Safety and Outcome of Intravenous Thrombolysis in Stroke Patients on Prophylactic Doses of Low Molecular Weight Heparins at Stroke Onset.

Background and Purpose- There are limited data on intravenous thrombolysis treatment in patients with ischemic stroke who have received prophylactic doses of low molecular weight heparins (LMWHs). We aimed to evaluate the safety and outcomes of intravenous thrombolysis treatment in stroke patients taking thromboprophylactic doses of LMWH. Methods- We analyzed 109 291patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke International Thrombolysis Register between 2003 and 2017 not taking oral anticoagulants or therapeutic doses of heparin at stroke onset.

Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial.

Background: Pulsed-wave ultrasound increases the exposure of an intracranial thrombus to alteplase (recombinant tissue plasminogen activator), potentially facilitating early reperfusion. We aimed to ascertain if a novel operator-independent transcranial ultrasound device delivering low-power high-frequency ultrasound could improve functional outcome in patients treated with alteplase after acute ischaemic stroke.

Methods: We did a multicentre, double-blind, phase 3, randomised controlled trial (CLOTBUST-ER) at 76 medical centres in 14 countries.

Clinical Efficacy, Safety and Tolerability of a New Subcutaneous Immunoglobulin 16.5% (Octanorm [Cutaquig®]) in the Treatment of Patients With Primary Immunodeficiencies.

Subcutaneously administered immunoglobulin (SCIG) is increasingly used to treat patients with primary immunodeficiencies (PIDs). Octanorm (marketed as cutaquig® in USA and Canada) is a new 16.5% solution of human SCIG, manufactured by a process based on that of the intravenous preparation (IVIG) octagam®.

CVID-Associated Tumors: Czech Nationwide Study Focused on Epidemiology, Immunology, and Genetic Background in a Cohort of Patients With CVID.

Common variable immunodeficiency disorder (CVID) is one of the most frequent inborn errors of immunity, increased occurrence of malignancies, particularly lymphomas, and gastric cancers, has long been noted among CVID patients. Multifactorial etiology, including immune dysregulation, infections, chronic inflammation, or genetic background, is suggested to contribute to tumor development. Here, we present the results of the first Czech nationwide study focused on epidemiology, immunology and genetic background in a cohort of CVID patients who also developed tumors The cohort consisted of 295 CVID patients followed for 3,070 patient/years.

Are you suffering from a large arterial occlusion? Please raise your arm!

Background And Purpose: Triage tools to identify candidates for thrombectomy are of utmost importance in acute stroke. No prognostic tool has yet gained any widespread use. We compared the predictive value of various models based on National Institutes of Health Stroke Scale (NIHSS) subitems, ranging from simple to more complex models, for predicting large artery occlusion (LAO) in anterior circulation stroke.

Safety of urgent endarterectomy in acute non-disabling stroke patients with symptomatic carotid artery stenosis: an international multicenter study.

Background And Purpose: International recommendations advocate that carotid endarterectomy (CEA) should be performed within 2 weeks from the index event in symptomatic carotid artery stenosis (sCAS) patients. However, there are controversial data regarding the safety of CEA performed during the first 2 days of ictus. The aim of this international, multicenter study was to prospectively evaluate the safety of urgent (0-2 days) in comparison to early (3-14 days) CEA in patients with sCAS.

Treatment of Hereditary Angioedema Attacks with Icatibant and Recombinant C1 Inhibitor During Pregnancy.

Purpose: Hereditary angioedema (HAE) is a rare disease caused by a C1 inhibitor (C1-INH) deficit. Clinically, HAE is manifested by repeated episodes of localized subcutaneous or submucosal oedema attacks. Managing HAE patients in pregnancy is challenging, since there are only limited data on the safety and efficacy of various therapeutic approaches.

Absence of Surface IgD Does Not Impair Naive B Cell Homeostasis or Memory B Cell Formation in Haploinsufficient Humans.

Surface IgD is coexpressed with IgM on naive mature B cells. Still, the role of surface IgD remains enigmatic even 50 y after its initial discovery. In this study, we examined the in vivo role of surface IgD in human B cell homeostasis and Ab responses in four individuals with heterozygous nonsense mutations in All heterozygous individuals had normal numbers of B cells and serum Igs and did not show signs of immunodeficiency or immune dysregulation.

Hyper-IgE in the allergy clinic--when is it primary immunodeficiency?

The 2017 International Union of Immunological Societies (IUIS) classification recognizes 3 hyper-IgE syndromes (HIES), including the prototypic Job's syndrome (autosomal dominant STAT3-loss of function) and autosomal recessive PGM3 and SPINK5 syndromes. Early diagnosis of PID can direct life-saving or transformational interventions; however, it remains challenging owing to the rarity of these conditions. This can result in diagnostic delay and worsen prognosis.

Casein kinase 1 is a therapeutic target in chronic lymphocytic leukemia.

Casein kinase 1δ/ε (CK1δ/ε) is a key component of noncanonical Wnt signaling pathways, which were shown previously to drive pathogenesis of chronic lymphocytic leukemia (CLL). In this study, we investigated thoroughly the effects of CK1δ/ε inhibition on the primary CLL cells and analyzed the therapeutic potential in vivo using 2 murine model systems based on the Eµ-TCL1-induced leukemia (syngeneic adoptive transfer model and spontaneous disease development), which resembles closely human CLL. We can demonstrate that the CK1δ/ε inhibitor PF-670462 significantly blocks microenvironmental interactions (chemotaxis, invasion and communication with stromal cells) in primary CLL cells in all major subtypes of CLL.

Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells.

The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors (TFs) and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchronized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression.

How to make usage of the standardized EuroFlow 8-color protocols possible for instruments of different manufacturers.

A critical component of the EuroFlow standardization of leukemia/lymphoma immunophenotyping is instrument setup. Initially, the EuroFlow consortium developed a step-by-step standard operating protocol for instrument setup of ≥8-color flow cytometers that were available in 2006, when the EuroFlow activities started. Currently, there are 14 instruments from 9 manufacturers capable of 3-laser excitation and ≥8 color measurements.

Central sympathetic nervous system reinforcement in obstructive sleep apnoea.

The available studies on cerebrovascular reactivity and cerebral oxygenation in obstructive sleep apnoea (OSA) patients brought conflicting results, yet the overall evidence suggests that resting state cerebral perfusion is diminished in these patients. Interestingly, in a group of healthy professional breath-hold divers who are exercising very long apnoeas - episodes corresponding to the ones observed in patients with OSA - demonstrated that cerebral oxygenation may remain stable at the expense of extreme sympathetic nervous system (SNS) activation. In the present review we address several mechanisms that could potentially explain these discrepancies.

Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial.

Background: Hereditary angio-oedema is a recurrent, oedematous disorder caused by deficiency of functional C1 inhibitor. Infusions of plasma-derived C1 esterase inhibitor deter attacks of hereditary angio-oedema, but the prophylactic effect of recombinant human C1 esterase inhibitor has not been rigorously studied. We aimed to assess the efficacy of recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema.

Selective IgM Deficiency: Clinical and Laboratory Features of 17 Patients and a Review of the Literature.

Purpose: Primary selective IgM deficiency (sIgMD) is a primary immunodeficiency with unclear pathogenesis and a low number of published cases.

Methods: We reviewed clinical and laboratory manifestations of 17 sIgMD patients. Serum IgM, IgG, and its subclasses, IgA, IgE, antibodies against tetanus toxoid, pneumococcal polysaccharides and Haemophilus influenzae type b, isohemagglutinins, and T and B lymphocyte subsets, expressions of IgM on B cells and B lymphocyte production of IgM were compared with previously reported case reports and a small series of patients, which included 81 subjects in total.

Increased inspiratory resistance affects the dynamic relationship between blood pressure changes and subarachnoid space width oscillations.

Background And Objective: Respiration is known to affect cerebrospinal fluid (CSF) movement. We hypothesised that increased inspiratory resistance would affect the dynamic relationship between blood pressure (BP) changes and subarachnoid space width (SAS) oscillations.

Methods: Experiments were performed in a group of 20 healthy volunteers undergoing controlled intermittent Mueller Manoeuvres (the key characteristic of the procedure is that a studied person is subjected to a controlled, increased inspiratory resistance which results in marked potentiation of the intrathoracic negative pressure).

Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation.

Checkpoint-mediated dependency of tumor cells can be deployed to selectively kill them without substantial toxicity to normal cells. Specifically, loss of CHK1, a serine threonine kinase involved in the surveillance of the G-M checkpoint in the presence of replication stress inflicted by DNA-damaging drugs, has been reported to dramatically influence the viability of tumor cells. CHK1's pivotal role in maintaining genomic stability offers attractive opportunity for increasing the selectivity, effectivity, and reduced toxicity of chemotherapy.

Early Neurological Deterioration During Alteplase Infusion for Acute Ischemic Stroke: An Uncommon Complication of Intravenous Thrombolysis.

Introduction: Recognizing new-territory ischemic stroke as an uncommon complication of intravenous thrombolysis is very important as it can lead to neurological deterioration during tissue-plasminogen-activator infusion.

Case Report: We report a case of an 80-year-old patient that has been treated with intravenous thrombolysis for right middle cerebral artery acute ischemic stroke. During infusion he had an abrupt neurological deterioration that proved to be a distal embolization of an asymptomatic non-occluding tip-of-the-basilar thrombus to the territory of left posterior cerebral artery that has been missed by the treating neurologist and radiologist in the pretreatment computed tomography angiography.

Whole-body low-dose computed tomography in multiple myeloma staging: Superior diagnostic performance in the detection of bone lesions, vertebral compression fractures, rib fractures and extraskeletal findings compared to radiography with similar radiation exposure.

The primary objective of the present prospective study was to compare the diagnostic performance of conventional radiography (CR) and whole-body low-dose computed tomography (WBLDCT) with a comparable radiation dose reconstructed using hybrid iterative reconstruction technique, in terms of the detection of bone lesions, skeletal fractures, vertebral compressions and extraskeletal findings. The secondary objective was to evaluate lesion attenuation in relation to its size. A total of 74 patients underwent same-day skeletal survey by CR and WBLDCT.

Compensatory functional reorganization may precede hypertension-related brain damage and cognitive decline: a functional magnetic resonance imaging study.

Objectives: Our study aimed at exploring structural and functional differences in the brain during higher cognitive processing between middle-aged hypertensive patients and controls matched for sex, age and years of education.

Methods: Two groups of 20 patients took part in MRI examinations. This article reports the results of functional MRI during a Stroop color interference task and structural evaluations based on a modified Fazekas scale.

Albuminuria in Association with Cognitive Function and Dementia: A Systematic Review and Meta-Analysis.

Objectives: Cerebral microvascular disease is considered to contribute to cognitive dysfunction. We opted to explore whether albuminuria, a marker of systemic microangiopathy, is associated with cognitive impairment, dementia, and cognitive function.

Design: Systematic review; independent reviewers screened 2359 articles, derived through the search strategy, for identification of observational studies quantifying an association of albuminuria with the outcomes of interest, abstracted data on study characteristics and results and evaluated studies on quality using the Newcastle-Ottawa scale.