Early lung ultrasonography predicts the occurrence of acute respiratory distress syndrome in blunt trauma patients

PURPOSE: Extent of lung contusion on initial computed tomography (CT) scan predicts the occurrence of acute respiratory distress syndrome (ARDS) in blunt chest trauma patients. We hypothesized that lung ultrasonography (LUS) on admission could also predict subsequent ARDS. METHODS: Forty-five blunt trauma patients were prospectively studied. Clinical examination, chest radiography, and LUS were performed on arrival at the emergency room. Lung contusion extent was quantified using a LUS score and compared to CT scan measurements. The ability of the LUS score to predict ARDS was tested using the area under the receiver operating characteristic curve (AUC-ROC). The diagnostic accuracy of LUS was compared to that of combined clinical examination and chest radiography for pneumothorax, lung contusion, and hemothorax, with thoracic CT scan as reference. RESULTS: Lung contusion extent assessed by LUS on admission was predictive of the occurrence of ARDS within 72 h (AUC-ROC = 0.78 [95 % CI 0.64-0.92]). The extent of lung contusion on LUS correlated well with CT scan measurements (Spearman\u27s coefficient = 0.82). A LUS score of 6 out of 16 was the best threshold to predict ARDS, with a 58 % [95 % CI 36-77] sensitivity and a 96 % [95 % CI 76-100] specificity. The diagnostic accuracy of LUS was higher than that of combined clinical examination and chest radiography: (AUC-ROC) 0.81 [95 % CI 0.50-1.00] vs. 0.74 [0.48-1.00] (p = 0.24) for pneumothorax, 0.88 [0.76-1.00] vs. 0.69 [0.47-0.92] (p < 0.05) for lung contusion, and 0.84 [0.59-1.00] vs. 0.73 [0.51-0.94] (p < 0.05) for hemothorax. CONCLUSIONS: LUS on admission identifies patients at risk of developing ARDS after blunt trauma. In addition, LUS allows rapid and accurate diagnosis of common traumatic thoracic injuries

Benefit of the Vittel criteria to determine the need for whole body scanning in a severe trauma patient.

OBJECTIVE: To evaluate the use of the Vittel criteria in addition to a clinical examination to determine the need for a whole body scan (WBS) in a severe trauma patient. MATERIALS AND METHODS: Between December 2008 and November 2009, 339 severe trauma patients with at least one Vittel criterion were prospectively evaluated with a WBS. The following data were collected: the Vittel criteria present, circumstances of the accident, traumatic injury on the WBS, and irradiation. The original intent to prescribe a computed tomography (CT) scan (whole body or a targeted region), based solely on clinical signs, was specified. RESULTS: Injuries were diagnosed in 55.75% of the WBS (n=189). The most common Vittel criteria were "global assessment" (n=266), "thrown, run over" (n=116), and "ejected from vehicle" (n=94). The multivariate analysis used the following as independent criteria for predicting severe traumatic injury on the WBS: Glasgow score less than 13, penetrating trauma, and colloid resuscitation greater than 11. Based solely on clinical factors, 164 patients would not have had any scan or (only) a targeted scan. In that case, 15% of the severe injuries would have been missed. CONCLUSION: Using the Vittel criteria to determine the need for a WBS in a severe trauma patient makes it possible to find serious injuries not suspected on the clinical examination, but at the cost of an increased number of normal scans

A Co-operative Regulation of Neuronal Excitability by UNC-7 Innexin and NCA/NALCN Leak Channel

Gap junctions mediate the electrical coupling and intercellular communication between neighboring cells. Some gap junction proteins, namely connexins and pannexins in vertebrates, and innexins in invertebrates, may also function as hemichannels. A conserved NCA/Dmα1U/NALCN family cation leak channel regulates the excitability and activity of vertebrate and invertebrate neurons. In the present study, we describe a genetic and functional interaction between the innexin UNC-7 and the cation leak channel NCA in Caenorhabditis elegans neurons. While the loss of the neuronal NCA channel function leads to a reduced evoked postsynaptic current at neuromuscular junctions, a simultaneous loss of the UNC-7 function restores the evoked response. The expression of UNC-7 in neurons reverts the effect of the unc-7 mutation; moreover, the expression of UNC-7 mutant proteins that are predicted to be unable to form gap junctions also reverts this effect, suggesting that UNC-7 innexin regulates neuronal activity, in part, through gap junction-independent functions. We propose that, in addition to gap junction-mediated functions, UNC-7 innexin may also form hemichannels to regulate C. elegans' neuronal activity cooperatively with the NCA family leak channels

TRα Mutations in Human

Resistance to thyroid hormone alpha is an emerging syndrome, with up to now a limited number of published cases. Some features are common to most of the patients, but there is still some work to provide a comprehensive description of the full spectrum of the syndrome. A survey of the strategy to screen for and characterize the mutations in TR α gene is given

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Current and Calcium Responses to Local Activation of Axonal NMDA Receptors in Developing Cerebellar Molecular Layer Interneurons

In developing cerebellar molecular layer interneurons (MLIs), NMDA increases spontaneous GABA release. This effect had been attributed to either direct activation of presynaptic NMDA receptors (preNMDARs) or an indirect pathway involving activation of somato-dendritic NMDARs followed by passive spread of somatic depolarization along the axon and activation of axonal voltage dependent Ca2+ channels (VDCCs). Using Ca2+ imaging and electrophysiology, we searched for preNMDARs by uncaging NMDAR agonists either broadly throughout the whole field or locally at specific axonal locations. Releasing either NMDA or glutamate in the presence of NBQX using short laser pulses elicited current transients that were highly sensitive to the location of the spot and restricted to a small number of varicosities. The signal was abolished in the presence of high Mg2+ or by the addition of APV. Similar paradigms yielded restricted Ca2+ transients in interneurons loaded with a Ca2+ indicator. We found that the synaptic effects of NMDA were not inhibited by blocking VDCCs but were impaired in the presence of the ryanodine receptor antagonist dantrolene. Furthermore, in voltage clamped cells, bath applied NMDA triggers Ca2+ elevations and induces neurotransmitter release in the axonal compartment. Our results suggest the existence of preNMDARs in developing MLIs and propose their involvement in the NMDA-evoked increase in GABA release by triggering a Ca2+-induced Ca2+ release process mediated by presynaptic Ca2+ stores. Such a mechanism is likely to exert a crucial role in various forms of Ca2+-mediated synaptic plasticity

Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents

<p>Abstract</p> <p>Background</p> <p>Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents.</p> <p>Methods</p> <p>An analytical, cross-sectional and population-based study was performed in forty-four public primary schools in Campeche City, Mexico. A total of 466 obese children and adolescents between 11-13 years of age were recruited. Fasting glucose and insulin concentrations, high density lipoprotein cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressures were measured; insulin resistance and metabolic syndrome were also evaluated.</p> <p>Results</p> <p>Out of the total population studied, 69% presented low values of high density lipoprotein cholesterol, 49% suffered from abdominal obesity, 29% had hypertriglyceridemia, 8% presented high systolic and 13% high diastolic blood pressure, 4% showed impaired fasting glucose, 51% presented insulin resistance and 20% metabolic syndrome. In spite of being obese, 13% of the investigated population did not present any metabolic disorder. For each one of the components of the metabolic syndrome, when insulin resistance increased so did odds ratios as cardiometabolic risk factors.</p> <p>Conclusions</p> <p>Regardless of age and gender an increased degree of insulin resistance is associated with a higher prevalence of disorders in each of the components of the metabolic syndrome and with a heightened risk of suffering metabolic syndrome among obese children and adolescents.</p