Feasibility of switching from alteplase to tenecteplase for stroke thrombolysis - A retrospective cohort analysis.

Introduction: Tenecteplase (TNK-tPA) has several benefits over alteplase (tPA) in treatment of acute ischaemic stroke. Randomised controlled trials have shown promising results. In June 2017, the Stroke Unit at Sundsvall County Hospital switched from tPA to TNK-tPA in standard clinical practice. This study examines the effects of that shift. Methods: All thrombolysis treatments performed during the first twenty-four months with TNK-tPA (168) were compared to the last twenty-four months with tPA (191). Data were collected from patient records. Follow-up time was 30 days. Co-primary outcomes were death and symptomatic intracranial haemorrhage (SICH). Secondary outcomes were types of intracerebral bleeding and cause of death. Tertiary outcome was door-to-needle time (DNT). Results: Treatment groups were of comparable age (75.7 ± 0.2 years). tPA-treated patients had an NIHSS (National Institutes of Health Stroke Scale) score of 9.2 versus 7.5 for TNK-tPA. Patients older than 80 had more severe strokes (median NIHSS 9 versus 5). SICH occurred in 6 (3.6 %) patients in the TNK-tPA group and in 2 (1.0 %) treated with tPA, odds ratio (OR) 3.41 (0.70-16.7). Numbers for death were 21 (12.5 %) and 31 (15.2 %), OR 0.77 (0.46-1.29), meaning no statistically significant differences in primary outcomes. There were no significant differences in secondary outcomes. Predominant cause of death was cerebral infarction. DNT with tenecteplase was shorter: mean 44 versus 26, and median 35 versus 19 min. Conclusions: Switching from alteplase to tenecteplase was associated with shorter time to treatment. To draw certain conclusions regarding safety or efficacy would require a larger material.

HSC70 is a novel binding partner involved in the capture of immunoglobulins on B cells in the NOD mouse.

B cells have been shown to be essential for Type 1 diabetes development in the non-obese diabetic mouse, where their contribution as antigen presenting cells has been emphasised. Other important functions for B cells include surface capture of immunoglobulins and transportation of immune complexes, with subsequent endocytosis, antigen processing and antigen presentation. We have previously demonstrated that NOD B cells capture IgM and IgG immune complexes through an unknown surface molecule. In this study, we revealed the presumptive immunoglobulin-binding molecule to be HSC70. Moreover, we detected increased levels of HSC70 on NOD B cells. HSC70 has been shown to play a role in antigen processing and presentation as well as being important in several autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus. Due to its protein stabilising properties, increased HSC70 could contribute to enhanced self-antigen collection and presentation and thereby contribute to the development of Type 1 diabetes.

Enhanced capture of extramembranous IgM and IgG on B cells in the NOD mouse--implications for immune complex trapping.

Binding of various antibody isotypes to B cells through either FcgammaRs or complement receptors has been attributed to play several roles, e.g. in immune complex (IC) transportation and regulation of B cell receptor signaling. We have revealed a novel B cell intrinsic receptor for IgM and IgG which is present in C57BL/6 (B6) mice and is more abundant in non-obese diabetic (NOD) mice. As a consequence, the level of extramembranous IgG monomers and IgM pentamers on peripheral blood B cells from NOD mice was significantly higher compared with B6 mice. The effect of this aberration was that all B cells in peripheral blood of (NOD.IgH(a) x B6(IgH(b)))F(1) mice carried both IgM allotypes on their surface. In addition, analysis of IC binding using IgG- or IgM-opsonized bacterial particles revealed a higher degree of binding in NOD mice compared with B6. We hypothesize that this novel Ig-binding receptor is part of the normal immune system function. The aberrant function in the NOD mouse could contribute to the development of Type 1 diabetes by altering normal B cell functions such as activation, IC transportation and B cell homeostasis.