceae and vancomycin-resistant Enterococcus faecium were identified. Forty-five patients had lesion sample collection, and 28/45 had a positive culture. The most frequently isolated pathogens were Enterobacter cloacae, Pseudomonas aeruginosa, and Escherichia coli. For eight patients, a MDRB was isolated from the wound, mainly ESBL-E (7/8) but also one methicillin-resistant Staphylococcus aureus and one imipenem-resistant Acinetobacter baumannii. Among ESBL-E, the PCR evidenced the high prevalence of CTX-M15 enzymes. Rep-PCR performed on the 23 ESBL-producing E. coli isolates highlighted numerous profiles. CONCLUSIONS: Controlling the spread of ESBL-E is currently challenging for French Armed Forces. Despite any evidence of an epidemic clone, a high-level compliance with hygiene precautions is required throughout the chain of care to avoid cross contamination.

[Skin engineering for severe burns]. / L'ingénierie cutanée pour le traitement des brûlures graves.

Severe burned patients need definitive and efficient wound coverage. Outcome of massive burns has been improved by using cultured epithelial autografts (CEA). Despite fragility, percentages of success take, cost of treatment and long-term tendency to contracture, this surgical technique has been developed in few burn centres. First improvements were to combine CEA and dermis-like substitute. Cultured skin substitutes provide earlier skin closure and satisfying functional result. These methods have been used successfully in massive burns. Second improvement was to allow skin regeneration by using epidermal stem cells. Stem cells have capacity to differentiate into keratinocytes, to promote wound repair and to regenerate skin appendages. Human mesenchymal stem cells contribute to wound healing and were evaluated in cutaneous radiation syndrome. Skin regeneration and tissue engineering methods remain a complex challenge and offer the possibility of new treatment for injured and burned patients.

[Not Available]. / Transport aérien longue distance des brûlés graves: revue de la littérature et application pratique.

The best treatment for victims of severe burns is provided in highly specialised burn centres. Due to the paucity of these centres, long distance aeromedical evacuation is often required. However, published data regarding such transfers are scarce. In this review, in order to help optimize patient management when air transportation is decided or even only considered, we propose simple principles derived from this limited literature and backed by the practical experience of the French military. We first describe how specific flight conditions may impact transportation of severe burn patients aboard aircraft. We then focus on the planning and organisation of these transfers discussing the risks associated with air transportation of such patients and their implications on indication, timing and modality of transport. Finally, provide an end-to-end view of the process from pre-flight equipment preparation, pre-boarding patient assessment and conditioning, to in-flight care.

Epidemiology of filamentous fungal infections in burned patients: A French retrospective study.

INTRODUCTION: Filamentous fungal infections (FFI) seem to become more frequent in burn patients, in whom they are usually accepted to cause severe. However published data regarding their incidence and consequences in that context remain scarce. The aim of this study was to evaluate the incidence of mould infections in our burn centre, and to review characteristics and outcomes of patients with such infections. METHODS: This retrospective single-centre study reviews all patients admitted in our centre with acute burns (2000-2011) and positive culture for moulds. Wound infections were defined as follows: fungal wound colonisations (FWC) for positive mycological cultures without signs of wound infection; fungal wound infections (FWI) for positive mycological cultures with local signs of wound infection; disseminated infection (DI) for FWI with a positive blood culture or a positive galactomannan (for aspergillosis) or severe sepsis or secondary organ localisation(s). RESULTS: Among 1849 patients, 31 patients presented a FFI. For 29 patients (93%), positive fungal samples were cutaneous: 20 Aspergillosis ASP (5 FWC, 8 FWI and 7 DI), 9 mucormycosis MMC (3 FWC and 6 FWI) and 3 fusariosis FUS (3 FWI). Two patients presented a catheter colonisation or a pulmonary colonisation (Aspergillus fumigatus). Incidence of FFI was 1.7%. Total body surface area burned, full-thickness burn surface area, Unit Burn Standard, Tobiasen score and SAPS2 (respectively 55% [40-73], 45% [30-63], 180 [129-259], 11 [8-12] and 50 [40-62]) were markedly higher than in burned patients without FFI hospitalised during the same time period. 30% of the patients with burn wound ASP (6/22) died. Mean length of stay was 111±67 days. CONCLUSION: FFI are essentially cutaneous, infrequent and occur in the most severe burned patients. ASP seems to be more serious than other FFI.

Successful management of a severe combat penetrating brain injury.

We report the case of successful management of a transcranial penetrating high-energy transfer injury in a 20-year-old soldier. The bullet traversed both cerebral hemispheres and lacerated the superior sagittal sinus rendering him unconscious. We detail the care received at all stages following injury from 'Buddy Aid' on the battlefield, resuscitation by a forward medical team through to prompt neurosurgery within 2 h of injury. Subsequent aeromedical evacuation and continuing aggressive critical care has allowed the patient to survive with acceptable neurological impairment after what is generally considered an unsurvivable injury.

[Management of penetrating abdominal trauma: what we need to know?]. / Prise en charge des traumatismes pénétrants de l'abdomen : des spécificités à connaître.

Penetrating traumas are rare in France and mainly due to stabbing. Knives are less lethal than firearms. The initial clinical assessment is the cornerstone of hospital care. It remains a priority and can quickly lead to a surgical treatment first. Urgent surgical indications are hemorrhagic shock, evisceration and peritonitis. Dying patients should be immediately taken to the operating room for rescue laparotomy or thoracotomy. Ultrasonography and chest radiography are performed before damage control surgery for hemodynamic unstable critical patients. Stable patients are scanned by CT and in some cases may benefit from non-operative strategy. Mortality remains high, initially due to bleeding complications and secondarily to infectious complications. Early and appropriate surgery can reduce morbidity and mortality. Non-operative strategy is only possible in selected patients in trained trauma centers and with intensive supervision by experienced staff.

Sigmoid diverticulitis perforation in burns: case reports and review of the literature.

Burned patients are prone to develop severe intestinal complications because of decreased splanchnic circulation. We report three cases of sigmoid perforation in burn patients appearing late during hospitalization. The common aetiological factor was a state of septic shock treated with infusion of vasopressors. Two patients also received corticosteroids as treatment for acute respiratory distress syndrome. These cases underline the necessity to maintain adequate organ perfusion and to prevent intestinal ischaemia in severe burns.

Cell therapy of burns.

Severe burns remain a life-threatening local and general inflammatory condition often with serious sequelae, despite remarkable progress in their treatment over the past three decades. Cultured epidermal autografts, the first and still most up-to-date cell therapy for burns, plays a key role in that progress, but drawbacks to this need to be reduced by using cultured dermal-epidermal substitutes. This review focuses on what could be, in our view, the next major breakthrough in cell therapy of burns - use of mesenchymal stromal cells (MSCs). After summarizing current knowledge, including our own clinical experience with MSCs in the pioneering field of cell therapy of radiation-induced burns, we discuss the strong rationale supporting potential interest in MSCs in treatment of thermal burns, including limited but promising pre-clinical and clinical data in wound healing and acute inflammatory conditions other than burns. Practical options for future therapeutic applications of MSCs for burns treatment, are finally considered.

[Present and future of cell therapy in burns]. / Présent et futur de la thérapie cellulaire des brûlures.

Severe burned patients need definitive and efficient wound coverage. Outcome of massive burns has been improved by using cultured epithelial autografts (CEA). Despite fragility, percentages of success take, cost of treatment and long-term tendency to contracture, this surgical technique has been developed in few burn centres. First improvements were to combine CEA and dermis-like substitute. Cultured skin substitutes provide earlier skin closure and satisfying functional result. These methods have been used successfully in massive burns. Second improvement was to allow skin regeneration by using epidermal stem cells. Stem cells have capacity to differentiate into keratinocytes, to promote wound repair and to regenerate skin appendages. Human mesenchymal stem cells contribute to wound healing and were evaluated in cutaneous radiation syndrome. Skin regeneration and tissue engineering methods remain a complex challenge and offer the possibility of new treatment for injured and burned patients.

[Burns care following a nuclear incident]. / Soins Aux Brules Apres Un Accident Nucleaire.

Radiation injuries are usually caused by radioactive isotopes in industry. Detonations of nuclear reactors, the use of military nuclear weapons, and terrorist attacks represent a risk of mass burn casualties. Ionizing radiation creates thermal burns, acute radiation syndrome with pancytopenia, and a delayed cutaneous syndrome. After a latency period, skin symptoms appear and the depth of tissue damages increase with dose exposure. The usual burn resuscitation protocols have to be applied. Care of these victims also requires assessment of the level of radiation, plus decontamination by an experienced team. In nuclear disasters, the priority is to optimize the available resources and reserve treatment to patients with the highest probability of survival. After localized nuclear injury, assessment of burn depth and surgical techniques of skin coverage are the main difficulties in a burn centre. Training in medical facilities and burn centres is necessary in the preparation for management of the different types of burn injuries.

[Promotility drugs use in critical care: indications and limits?]. / Utilisation des médicaments prokinétiques en réanimation: indications et limites?

Enteral feeding is often limited by gastric and intestinal motility disturbances in critically ill patients, particularly in patients with shock. So, promotility agents are frequently used to improve tolerance to enteral nutrition. This review summaries the pathophysiology, presents the available pharmacological strategies, the clinical data, the counter-indications and the principal limits. The clinical data are poor. No study demonstrates a positive effect on clinical outcomes. Metoclopramide and erythromycin seems to be the more effective. Considering the risk of antibiotic resistance, the first line use of erythromycin should be avoided in favor of metoclopramide.

[Incidence and microbiology of infectious complications with the use of artificial skin Integra in burns]. / Incidence et microbiologie des complications infectieuses lors d'utilisation de la peau artificielle Integra chez le brûlé.

Integra dermal substitute is used as biomaterial after thermal injury. This artificial skin allows temporary coverage after burns excision, transformation of matrix in neo dermis and definitive engraftment. Infections are the most common complication of this technique. The objectives were to evaluate incidence of sepsis, to analyse microbiology and risk factors of developing Integra infections. Patients with acute burns and indications of Integra during five years were retrospectively enrolled. Demographic data, surgical procedures and microbiologic biopsies were collected. Fifty patients (40 + or - 15 years) were studied and 71 surgical procedures using Integra were performed. Burns were extended 45 + or - 21% total body surface area. Placement of Integra was made 15 + or - 11 days after burns and autografts 31 + or - 9 days after placement of Integra. Twenty-one patients had infected Integra (42% of population). A total of 23 Integra infected sites were observed (15 local and eight invasive). Diagnosis of infection was made after 13 + or - 5 days using quantitative cultures. Other sites of infection were respiratory tract (46 pneumonias) and others burned wounds (17 infections outside of Integra. Any risk factor was identified between burns who developed Integra infections and the others. Incidence of infected Integra was higher than in previous studies. Delayed application of Integra after burns could explain higher incidence of infection. Pseudomonas aeruginosa and Staphylococcus aureus were more frequently isolated than other pathogens. Standardized technique for wounds coverage with Integra is necessary to reduce incidence of infections and improve functional results in burns patients.

[Mamba envenomation in mainland France: management of exotic envenomations needs rethinking]. / Envenimation cobraïque en France métropolitaine : repenser la prise en charge des envenimations exotiques.

We report a case of accidental green mamba (Dendroaspis viridis) envenomation in the suburbs of Paris. Although moderate, neurotoxic symptoms were clearly present. Immunotherapy with polyvalent serum FAV-Afrique was decided, but logistical problems prevented reasonably quick serum delivery to the hospital. Despite a spontaneously favourable outcome probably due to minimal envenomation, this case exemplifies a near-miss of the care system. Given the increasing incidence of potentially life-threatening exotic envenomations, management of similar cases should be improved. Besides breeders and health care professionals' information, we suggest that victims of an exotic envenomation be referred to a facility with experienced staff and ready access to a limited bank of carefully chosen antivenins.

[Paraspecific antivenins and exotic bites of snakes: about two case reports]. / Antivenins paraspécifiques et morsures de serpents exotiques : à propos de deux cas cliniques.

Envenomation from bite of exotic snakes is rare in France and represent a serious therapeutic problem: only an adapted antivenom is effective and obtaining such a treatment is a real difficulty. The authors report two clinical cases of envenomation with defibrination after bite by pit vipers from South America. The two patients were treated with nonspecific antivenom therapy with divergent results. The use of the paraspecific effects of antivenom can allow an effective treatment in the absence of specific antivenom, but requires to be known better.

[Treatment of a septic shock due to multiresistant Acinetobacter baumannii with tigecycline in combination]. / Traitement d'un choc septique à Acinetobacter baumannii multirésistant par tigécycline en association.

We report a case of pulmonary and bloodstream infection due to multiresistant Acinetobacter baumannii six days after a severe trauma. Clinical condition transiently improved following antimicrobial treatment with ticarcillin-clavulanate and rifampicin. However, a septic shock developed on the fourth day due to the emergence of a strain only sensible to cotrimoxazole, colistin and tigecycline. Cure was achieved after a two week treatment with piperacillin-tazobactam, cotrimoxazole and tigecycline. This case shows that combined antimicrobial therapy including tigecycline can be relevant in some severe pulmonary infections due to multiresistant A. baumannii.

[Severe complications after a translaryngeal tracheotomy]. / Complication sévère après une trachéotomie translaryngée.

We report the case of a 71-year-old man receiving anticoagulant treatment because of a mechanical aortic valve. Because of an unsuccessful weaning after abdominal surgery, a translaryngeal tracheostomy was realised without incident. The patient died few days later after a hypoxic cardiac arrest due to a severe haemorrhage after the first recannulation. This case illustrates a severe complication because of the recannulation after a translaryngeal tracheostomy and how cautions one should be before realizing a percutaneous tracheostomy in a patient under anticoagulant treatment.

NF-kappa B mediates up-regulation of CFTR gene expression in Calu-3 cells by interleukin-1beta.

Inflammation of the airways is a major feature of the inherited disease cystic fibrosis. Previous studies have shown that the pro-inflammatory cytokines tumor necrosis factor alpha and interferon gamma reduce the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (CFTR) in HT-29 and T84 cells by acting post-transcriptionally. We have investigated the effect of the pro-inflammatory peptide interleukin 1beta (IL-1beta) on the expression of the CFTR in Calu-3 cells. IL-1beta increased the production of CFTR mRNA in a dose- and time-dependent manner. Its action was inhibited by inhibitors of the NF-kappaB pathway, including N-acetyl-l-cysteine, pyrrolidine dithiocarbamate, and a synthetic cell-permeable peptide containing the NF-kappaB nuclear localization signal sequence. Gel shift analysis showed that IL-1beta activated NF-kappaB in Calu-3 cells, and transfection experiments using p50 and RelA expressing vectors showed that exogenous transfected NF-kappaB subunits increased the concentration of CFTR mRNA. Gel shift analysis with antibody supershifting also showed that IL-1beta caused the binding of NF-kappaB to a kappaB-like response element at position -1103 to -1093 in the CFTR 5'-flanking region. Transfection experiments using -2150 to +52 CFTR reporter gene constructs showed that the activity of the CFTR promoter is enhanced by exogenous transfected NF-kappaB and IL-1beta and that this enhancement is due, at least in part, to the -1103 to -1093 kappaB site. We conclude that the intracellular signaling that leads to increased CFTR mRNA in response to IL-1beta in Calu-3 cells includes the binding of NF-kappaB to the -1103 kappaB element and a subsequent increase in CFTR promoter activity.

Modulation of CFTR gene expression in HT-29 cells by extracellular hyperosmolarity.

Hypertonicity has pleiotropic effects on cell function, including activation of transporters and regulation of gene expression. It is important to investigate the action of hypertonicity on cystic fibrosis gene expression because cystic fibrosis transmembrane conductance regulator (CFTR), the cAMP-regulated Cl(-) channel, regulates ion transport across the secretory epithelia, which are often in a hypertonic environment. We found that adding >150 mosmol/l NaCl, urea, or mannitol to the culture medium reduced the amount of CFTR mRNA in colon-derived HT-29 cells in a time-dependent manner. Studies with inhibitors of various kinases [H-89 (protein kinase A inhibitor), bisindolylmaleimide (protein kinase C inhibitor), staurosporine (serine/threonine kinase inhibitor) and herbimycin A (tyrosine kinase inhibitor), SB-203580 and PD-098059 (mitogen-activated protein kinase inhibitors)] showed that CFTR gene expression and its decrease by added NaCl required p38 kinase cascade activity. The CFTR gene activity is regulated at the transcriptional level, since adding NaCl diminished the luciferase activity of HeLa cells transiently transfected with the CFTR promoter. This regulation requires protein synthesis. The complexity of the reactions involved in blocking CFTR gene transcription by NaCl strongly suggests that the decrease in CFTR mRNA is part of a general cell response to hyperosmolar stress.