Cardiovascular parameters on computed tomography are independently associated with in-hospital complications and outcomes in level-1 trauma patients

Background: In-hospital complications after trauma may result in prolonged stays, higher costs, and adverse functional outcomes. Among reported risk factors for complications are pre-existing cardiopulmonary comorbidities. Objective and quick evaluation of cardiovascular risk would be beneficial for risk assessment in trauma patients. Studies in non-trauma patients suggested an independent association between cardiovascular abnormalities visible on routine computed tomography (CT) imaging and outcomes. However, whether this applies to trauma patients is unknown.Purpose: To assess the association between cardiopulmonary abnormalities visible on routine CT images and the development of in-hospital complications in patients in a level-1 trauma center.Methods: All trauma patients aged 16 years or older with CT imaging of the abdomen, thorax, or spine and admitted to the UMC Utrecht in 2017 were included. Patients with an active infection upon admission or severe neurological trauma were excluded. Routine trauma CT images were analyzed for visible abnormalities: pulmonary emphysema, coronary artery calcifications, and abdominal aorta calcification severity. Drug-treated complications were scored. The discharge condition was measured on the Glasgow Outcome Scale.Results: In total, 433 patients (median age 50 years, 67% male, 89% ASA 1–2) were analyzed. Median Injury Severity Score and Glasgow Coma Scale score were 9 and 15, respectively. Seventy-six patients suffered from at least one complication, mostly pneumonia (n = 39, 9%) or delirium (n = 19, 4%). Left main coronary artery calcification was independently associated with the development of any complication (OR 3.9, 95% CI 1.7–8.9). An increasing number of calcified coronary arteries showed a trend toward an association with complications (p = 0.07) and was significantly associated with an adverse discharge condition (p = 0.02). Pulmonary emphysema and aortic calcifications were not associated with complications.Conclusion: Coronary artery calcification, visible on routine CT imaging, is independently associated with in-hospital complications and an adverse discharge condition in level-1 trauma patients. The findings of this study may help to identify trauma patients quickly and objectively at risk for complications in an early stage without performing additional diagnostics or interventions.</p

Is a chest radiograph indicated after chest tube removal in trauma patients? A systematic review

PURPOSE The aim of this systematic review was to assess the necessity of routine chest radiographs after chest tube removal in ventilated and nonventilated trauma patients. METHODS A systematic literature search was conducted in MEDLINE, Embase, CENTRAL, and CINAHL on May 15, 2020. Quality assessment was performed using the Methodological Index for Nonrandomized Studies criteria. Primary outcome measures were abnormalities on postremoval chest radiograph (e.g., recurrence of a pneumothorax, hemothorax, pleural effusion) and reintervention after chest tube removal. Secondary outcome measures were emergence of new clinical symptoms or vital signs after chest tube removal. RESULTS Fourteen studies were included, consisting of seven studies on nonventilated patients and seven studies on combined cohorts of ventilated and nonventilated patients, all together containing 1,855 patients. Nonventilated patients had abnormalities on postremoval chest radiograph in 10% (range across studies, 0-38%) of all chest tubes and 24% (range, 0-78%) of those underwent reintervention. In the studies that reported on clinical symptoms after chest tube removal, all patients who underwent reintervention also had symptoms of recurrent pathology. Combined cohorts of ventilated and nonventilated patients had abnormalities on postremoval chest radiograph in 20% (range, 6-49%) of all chest tubes and 45% (range, 8-63%) of those underwent reintervention. CONCLUSION In nonventilated patients, one in ten developed recurrent pathology after chest tube removal and almost a quarter of them underwent reintervention. In two studies that reported on clinical symptoms, all reinterventions were performed in patients with symptoms of recurrent pathology. In these two studies, omission of routine postremoval chest radiograph seemed safe. However, current literature remains insufficient to draw definitive conclusions on this matter, and future studies are needed. LEVEL OF EVIDENCE Systematic review study, level IV

The association of radiologic body composition parameters with clinical outcomes in level-1 trauma patients

Purpose: The present study aims to assess whether CT-derived muscle mass, muscle density, and visceral fat mass are associated with in-hospital complications and clinical outcome in level-1 trauma patients. Methods: A retrospective cohort study was conducted on adult patients admitted to the University Medical Center Utrecht following a trauma between January 1 and December 31, 2017. Trauma patients aged 16 years or older without severe neurological injuries, who underwent a CT that included the abdomen within 7 days of admission, were included. An artificial intelligence (AI) algorithm was used to retrieve muscle areas to calculate the psoas muscle index and to retrieve psoas muscle radiation attenuation and visceral fat (VF) area from axial CT images. Multivariable logistic and linear regression analyses were performed to assess associations between body composition parameters and outcomes. Results: A total of 404 patients were included for analysis. The median age was 49 years (interquartile range [IQR] 30–64), and 66.6% were male. Severe comorbidities (ASA 3–4) were seen in 10.9%, and the median ISS was 9 (IQR 5–14). Psoas muscle index was not independently associated with complications, but it was associated with ICU admission (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.65–0.95), and an unfavorable Glasgow Outcome Scale (GOS) score at discharge (OR 0.62, 95% CI 0.45–0.85). Psoas muscle radiation attenuation was independently associated with the development of any complication (OR 0.60, 95% CI 0.42–0.85), pneumonia (OR 0.63, 95% CI 0.41–0.96), and delirium (OR 0.49, 95% CI 0.28–0.87). VF was associated with developing a delirium (OR 1.95, 95% CI 1.12–3.41). Conclusion: In level-1 trauma patients without severe neurological injuries, automatically derived body composition parameters are able to independently predict an increased risk of specific complications and other poor outcomes

Dendritic position is a major determinant of presynaptic strength

Different regulatory principles influence synaptic coupling between neurons, including positional principles. In dendrites of pyramidal neurons, postsynaptic sensitivity depends on synapse location, with distal synapses having the highest gain. In this paper, we investigate whether similar rules exist for presynaptic terminals in mixed networks of pyramidal and dentate gyrus (DG) neurons. Unexpectedly, distal synapses had the lowest staining intensities for vesicular proteins vGlut, vGAT, Synaptotagmin, and VAMP and for many nonvesicular proteins, including Bassoon, Munc18, and Syntaxin. Concomitantly, distal synapses displayed less vesicle release upon stimulation. This dependence of presynaptic strength on dendritic position persisted after chronically blocking action potential firing and postsynaptic receptors but was markedly reduced on DG dendrites compared with pyramidal dendrites. These data reveal a novel rule, independent of neuronal activity, which regulates presynaptic strength according to dendritic position, with the strongest terminals closest to the soma. This gradient is opposite to postsynaptic gradients observed in pyramidal dendrites, and different cell types apply this rule to a different extent

Nonoperative treatment of multiple rib fractures, the results to beat: International multicenter prospective cohort study among 845 patients

BACKGROUND Optimal treatment (i.e., nonoperative or operative) for patients with multiple rib fractures remains debated. Studies that compare treatments are rationalized by the alleged poor outcomes of nonoperative treatment. METHODS The aim of this prospective international multicenter cohort study (between January 2018 and March 2021) with 1-year follow-up, was to report contemporary outcomes of nonoperatively treated patients with multiple rib fractures. Including 845 patients with three or more rib fractures. Primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay (HLOS), (pulmonary) complications, and quality of life. RESULTS Mean age was 57.7 ± 17.0 years, median Injury Severity Score was 17 (13-22) and the median number of rib fractures was 6 (4-8). In-hospital mortality rate was 1.5% (n = 13), 112 (13.3%) patients had pneumonia and four (0.5%) patients developed a symptomatic nonunion. The median HLOS was 7 days (4-13 days), and median intensive care unit length of stay was 2 days (1-5 days). Mean 5-Level Quality of Life Questionnaire index value was 0.83 ± 0.18 1 year after trauma. Polytrauma patients had a median HLOS of 10 days (6-18 days), a pneumonia rate of 17.6% (n = 77) and mortality rate of 1.7% (n = 7). Elderly patients (≥65 years) had a median HLOS of 9 days (5-15 days), a pneumonia rate of 19.7% (n = 57) and mortality rate of 4.1% (n = 12). CONCLUSION Overall, nonoperative treatment of patients with multiple rib fractures shows low mortality and morbidity rate and good quality of life after 1 year. Future studies evaluating the benefit of operative stabilization should use contemporary outcomes to establish the therapeutic margin of rib fixation. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III

In patients with combined clavicle and multiple rib fractures, does fracture fixation of the clavicle improve clinical outcomes? A multicenter prospective cohort study of 232 patients

BACKGROUND Clavicle and rib fractures are often sustained concomitantly. The combination of injuries may result in decreased stability of the chest wall, making these patients prone to (respiratory) complications and prolonged hospitalization. This study aimed to assess whether adding chest wall stability by performing clavicle fixation improves clinical outcomes in patients with concurrent clavicle and rib fractures. METHODS A prospective multicenter study was performed including all adult patients admitted between January 2018 and March 2021 with concurrent ipsilateral clavicle and rib fractures. Patients treated operatively versus nonoperatively for their clavicle fracture were matched using propensity score matching. The primary outcome was hospital length of stay (HLOS). Secondary outcomes were intensive care unit length of stay, duration of mechanical ventilation, pain, complications, and quality of life at 6 weeks and 12 months of follow-up. RESULTS In total, 232 patients with concomitant ipsilateral clavicle and rib fractures were included. Fifty-two patients (22%) underwent operative treatment of which 39 could be adequately matched to 39 nonoperatively treated patients. No association was observed between clavicle plate fixation and HLOS (mean difference, 2.3 days; 95% confidence interval, -2.1 to 6.8; p = 0.301) or any secondary endpoint. Eight of the 180 nonoperatively treated patients (4%) had a symptomatic nonunion, for which 5 underwent secondary clavicle fixation. CONCLUSION We found no evidence that, in patients with combined clavicle and multiple rib fractures, plate fixation of the clavicle reduces HLOS, pain, or (pulmonary) complications, nor that it improves quality of life. STUDY TYPE Therapeutic/Care Management; Level III

Automated analysis of neuronal morphology, synapse number and synaptic recruitment

The shape, structure and connectivity of nerve cells are important aspects of neuronal function. Genetic and epigenetic factors that alter neuronal morphology or synaptic localization of pre- and post-synaptic proteins contribute significantly to neuronal output and may underlie clinical states. To assess the impact of individual genes and disease-causing mutations on neuronal morphology, reliable methods are needed. Unfortunately, manual analysis of immuno-fluorescence images of neurons to quantify neuronal shape and synapse number, size and distribution is labor-intensive, time-consuming and subject to human bias and error. We have developed an automated image analysis routine using steerable filters and deconvolutions to automatically analyze dendrite and synapse characteristics in immuno-fluorescence images. Our approach reports dendrite morphology, synapse size and number but also synaptic vesicle density and synaptic accumulation of proteins as a function of distance from the soma as consistent as expert observers while reducing analysis time considerably. In addition, the routine can be used to detect and quantify a wide range of neuronal organelles and is capable of batch analysis of a large number of images enabling high-throughput analysis

Functional Gene Group Analysis Reveals a Role of Synaptic Heterotrimeric G Proteins in Cognitive Ability

Although cognitive ability is a highly heritable complex trait, only a few genes have been identified, explaining relatively low proportions of the observed trait variation. This implies that hundreds of genes of small effect may be of importance for cognitive ability. We applied an innovative method in which we tested for the effect of groups of genes defined according to cellular function (functional gene group analysis). Using an initial sample of 627 subjects, this functional gene group analysis detected that synaptic heterotrimeric guanine nucleotide binding proteins (G proteins) play an important role in cognitive ability (PEMP = 1.9 × 10-4). The association with heterotrimeric G proteins was validated in an independent population sample of 1507 subjects. Heterotrimeric G proteins are central relay factors between the activation of plasma membrane receptors by extracellular ligands and the cellular responses that these induce, and they can be considered a point of convergence, or a "signaling bottleneck." Although alterations in synaptic signaling processes may not be the exclusive explanation for the association of heterotrimeric G proteins with cognitive ability, such alterations may prominently affect the properties of neuronal networks in the brain in such a manner that impaired cognitive ability and lower intelligence are observed. The reported association of synaptic heterotrimeric G proteins with cognitive ability clearly points to a new direction in the study of the genetic basis of cognitive ability

SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse

© 2019 Elsevier Inc.Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders (“synaptopathies”). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2,922 annotations for 1,112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variations associated with intelligence, educational attainment, ADHD, autism, and bipolar disorder and among de novo variants associated with neurodevelopmental disorders, including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis platform for interpretation of large-scale -omics data (https://syngoportal.org and http://geneontology.org). The SynGO consortium presents a framework to annotate synaptic protein locations and functions and annotations for 1,112 synaptic genes based on published experimental evidence. SynGO reports exceptional features and disease associations for synaptic genes and provides an online data analysis platfor

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

International audienceBackground: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk.Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels.Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43.Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)