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Objectives: Although patients suffering from severe traumatic brain injury (sTBI) and severe trauma patients (STP) have been extensively studied separately, there is scarce evidence concerning STP with concomitant sTBI. In particular, there are no guidelines regarding the emergency surgical management of patients presenting a concomitant life-threatening intracranial hematoma (ICH) and a life-threatening non-compressible extra-cranial hemorrhage (NCEH). Materials and Methods: A scoping review was conducted on Medline database from inception to September 2021. Results: The review yielded 138 articles among which 10 were retained in the quantitative analysis for a total of 2086 patients. Seven hundrer and eighty-seven patients presented concomitant sTBI and extra-cranial severe injuries. The mean age was 38.2 years-old and the male to female sex ratio was 2.8/1. Regarding the patients with concomitant cranial and extra-cranial injuries, the mean ISS was 32.1, and the mean AIS per organ were 4.0 for the head, 3.3 for the thorax, 2.9 for the abdomen and 2.7 for extremity. This review highlighted the following concepts: emergency peripheric osteosynthesis can be safely performed in patients with concomitant sTBI (grade C). Invasive intracranial pressure monitoring is mandatory during extra-cranial surgery in patients with sTBI (grade C). The outcome of STP with concomitant sTBI mainly depends on the seriousness of sTBI, independently from the presence of extra-cranial injuries (grade C). After exclusion of early-hospital mortality, the impact of extra-cranial injuries on mortality in patients with concomitant sTBI is uncertain (grade C). There are no recommendations regarding the combined surgical management of patients with concomitant ICH and NCEH (grade D). Conclusion: This review revealed the lack of evidence for the emergency surgical management of patients with concomitant ICH and NCEH. Hence, we introduce the concept of combined cranial and extra-cranial surgery. This damage-control surgical strategy aims to reduce the time spent with intracranial hypertension and to hasten the admission in the intensive care unit. Further studies are required to validate this concept in clinical practice.

Introduction Total elbow arthroplasty (TEA) is one option in distal humerus fracture in elderly osteoporotic patients. Hypothesis The study hypothesis was that, in patients aged 70 years or more, TEA provides functional results and ranges of motion compatible with everyday activity, with a complications rate equal to or lower than with internal fixation, and no loss of autonomy or cognitive impairment. Material and methods In this retrospective study, 21 patients receiving TEA for distal humerus fracture were included. Mean follow-up was 3.2 years, with functional (Quick DASH and MEPS), cognitive (MMSE), autonomy-related (ADL) and radiological assessment (Morrey). Results Mean MEPS was 84 and QuickDASH 32.4. Mean extension deficit was 22°, and mean flexion 125°. There was no loss of autonomy or cognitive impairment. The complications rate was 9.5%. There were no revision surgeries. Discussion TEA proved reliable in comminuted distal humerus fracture in elderly patients. Functional results were comparable to those in the literature, and the complications rate was lower. Long-term implant survival needs confirmation to validate this option as a treatment of choice in these indications in geriatric traumatology. Type of study Retrospective non-comparative, single-center. Level of evidence 4.

Background: The main difficulty with this ALL reconstruction method is the placement of the femoral tunnel as isometrically as possible. The femoral insertion of the ALL is usually located one centimeter posteriorly and proximal to the lateral epicondyle, at the level of the Lemaire vessels. The purpose of our study was to evaluate the placement of the femoral tunnel in ligament reconstruction by combined ACL and ALL reconstruction with a single femoral tunnel using the outside-in technique. Our hypothesis was that a single femoral tunnel by outside-in technique would allow satisfactory placement of the femoral insertion of the ALL.. Methods: We conducted a retrospective bi-centric study of all patients who underwent combined ACL and ALL reconstruction surgery with a common outside-in femoral technique. A postoperative low-dose knee CT scan with multiplane reconstructions was performed after patient consent. After locating the top of the epicondyle on three-dimensional CT scan reconstructions, the distances between the top of the lateral epicondyle and the center of the femoral tunnel in the frontal and sagittal planes were measured. These measurements were taken by a surgeon and a radiologist. Results: 45 patients were included and the average age was 29 years (17-39). 30 patients had a CT scan. Analysis of the placement of the femoral tunnel showed that 10 tunnels were placed posteriorly and proximal to the top of the lateral epicondyle. Conclusion: This study did not confirm our hypothesis. Combined ACL and ALL reconstruction by a single tunnel did not provide access to the isometric point of the femoral insertion of the ALL in a reproducible manner, despite open intra-operative identification of this point. This study highlights the difficulty of locating the femoral isometric point with a standard outside-in femoral guide. Developing a specific femoral guide might be useful.

Introduction Intramedullary (IM) nailing is the gold standard for treating long bone fractures in developed countries because of its minimally-invasive application and good biomechanical properties. In precarious conditions, external fixation or open plate fixation are often performed because surgeons do not have the means to carry out IM nailing. However, these procedures can lead to infection-related complications and mechanical failures. The aim of our study was to describe the outcomes and postoperative complications of IM nailing of closed, long bone fractures in patients operated in a French front-line combat surgical unit (role 2+). Our hypothesis was that IM nailing is a reliable technique with low morbidity for the initial treatment of long bone fractures, even in precarious situations. Material and methods This was a prospective, single-center, descriptive study of patients operated on between April 2016 and November 2017. All the patients with a closed femur or tibia fracture who were treated by IM nailing were eligible, no matter their time to surgery. The minimum follow-up was 6 months. The primary endpoint was the absence of infection-related complications and the secondary endpoint was fracture union. Results Fifty-eight patients were reviewed after an average follow-up of 4.7 months (range, 3–15 months). The mean patient age was 35.2 years (15–85 years) and the majority of patients were men (52 of 58). The fracture was in the femur in 74.1% (n = 43) of cases and in the tibia in 25.9% (n = 15) of cases. The time to surgery averaged 122.3 days (7–720 days) with a median of 60 days. In 74% of cases (n = 43), fracture realignment required an open surgical approach. The postoperative course was considered normal in 96.6% of cases (n = 51). No infections were reported as of the last follow-up visit. Union occurred in an average of 4 months in 70.7% of cases (n = 41). There were three cases of nonunion after 6 months. Discussion Even in precarious situations, IM nailing is an effective, reliable method with a low complication risk and high union rate for the treatment of neglected long bone fractures. This surgical treatment is well suited to the poor sanitary conditions on the African continent. Level of evidence II, low-powered prospective study.

Although cardiac cytosolic cyclic 3′,5′-adenosine monophosphate (cAMP) regulates multiple processes, such as beating, contractility, metabolism and apoptosis, little is known yet on the role of this second messenger within cardiac mitochondria. Using cellular and subcellular approaches, we demonstrate here the local expression of several actors of cAMP signaling within cardiac mitochondria, namely a truncated form of soluble AC (sACt) and the exchange protein directly activated by cAMP 1 (Epac1), and show a protective role for sACt against cell death, apoptosis as well as necrosis in primary cardiomyocytes. Upon stimulation with bicarbonate (HCO3−) and Ca2+, sACt produces cAMP, which in turn stimulates oxygen consumption, increases the mitochondrial membrane potential (ΔΨm) and ATP production. cAMP is rate limiting for matrix Ca2+ entry via Epac1 and the mitochondrial calcium uniporter and, as a consequence, prevents mitochondrial permeability transition (MPT). The mitochondrial cAMP effects involve neither protein kinase A, Epac2 nor the mitochondrial Na+/Ca2+ exchanger. In addition, in mitochondria isolated from failing rat hearts, stimulation of the mitochondrial cAMP pathway by HCO3− rescued the sensitization of mitochondria to Ca2+-induced MPT. Thus, our study identifies a link between mitochondrial cAMP, mitochondrial metabolism and cell death in the heart, which is independent of cytosolic cAMP signaling. Our results might have implications for therapeutic prevention of cell death in cardiac pathologies.

Introduction: The development of damage control orthopedics (DCO) procedures has led to the development of temporary unicortical external fixators (TUEFs) intended to limit deep infectious complications and facilitate early conversion to internal fixation. Methods: A retrospective study was conducted in two French military trauma centers, including on patients being treated for tibial fractures with a TUEF (UNYCO® − Orthofix®) followed by an early conversion to intramedullary nailing. Results: Eleven patients with an average age of 41 were included between September 2015 and June 2017. A total of 12 TUEFs were implanted for one closed fracture and 11 open fractures, including one type I, eight types II, and two Gustilo types IIIB. The indication of DCO was related to hemodynamic instability in three cases, to the severity of soft tissue lesions in eight cases, and to the context of treatment in one case. The conversion to IM nailing was made after an average of 7.6 days. No significant loss of reduction was observed until internal osteosynthesis, which was performed with “fixator in place” in ten cases. The coverage of Gustilo type III injuries was performed by free flap transfers at the same time as IM nailing. All the patients were reviewed with an average follow-up of 16.5 months. Bone union was achieved in all cases. Two IM nailing dynamizations were carried out, but no bone grafting was required. Two cases of pandiaphysitis were observed and treated without functional complications. Discussion: Despite a limited number of patients, this study demonstrates the reliability of the TUEF to maintain the reduction of tibial fractures and facilitate early conversion to IM nailing. Unicortical fixation does not prevent septic complications related to the severity of soft tissue injuries.

The synthesis of new 4,6-disubstituted dihydrodipyridopyrazines starting from corresponding carboxaldehydes via lithiation directed by alpha-amino alkoxides is described. The N,N,N'-trimethylethylenediamine was used as amine component for in situ formation of the alpha-amino alkoxides. After optimization, this reaction allowed easy access to new interesting starting materials for further applications by palladium-catalyzed reactions.

International audience; interventions are crucial as they offer simple and inexpensive public health solutions that will be useful over the long term use. A Task Force on designing trials of nutritional interventions to slow cognitive decline in older adults was held in Toulouse in September 2012. The aim of the Task Force was to bring together leading experts from academia, the food industry and regulatory agencies to determine the best trial designs that would enable us to reach our goal of maintaining or improving cognitive function in apparently healthy aging people. An associated challenge for this Task Force was to determine the type of trials required by the Public Food Agencies for assessing the impact of nutritional compounds in comparison to well established requirements for drug trials. Although the required quality of the study design, rationale and statistical analysis remains the same, the studies designed to show reduction of cognitive decline require a long duration and the objectives of this task force was to determine best design for these trials. Two specific needs were identified to support trials of nutritional interventions: 1- Risk-reduction strategies are needed to tackle the growing burden of cognitive decline that may lead to dementia, 2- Innovative study designs are needed to improve the quality of these studies.

Knowledge of the conformation at the amide N atom of N-3-methoxyphenyl-2-(5-methoxyindole)carboxamide, C 17 H 16 N 2 O 3 , and N-methyl-N-phenyl-2-(5-methoxyindole)carboxamide, C 17 H 16 N 2 O 2 , allows an interpretation of the 1 H NMR behaviour of the two compounds. The structures and conformations of the two molecules are compared.

Crystal structure analysis of the title compound, C 21 H 31 NS, showed that demethylation resulted in a thioalkyl group at the 2 position rather than the loss of the methyl group at the 5 position. The structural and conformational features of the molecule are discussed and compared with the results of molecular-mechanics calculations

Of the two possible keto-enol tautomeric species of the title compound, C 13 H 13 NO, it is the keto one that is found in the crystal; it involves an intermolecular N-H...O=C hydrogen bond between molecules, related by the 1/2+x, 1/2−y, 1/2+z symmetry operation of the P2 1 /n space group, which run in chains along the x axis. IR data of the solid product are assigned and it is deduced from the 1 H and 13 C NMR spectra that this hydrogen bond is also active in solution in DMSO. The relevant structural parameters of the molecule in the crystal are compared with those calculated by molecular mechanics for the isolated structure

The complex base-induced reaction of arynes with enolates of cyclic ketones proved useful for the synthesis of polycyclic aromatic compounds. The goal of applying this reaction to the synthesis of biologically active compounds is currently being pursued

Objective To evaluate the use and costs of medical resources before and after a diagnosis of fibromyalgia syndrome (FMS) in a large primary care population in the UK. Methods We applied an existing data set for medical resource use among patients with a coded diagnosis of FMS. The observed quantities of 157 types of medical resource use before and after the diagnosis of FMS were multiplied by unit costs in order to calculate the cost of care (general practitioner [GP] visits, drugs, referrals, and diagnostics) within the National Health Service, excluding hospital costs. Costs before diagnosis were used in a trend analysis to predict later costs, assuming the diagnosis had never been made, and these predicted costs were compared with the observed costs after diagnosis. Results Following a diagnosis of FMS, a decrease in costs as compared with the predicted trend was observed. In the 4 years after diagnosis, the average difference between the predicted and observed cost was £66.21 per 6 months per patient. This suggests that making the diagnosis leads to savings and a decrease in resource use. The main effect was observed for tests and imaging (£24.02 per 6 months), followed by pharmaceuticals (£22.27), referrals (£15.56), and GP visits (£4.36). Conclusion Failure to diagnose a true case of FMS has its own costs, largely in excess GP visits, investigations, and prescriptions.

The stereoselectivity of reduction of selected ketones by a variety of Complex Reducing Agents (resulting from the Aggregative Activation of NaH and symbolized MCRA's) has been investigated. The stereochemistry of reduction is shown to be dependent on the nature of the metal. Steric hindrance plays an important role and the apparent size of the reagents follows the trend MnCRA's>ZnCRA's, CdCRA's>NiCRA's, CoCRAs. On the other hand NiCRA's and CoCRA's have been found as very strong isomerizing reagents. Insertion of the metal species into the C-O bond with formation of metallacycles appears as one of the possible mechanisms intervening during the reduction of ketones by MCRA's

Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain and fatigue. Its prevalence is estimated to be at 3.4% in women and 0.5% in men. It is a major cause of morbidity. Our objective was to evaluate, using a self-questionnaire sent by mail, the level of knowledge of French physicians, general practitioners, and rheumatologists on fibromyalgia and to analyse their therapeutic approach.The demographic characteristics of a sample of general practitioners and rheumatologists were compared to those of the overall data available. This comparison demonstrated the good representativeness of our sample.Fibromyalgia was considered as a disease by 23% of rheumatologists and 33% of general practitioners. While on average, each rheumatologist followed 30 fibromyalgia patients, each general practitioner followed 6.1 patients (i.e., 2 to 5% of their practice's patient base). Among rheumatologists, 6.4% made no distinction between this disease and depression vs. 13.1% of general practitioners. The diagnosis of fibromyalgia was made based on tenderness that occurs in precise, localized areas of the body (trigger points) by 94% of rheumatologists and 79.1% of general practitioners. Of general practitioners and rheumatologists, 93.7% and 73.7% respectively, have not received any medical school training on fibromyalgia or chronic fatigue syndrome.Given the lack of medical school training and continuing professional education concerning fibromyalgia (rare use of pain rating scales, confusion in the classification of rheumatic diseases), there is an urgent need to initiate an explicit teaching effort on chronic pain, and on fibromyalgia in particular.

Knowledge of the position of the ethylthio group in the title compound, C 23 H 28 N 2 OS, allows generalization of the behaviour of two families of indoles undergoing alkylthiolation reactions. The 'H NMR spectrum of this compound is in agreement with that recently observed for other 1-carboxamide indole derivatives. The structure and conformation of the molecule is discussed and compared with that of the analogous compound N-methyl-N-phenyl-2-(5-methoxyindole)carboxamide.

Maternal uniparental disomy (UPD) for chromosome 14 (upd(14)mat) has been associated with a distinct phenotype. We describe the first case of maternal uniparental isodisomy for chromosome 14 detected prenatally, in a pregnancy with mosaicism for trisomy 14 observed in both a chorionic villus sample (CVS) and in amniocytes. Detailed analysis of polymorphic microsatellites showed that the fetus was essentially isodisomic for one of the mother's chromosomes 14 and that recombination had introduced a mid-long arm region of heterodisomy. The fetus, which died in utero at 18 weeks, showed no apparent pathological features. The case demonstrates for the first time a maternal meiosis II non-disjunction of chromosome 14 leading to a trisomic conception which has been incompletely corrected by 'rescue' in the early embryo.

Methylenecyclobutanols 1, conveniently obtained by 1,2-cycladiene condensation of ketone enolates, were used as starting materials for the easy preparation of polycyclic cyclopentane derivatives. Thus, the transposition and transposition-elimination of triol derivatives 3, 5, and 6 led to the synthesis of a series of polycyclic cyclopentan- or cyclopentenones. The stereochemistries of the transpositions were studied and mechanisms were proposed

Desulfurdimerization of various aromatic dithioketals is efficiently induced by a 2,2′-bipyridine ligated nickel(0) complex under mild conditions.