Intravenous N-Acetylcysteine to Prevent Cisplatin-Induced Hearing Loss in Children: A Nonrandomized Controlled Phase I Trial.

Purpose: Cisplatin-induced hearing loss (CIHL) is common and permanent. As compared with earlier otoprotectants, we hypothesized N-acetylcysteine (NAC) offers potential for stronger otoprotection through stimulation of glutathione (GSH) production. This study tested the optimal dose, safety, and efficacy of NAC to prevent CIHL.

Safety of intra-arterial chemotherapy with or without osmotic blood-brain barrier disruption for the treatment of patients with brain tumors.

Background: Intra-arterial administration of chemotherapy with or without osmotic blood-brain barrier disruption enhances delivery of therapeutic agents to brain tumors. The aim of this study is to evaluate the safety of these procedures.

Methods: Retrospectively collected data from a prospective database of consecutive patients with primary and metastatic brain tumors who received intra-arterial chemotherapy without osmotic blood-brain barrier disruption (IA) or intra-arterial chemotherapy with osmotic blood-brain barrier disruption (IA/OBBBD) at Oregon Health and Science University (OHSU) between December 1997 and November 2018 is reported.

Pharmacological reduction of coagulation factor XI reduces macrophage accumulation and accelerates deep vein thrombosis resolution in a mouse model of venous thrombosis.

Background: Deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS) remain highly prevalent despite modern medical therapy. Contact activation is a promising target for safe antithrombotic anticoagulation. The anti-factor XI (FXI) monoclonal antibody 14E11 reduces circulating levels of FXI without compromising hemostasis.

Advances in Intraarterial Chemotherapy Delivery Strategies and Blood-Brain Barrier Disruption.

Chemotherapeutics play a significant role in the management of most brain tumors. First pass effect, systemic toxicity, and more importantly, the blood-brain barrier pose significant challenges to the success of chemotherapy. Over the last 80 years, different techniques of intraarterial chemotherapy delivery have been performed in many studies but failed to become standard of care.

Blood-brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses.

Intracarotid arterial hyperosmolar mannitol (ICAHM) blood-brain barrier disruption (BBBD) is effective and safe for delivery of therapeutics for central nervous system malignancies. ICAHM osmotically alters endothelial cells and tight junction integrity to achieve BBBD. However, occurrence of neuroinflammation following hemispheric BBBD by ICAHM remains unknown.

Radiation enhances the delivery of antisense oligonucleotides and improves chemo-radiation efficacy in brain tumor xenografts.

Overexpression of O-methylguanine DNA methyltransferase (MGMT) contributes to resistance to chemo-radiation therapy (CRT) in brain tumors. We previously demonstrated that non-ablative radiation improved delivery of anti-MGMT morpholino oligonucleotides (AMONs) to reduce MGMT levels in subcutaneous tumor xenografts. We evaluate this approach to enhance CRT efficacy in rat brain tumor xenograft models.

Long-Term Outcomes of Intra-Arterial Chemotherapy for Progressive or Unresectable Pilocytic Astrocytomas: Case Studies.

Background: Progressive and/or unresectable pilocytic astrocytomas (PAs) carry a poor prognosis compared to typical PA. Early radiotherapy (RT) may have severe long-term neurocognitive side effects in this patient population. Intra-arterial (IA) chemotherapy is a viable alternative or addition to intravenous (IV) chemotherapy, which may be beneficial in avoidance of early RT.

Risk Factors and Disease Course for Blood-Brain Barrier Disruption-Associated Maculopathy.

Importance: Blood-brain barrier disruption (BBBD) is a systemic therapy for malignant central nervous system (CNS) tumors that has been linked to poorly understood pigmentary maculopathy.

Objectives: To examine the rate of and risk factors for the development of BBBD-associated maculopathy and to assess whether there can be visually significant progression after completion of systemic therapy.

Design, Setting, And Participants: In this retrospective case series, data from February 1, 2006, through December 31, 2019, were collected from patients treated with osmotic BBBD at a single tertiary referral center who had subsequent ophthalmic evaluation.

Distinguishing Extravascular from Intravascular Ferumoxytol Pools within the Brain: Proof of Concept in Patients with Treated Glioblastoma.

Background And Purpose: Glioblastoma-associated macrophages are a major constituent of the immune response to therapy and are known to engulf the iron-based MR imaging contrast agent, ferumoxytol. Current ferumoxytol MR imaging techniques for localizing macrophages are confounded by contaminating intravascular signal. The aim of this study was to assess the utility of a newly developed MR imaging technique, segregation and extravascular localization of ferumoxytol imaging, for differentiating extravascular-from-intravascular ferumoxytol contrast signal at a delayed 24-hour imaging time point.

Maculopathy Associated With Osmotic Blood- Brain Barrier Disruption and Chemotherapy in Patients With Primary CNS Lymphoma.

Background And Objective: To describe the incidence, characteristics, and risk factors of a pigmentary maculopathy in patients with primary central nervous system (CNS) lymphoma treated with blood-brain barrier disruption (BBBD) therapy.

Patients And Methods: This retrospective chart review included patients with biopsy-proven primary CNS lymphoma treated with or without BBBD therapy who underwent an ophthalmic examination after starting systemic treatment. Clinical data and all available retinal imaging were analyzed.

Impact of maintenance rituximab on duration of response in primary central nervous system lymphoma.

Purpose: The role of maintenance immunotherapy with anti-CD20 monoclonal antibody rituximab in primary central nervous system lymphoma (PCNSL) is unclear. We retrospectively reviewed the medical records of all immunocompetent adults with newly diagnosed PCNSL treated at our institution between1996 and 2017.

Methods: We identified 66 patients who attained complete response (CR) after completion of first-line regimen; 20 received maintenance therapy (maintenance therapy group) and 46 were observed with serial MRI scans without maintenance therapy (no-maintenance therapy group).

Diagnostic impact of preoperative corticosteroids in primary central nervous system lymphoma.

Purpose: High dose corticosteroids are an effective tool for rapidly alleviating neurologic symptoms caused by intracranial mass lesions. However, there is concern that preoperative corticosteroids limit the ability to obtain a definitive pathologic diagnosis, particularly if imaging features suggest primary central nervous system lymphoma (PCNSL).

Methods: To explore the impact of preoperative corticosteroids in newly diagnosed PCNSL patients, from 2009 to 2018 treated at our institution.

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI.

Background Ferumoxytol is approved for use in the treatment of iron deficiency anemia, but it can serve as an alternative to gadolinium-based contrast agents. On the basis of postmarketing surveillance data, the Food and Drug Administration issued a black box warning regarding the risks of rare but serious acute hypersensitivity reactions during fast high-dose injection (510 mg iron in 17 seconds) for therapeutic use. Whereas single-center safety data for diagnostic use have been positive, multicenter data are lacking.

Toll-like Receptor 4 Signaling and Downstream Neutrophilic Inflammation Mediate Endotoxemia-Enhanced Blood-Labyrinth Barrier Trafficking.

Hypothesis: Both toll-like receptor 4 (TLR4) and downstream neutrophil activity are required for endotoxemia-enhanced blood-labyrinth barrier (BLB) trafficking.

Background: Aminoglycoside and cisplatin are valuable clinical therapies; however, these drugs often cause life-long hearing loss. Endotoxemia enhances the ototoxicity of aminoglycosides and cisplatin in a TLR4 dependent mechanism for which downstream proinflammatory signaling orchestrates effector immune cells including neutrophils.