Surgery is curative for most meningiomas, but a minority of these tumors recur and progress after resection. Initial trials of medical therapies for meningioma utilized nonspecific cytotoxic chemotherapies. The presence of hormone receptors on meningioma ushered in trials of hormone-mimicking agents. While these trials expanded clinical understanding of meningioma, they ultimately had limited efficacy in managing aggressive lesions. Subsequent detection of misregulated proteins and genomic aberrancies motivated the study of therapies targeting specific biological disturbances observed in meningioma. These advances led to trials of targeted kinase inhibitors and immunotherapies, as well as combinations of these agents together with chemotherapies. Prospective trials currently recruiting participants are testing a diverse range of medical therapies for meningioma, and some studies now require the presence of a specific protein alteration or genetic mutation as an inclusion criterion. Increasing understanding of the unique and heterogeneous nature of meningiomas will continue to spur the development of novel medical therapies for the arsenal against aggressive tumors.
Saksham Gupta, Wenya Linda Bi and Ian F. Dunn
Saksham Gupta, Wenya Linda Bi, Alexandra Giantini Larsen, Sally Al-Abdulmohsen, Malak Abedalthagafi and Ian F. Dunn
Craniopharyngiomas are among the most challenging of intracranial tumors to manage because of their pattern of growth, associated morbidities, and high recurrence rate. Complete resection on initial encounter can be curative, but it may be impeded by the risks posed by the involved neurovascular structures. Recurrent craniopharyngiomas, in turn, are frequently refractory to additional surgery and adjuvant radiation or chemotherapy.
The authors conducted a review of primary literature.
Recent advances in the understanding of craniopharyngioma biology have illuminated potential oncogenic targets for pharmacotherapy. Specifically, distinct molecular profiles define two histological subtypes of craniopharyngioma: adamantinomatous and papillary. The discovery of overactive B-Raf signaling in the adult papillary subtype has led to reports of targeted inhibitors, with a growing acceptance for refractory cases. An expanding knowledge of the biological underpinnings of craniopharyngioma will continue to drive development of targeted therapies and immunotherapies that are personalized to the molecular signature of each individual tumor.
The rapid translation of genomic findings to medical therapies for recurrent craniopharyngiomas serves as a roadmap for other challenging neurooncological diseases.
Saksham Gupta, Monty Khajanchi, Vineet Kumar, Nakul P. Raykar, Blake C. Alkire, Nobhojit Roy and Kee B. Park
Traumatic brain injury (TBI) is a global epidemic with an increasing incidence in low- and middle-income countries (LMICs). The time from arrival at the hospital to receiving appropriate treatment (“third delay”) can vary widely in LMICs, although its association with mortality in TBI remains unknown.
A retrospective cohort analysis with multivariable logistic regression was conducted using the Toward Improved Trauma Care Outcomes in India database, which contains data from 4 urban trauma centers in India from 2013–2015.
There were 6278 TBIs included in the cohort. The patients’ median age was 39 years (interquartile range 27–52 years) and 80% of patients were male. The most frequent mechanisms of injury were road traffic accidents (52%) and falls (34%). A majority of cases were transfers from other facilities (79%). In-hospital 30-day mortality was 27%; of patients who died, 21% died within 24 hours of arrival. The median third delay was 10 minutes (interquartile range 0–60 minutes); 34% of cases had moderate third delay (10–60 minutes) and 22% had extended third delay (≥ 61 minutes). Overall 30-day mortality was associated with moderate third delay (OR 1.3, p = 0.001) and extended third delay (OR 1.3, p = 0.001) after adjustment by pertinent covariates. This effect was pronounced for 24-hour mortality: moderate and extended third delays were independently associated with ORs of 3.4 and 3.8, respectively, for 24-hour mortality (both p < 0.001).
Third delay is associated with early mortality in patients with TBI, and represents a target for process improvement in urban trauma centers.
Saksham Gupta, Blake M. Hauser, Mark M. Zaki, Edward Xu, David J. Cote, Yi Lu, John H. Chi, Michael Groff, Ayaz M. Khawaja, Mitchel B. Harris, Timothy R. Smith and Hasan A. Zaidi
Sports injuries present a considerable risk of debilitating spinal injury. Here, the authors sought to profile the epidemiology and clinical risk of traumatic spinal injuries (TSIs) in pediatric sports injuries.
The authors conducted a retrospective cohort analysis of pediatric patients who had experienced a sports-related TSI, including spinal fractures and spinal cord injuries, encoded in the National Trauma Data Bank in the period from 2011 to 2014.
Included in the analysis were 1723 cases of pediatric sports-related TSI, which represented 3.7% of all pediatric sports-related trauma. The majority of patients with TSI were male (81%), and the median age was 15 years (IQR 13–16 years). TSIs arose most often from cycling accidents (47%) and contact sports (28%). The most frequently fractured regions were the thoracic (30%) and cervical (27%) spine. Among patients with spinal cord involvement (SCI), the cervical spine was involved in 60% of cases.
The average length of stay for TSIs was 2 days (IQR 1–5 days), and 32% of the patients required ICU-level care. Relative to other sports-related trauma, TSIs without SCI were associated with an increased adjusted mean length of stay by 1.8 days (95% CI 1.6–2.0 days), as well as the need for ICU-level care (adjusted odds ratio [aOR] 1.6, 95% CI 1.3–1.9). Also relative to other sports-related trauma, TSIs with SCI had an increased length of stay by 2.1 days (95% CI 1.8–2.6 days) and the need for ICU-level care (aOR 3.6, 95% CI 2.6–4.8).
TSIs without SCI were associated with discharge to or with rehabilitative services (aOR 1.7, 95% CI 1.5–2.0), as were TSIs with SCI (aOR 4.0, 95% CI 3.2–4.9), both relative to other sports-related trauma. Among the patients with TSIs, predictors of the need for rehabilitation at discharge were having a laminectomy or fusion, concomitant lower-extremity injury, head injury, and thoracic injury. Although TSIs affected 4% of the study cohort, these injuries were present in 8% of patients discharged to or with rehabilitation services and in 17% of those who died in the hospital.
Traumatic sports-related spinal injuries cause significant morbidity in the pediatric population, especially if the spinal cord is involved. The majority of TSI cases arose from cycling and contact sports accidents, underscoring the need for improving education and safety in these activities.
Michael C. Dewan, Abbas Rattani, Saksham Gupta, Ronnie E. Baticulon, Ya-Ching Hung, Maria Punchak, Amit Agrawal, Amos O. Adeleye, Mark G. Shrime, Andrés M. Rubiano, Jeffrey V. Rosenfeld and Kee B. Park
Traumatic brain injury (TBI)—the “silent epidemic”—contributes to worldwide death and disability more than any other traumatic insult. Yet, TBI incidence and distribution across regions and socioeconomic divides remain unknown. In an effort to promote advocacy, understanding, and targeted intervention, the authors sought to quantify the case burden of TBI across World Health Organization (WHO) regions and World Bank (WB) income groups.
Open-source epidemiological data on road traffic injuries (RTIs) were used to model the incidence of TBI using literature-derived ratios. First, a systematic review on the proportion of RTIs resulting in TBI was conducted, and a meta-analysis of study-derived proportions was performed. Next, a separate systematic review identified primary source studies describing mechanisms of injury contributing to TBI, and an additional meta-analysis yielded a proportion of TBI that is secondary to the mechanism of RTI. Then, the incidence of RTI as published by the Global Burden of Disease Study 2015 was applied to these two ratios to generate the incidence and estimated case volume of TBI for each WHO region and WB income group.
Relevant articles and registries were identified via systematic review; study quality was higher in the high-income countries (HICs) than in the low- and middle-income countries (LMICs). Sixty-nine million (95% CI 64–74 million) individuals worldwide are estimated to sustain a TBI each year. The proportion of TBIs resulting from road traffic collisions was greatest in Africa and Southeast Asia (both 56%) and lowest in North America (25%). The incidence of RTI was similar in Southeast Asia (1.5% of the population per year) and Europe (1.2%). The overall incidence of TBI per 100,000 people was greatest in North America (1299 cases, 95% CI 650–1947) and Europe (1012 cases, 95% CI 911–1113) and least in Africa (801 cases, 95% CI 732–871) and the Eastern Mediterranean (897 cases, 95% CI 771–1023). The LMICs experience nearly 3 times more cases of TBI proportionally than HICs.
Sixty-nine million (95% CI 64–74 million) individuals are estimated to suffer TBI from all causes each year, with the Southeast Asian and Western Pacific regions experiencing the greatest overall burden of disease. Head injury following road traffic collision is more common in LMICs, and the proportion of TBIs secondary to road traffic collision is likewise greatest in these countries. Meanwhile, the estimated incidence of TBI is highest in regions with higher-quality data, specifically in North America and Europe.