Real-world safety and effectiveness of recombinant porcine sequence factor VIII in acquired haemophilia A: A non-interventional, post-authorization safety study.

INTRODUCTION: Recombinant porcine factor VIII (rpFVIII, susoctocog alfa) is indicated for the treatment of bleeding episodes in adults with acquired haemophilia A (AHA). AIM: To provide long-term real-world safety and effectiveness data for rpFVIII in the management of AHA bleeding episodes. METHODS: US PASS (NCT02610127) was a multicentre, uncontrolled, open-label, post-marketing safety surveillance study conducted in adults with AHA. Data were collected retrospectively or prospectively for 180 days after rpFVIII treatment. The primary outcome was the incidence of treatment-related serious adverse events (SAEs). Secondary outcomes included haemostatic effectiveness of rpFVIII and rpFVIII utilization. RESULTS: Fifty-three patients were enrolled from December 2015 to June 2019 (prospective, n = 30; retrospective, n = 23). Six patients experienced seven treatment-related SAEs (incidence 12.0%). The most common treatment-related SAE was FVIII inhibition (inhibiting antibodies to rpFVIII; incidence 8.0%, 95% CI: 2.2-19.2). Five patients reported seven thromboembolic events; one was an SAE and possibly related to rpFVIII. Of bleeding events treated with rpFVIII, 80.3% (57/71) of bleeds resolved with rpFVIII. The median (range) dose of rpFVIII per infusion was 50 (10-300) units/kg, with a median (range) of 6.0 (1-140) infusions and a median (range) time from bleed onset to bleed resolution of 14.0 (2.0-132.7) days. CONCLUSION: In this real-world study of rpFVIII for AHA, no new safety signals were identified compared with previous clinical trial findings. Eighty percent of bleeds resolved with rpFVIII treatment.

Antiplatelet Therapy in Neurointervention.

The aim of this review is to provide an overview of the use of antiplatelet medication in neurointervention, with a focus on the clinical indications for antiplatelet use in both preventing and reducing platelet aggregation. This review will cover current antiplatelet medications, pharmacokinetics, and pharmacodynamics. We will provide an overview of different endovascular devices and discuss the antiplatelet regimes in neurointervention, highlighting gaps in evidence and scope for future studies.Two randomized controlled trials have evaluated antiplatelet use in the setting of acute large vessel occlusion stroke, with neither demonstrating benefit in their overall cohorts. Evidence on antiplatelet medication for both acute and elective stenting for acute stroke and treatment of cerebral aneurysms is currently based on large case series, and practice in neurointervention has increasingly utilized dual antiplatelet regimes with clopidogrel and second-line agents like prasugrel and ticagrelor. Clopidogrel function testing has an increasing role in neurointerventional procedures, particularly for high metal surface area stents such as the braided flow diverter type stents. Intravenous glycoprotein IIB/IIIA inhibitors have been utilized for both acute bridging and rescue therapy.Antiplatelet decision making is complex, and there are few randomized control trials to guide clinical practice. Comparative trials to guide decision making remain important in both the acute and elective settings. Standardised protocols incorporating platelet function testing may play a role in assisting decision making until more robust clinical evidence is available, particularly in the context of acute neurointerventional stenting for stroke and ruptured cerebral aneurysms.

Robotic Interventional Neuroradiology: Progress, Challenges, and Future Prospects.

Advances in robotic technology have improved standard techniques in numerous surgical and endovascular specialties, offering more precision, control, and better patient outcomes. Robotic-assisted interventional neuroradiology is an emerging field at the intersection of interventional neuroradiology and biomedical robotics. Endovascular robotics can automate maneuvers to reduce procedure times and increase its safety, reduce occupational hazards associated with ionizing radiations, and expand networks of care to reduce gaps in geographic access to neurointerventions. To date, many robotic neurointerventional procedures have been successfully performed, including cerebral angiography, intracranial aneurysm embolization, carotid stenting, and epistaxis embolization. This review aims to provide a survey of the state of the art in robotic-assisted interventional neuroradiology, consider their technical and adoption limitations, and explore future developments critical for the widespread adoption of robotic-assisted neurointerventions.

Endovascular and microsurgical management of blister aneurysms: a multi-centre review.

Blister aneurysms (BA) are high-risk cerebrovascular lesions accounting for 1% of intracranial aneurysms. The defective vessel wall and broad-based neck make this clinical entity difficult to treat, with high rates of re-rupture and mortality in patients presenting with acute subarachnoid haemorrhage. Blister aneurysms pose substantial challenges for both endovascular and microsurgical management. The objective of this study is to evaluate endovascular and microsurgical outcomes in intracranial blister aneurysm management across two tertiary hospitals. A review of two tertiary hospitals with a systematic imaging database search for term of "blister" in modalities from January 2010 to October 2022 was conducted. Operation reports were screened for the 5-year period since cerebral angiogram reports transitioned to surgical database. Identified reports were screened and reviewed for confirmed diagnosis by consultant neuroradiologist. A total of 21 cases of blister aneurysms managed at respective facilities were included. Sixteen cases (76%) were managed endovascularly. Four cases (19%) were managed surgically-2 with primary clipping, and 2 wrap and clipping. One case was managed conservatively (5%). Clinical outcomes were discharge disposition, aneurysm exclusion and post-operative complications. BAs have challenging considerations with high mortality and morbidity. Endovascular treatment offers a less invasive modality with lower rates of intraoperative rupture and morbidity. Mortality rates and patients discharged home were comparable. Commencement of dual anti-platelet therapy was safe in patients with flow diversion stents despite sub-arachnoid blood volume. Management of blister aneurysms is complex. Endovascular treatment shows promise for acute management but careful collaborative consideration of antithrombotic regime and requirement for further surgery should be considered.

Cerebral venous disorders: Diagnosis and endovascular management.

The role of the venous circulation in neurological diseases has been underestimated. In this review, we present an overview of the intracranial venous anatomy, venous disorders of the central nervous system, and options for endovascular management. We discuss the role the venous circulation plays in various neurological diseases including cerebrospinal fluid (CSF) disorders (intracranial hypertension and intracranial hypotension), arteriovenous diseases, and pulsatile tinnitus. We also shed light on emergent cerebral venous interventions including transvenous brain-computer interface implantation, transvenous treatment of communicating hydrocephalus, and the endovascular treatment of CSF-venous disorders.

The incidence of cerebral arterial vasospasm following aneurysmal subarachnoid haemorrhage: a systematic review and meta-analysis.

PURPOSE: To describe a pooled estimated incidence of cerebral arterial vasospasm (aVSP) following aneurysmal subarachnoid haemorrhage (aSAH) and to describe sources of variation in the reported incidence. METHODS: We performed a systematic review and meta-analysis of randomised clinical trials (RCTs) and cohort studies. The primary outcome was the proportion of study participants diagnosed with aVSP. We assessed for heterogeneity based on mode of imaging, indication for imaging, study design and clinical characteristics at a study level. RESULTS: We identified 120 studies, including 19,171 participants. More than 40 different criteria were used to diagnose aVSP. The pooled estimate of the proportion of patients diagnosed with aVSP was 0.42 (95% CI 0.39 to 0.46, I2 = 96.5%). There was no evidence that the incidence aVSP was different, nor that heterogeneity was reduced, when the estimate was assessed by study type, imaging modalities, the proportion of participants with high grade CT scores or poor grade clinical scores. The pooled estimate of the proportion of study participants diagnosed with aVSP was higher in studies with routine imaging (0.47, 95% CI 0.43 to 0.52, I2 = 96.5%) compared to those when imaging was performed when indicated (0.30, 95% CI 0.25 to 0.36, I2 = 94.0%, p for between-group difference < 0.0005). CONCLUSION: The incidence of cerebral arterial vasospasm following aSAH varies widely from 9 to 93% of study participants. Heterogeneity in the reported incidence may be due to variation in the criteria used to diagnose aVSP. A standard set of diagnostic criteria is necessary to resolve the role that aVSP plays in delayed neurological deterioration following aSAH. PROSPERO REGISTRATION: CRD42020191895.

Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion: A Multicenter Experience.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. METHODS: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. RESULTS: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3-5), and 10 (20%) died. CONCLUSIONS: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients.

First-year college students' alcohol and hookup behaviours: sexual scripting and implications for sexual health promotion.

This study used a sexual scripting framework to analyse data from the Online College Social Life Survey to examine the role of individual, (e.g. gender, race and alcohol use), relational (partner type, condom use behaviours), and contextual factors (sex ratios and fraternity/sorority affiliation) influencing 4,292 first-year college students' hookup experiences. Results suggest that hookups are relatively "safe", with the the majority involving non-penetrative sexual behaviour, condom use, and familiar partners. However, alcohol use affected hookup behaviours and lower levels of condom use were associated with heavy alcohol use, even with less well known partners. Findings point to the importance of interventions that reinforce first-year students' positive behaviours and present them with protective behavioural strategies to use in the context of alcohol, and with repeat or well-known partners to reduce risk and have enjoyable, consensual sexual experiences.

Heparin-induced thrombocytopenia associated with collection of hematopoietic progenitor cells by apheresis.

Heparin-induced thrombocytopenia (HIT) can occur following exposure to heparin and is characterized by thrombocytopenia with increased risk for thrombosis. This condition is mediated by formation of immunoglobulin G antibodies against platelet factor 4/heparin complexes that can subsequently lead to platelet activation. Herein, we detail the clinical and laboratory findings, treatments, and outcomes of two patients who developed HIT and thrombosis after undergoing collection of hematopoietic progenitor cells by apheresis (HPC-A) for autologous HPC transplant. Given that heparin may be used during HPC-A collections, these cases emphasize the importance of prompt consideration of HIT in patients that develop thrombocytopenia and thrombosis following HPC-A collection with heparin anticoagulation.

Subarachnoid hemorrhage guidance in the era of the COVID-19 pandemic - An opinion to mitigate exposure and conserve personal protective equipment.

Aneurysmal subarachnoid hemorrhage (SAH) patients require frequent neurological examinations, neuroradiographic diagnostic testing and lengthy intensive care unit stay. Previously established SAH treatment protocols are impractical to impossible to adhere to in the current COVID-19 crisis due to the need for infection containment and shortage of critical care resources, including personal protective equipment (PPE). Centers need to adopt modified protocols to optimize SAH care and outcomes during this crisis. In this opinion piece, we assembled a multidisciplinary, multicenter team to develop and propose a modified guidance algorithm that optimizes SAH care and workflow in the era of the COVID-19 pandemic. This guidance is to be adapted to the available resources of a local institution and does not replace clinical judgment when faced with an individual patient.

Bortezomib for Refractory Immune-Mediated Thrombocytopenia Purpura.

The treatment of refractory immune-mediated thrombocytopenia purpura (ITP) can be challenging. This case report describes treatment of refractory ITP with bortezomib, a proteasome inhibitor. This strategy has been successful in relapsing thrombotic thrombocytopenic purpura but is a novel therapeutic approach for ITP. Further research use of proteasome inhibition in refractory ITP may be warranted.

The Association between Incarceration and Transactional Sex among HIV-infected Young Men Who Have Sex with Men in the United States.

Criminal justice practices in the USA disproportionately affect sexual and racial/ethnic minority men, who are at higher risk of incarceration. Previous research demonstrates associations between incarceration and sexual risk behaviors for men who have sex with men (MSM). However, little of this work focuses on young MSM (YMSM), particularly HIV-infected YMSM, despite nearly one-third reporting engagement in sexual risk behaviors, such as transactional sex. We therefore explored the association between incarceration and transactional sex among HIV-infected YMSM. We recruited 97 HIV-infected YMSM across 14 clinical sites in urban centers from August 2015 to February 2016. We used multivariate logistic regression to examine the relationship between incarceration and transactional sex among YMSM. The majority was 24 years old (78%) and racial/ethnic minority (95%); over half were not in school and reported an annual income of < $12,000. In the multivariate model, having ever been incarcerated (aOR = 3.20; 95% CI 1.07-9.63) was independently associated with a history of transactional sex. Being 24 years vs. younger (aOR = 9.68; 95% CI 1.42-65.78) and having ever been homeless (aOR = 3.71, 95% CI 1.18-11.65) also remained independently associated with a history of transactional sex. This analysis fills a gap in the literature by examining the relationship between incarceration and transactional sex among HIV-infected YMSM. Facilitating youths' engagement with social services available in their HIV clinic may serve as a key strategy in promoting health. Public health efforts need to address social-structural factors driving disproportionate rates of arrest and incarceration and related harms among this population.

The Intersection Between Women's Reproductive Desires and HIV Care Providers' Reproductive Health Practices: A Mixed Methods Analysis.

Background HIV-positive women in the United States can have healthy pregnancies and avoid transmitting HIV to their children. Yet, little is known about the extent to which HIV care providers' reproductive health practices match women's pregnancy desires. Accordingly, we explored young HIV-positive women's pregnancy desires and reproductive health behaviors and examined reproductive health information offered by HIV care clinics. Methods A mixed-method analysis was conducted using data from a 14-site Adolescent Medicine Trials Network (ATN) study. We conducted descriptive statistics on data from 25 HIV-positive women (e.g., demographics, pregnancy desires, and sexual- and health-related behaviors). Qualitative interviews with 58 adolescent and adult clinic providers were analyzed using the constant comparative method. Results About half of the women reported using reproductive health care services (i.e., contraception and pregnancy tests) (n = 12) and wanted a future pregnancy (n = 13). Among women who did not desire a future pregnancy (n = 5), three used dual methods and two used condoms at last sexual encounter. Qualitative themes related to clinics' approaches to reproductive health (e.g., "the emphasis…is to encourage use of contraceptives") and the complexity of merging HIV and reproductive care (e.g., "We [adolescent clinic] transition pregnant moms from our care back and forth to adult care"). Discussion Despite regular HIV-related medical appointments, HIV-positive women may have unaddressed reproductive health needs (e.g., pregnancy desire with providers focused on contraceptive use). Findings from this study suggest that increased support for young HIV-positive women's reproductive health is needed, including supporting pregnancy desires (to choose when, how, and if, to have children).

Transitioning HIV-infected adolescents to adult care at 14 clinics across the United States: using adolescent and adult providers' insights to create multi-level solutions to address transition barriers.

HIV-infected adolescents have disproportionately low rates of care retention and viral suppression. Approximately half disengage from care while transitioning to adult clinics, in part due to fragmented care systems and lack of streamlined protocols. We conducted 58 qualitative interviews with social service and health care providers across 14 Adolescent Trials Network clinics (n = 28) and 20 adult clinics that receive transitioning adolescents (n = 30) from August 2015-June 2016. We used the constant comparative approach to examine processes, barriers, and facilitators of adult care transition. Transition barriers coalesced around three levels. Structural: insurance eligibility, transportation, and HIV-related stigma; Clinical: inter-clinic communication, differences in care cultures, and resource/personnel limitations; and Individual: adolescents' transition readiness and developmental capacity. Staff-initiated solutions (e.g., grant-funded transportation) were often unsustainable and applied individual-level solutions to structural-level barriers. Comprehensive initiatives, which develop collaborative policies and protocols that support providers' ability to match the solution and barrier level (i.e., structural-to-structural), are sorely needed. These initiatives should also support local systematic planning to facilitate inter-clinic structures and communication. Such approaches will help HIV-infected adolescents transition to adult care and improve long-term health outcomes.

Five hematologic tests and treatments to question.

Choosing Wisely(®) is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. The American Society of Hematology (ASH) released its first Choosing Wisely(®) list in 2013. Using the same evidence-based methodology as in 2013, ASH has identified 5 additional tests and treatments that should be questioned by clinicians and patients under specific, indicated circumstances. The ASH 2014 Choosing Wisely(®) recommendations include: (1) do not anticoagulate for more than 3 months in patients experiencing a first venous thromboembolic event in the setting of major, transient risk factors for venous thromboembolism; (2) do not routinely transfuse for chronic anemia or uncomplicated pain crises in patients with sickle cell disease; (3) do not perform baseline or surveillance computed tomography scans in patients with asymptomatic, early-stage chronic lymphocytic leukemia; (4) do not test or treat for heparin-induced thrombocytopenia if the clinical pretest probability of heparin-induced thrombocytopenia is low; and (5) do not treat patients with immune thrombocytopenia unless they are bleeding or have very low platelet counts.

Importance of pharmacokinetic studies in the management of acquired factor X deficiency.

Up to 14% of individuals with systemic AL amyloidosis develop acquired factor X deficiency, which occurs due to adsorption of factor X onto amyloid fibrils. Although baseline factor X levels are not predictive of bleeding risk in these patients, serious hemorrhagic complications can occur, particularly during invasive procedures. Optimal management strategies to attenuate bleeding risk in these patients are unknown. We describe our experience in the management of acquired factor X deficiency, secondary to systemic AL amyloidosis, in a case series of three patients who received prothrombin complex concentrates (PCCs) for treatment and prevention of bleeding events. We performed a retrospective review extracting information on baseline demographics, laboratory data, pharmacokinetic (PK) studies, and clinically documented bleeding events. Our case series demonstrates that individuals with acquired factor X deficiency secondary to amyloidosis have variable laboratory and clinical responses to PCCs. This is likely due to distinct amyloid loads and fibril sequences, leading to different binding avidities for factor X. Our data emphasize the importance of performing PK testing prior to any invasive procedures to determine the dose and frequency interval to achieve adequate factor X levels for hemostasis, given the variable response between individuals.

Identifying existing Choosing Wisely recommendations of high relevance and importance to hematology.

Choosing Wisely (CW) is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. In an effort to learn from and leverage the work of others, the American Society of Hematology CW Task Force developed a method to identify and prioritize CW recommendations from other medical societies of high relevance and importance to patients with blood disorders and their physicians. All 380 CW recommendations were reviewed and assessed for relevance and importance. Relevance was assessed using the MORE(TM) relevance scale. Importance was assessed with regard to six guiding principles: harm avoidance, evidence, aggregate cost, relevance, frequency and impact. Harm avoidance was considered the most important principle. Ten highly relevant and important recommendations were identified from a variety of professional societies. Recommendations focused on decreasing unnecessary imaging, blood work, treatments and transfusions, as well as on increasing collaboration across disciplines and considering value when recommending treatments. Many CW recommendations have relevance beyond the society of origin. The methods developed by the ASH CW Task Force could be easily adapted by other Societies to identify additional CW recommendations of relevance and importance to their fields. Am. J. Hematol. 91:787-792, 2016. © 2016 Wiley Periodicals, Inc.