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

Schumpeter and Venture Finance: Radical Theorist, Broke Investor and Enigmatic Teacher

Schumpeter's relation to venture finance constitutes a fascinating yet so far unacknowledged chapter of his biography and financial history. Presenting new historical evidence and pointing out connections that have so far escaped attention, we first discuss Schumpeter's venture theory of money and banking, then his personal history as a broke investor in Vienna, and finally his influence on the emerging venture industry during his later years at Harvard. We show how the theoretical vision inspired his failed effort as a venture investor in the 1920s, and provided a powerful intellectual frame for the later development of venture finance in the 1940s

De novo aneurysm formation and regression after brain arteriovenous malformation embolization: case report.

BACKGROUND: The formation of de novo aneurysms is a known complication of vessel occlusion (Wright RL, Sweet WH. Carotid or vertebral occlusion in the treatment of intracranial aneurysms: value of early and late readings of carotid and retinal pressures. Clin Neurosurg 1962:9;163-192). Aneurysms most commonly develop on newly formed primary collateral routes as a result of increased flow through these collaterals. Development of aneurysms is not commonly seen in vessels whose flow has been directly decreased by therapeutic or natural occlusion. CASE DESCRIPTION: A 53-year-old woman with an intracerebral hemorrhage underwent cerebral angiography which demonstrated a right parietal AVM. An enlarged right ACA gave rise to 3 direct feeding pedicles. Leptomeningeal collaterals from the right MCA as well as the right PCA also gave collateral supply to the AVM. The lesion had superficial drainage into the superior sagittal sinus and deep venous drainage into the right posterior pericallosal vein. No feeding artery aneurysms or intranidal aneurysms were present. Treatment plan included preoperative embolization followed by surgical resection. CONCLUSION: To our knowledge, this is the first reported case of a de novo aneurysm forming and regressing in an artery hemodynamically related to an embolized AVM. The short timescale of its development (6 weeks) is also noteworthy. The spontaneous regression suggests that at least some aneurysms forming in vessels after abrupt decrease in distal runoff may have a self-limited course. Such lesions may do best if not subjected to direct endovascular or surgical treatment

Admission angiographic cerebral circulation time may predict subsequent angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Angiographic cerebral vasospasm occurs in approximately 70% of patients hospitalized after aneurysmal subarachnoid hemorrhage (SAH) and is associated with poor outcome. In this study, we examined whether or not cerebral circulation time (CCT) measured with digital subtraction angiography was associated with angiographic vasospasm. METHODS: Patients who underwent cerebral angiography within 24 hours of SAH were analyzed. Contrast dye transit time from the arterial to the venous phase was measured to obtain CCT (supraclinoid internal carotid artery to parietal cortical veins) and microvascular CCT (cortical middle cerebral artery to parietal cortical veins). Patients with ruptured anterior circulation aneurysms and vasospasm on follow-up angiography (Group A) were compared with patients with SAH without vasospasm (Group B) and with normal control subjects (Group C). RESULTS: There were 20 patients in Group A (mean age, 51 +/- 13 yr), 17 patients in Group B (56 +/- 12 yr), and 98 patients in Group C (52 +/- 12 yr). CCT in patients in Group A (7.7 +/- 1.9 s) was significantly longer than those in Groups B (6.6 +/- 1.2 s; P = 0.005) and C (5.9 +/- 1 s; P \u3c 0.001). Microvascular CCT in patients in Group A (7.1 +/- 1.8 s) was significantly longer than those in Groups B (6.1 +/- 1.2 s; P = 0.003) and C (5.4 +/- 0.9 s; P \u3c 0.001). CONCLUSION: Prolonged CCT, a measurement of increased small vessel resistance, can be identified within 24 hours after SAH and is associated with subsequent angiographic vasospasm. These results suggest that microcirculation changes may be involved in vasospasm

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