• Zimmermann Steenberg posted an update 6 months, 1 week ago

    rapy in older stroke patients as well as in younger.Thrombin is increasingly recognized to be of importance for cardiovascular disease. The aim of this study was to investigate the prognostic value of thrombin generation variables in a cohort of patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Thrombin generation potential measured by calibrated automated thrombogram (CAT) and prothrombin fragment F1 + 2 was determined in the acute and convalescent phases for a cohort of 190 patients with AIS/TIA. Microvesicle (MV)-induced thrombin generation potential was determined for a subset of patients using modified CAT. Primary outcome was a composite of fatal and nonfatal AIS or myocardial infarction as documented in Swedish registers during a total follow-up of 986 patient-years. Hazard ratios (HRs) were calculated using Cox regression based on variable median split. Peak thrombin and endogenous thrombin potential (ETP) above median in the acute phase were associated with a reduced risk of primary outcome after adjustment for cardiovascular risk factors, HR 0.50 (0.27-0.92), p = 0.026 and HR 0.53 (0.28-0.99), p = 0.048, respectively. F1 + 2 was lower in patients than in healthy controls but not associated with outcome. MV-induced peak thrombin above median in the acute phase was associated with recurrent AIS, unadjusted HR 2.65 (1.03-6.44), p = 0.044. Contrary to expectation, high thrombin generation potential is associated with a reduced risk of recurrent ischemic event in patients with AIS/TIA. Low ETP/peak thrombin combined with high MV-induced peak thrombin can potentially identify patients at high risk of recurrence.

     Minimally invasive surgery is increasingly performed for isolated aortic or mitral valve procedures. However, combined minimally invasive aortic and mitral valve surgery is rare. We report our initial experience performing multiple valve procedures through a right-sided mini-thoracotomy (RMT) compared with sternotomy.

     A total of 264 patients underwent aortic and mitral with or without tricuspid valve surgery through RMT (

     = 25) or sternotomy (

     = 239). Propensity score matching was used for outcome comparisons.

     Of the 264 patients, 25 (age 72 ± 10 years; 72% male) underwent double (

     = 19) and triple valve surgery (

     = 6) through RMT and 239 (age 71 ± 11 years; 54% male) underwent double (

     = 176) and triple valve surgery (

     = 63) through sternotomy. Sternotomy patients had more co-morbidities and preoperative risk factors (EuroSCORE II 10.25 ± 10.89 vs. RMT 3.58. ± 4.98;

     < 0.001). RMT procedures were uneventful without intraoperative complications or conversions to sternotomy. After propensity score matching, surgical procedures were comparable between groups with a higher valve repair rate in RMT. Despite longer cardiopulmonary bypass times in RMT, there was no evidence for differences in 30-day mortality (RMT

     = 2 vs. sternotomy

     = 2) and there were no significant differences in other outcomes. During 5-year follow-up, reoperation was required in sternotomy patients only (

     = 2). read more Follow-up echocardiography showed durable results after valve surgery. RMT patients showed higher survival probability compared with sternotomy, although this difference was not significant (hazard ratio = 0.33; 95% confidence interval 0.06-1.65;

     = 0.18).

     Combined aortic plus mitral with or without tricuspid valve surgery can safely be performed through a RMT with a trend toward better mid-term outcomes.

     Combined aortic plus mitral with or without tricuspid valve surgery can safely be performed through a RMT with a trend toward better mid-term outcomes.

    The field of antisense oligonucleotide therapeutics is rapidly growing and in addition to small molecules and therapeutic antibodies, oligonucleotide-based gene expression modifiers have been developed as fully accepted therapeutics. Antisense oligonucleotides are designed to modify gene expression of their specific target genes. However, as their effect relies on Watson-Crick base pairing, they could also bind to other unintended complementary RNAs showing sufficient sequence homology, which in turn could lead to off-target effects. It is assumed that these off-target effects depend on the degree of complementarity between the antisense oligonucleotides and off-target sequences.

    Aim of this study was the investigation of the effects of antisense oligonucleotides on the expression of potential off-targets having a defined number of mismatches to the oligonucleotide sequence.

    We extend recent studies by investigating the off-target profile of two 17-mer antisense oligonucleotides in two distinct human cell lines by a whole-transcriptome study using RNA sequencing.

    The relatively high percentage of significantly downregulated off-target genes for which one mismatch is present corroborates the requirement for intense bioinformatic screens and stringent specificity criteria to design antisense oligonucleotides with only minimal sequence complementarity to any non-target sequence.

    Avoiding suppression of off-target genes by a thorough bioinformatics screen should strongly reduce the risk for toxicities caused by antisense oligonucleotide-mediated off-target RNA suppression and finally result in safer antisense oligonucleotide-based therapeutics.

    Avoiding suppression of off-target genes by a thorough bioinformatics screen should strongly reduce the risk for toxicities caused by antisense oligonucleotide-mediated off-target RNA suppression and finally result in safer antisense oligonucleotide-based therapeutics.The numbers of patients with dementia and patients with epilepsy are increasing in the global population. In fact, these two conditions are related, and it is estimated that at least 5-10% of seizures or epilepsy in older individuals (aged > 60 years) are caused by a neurodegenerative dementia. In the vast majority, one of the four following diseases is involved Alzheimer’s disease, Lewy body dementia, frontotemporal dementia, or vascular dementia. These diseases cause, not only seizures or epilepsy in affected patients, but cognitive, behavioral, and motor disorders as well. As a result, the challenges of treating seizures in older patients with neurodegenerative disease go beyond the usual limitations associated with this age group (i.e., lower fluid compartment, lower protein binding, increased risk of drug-drug interactions) by imposing other issues and pitfalls. In this setting, the drug-related potential aggravation of neurodegenerative symptoms must be taken into account. As cognition is particularly vulnerable, the prescription of antiseizure medications in dementia must consider the potential neurocognitive impact and limit it as much as possible.

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