Successful Treatment of Ibrutinib-Associated Central Nervous System Hemorrhage with Platelet Transfusion Support

Ibrutinib is a novel targeted therapy for B-cell malignancies. Hemorrhagic events were reported in the original trials, however the mechanism of bleeding is just being elucidated. Recent studies have demonstrated platelet dysfunction as a mechanism of bleeding. Currently we report two patients who developed life-threatening central nervous system hemorrhage while receiving ibrutinib for chronic lymphoid leukemia (CLL) and mantle cell lymphoma, respectively. Both patients improved rapidly after platelet transfusions even though their platelet counts were normal or only mildly reduced at the time of hemorrhage. We suggest that platelet transfusions can ameliorate the platelet dysfunction defect of ibrutinib and can support the patient through the critical period until new platelet production occurs

Plasma Dynamics

Contains research objectives and summary of research on eighteen research projects split into seven sections and reports on four research projects.U.S. Atomic Energy Commission (Contract AT(l1-1)-3070)National Science Foundation (Grant GK-37979X1

Root Suberin Forms an Extracellular Barrier That Affects Water Relations and Mineral Nutrition in Arabidopsis

Though central to our understanding of how roots perform their vital function of scavenging water and solutes from the soil, no direct genetic evidence currently exists to support the foundational model that suberin acts to form a chemical barrier limiting the extracellular, or apoplastic, transport of water and solutes in plant roots. Using the newly characterized enhanced suberin1 (esb1) mutant, we established a connection in Arabidopsis thaliana between suberin in the root and both water movement through the plant and solute accumulation in the shoot. Esb1 mutants, characterized by increased root suberin, were found to have reduced day time transpiration rates and increased water-use efficiency during their vegetative growth period. Furthermore, these changes in suberin and water transport were associated with decreases in the accumulation of Ca, Mn, and Zn and increases in the accumulation of Na, S, K, As, Se, and Mo in the shoot. Here, we present direct genetic evidence establishing that suberin in the roots plays a critical role in controlling both water and mineral ion uptake and transport to the leaves. The changes observed in the elemental accumulation in leaves are also interpreted as evidence that a significant component of the radial root transport of Ca, Mn, and Zn occurs in the apoplast

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Endovascular Treatment of Intracranial Dural Arteriovenous Fistulae Using Onyx: A Case Series

OBJECTIVE: An endovascular approach is often the first-line treatment of dural arteriovenous fistulae (DAVFs). Information on the use of Onyx (ev3 Neurovascular, Irvine, CA) for treating DAVFs, however, is limited. Therefore, we present our early experience, technical considerations, and complications associated with the use of Onyx for DAVF embolization. METHODS: Twenty-eight patients with 29 DAVFs treated with Onyx embolization were included in this analysis. Hospital records, operative reports, and angiograms were reviewed and analyzed. RESULTS: Forty Onyx procedures, including 39 transarterial and 1 transvenous approaches, were performed. Fifty-one external carotid artery branches, 8 posterior meningeal artery branches, and 3 internal carotid artery branches were used for Onyx embolization. Branches of the middle meningeal artery were embolized 32 times, and the occipital artery was embolized 15 times. Twenty-one fistulae (72%) were cured angiographically with endovascular therapy. Transarterial embolization via the middle meningeal artery cured 12 DAVFs (41%). Four complications (9.7%) were recorded, including 3 transient (7.3%) and 1 permanent neurological deficits (2.4%). Follow-up imaging, which was available for 8 fistulae with angiographic cures, showed no evidence of recurrence. CONCLUSION: Transarterial Onyx embolization of external carotid artery branches, particularly the middle meningeal artery, offers a high likelihood of cure. This technique provides a safe and effective method of embolization with few side effects and complications. However, long-term follow-up is needed to establish its efficacy. © 2009 by the Congress of Neurological Surgeons