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. Chemotherapy-related complications are detailed per Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Procedure-related complications are grouped as major and minor. Results: 4939 procedures (1102 IA; 3837 IA/OBBBD) were performed on 436 patients with various pathologies (primary central nervous system lymphoma [26.4%], glioblastoma [18.1%], and oligodendroglioma [14.7%]). Major procedure-related complications (IA: 12, 1%; IA/OBBBD: 27, 0.7%; P = .292) occurred in 39 procedures including 3 arterial dissections requiring intervention, 21 symptomatic strokes, 3 myocardial infarctions, 6 cervical cord injuries, and 6 deaths within 3 days. Minor procedure-related complications occurred in 330 procedures (IA: 41, 3.7%; IA/OBBBD: 289, 7.5%; P = .001). Chemotherapy-related complications with a CTCAE attribution and grade higher than 3 was seen in 359 (82.3%) patients. Conclusions: We provide safety and tolerability data from the largest cohort of consecutive patients who received IA or IA/OBBBD. Our data demonstrate that IA or IA/OBBBD safely enhance drug delivery to brain tumors and brain around the tumor.

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. OBJECTIVE: To evaluate the safety and efficacy of IA chemotherapy in this subset of patients. METHODS: This is a retrospective review of medical records of PA patients who are treated with IA chemotherapy at Oregon Health & Science University from 1997 until 2019. Response to treatment was categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Progression free survival (PFS) and overall survival (OS) are also reported. RESULTS: Twelve patients were identified. All patients experienced progression prior to initiation of IA chemotherapy. The most common grade 3 or 4 toxicities related to chemotherapy were thrombocytopenia (66%), neutropenia (66%), leukopenia (50%), anemia (33%), and lymphopenia (16%). Responses achieved were CR in 1, PR in 3, SD in 7, and PD in 1. Median PFS and median OS were 16.5 and 83.5 mo, respectively. A total of 112 procedures (IA injections) were performed and 250 arteries were catheterized. There were 3 minor and no major complications attributable to procedures. CONCLUSION: This study demonstrates that IA chemotherapy can be safely used in patients with unresectable or progressive PA.

Postdischarge Care of Pediatric Traumatic Brain Injury in Argentina: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To develop, in partnership with families of children with traumatic brain injury, a postdischarge intervention that is effective, simple, and sustainable. DESIGN: Randomized Controlled Trial. SETTING: Seven Level 1 Pediatric Trauma Centers in Argentina. PATIENTS: Persons less than 19 years of age admitted to one of the study hospitals with a diagnosis of severe, moderate, or complicated mild traumatic brain injury and were discharged alive. INTERVENTIONS: Patients were randomly assigned to either the intervention or standard care group. A specially trained Community Resource Coordinator was assigned to each family in the intervention group. We hypothesized that children with severe, moderate, and complicated mild traumatic brain injury who received the intervention would have significantly better functional outcomes at 6 months post discharge than those who received standard care. We further hypothesized that there would be a direct correlation between patient outcome and measures of family function. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was a composite measured at 6 months post injury. There were 308 patients included in the study (61% men). Forty-four percent sustained a complicated mild traumatic brain injury, 18% moderate, and 38% severe. Sixty-five percent of the patients were 8 years old or younger, and over 70% were transported to the hospital without ambulance assistance. There was no significant difference between groups on the primary outcome measure. There was a statistically significant correlation between the primary outcome measure and the scores on the Family Impact Module of the Pediatric Quality of Life Inventory (ρ = 0.57; p < 0.0001). Children with better outcomes lived with families reporting better function at 6 months post injury. CONCLUSIONS: Although no significant effect of the intervention was demonstrated, this study represents the first conducted in Latin America that documents the complete course of treatment for pediatric patients with traumatic brain injury spanning hospital transport through hospital care and into the postdischarge setting.

Safety Report of Ferumoxytol for Magnetic Resonance Imaging in Children and Young Adults.

OBJECTIVE: The aim of this study was to assess the safety profile of ferumoxytol as an intravenous magnetic resonance imaging contrast agent in children. MATERIALS AND METHODS: We prospectively evaluated the safety of ferumoxytol administrations as an "off-label" contrast agent for magnetic resonance imaging in nonrandomized phase 4 clinical trials at 2 centers. From September 2009 to February 2015, 49 pediatric patients (21 female and 28 male, 5-18 years) and 19 young adults (8 female and 11 male, 18-25 years) were reported under an investigator-initiated investigational new drug investigation with institutional review board approval, in health insurance portability and accountability act compliance, and after written informed consent of the child's legal representative or the competent adult patient was obtained. Patients received either a single dose (5 mg Fe/kg) or up to 4 doses of ferumoxytol (0.7-4 mg Fe/kg) intravenously, which were approximately equivalent to one third of the dose for anemia treatment. We monitored vital signs and adverse events directly for up to 1 hour after injection. In addition, we examined weekly vitals, hematologic, renal, and liver serum panels for 1 month after injection in over 20 pediatric patients. At fixed time points before and after ferumoxytol injection, data were evaluated for significant differences by a repeated measures linear mixed model. RESULTS: Four mild adverse events, thought to be related to ferumoxytol, were observed within 1 hour of 85 ferumoxytol injections: 2 episodes of mild hypotension and 1 case of nausea in 65 injections in pediatric patients without related clinical symptoms. One young adult patient developed warmness and erythema at the injection site. All adverse events were self-resolving. No spontaneous serious adverse events were reported. At a dose of 5 mg Fe/kg or lower, intravenous ferumoxytol injection had no clinical relevance or statistically significant effect (P > 0.05) on vital signs, hematological parameters, kidney function, or liver enzymes within 1 month of the injection. CONCLUSIONS: Ferumoxytol was overall well tolerated among 49 pediatric and 19 young adult patients experiencing various tumors or kidney transplants without major adverse events or signs of hematologic and kidney impairment or liver toxicity. Larger studies are needed to determine the incidence of anaphylactic reactions.

Concussion guidelines step 1: systematic review of prevalent indicators.

BACKGROUND: Currently, there is no evidence-based definition for concussion that is being uniformly applied in clinical and research settings. OBJECTIVE: To conduct a systematic review of the highest-quality literature about concussion and to assemble evidence about the prevalence and associations of key indicators of concussion. The goal was to establish an evidence-based foundation from which to derive, in future work, a definition, diagnostic criteria, and prognostic indicators for concussion. METHODS: Key questions were developed, and an electronic literature search from 1980 to 2012 was conducted to acquire evidence about the prevalence of and associations among signs, symptoms, and neurologic and cognitive deficits in samples of individuals exposed to potential concussive events. Included studies were assessed for potential for bias and confound and rated as high, medium, or low potential for bias and confound. Those rated as high were excluded from the analysis. Studies were further triaged on the basis of whether the definition of a case of concussion was exclusive or inclusive; only those with wide, inclusive case definitions were used in the analysis. Finally, only studies reporting data collected at fixed time points were used. For a study to be included in the conclusions, it was required that the presence of any particular sign, symptom, or deficit be reported in at least 2 independent samples. RESULTS: From 5437 abstracts, 1362 full-text publications were reviewed, of which 231 studies were included in the final library. Twenty-six met all criteria required to be used in the analysis, and of those, 11 independent samples from 8 publications directly contributed data to conclusions. Prevalent and consistent indicators of concussion are (1) observed and documented disorientation or confusion immediately after the event, (2) impaired balance within 1 day after injury, (3) slower reaction time within 2 days after injury, and/or (4) impaired verbal learning and memory within 2 days after injury. CONCLUSION: The results of this systematic review identify the consistent and prevalent indicators of concussion and their associations, derived from the strongest evidence in the published literature. The product is an evidence-based foundation from which to develop diagnostic criteria and prognostic indicators.

Patients' perspectives on total knee replacement.

OBJECTIVE: Because patients' perspectives on total knee replacement (TKR) surgery have rarely been the topic of research, this study sought to describe their pre- and postoperative experiences. METHODS: Using a qualitative descriptive design, researchers collected data from a convenience sample of 27 patients who were about to undergo or had recently undergone TKR. Preoperative data were obtained in focus group sessions (n = 17); postoperative data were obtained in individual interviews (n = 10). All data-collection sessions were tape-recorded and transcribed, and transcripts were analyzed. The researchers isolated themes by identifying recurrent words and phrases and then sorted the data into thematic categories. RESULTS: Four main themes emerged. First, many participants delayed surgery for months to years, despite increasing pain and limitation. Second, once participants decided to proceed with surgery, they entered a period of waiting and worrying about what would happen during and after surgery. Third, both pre- and postoperative participants struggled with the need for independence, as well as with learning to accept the new knee. And fourth, patients experienced postoperative pain associated with surgery and rehabilitation, yet reported having hope that they'd regain function. CONCLUSIONS: These findings suggest that patients need to be better educated and supported before and after TKR surgery. More research is needed to shed light on how patients' experiences influence their decisions about the surgery and its outcomes.