The association of neutrophil-lymphocyte ratio and lymphocyte-monocyte ratio with 3-month clinical outcome after mechanical thrombectomy following stroke

Background and aim Neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) are associated with clinical outcomes in malignancy, cardiovascular disease and stroke. Here we investigate their association with outcome after acute ischaemic stroke treated by mechanical thrombectomy (MT). Methods Patients were selected using audit data for MT for acute anterior circulation ischaemic stroke at a UK centre from May 2016–July 2017. Clinical and laboratory data including neutrophil, lymphocyte and monocyte count tested before and 24 h after MT were collected. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3–6 at 3 months. Multivariable logistic regression analyses were performed to explore the relationship of NLR and LMR with functional outcome. Results One hundred twenty-one patients (mean age 66.4 ± 16.7, 52% female) were included. Higher NLR (adjusted OR 0.022, 95% CI, 0.009–0.34, p = 0.001) and lower LMR (adjusted OR − 0.093, 95% CI (− 0.175)−(− 0.012), p = 0.025) at 24-h post-MT were significantly associated with poorer functional outcome when controlling for age, baseline NIHSS score, infarct size, presence of good collateral supply, recanalisation and symptomatic intracranial haemorrhage on multivariate logistic regression. Admission NLR or LMR were not significant predictors of mRS at 3 months. The optimal cut-off values of NLR and LMR at 24-h post-MT that best discriminated poor outcome were 5.5 (80% sensitivity and 60% specificity) and 2.0 (80% sensitivity and 50% specificity), respectively on receiver operating characteristic curve analysis. Conclusion NLR and LMR tested at 24 h after ictus or intervention may predict 3-month functional outcome

High on-clopidogrel platelet reactivity in ischaemic stroke or transient ischaemic attack: Systematic review and meta-analysis

Objectives To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients. Methods We conducted a comprehensive search of PubMed and EMBASE from their inceptions to March 9, 2019. Studies that reported absolute numbers/percentages of HCRP at any time point after IS/TIA onset evaluated with any type of platelet function tests, clinical outcomes and genotyping data were included. Results Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24–32%; high heterogeneity: I2 = 88.2%, p < 0.001). Heterogeneity degree diminished across groups defined by the HCPR testing method. Clopidogrel non-responder IS/TIA patients had poorer outcome compared to responders (RR = 2.09, 95%CI: 1.61–2.70; p = 0.036; low heterogeneity across studies: I2 = 27.4%, p = 0.210). IS/TIA carriers of CYP2C19*2 or CYP2C19*3 loss of function alleles had a higher risk of HCPR compared to wild type (RR = 1.69, 95%CI: 1.47–1.95; p < 0.001; I2 = 0.01%, p = 0.475). Conclusions This systematic review shows a high prevalence of clopidogrel resistance in IS/TIA and poor outcome in these patients. CYP2C19 polymorphisms may potentially influence clopidogrel resistance

A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations

BACKGROUND: The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance.METHODS AND RESULTS: We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features.CONCLUSION: We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.<br/

Cerebral amyloid angiopathy distribution in older people: a cautionary note

Introduction Radiolabeled ligands for fibrillar amyloid beta (Aβ) peptides are used in positron emission tomography (PET) for dementia diagnosis. Current ligands do not discriminate parenchymal amyloid plaques from cerebral amyloid angiopathy (CAA). Methods We undertook neuropathological examination of 65 older people (81.6 ± 7.96 (mean ± SD) years, 27F/38M): 15 with neuropathological diagnosis of AD, 25 with neuropathological diagnosis of other neurodegenerative dementias (Lewy body dementia and Parkinson disease dementia), and 25 without significant neurodegenerative pathology. Results We observed CAA in non‐Alzheimer's dementia (non‐AD dementia) and control brains, of comparable extent to those with neuropathologically confirmed AD. Aβ‐positive vessel density did not differ significantly between non‐AD dementia and control groups. Across all subjects there was a highly significant correlation between vessel Aβ40 density and vessel Aβ42 density (Spearman rho = 0.855, P < .001). CAA was absent or sparse in subcortical white matter across all patient groups. Conclusion Our data indicate that CAA can be abundant in non‐AD brains and raise a cautionary note regarding interpretation of amyloid PET imaging

Defining The Genetic Basis Of Three Hereditary Neurological Conditions In Families From The Indian Subcontinent

Neurogenetic studies have revolutionised our understanding of the genetic and molecular basis of inherited neurological disorders, primarily as a result of the identification of single disease-causing genes. The incidence of such disorders is increased amongst populations with common shared ancestry or a high rate of consanguinity. Hence, the investigation of inherited neurological conditions in genetic isolates provides a robust opportunity to define the molecular pathogenic basis of these conditions. Neurological and neurodevelopmental disorders present important public health issues in the developing countries in the Indian subcontinent. The global burden of these disorders is worsened by the lack of targeted research funding and relevant in-country research capacity. This project, undertaken as part of a wider research study investigating inherited disorders in the Indian subcontinent, aimed to define the molecular genetic bases of three extended families with distinct neurological and neurodevelopmental disorders. In the first family with multiple individuals affected by a severe autosomal recessive form of neurodevelopmental delay with microcephaly, genetic studies identified mutation in a gene (MFSD2A), not previously associated with inherited disease, which led to a reduction of fatty acid transportation in patients homozygous for the disease-causing mutation. In the second family, genotyping identified a complex chromosomal rearrangement associated with diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome, among ten chromosomally-imbalanced affected individuals. In the third family, a duplication event on chromosome 15q24 encompassing the LINGO1 gene was identified as a likely cause of dystonic tremor in affected individuals. Together these molecular discoveries provide fundamentally important biological insight into the pathogenic basis of abnormal brain growth and control of movement with the potential diagnostic and treatment applications

New leasing standard IFRS 16 and its effects on financial statements and key financial ratios

The lease standard IAS 17 Lease has been long criticized because of the complicated lease classifications, which allows a huge amount of off-balance sheet leased assets and liabilities. After long lasting discussions IASB issued a new lease standard IFRS 16, which will have an effective date of 1 January 2019. According to the new standard, lessee has to recognize all lease activities on the balance sheet, therefore it is expected to have great impact on leasing-intensive industries. This master thesis explains the scope of upcoming standard, the changes it will bring and the impact it will make on financial performance indicators of certain companies. This research presents theoretical background and framework of IAS 17 and IFRS 16, and analyses the new rules and changes in the previous regulation. Furthermore, a research is conducted by applying constructive capitalization method to analyze the expected impact of IFRS 16 on the financial statements and key financial figures of two largest German companies listed on DAX exchange (Imhoff et al.,1991). For the purpose of research, annual consolidated financial statements and relevant footnotes of two companies for the year 2017 were retrieved. The results of two sample companies are used to analyze the effect of IFRS 16 on balance sheet and key financial ratios, where we verify the chemical industry to be the least affected. At the same time the airline industry is affected moderately in comparison with the chemical industry. However, the impact is not as significant as previous research results presented by IFRS Foundation (2016). When capitalizing off-balance sheet lease items, we find evidence, that the most significant effect of the new standard is expected to be an increase in lease assets and liabilities for both companies. However, the effect on the equity will be insignificant. As a result of the measurement of some financial ratios, such as Debt to Equity, Debt to Asset, Return on Asset and Return on Equity for two companies, we recognized that the effect of the new standard can vary from company to company within the same industry. It is highly dependent on how intensive the company uses lease financing

Hypersensitivity reactions to recombinant tissue plasminogen activator.

Recombinant tissue plasminogen activator (rtPA) is currently the only approved thrombolytic agent for treating acute ischaemic stroke that is widely used in clinical practice. However, it may cause haemorrhage and hypersensitivity reactions. Orolingual angioedema is an infrequent, usually mild but potentially life threatening, hypersensitivity reaction to rtPA. Our understanding of the basic biology of angioedema has increased in recent years. There is growing evidence that rtPA-induced orolingual angioedema is driven mainly by bradykinin generation rather than it being an anaphylactic response. Monitoring is important because orolingual angioedema may evolve and compromise airways and a small number do have angioedema as part of systemic anaphylaxis. There are no published guidelines for treating rtPA-induced orolingual angioedema, although some evidence suggests that those refractory to standard antianaphylactic agents may resolve with bradykinin B2 receptor antagonists. It is important that responses to orolingual angioedema are proportionate and that patients are closely monitored

Experimental Study of the Tl4PbTe3-Tl9TbTe6-Tl9BiTe6 Section of the Tl-Pb-Bi-Tb-Te System

<div><p>The aim of the present study was to determine the phase relations in the Tl4PbTe3-Tl9TbTe6-Tl9BiTe6 section of the Tl-Pb-Bi-Tb-Te system. Based on a set of the methods of the physicochemical analysis (differential thermal analysis, powder X-ray diffraction method as well as microhardness measurements), the phase diagram of the Tl4PbTe3-Tl9TbTe6 boundary system, some isopleth sections, liquidus and solidus surfaces projections, as well as isothermal sections at 840 and 860 K, were plotted. Unlimited solid solutions with the Tl5Te3 structure (δ-phase) were found in the system, which are of interest as a thermoelectric materials.</p></div