302 research outputs found

    Evaluation of the deep vein recanalisation and function after low molecular weight heparin (calcium nadroparine) therapy of deep vein thrombosis. Preliminary report

    Get PDF
    Introduction. The standard treatment for acute episode of deep vein thrombosis (DVT) included at least five days administration of unfractionated heparin followed by oral anticoagulants (OAs) in the subsequent months. In the early 2000s the use of low-molecular-weight heparins (LMWH) was recommended and validated as the equivalent for the standard therapy of acute episode of DVT. The aim of this study was to evaluate the patency of thrombotic venous segments and indirectly the function of valves after therapy with calcium nadroparine in the 10 days ambulatory treatment and three-month secondary prophylaxis of acute DVT. Material and methods. The study group consisted of 50 patients (10 females and 40 males), aged 33 to 92 years (mean age 62.3 years) with first episode of acute, symptomatic deep vein thrombosis of the lower extremities, below the inguinal ligament, who were followed-up during their 10 days ambulatory treatment and three-month secondary prophylaxis with calcium nadroparine. Each patient had clinical examinations and ultrasound of the veins of the lower extremities, using the colour-coded power Doppler ultrasound (CDU) performed by the same experienced physician, using TOSHIBA device (linear probe 6–12 MHz), on day 1 and 10 of the treatment period and after 1 and 3 months of secondary prophylaxis phase. All patients underwent the following laboratory tests: before treatment the coagulation profile, blood group and complete blood count; the control platelet count was performed after 7 to 10 days of LMWH treatment, and then every 10 days. Results. The thrombosis was revealed in the femoro-popliteal segment in 35 (70%) subjects and below the knee in the remaining 15 (30%) patients. There was no case of DVT recurrence, thromboembolic event or death in patients who received LMWH therapy during the 3-month follow-up period. No adverse effects of the treatment were observed. CDU revealed the complete venous recanalisation in 40 (80%) patients and partial recanalisation with residual thrombi and/or wall thickening in the remaining 10 (20%) subjects. After the 3-month treatment period deep vein reflux was not observed in 30 (60%) patients, whereas the remaining 20 (40%) were diagnosed with only an insignificant reflux (lasting 1–2 seconds). Conclusions. The calcium nadroparine therapy is an efficient, safe and well tolerated method of ambulatory treatment and secondary prophylaxis of the acute, symptomatic deep vein thrombosis of the lower extremities. Further, longer and prospective, multi-centre studies are required for better evaluation of the early and late results of DVT treatment with LMWH. They would allow investigating their effect on venous recanalisation, its function and prevention of post-thrombotic syndrome

    Cortisol levels and neuropsychiatric diagnosis as markers of postoperative delirium: a prospective cohort study

    Get PDF
    Polish Ministry of Science and Higher Education, Grant No. 0174/P01/2010/70; 504-06-011

    Subsystems for future access networks

    Get PDF
    Current evolution and tendencies of Telecom Networks in general and more specifically optical Metro and Access Networks and their convergence are reported. Based on this evolution, a set of research lines are foreseen regarding subsystems and devices as: high speed optical sources, modulators and receivers, for the next generation of Passive Optical Networks. The ICT project EURO-FOS is achieving European level cooperative research among academia and industry, enabling future telecommunication networks

    A UK wide cohort study describing management and outcomes for infants with surgical Necrotising Enterocolitis

    Get PDF
    The Royal College of Surgeons have proposed using outcomes from necrotising enterocolitis (NEC) surgery for revalidation of neonatal surgeons. The aim of this study was therefore to calculate the number of infants in the UK/Ireland with surgical NEC and describe outcomes that could be used for national benchmarking and counselling of parents. A prospective nationwide cohort study of every infant requiring surgical intervention for NEC in the UK was conducted between 01/03/13 and 28/02/14. Primary outcome was mortality at 28-days. Secondary outcomes included discharge, post-operative complication, and TPN requirement. 236 infants were included, 43(18%) of whom died, and eight(3%) of whom were discharged prior to 28-days post decision to intervene surgically. Sixty infants who underwent laparotomy (27%) experienced a complication, and 67(35%) of those who were alive at 28 days were parenteral nutrition free. Following multi-variable modelling, presence of a non-cardiac congenital anomaly (aOR 5.17, 95% CI 1.9-14.1), abdominal wall erythema or discolouration at presentation (aOR 2.51, 95% CI 1.23-5.1), diagnosis of single intestinal perforation at laparotomy (aOR 3.1 95% CI 1.05-9.3), and necessity to perform a clip and drop procedure (aOR 30, 95% CI 3.9-237) were associated with increased 28-day mortality. These results can be used for national benchmarking and counselling of parents

    COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis

    Get PDF
    To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19

    SARS-CoV-2 variant Alpha has a spike-dependent replication advantage over the ancestral B.1 strain in human cells with low ACE2 expression

    Get PDF
    Epidemiological data demonstrate that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) Alpha and Delta are more transmissible, infectious, and pathogenic than previous variants. Phenotypic properties of VOC remain understudied. Here, we provide an extensive functional study of VOC Alpha replication and cell entry phenotypes assisted by reverse genetics, mutational mapping of spike in lentiviral pseudotypes, viral and cellular gene expression studies, and infectivity stability assays in an enhanced range of cell and epithelial culture models. In almost all models, VOC Alpha spread less or equally efficiently as ancestral (B.1) SARS-CoV-2. B.1. and VOC Alpha shared similar susceptibility to serum neutralization. Despite increased relative abundance of specific sgRNAs in the context of VOC Alpha infection, immune gene expression in infected cells did not differ between VOC Alpha and B.1. However, inferior spreading and entry efficiencies of VOC Alpha corresponded to lower abundance of proteolytically cleaved spike products presumably linked to the T716I mutation. In addition, we identified a bronchial cell line, NCI-H1299, which supported 24-fold increased growth of VOC Alpha and is to our knowledge the only cell line to recapitulate the fitness advantage of VOC Alpha compared to B.1. Interestingly, also VOC Delta showed a strong (595-fold) fitness advantage over B.1 in these cells. Comparative analysis of chimeric viruses expressing VOC Alpha spike in the backbone of B.1, and vice versa, showed that the specific replication phenotype of VOC Alpha in NCI-H1299 cells is largely determined by its spike protein. Despite undetectable ACE2 protein expression in NCI-H1299 cells, CRISPR/Cas9 knock-out and antibody-mediated blocking experiments revealed that multicycle spread of B.1 and VOC Alpha required ACE2 expression. Interestingly, entry of VOC Alpha, as opposed to B.1 virions, was largely unaffected by treatment with exogenous trypsin or saliva prior to infection, suggesting enhanced resistance of VOC Alpha spike to premature proteolytic cleavage in the extracellular environment of the human respiratory tract. This property may result in delayed degradation of VOC Alpha particle infectivity in conditions typical of mucosal fluids of the upper respiratory tract that may be recapitulated in NCI-H1299 cells closer than in highly ACE2-expressing cell lines and models. Our study highlights the importance of cell model evaluation and comparison for in-depth characterization of virus variant-specific phenotypes and uncovers a fine-tuned interrelationship between VOC Alpha- and host cell-specific determinants that may underlie the increased and prolonged virus shedding detected in patients infected with VOC Alpha

    Nonproductive exposure of PBMCs to SARS‐CoV ‐2 induces cell‐intrinsic innate immune responses

    Get PDF
    Cell-intrinsic responses mounted in PBMCs during mild and severe COVID-19 differ quantitatively and qualitatively. Whether they are triggered by signals emitted by productively infected cells of the respiratory tract or result from physical interaction with virus particles remains unclear. Here, we analyzed susceptibility and expression profiles of PBMCs from healthy donors upon ex vivo exposure to SARS-CoV and SARS-CoV-2. In line with the absence of detectable ACE2 receptor expression, human PBMCs were refractory to productive infection. RT-PCR experiments and single-cell RNA sequencing revealed JAK/STAT-dependent induction of interferon-stimulated genes (ISGs) but not proinflammatory cytokines. This SARS-CoV-2-specific response was most pronounced in monocytes. SARS-CoV-2-RNA-positive monocytes displayed a lower ISG signature as compared to bystander cells of the identical culture. This suggests a preferential invasion of cells with a low ISG baseline profile or delivery of a SARS-CoV-2-specific sensing antagonist upon efficient particle internalization. Together, nonproductive physical interaction of PBMCs with SARS-CoV-2- and, to a much lesser extent, SARS-CoV particles stimulate JAK/STAT-dependent, monocyte-accentuated innate immune responses that resemble those detected in vivo in patients with mild COVID-19
    corecore