French recommendations for the management of patients with spinal cord injury or at risk of spinal cord injury.

OBJECTIVES: To update the French guidelines on the management of trauma patients with spinal cord injury or suspected spinal cord injury. DESIGN: A consensus committee of 27 experts was formed. A formal conflict-of-interest (COI) policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. METHODS: The committee studied twelve questions: (1) What are the indications and arrangements for spinal immobilisation? (2) What are the arrangements for pre-hospital orotracheal intubation? (3) What are the objectives of haemodynamic resuscitation during the lesion assessment, and during the first few days in hospital? (4) What is the best way to manage these patients to improve their long-term prognosis? (5) What is the place of corticosteroid therapy in the initial phase? (6) What are the indications for magnetic resonance imaging in the lesion assessment phase? (7) What is the optimal time for surgical management? (8) What are the best arrangements for orotracheal intubation in the hospital environment? (9) What are the specific conditions for weaning these patients from mechanical ventilation for? (10) What are the procedures for analgesic treatment of these patients? (11) What are the specific arrangements for installing and mobilising these patients? (12) What is the place of early intermittent bladder sampling in these patients? Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® Methodology. RESULTS: The experts' work synthesis and the application of the GRADE method resulted in 19 recommendations. Among the recommendations formalised, 2 have a high level of evidence (GRADE 1+/-) and 12 have a low level of evidence (GRADE 2+/-). For 5 recommendations, the GRADE method could not be applied, resulting in expert advice. After two rounds of scoring and one amendment, strong agreement was reached on all the recommendations. CONCLUSIONS: There was significant agreement among experts on strong recommendations to improve practices for the management of patients with spinal cord injury.

Prehospital parameters can help to predict coagulopathy and massive transfusion in trauma patients.

BACKGROUND: This study aimed to evaluate the accuracy of prehospital parameters, including vital signs and resuscitation (fluids, vasopressor), to predict trauma-induced coagulopathy (TIC, fibrinogen <1·5 g/l or PTratio > 1·5 or platelet count <100 × 109 /l), and a massive transfusion (MT, ≥10 RBC units within the first 24 h). METHODS: From a trauma registry (2011-2015), in which patients are prospectively included, we retrospectively retrieved the heart rate (HR), systolic blood pressure (SBP), volume of prehospital fluids and administration of noradrenaline. We calculated the shock index (SI: HR/SBP), the MGAP prehospital triage score and the Injury Severity Score (ISS). We also identified patients who had positive criteria from the Resuscitation Outcome Consortium (ROC, SBP < 70 mmHg or SBP 70-90 and HR > 107 pulse/min). For these parameters, we drew a ROC curve and defined a cut-off value to predict TIC or MT. The strength of association between prehospital parameters and TIC as well as MT was assessed using logistic regression, and cut-off values were determined using ROC curves. RESULTS: Among the 485 patients included in the study, TIC was observed in 112 patients (23%) and MT in 22 patients (5%). For the prediction of TIC, ISS had good accuracy (AUC: 0·844, 95% confidence interval, CI: 0·799-0·879), as did the volume of fluids (>1000 ml) given during prehospital care (AUC: 0·801, 95% CI: 0·752-0·842). For the prediction of MT, ISS had excellent accuracy (AUC: 0·932, 95% CI: 0·866-0·966), whereas good accuracy was found for SI (> 0·9; AUC: 0·859, 95% CI: 0·705-0·936), vasopressor administration (AUC: 0·828, 95% CI: 0·736-0·890) and fluids (>1000 ml; AUC: 0·811, 95% CI: 0·737-0·867). Vasopressor administration, ISS and SI were independent predictors of TIC and MT, whereas fluid volume and ROC criteria were independent predictor of TIC but not MT. No independent relationship was found between MGAP and TIC or MT. CONCLUSIONS: Prehospital parameters including the SI and resuscitation may help to better identify the severity of bleeding in trauma patients and the need for blood product administration at admission.

Mutant p53 gains new function in promoting inflammatory signals by repression of the secreted interleukin-1 receptor antagonist.

The TP53 tumor-suppressor gene is frequently mutated in human cancer. Missense mutations can add novel functions (gain-of-function, GOF) that promote tumor malignancy. Here we report that mutant (mut) p53 promotes tumor malignancy by suppressing the expression of a natural occurring anti-inflammatory cytokine, the secreted interleukin-1 receptor antagonist (sIL-1Ra, IL1RN). We show that mutp53 but not wild-type (wt) p53 suppresses the sIL-1Ra production in conditioned media of cancer cells. Moreover, mutp53, but not wtp53, binds physically the sIL-1Ra promoter and the protein-protein interaction with the transcriptional co-repressor MAFF (v-MAF musculoaponeurotic fibrosarcoma oncogene family, protein F) is required for mutp53-induced sIL-1Ra suppression. Remarkably, when exposed to IL-1 beta (IL-1ß) inflammatory stimuli, mutp53 sustains a ready-to-be-activated in vitro and in vivo cancer cells' response through the sIL-1Ra repression. Taken together, these results identify sIL-1Ra as a novel mutp53 target gene, whose suppression might be required to generate a chronic pro-inflammatory tumor microenvironment through which mutp53 promotes tumor malignancy.

Update on prehospital emergency care of severe trauma patients.

The prognosis of severe trauma patients is determined by the ability of a healthcare system to provide high intensity therapeutic treatment on the field and to transport patients as quickly as possible to the structure best suited to their condition. Direct admission to a specialized center ("trauma center") reduces the mortality of the most severe trauma at 30 days and one year. Triage in a non-specialized hospital is a major risk of loss of chance and should be avoided whenever possible. Medical dispatching plays a major role in determining patient care. The establishment of a hospital care network is an important issue that is not formalized enough in France. The initial triage of severe trauma patients must be improved to avoid taking patients to hospitals that are not equipped to take care of them. For this purpose, the MGAP score can predict severity and help decide where to transport the patient. However, it does not help predict the need for urgent resuscitation procedures. Hemodynamic management is central to the care of hemorrhagic shock and severe head trauma. Transport helicopter with a physician on board has an important role to allow direct admission to a specialized center in geographical areas that are difficult to access.

Idiopathic environmental intolerances (IEI): from molecular epidemiology to molecular medicine.

Inherited or acquired impairment of xenobiotics metabolism is a postulated mechanism underlying environment-associated pathologies such as multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, dental amalgam disease, and others, also collectively named idiopathic environmental intolerances (IEI). In view of the poor current knowledge of their etiology and pathogenesis, and the absence of recognised genetic and metabolic markers of the diseases. They are often considered "medically unexplained syndromes",. These disabling conditions share the features of polysymptomatic multi-organ syndromes, considered by part of the medical community to be aberrant responses triggered by exposure to low-dose organic and inorganic chemicals and metals, in concentrations far below average reference levels admitted for environmental toxicants. A genetic predisposition to altered biotransformation of environmental chemicals, drugs, and metals, and of endogenous low-molecular weight metabolites, caused by polymorphisms of genes coding for xenobiotic metabolizing enzymes, their receptors and transcription factors appears to be involved in the susceptibility to these environment-associated pathologies, along with epigenetic factors. Free radical/antioxidant homeostasis may also be heavily implicated, indirectly by affecting the regulation of xenobiotic metabolizing enzymes, and directly by causing increased levels of oxidative products, implicated in the chronic damage of cells and tissues, which is in part correlated with clinical symptoms. More systematic studies of molecular epidemiology, toxico- and pharmaco-genomics, elucidating the mechanisms of regulation, expression, induction, and activity of antioxidant/detoxifying enzymes, and the possible role of inflammatory mediators, promise a better understanding of this pathologically increased sensitivity to low-level chemical stimuli, and a solid basis for effective individualized antioxidant- and/or chelator-based treatments.

The chemical defensive system in the pathobiology of idiopathic environment-associated diseases.

Chemical defensive system consisting of bio-sensoring, transmitting, and responsive elements has been evolved to protect multi-cellular organisms against environmental chemical insults (xenobiotics) and to maintain homeostasis of endogenous low molecular weight metabolites (endobiotics). Both genetic and epigenetic defects of the system in association with carcinogenesis and individual sensitivity to anti-tumor therapies have been intensely studied. Recently, several non-tumor human pathologies with evident environmental components such as rather rare functional syndromes (multiple chemical sensitivity, chronic fatigue, Persian Gulf, and fibromyalgia now collectively labeled as idiopathic environmental intolerances) and common diseases (vitiligo and systemic lupus erythematosus) have become subjects of the research on the impaired metabolism and detoxification of xenobiotics and endogenous toxins. Here, we collected and critically reviewed epidemiological, genetic, and biochemical data on the involvement and possible role of cytochrome P450 super family enzymes, glutathione-S-transferase isozymes, catechol-O-methyl-transferase, UDP-glucuronosyl transferases, and proteins detoxifying inorganic and organic peroxides (catalase, glutathione peroxidase, and peroxiredoxin) in the above pathologies. Genetic predisposition assessed mainly by single nucleotide polymorphism and gene expression analyses revealed correlations between defects in genes encoding xenobiotic-metabolizing and/or detoxifying enzymes and risk/severity of these syndromes/diseases. Proteome analysis identified abnormal expression of the enzymes. Their functions were affected epigenetically leading to metabolic impairment and, as a consequence, to the negative health outcomes shared by some of these pathologies. Data obtained so far suggest that distinct components of the chemical defensive system could be suitable molecular targets for future pathogenic therapies.

[Pneumomediastinum and bilateral tension pneumothorax as a complication of oxygen therapy using a nasal cannula]. / Pneumomédiastin et pneumothorax bilatéral compressif compliquant une oxygénothérapie délivrée par sonde nasale.

We report the case of a patient who developed a subcutaneous and submucosal emphysema in association with a pneumomediastinum, a bilateral pneumothorax and a pneumoperitoneum. This complication was secondary to oxygen supply via a nasal cannula, which allowed a wrong submucosal pathway previously, created by the traumatic placement of a nasogastric tube. The evolution was uneventful. We comment the pathophysiological mechanism of such a complication and propose simple actions to prevent the reproduction.

Long-acting versus short-acting cephalosporins for preoperative prophylaxis in breast surgery: A randomized double-blind trial involving 1,766 patients.

Postoperative infectious complications after breast surgery may result in significant morbidity, psychological trauma, and additional costs. We assessed the efficacy of preoperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1,766 patients undergoing breast surgery. From January 1, 1996 to August 31, 1997, all eligible patients were assigned randomly to receive a single dose of ceftriaxone (2 g) or ceftazidime (2 g) given intravenously at the induction of anesthesia, with no further doses. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. The patients who received ceftriaxone prophylaxis had 54. 4% fewer overall infections than those who received ceftazidime prophylaxis. Wound infection occurred in 0.45% of the ceftriaxone recipients (2 of 883) and 0.91% of the ceftazidime recipients (8 of 883). This prospective randomized double-blind study showed that the long-acting regimen containing ceftriaxone is more cost-effective than the short-acting ceftazidime in preventing postoperative infections in patients subjected to breast surgery.