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Hydroxyurea Therapy Does Not Impact Current Survival Estimates in the East London Sickle Cell Newborn Cohort Study
Conclusions: The study is the first to evaluate survival in a newborn cohort past the age of 20 years. We have confirmed a low mortality rate in childhood, but increased number of deaths in young adults including those with HbSC. This study provides evidence of the benefit of newborn screening and comprehensive care which is accessible at all ages, free of charge. The uptake of HU, particularly at a young age, has been low and a positive effect of HU on survival as described in other studies has not yet been observed in this cohort. Earlier initiation of disease-modifying treatment and longer-term follow-up will be require...
Source: Blood - November 21, 2018 Category: Hematology Authors: Telfer, P., Kaya, B., Tsitsikas, D. A., Barroso, F., Sangarappillai, C. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster III Source Type: research

Induced Pluripotent Stem Cells: The Most Versatile Source for Stem Cell Therapy.
This article describes the advantages and hurdles for the use of induced pluripotent cells as the starting material for a source of replacement cells for regenerative medicine. PMID: 30049501 [PubMed - as supplied by publisher]
Source: Clinical Therapeutics - July 23, 2018 Category: Drugs & Pharmacology Authors: Glicksman MA Tags: Clin Ther Source Type: research

Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.
Authors: Dong AC, Rivella S Abstract Beta-thalassemia and sickle cell anemia are two of the most common diseases related to the hemoglobin protein. In these diseases, the beta-globin gene is mutated, causing severe anemia and ineffective erythropoiesis. Patients can additionally present with a number of life-threatening co-morbidities, such as stroke or spontaneous fractures. Current treatment involves transfusion and iron chelation; allogeneic bone marrow transplant is the only curative option, but is limited by the availability of matching donors and graft-versus-host disease. As these two diseases are monogenic ...
Source: Advances in Experimental Medicine and Biology - November 13, 2017 Category: Research Tags: Adv Exp Med Biol Source Type: research

Attenuation of Myeloid Specific TGF β Signaling Induces Inflammatory Cerebrovascular Disease and Stroke.
Conclusions: Our studies show that TGFβ signaling in myeloid cells is required for maintenance of vascular health, and provide insight into inflammation-mediated cerebrovascular disease and stroke. PMID: 29051340 [PubMed - as supplied by publisher]
Source: Circulation Research - October 19, 2017 Category: Cardiology Authors: Hollander MC, Latour LL, Yang D, Ishii H, Xiao Z, Min Y, Ray-Choudhury A, Munasinghe J, Merchant AS, Lin PC, Hallenbeck J, Boehm M, Yang L Tags: Circ Res Source Type: research

Macrophage-Specific Expression of IL-37 in Hyperlipidemic Mice Attenuates Atherosclerosis.
This study was undertaken to elucidate the role of macrophage-expressed IL-37 in reducing the production and effects of proinflammatory cytokines, preventing foam cell formation, and reducing the development of atherosclerosis. Expression of human IL-37 was achieved with a macrophage-specific overexpression system, using the CD68 promoter in mouse primary bone marrow-derived macrophages via retroviral transduction. Macrophage IL-37 expression in vitro resulted in decreased mRNA (e.g., IL-1B, IL-6, and IL-12) and secreted protein production (e.g., IL-6, M-CSF, and ICAM-1) of key inflammatory mediators. IL-37 expression also...
Source: Journal of Immunology - October 13, 2017 Category: Allergy & Immunology Authors: McCurdy S, Baumer Y, Toulmin E, Lee BH, Boisvert WA Tags: J Immunol Source Type: research

Microglial-mediated PDGF-CC activation increases cerebrovascular permeability during ischemic stroke
AbstractTreatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood –brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα). However, in vitro, activation of PDGF-CC by tPA is very inefficient and the mec...
Source: Acta Neuropathologica - July 19, 2017 Category: Neurology Source Type: research

20 years of Modifying Stroke Risk in Sickle Cell Disease (SCD) Patients: a Single Center Experience of Bone Marrow Transplant (BMT) in SCD (P6.256)
Conclusions:While BMT is curative for SCD, the impact on cerebral vasculopathy and ongoing stroke risk is unknown. Data from this sample suggests that BMT is associated with stabilization but not resolution of vasculopathy and dramatic reduction of stroke after the first year.Study Supported by:N/ADisclosure: Dr. Carpenter has nothing to disclose. Dr. Farias Moeller has nothing to disclose. Dr. Abraham has nothing to disclose. Dr. Khademian has nothing to disclose.
Source: Neurology - April 17, 2017 Category: Neurology Authors: Carpenter, J., Moeller, R. F., Abraham, A., Khademian, Z. Tags: Non-Atherosclerotic Angiopathies and Cerebral Venous Thrombosis Source Type: research

Sickle Cell Disease with Cyanotic Congenital Heart Disease: Long-Term Outcomes in 5 Children.
Abstract Sickle cell disease is a risk factor for cerebrovascular accidents in the pediatric population. This risk is compounded by hypoxemia. Cyanotic congenital heart disease can expose patients to prolonged hypoxemia. To our knowledge, the long-term outcome of patients who have combined sickle cell and cyanotic congenital heart disease has not been reported. We retrospectively reviewed patient records at our institution and identified 5 patients (3 girls and 2 boys) who had both conditions. Their outcomes were uniformly poor: 4 died (age range, 12 mo-17 yr); 3 had documented cerebrovascular accidents; and 3 dev...
Source: Texas Heart Institute Journal - November 30, 2016 Category: Cardiology Authors: Iannucci GJ, Adisa OA, Oster ME, McConnell M, Mahle WT Tags: Tex Heart Inst J Source Type: research

Endothelial Cell-Derived von Willebrand Factor Is the Major Determinant That Mediates von Willebrand Factor-Dependent Acute Ischemic Stroke by Promoting Postischemic Thrombo-Inflammation.
CONCLUSIONS: Plt-VWF, either in presence or absence of ADAMTS13, partially contributes to VWF-dependent injury and postischemic thrombo-inflammation after stroke. EC-VWF is the major determinant that mediates VWF-dependent ischemic stroke by promoting postischemic thrombo-inflammation. PMID: 27444201 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - July 20, 2016 Category: Cardiology Authors: Dhanesha N, Prakash P, Doddapattar P, Khanna I, Pollpeter MJ, Nayak MK, Staber JM, Chauhan AK Tags: Arterioscler Thromb Vasc Biol Source Type: research

Context-dependent effects of SOCS3 in angiotensin II-induced vascular dysfunction and hypertension in mice: mechanisms and role of bone marrow-derived cells
We examined direct effects of Ang II on carotid arteries from SOCS3-deficient (SOCS3+/–) mice and wild-type (WT) littermates using organ culture and then tested endothelial function with acetylcholine (ACh). A low concentration of Ang II (1 nmol/l) did not affect ACh-induced vasodilation in WT but reduced that of SOCS3+/– mice by ~50% (P < 0.05). In relation to mechanisms, effects of Ang II in SOCS3+/– mice were prevented by inhibitors of STAT3, IL-6, NF-B, or superoxide. Systemic Ang II (1.4 mg/kg per day for 14 days) also reduced vasodilation to ACh in WT. Surprisingly, SOCS3 deficiency prevented mos...
Source: AJP: Heart and Circulatory Physiology - June 30, 2016 Category: Cardiology Authors: Li, Y., Kinzenbaw, D. A., Modrick, M. L., Pewe, L. L., Faraci, F. M. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

Context-Dependent Effects of SOCS3 in Angiotensin II-Induced Vascular Dysfunction and Hypertension in Mice: Mechanisms and Role of Bone Marrow-Derived Cells.
We examined direct effects of Ang II on carotid arteries from SOCS3 deficient (SOCS3+/-) mice and wild-type (WT) littermates using organ culture, followed by testing endothelial function with acetylcholine (Ach). A low concentration of Ang II (1 nmol/L) did not affect Ach-induced vasodilation in WT, but reduced that of SOCS3+/- mice by ~50% (P<0.05). In relation to mechanisms, effects of Ang II in SOCS3+/- mice were prevented by inhibitors of STAT3, IL-6, NF-κB or superoxide. Systemic Ang II (1.4 mg/kg per day for 14 d) also reduced vasodilation to Ach in WT. Surprisingly, SOCS3 deficiency prevented most of the endothe...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 21, 2016 Category: Physiology Authors: Li Y, Kinzenbaw DA, Modrick ML, Pewe LL, Faraci FM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Thiamine Deficiency While on Total Parenteral Nutrition Mimicking Acute Stroke: A Case Report (P3.217)
CONCLUSIONS: Thiamine deficiency mimicking stroke while on total parenteral nutrition has been rarely documented. Recognition of this syndrome is critical as prompt treatment may reverse symptoms.Disclosure: Dr. Parker has nothing to disclose. Dr. Marafie has nothing to disclose. Dr. Wolf has nothing to disclose.
Source: Neurology - April 3, 2016 Category: Neurology Authors: Parker, A., Marafie, D., Wolf, V. Tags: Neurocritical Care: Clinical Science and Therapeutics Source Type: research

Light chain amyloidosis: Experience in a tertiary hospital: 2005–2013
Conclusions Cardiac involvement is the major determinant of prognosis. Yield of involved organ biopsy is high (100% heart biopsies). Antineoplastic treatment with bortezomib and/or autologous bone marrow transplantation achieves hematological responses with improvements in organ impairment.
Source: Revista Clinica Espanola - November 27, 2014 Category: Internal Medicine Source Type: research

The impact of Ly6Clow monocytes after cerebral hypoxia-ischemia in adult mice
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Source: Journal of Cerebral Blood Flow - April 30, 2014 Category: Neurology Authors: Jean-Philippe MichaudPedro Moreno Pimentel-CoelhoYannick TremblaySerge Rivest Tags: blood bone marrow transplantation innate immunity ischemia Ly6Clow monocytes stroke Source Type: research

Health status, late effects and long‐term survivorship of allogeneic bone marrow transplantation: a retrospective study
ConclusionThis study shows that allo‐HSCT patients are living with high burdens of chronic diseases that warrant lifelong surveillance and engagement with healthcare. Structured, multi‐disciplinary care as recommended by published guidelines for allo‐HSCT survivors may reduce long‐term effects and improve their outcomes.
Source: Internal Medicine Journal - February 17, 2014 Category: Internal Medicine Authors: G. Gifford, J. Sim, A. Horne, D. Ma Tags: Original Article Source Type: research

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