Traumatic subarachnoid pleural fistula in children: Case report, algorithm and classification proposal

Subarachnoid pleural fistulas are rare. They have been described as complications of thoracic surgery, penetrating injuries and spinal surgery, among others. We present the case of a 3-year-old female child, who suffer spinal cord trauma secondary to a car accident, developing a posterior subarachnoid pleural fistula. To our knowledge this is the first reported case of a pediatric patient with subarachnoid pleural fistula resulting from closed trauma, requiring intensive multimodal management. We also present a management algorithm and a proposed classification. The diagnosis of this pathology is difficult when not associated with neurological deficit. A high degree of suspicion, multidisciplinary management and timely surgical intervention allow optimal management

A Network Analysis of the Human T-Cell Activation Gene Network Identifies Jagged1 as a Therapeutic Target for Autoimmune Diseases

Understanding complex diseases will benefit the recognition of the properties of the gene networks that control biological functions. Here, we set out to model the gene network that controls T-cell activation in humans, which is critical for the development of autoimmune diseases such as Multiple Sclerosis (MS). The network was established on the basis of the quantitative expression from 104 individuals of 20 genes of the immune system, as well as on biological information from the Ingenuity database and Bayesian inference. Of the 31 links (gene interactions) identified in the network, 18 were identified in the Ingenuity database and 13 were new and we validated 7 of 8 interactions experimentally. In the MS patients network, we found an increase in the weight of gene interactions related to Th1 function and a decrease in those related to Treg and Th2 function. Indeed, we found that IFN-ß therapy induces changes in gene interactions related to T cell proliferation and adhesion, although these gene interactions were not restored to levels similar to controls. Finally, we identify JAG1 as a new therapeutic target whose differential behaviour in the MS network was not modified by immunomodulatory therapy. In vitro treatment with a Jagged1 agonist peptide modulated the T-cell activation network in PBMCs from patients with MS. Moreover, treatment of mice with experimental autoimmune encephalomyelitis with the Jagged1 agonist ameliorated the disease course, and modulated Th2, Th1 and Treg function. This study illustrates how network analysis can predict therapeutic targets for immune intervention and identified the immunomodulatory properties of Jagged1 making it a new therapeutic target for MS and other autoimmune diseases

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Risk and safety requirements for diagnostic and therapeutic procedures in allergology : World Allergy Organization Statement

Peer reviewe

IGF-I and the aging mammalian brain

Insulin-like growth factors (IGFs) are important modulators of organismal life-span all along phylogeny. These growth factors are widely viewed as detrimental for long life by reducing tissue resistance to oxidative stress. However, IGF-I has been consistently shown to be a potent neuroprotective factor in mammals, and as such, a deterrent of brain aging. Conversely, recent data suggest that IGF-I may contribute to amyloid neurodegeneration underlying Alzheimer's disease. These opposing observations underline an incomplete understanding of the significance of this ancestral hormone pathway in relation to brain aging. It is possible that these opposite results are the consequence of using different experimental approaches. Thus, brain amyloid injury is reduced in mutant mice partially defective in IGF-I receptor function, whereas IGF-I is neuroprotective when administered to animal models of neurodegenerative disease or normal brain aging. This approach-dependent effect of IGF-I highlights a fundamental gap in our knowledge of the relationship between peripheral and brain IGF-I function and the actual biological impact of experimental modulation of brain IGF-I function. We suggest to directly address brain IGF-I function in the varying experimental approaches used to confirm that changes have taken place in the desired way.Fil: Piriz, Joaquin. Instituto Cajal; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Muller, A.. Instituto Cajal; EspañaFil: Trejo, J. L.. Instituto Cajal; EspañaFil: Torres Aleman, I.. Instituto Cajal; Españ

Cable Augmentation for Distal Periprosthetic Femur Fractures

Introduction: Distal periprosthetic femur fractures (PFF) are increasing in incidence and have a high degree of morbidity and mortality, similar to that of the hip fracture population. The current primary operative approach for distal PFFs is plate and screw fixation. We aim to examine the outcomes of augmenting these plate and screw constructs with cable fixation. We hypothesize that cable augmentation (CA) provides improved post-operative outcomes compared to non-cable augmentation (NCA) for distal PFFs. Methods: We retrospectively analyzed patients ≥ 65 years old who underwent operative repair of a distal periprosthetic femur fracture, comparing patients who had cable augmentation to those without cable augmentation. The primary outcome was change in ambulatory status, defined as a change in baseline ambulatory level of independence (LOI) . LOIs were classified as ambulatory, assisted, and non-ambulatory. Secondary outcomes included length of stay (LOS), operative complications, and revisions. Data were analyzed using the t test, chi-square or Fisher’s exact tests where appropriate. A p-value of ≤0.05 indicated statistical significance. Results: A total of 40 patients were included, of which 13 (33%) had cable augmentation. In the cable augmented group, a lower proportion of patients exhibited a decline in level of independence [5 (38.5%) CA vs 19 (70.4%) NCA, p=0.09]. There were no operative revisions in the CA group, compared to 3 (11.5%) in the NCA group (p=0.5). There were no significant differences between the two groups in terms of LOS [7.5 ・} 3.9 CA vs 6.1 ・} 3.1 NCA, p=0.2] and complications [2 (15.4%) CA vs 1 (3.7%) NCA, p=0.2]. Conclusions: The presented data reveals that when cable augmented constructs were used for fixation of distal PFFs, a lower proportion of patients exhibited a decline in baseline ambulatory status. While this study is lacking power for statistical significance, the data does show a trend toward favorable outcomes with cable augmented constructs. This is logical given the stronger overall support provided by cables. Continued investigations should be considered to further examine cable augmentation for distal periprosthetic femur fractures

IGF-I and the aging mammalian brain

Insulin-like growth factors (IGFs) are important modulators of organismal life-span all along phylogeny. These growth factors are widely viewed as detrimental for long life by reducing tissue resistance to oxidative stress. However, IGF-I has been consistently shown to be a potent neuroprotective factor in mammals, and as such, a deterrent of brain aging. Conversely, recent data suggest that IGF-I may contribute to amyloid neurodegeneration underlying Alzheimer's disease. These opposing observations underline an incomplete understanding of the significance of this ancestral hormone pathway in relation to brain aging. It is possible that these opposite results are the consequence of using different experimental approaches. Thus, brain amyloid injury is reduced in mutant mice partially defective in IGF-I receptor function, whereas IGF-I is neuroprotective when administered to animal models of neurodegenerative disease or normal brain aging. This approach-dependent effect of IGF-I highlights a fundamental gap in our knowledge of the relationship between peripheral and brain IGF-I function and the actual biological impact of experimental modulation of brain IGF-I function. We suggest to directly address brain IGF-I function in the varying experimental approaches used to confirm that changes have taken place in the desired way. © 2010 Elsevier Inc.Peer Reviewe