The blood-brain barrier (BBB) presents a formidable challenge in the development of effective therapeutics in neuro-oncology. This has fueled several decades of efforts to develop strategies for disrupting the BBB, but progress has not been satisfactory. As such, numerous drug-and device-based methods are currently being investigated in humans. Through a focused assessment of completed, active, and pending clinical trials, our first aim in this review is to outline the scientific foundation, successes, and limitations of the BBBD strategies developed to date. Among 35 registered trials relevant to BBBD in neuro-oncology in the ClinicalTrials.gov database, mannitol was the most common drug-based method, followed by RMP-7 and regadenoson. MR-guided focused ultrasound was the most common device-based method, followed by MR-guided laser ablation, ultrasound, and transcranial magnetic stimulation. While most early-phase studies focusing on safety and tolerability have met stated objectives, advanced-phase studies focusing on survival differences and objective tumor response have been limited by heterogeneous populations and tumors, along with a lack of control arms. Based on shared challenges among all methods, our second objective is to discuss strategies for confirmation of BBBD, choice of systemic agent and drug design, alignment of BBBD method with real-world clinical workflow, and consideration of inadvertent toxicity associated with disrupting an evolutionarily-refined barrier. Finally, we conclude with a strategic proposal to approach future studies assessing BBBD.
BackgroundOutpatient thyroid surgery is gaining popularity as it can reduce length of hospital stay, decrease costs of care, and increase patient satisfaction. There remains a significant variation in the use of this practice including a perceived knowledge gap with regards to the safety of outpatient thyroidectomies and how to go about implementing standardized institutional protocols to ensure safe same-day discharge. This review summarizes the information available on the subject based on existing published studies and guidelines.MethodsThis is a scoping review of the literature focused on the safety, efficacy and patient satisfaction associated with outpatient thyroidectomies. The review also summarizes and editorializes the most recent American Thyroid Association guidelines.ResultsIn total, 11 studies were included in the analysis: 6 studies were retrospective analyses, 3 were retrospective reviews of prospective data, and 2 were prospective studies. The relative contraindications to outpatient thyroidectomy have been highlighted, including: complex medical conditions, anticipated difficult surgical dissection, patients on anticoagulation, lack of home support, and patient anxiety toward an outpatient procedure. Utilizing these identified features, an outpatient protocol has been proposed.ConclusionThe salient features regarding patient safety and selection criteria and how to develop a protocol implementing ambulatory thyroidectomies have been identified and reviewed. In conclusion, outpatient thyroidectomy is safe, associated with high patient satisfaction and decreased health costs when rigorous institutional protocols are established and implemented. Successful outpatient thyroidectomies require standardized preoperative selection, clear discharge criteria and instructions, and interprofessional collaboration between the surgeon, anesthetist and same-day nursing staff.
IMPORTANCE Button batteries (BBs) are commonly found in many household items and present a risk of severe injury to children if ingested. The direct apposition of the trachea and recurrent laryngeal nerves with the esophagus puts children at risk of airway injury secondary to the liquefactive necrotic effects of BB impactions.OBJECTIVE To review airway injuries, including long-term sequelae, after BB ingestion in children.EVIDENCE REVIEW For this systematic review, a comprehensive strategy was designed to search MEDLINE, Embase, Cochrane Database of Systematic Reviews, Web of Science, and CINAHL (Cumulative Index of Nursing and Allied Health Literature) from inception to July 31, 2021, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Additional cases were identified from the National Capital Poison Center BB registry. Individual authors were contacted for additional information. Studies with pediatric patients (<18 years) who developed airway injuries after BB ingestion were included. A total of 195 patients were included in the analysis; 95 were male. The mean (SD) age at BB ingestion was 17.8 (10.2) months. The mean (SD) time from BB ingestion to removal was 5.8 (9.0) days. The 2 most common airway sequelae observed in our series were 155 tracheoesophageal fistulae and 16 unilateral vocal cord paralyses. Twentythree children had bilateral vocal cord paralysis. The mean (SD) duration of ingestion leading to vocal cord paralysis was shorter than that of the general cohort (17.8 [22.5] hours vs 138.7 [216.7] hours, respectively). Children presenting with airway symptoms were likely to have a subsequent tracheoesophageal fistula or vocal cord paralysis.CONCLUSIONS AND RELEVANCE Airway injuries are a severe consequence of BB ingestion, occurring more often in younger children. This systematic review found that tracheoesophageal fistulae and vocal cord paralyses were the 2 most common airway injuries, often requiring tracheostomy. Vocal cord injury occurred after a shorter BB exposure time than other airway injuries. Continued efforts should be directed toward prevention strategies to avoid the devastating sequelae of BB-associated airway injury.
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