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Saksham Gupta, Wenya Linda Bi, and Ian F. Dunn

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.

Open access

Saksham Gupta, Wenya Linda Bi, Donald J. Annino, and Ian F. Dunn

BACKGROUND

Olfactory neuroblastomas are rare sinonasal tumors that arise from the olfactory epithelium. The authors presented a case of an olfactory neuroblastoma with extensive cranial invasion that demonstrated dramatic response to sorafenib, a tyrosine kinase inhibitor.

OBSERVATIONS

A 54-year-old man with history of prostate cancer and melanoma presented with left-sided proptosis and was found to have a 6.5-cm Kadish stage D olfactory neuroblastoma with cranial invasion that was refractory to chemotherapy and everolimus. However, it demonstrated dramatic response to sorafenib, causing extensive skull base defects that prompted operative repair. Genomic analysis of the tumor revealed mutations in TSC1 and SUFU. The patient developed disease progression with liver metastases 35 months after starting sorafenib, prompting a change to lenvatinib. He experienced progression of his olfactory neuroblastoma 10 months following this change and died in hospice 1 month later.

LESSONS

The authors reviewed the clinical presentation and management of a large olfactory neuroblastoma with dramatic response to sorafenib. They highlighted prior uses of targeted therapy in the management of refractory olfactory neuroblastoma within the context of current standard treatment regimens. Targeted therapies may play a vital role in the management of refractory olfactory neuroblastoma.

Restricted access

Saksham Gupta, Monty Khajanchi, Vineet Kumar, Nakul P. Raykar, Blake C. Alkire, Nobhojit Roy, and Kee B. Park

OBJECTIVE

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

Third delay is associated with early mortality in patients with TBI, and represents a target for process improvement in urban trauma centers.

Free access

Saksham Gupta, Wenya Linda Bi, Alexandra Giantini Larsen, Sally Al-Abdulmohsen, Malak Abedalthagafi, and Ian F. Dunn

OBJECTIVE

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.

METHODS

The authors conducted a review of primary literature.

RESULTS

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.

CONCLUSIONS

The rapid translation of genomic findings to medical therapies for recurrent craniopharyngiomas serves as a roadmap for other challenging neurooncological diseases.

Free access

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

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Restricted access

Samantha E. Hoffman, Blake M. Hauser, Mark M. Zaki, Saksham Gupta, Melissa Chua, Joshua D. Bernstock, Ayaz M. Khawaja, Timothy R. Smith, and Hasan A. Zaidi

OBJECTIVE

Despite understanding the associated adverse outcomes, identifying hospitalized patients at risk for sepsis is challenging. The authors aimed to characterize the epidemiology and clinical risk of sepsis in patients who underwent vertebral fracture repair for traumatic spinal injury (TSI).

METHODS

The authors conducted a retrospective cohort analysis of adults undergoing vertebral fracture repair during initial hospitalization after TSI who were registered in the National Trauma Data Bank from 2011 to 2014.

RESULTS

Of the 29,050 eligible patients undergoing vertebral fracture repair, 317 developed sepsis during initial hospitalization. Of these patients, most presented after a motor vehicle accident (63%) or fall (28%). Patients in whom sepsis developed had greater odds of being male (adjusted OR [aOR] 1.5, 95% CI 1.1–1.9), having diabetes mellitus (aOR 1.5, 95% CI 1.11–2.1), and being obese (aOR 1.9, 95% CI 1.4–2.5). Additionally, they had greater odds of presenting with moderate (aOR 2.7, 95% CI 1.8–4.2) or severe (aOR 3.9, 95% CI 2.9–5.2) Glasgow Coma Scale scores and of having concomitant abdominal injuries (aOR 1.9, 95% CI 1.5–2.5) but not cranial, thoracic, or lower-extremity injuries. Interestingly, cervical spine injury was significantly associated with developing sepsis (OR 1.4, 95% CI 1.1–1.8), but thoracic and lumbar spine injuries were not. Spinal cord injury (OR 1.9, 95% CI 1.5–2.5) was also associated with sepsis regardless of level. Patients with sepsis were hospitalized approximately 16 days longer. They had greater odds of being discharged to rehabilitative care or home with rehabilitative care (OR 2.4, 95% CI 1.8–3.2) and greater odds of death or discharge to hospice (OR 6.0, 95% CI 4.4–8.1).

CONCLUSIONS

Among patients undergoing vertebral fracture repair, those with cervical spine fractures, spinal cord injuries, preexisting comorbidities, and severe concomitant injuries are at highest risk for developing postoperative sepsis and experiencing adverse hospital disposition.

Open access

Melissa M. J. Chua, Saksham Gupta, Walid Ibn Essayed, Dustin J. Donnelly, Habibullah Ziayee, Juan Vicenty-Padilla, Alvin S. Das, Rosalind P. M. Lai, Saef Izzy, and Mohammad Ali Aziz-Sultan

BACKGROUND

Pure arterial malformations (PAMs) are rare vascular anomalies that are commonly mistaken for other vascular malformations. Because of their purported benign natural history, PAMs are often conservatively managed. The authors report the case of a ruptured PAM leading to subarachnoid hemorrhage (SAH) with intraventricular extension that was treated endovascularly.

OBSERVATIONS

A 38-year-old man presented with a 1-day history of headaches and nausea. A computed tomography scan demonstrated diffuse SAH with intraventricular extension, and angiography revealed a right posterior inferior cerebellar artery–associated PAM. The PAM was treated with endovascular Onyx embolization.

LESSONS

To the authors’ knowledge, only 2 other cases of SAH associated with PAM have been reported. In those 2 cases, surgical clipping was pursued for definitive treatment. Here, the authors report the first case of a ruptured PAM treated using an endovascular approach, showing its feasibility as a treatment option particularly in patients in whom open surgery is too high a risk.

Restricted access

Blake M. Hauser, Samantha E. Hoffman, Saksham Gupta, Mark M. Zaki, Edward Xu, Melissa Chua, Joshua D. Bernstock, Ayaz Khawaja, Timothy R. Smith, Mark R. Proctor, and Hasan A. Zaidi

OBJECTIVE

Venous thromboembolism (VTE) can cause significant morbidity and mortality in hospitalized patients, and may disproportionately occur in patients with limited mobility following spinal trauma. The authors aimed to characterize the epidemiology and clinical predictors of VTE in pediatric patients following traumatic spinal injuries (TSIs).

METHODS

The authors conducted a retrospective cohort analysis of children who experienced TSI, including spinal fractures and spinal cord injuries, encoded within the National Trauma Data Bank from 2011 to 2014.

RESULTS

Of the 22,752 pediatric patients with TSI, 192 (0.8%) experienced VTE during initial hospitalization. Proportionally, more patients in the VTE group (77%) than in the non-VTE group (68%) presented following a motor vehicle accident. Patients developing VTE had greater odds of presenting with moderate (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.4–4.8) or severe Glasgow Coma Scale scores (aOR 4.3, 95% CI 3.0–6.1), epidural hematoma (aOR 2.8, 95% CI 1.4–5.7), and concomitant abdominal (aOR 2.4, 95% CI 1.8–3.3) and/or lower extremity (aOR 1.5, 95% CI 1.1–2.0) injuries. They also had greater odds of being obese (aOR 2.9, 95% CI 1.6–5.5). Neither cervical, thoracic, nor lumbar spine injuries were significantly associated with VTE. However, involvement of more than one spinal level was predictive of VTE (aOR 1.3, 95% CI 1.0–1.7). Spinal cord injury at any level was also significantly associated with developing VTE (aOR 2.5, 95% CI 1.8–3.5). Patients with VTE stayed in the hospital an adjusted average of 19 days longer than non-VTE patients. They also had greater odds of discharge to a rehabilitative facility or home with rehabilitative services (aOR 2.6, 95% CI 1.8–3.6).

CONCLUSIONS

VTE occurs in a low percentage of hospitalized pediatric patients with TSI. Injury severity is broadly associated with increased odds of developing VTE; specific risk factors include concomitant injuries such as cranial epidural hematoma, spinal cord injury, and lower extremity injury. Patients with VTE also require hospital-based and rehabilitative care at greater rates than other patients with TSI.

Full access

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

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Free access

Blake M. Hauser, Saksham Gupta, Samantha E. Hoffman, Mark M. Zaki, Anne A. Roffler, David J. Cote, Yi Lu, John H. Chi, Michael W. Groff, Ayaz M. Khawaja, Timothy R. Smith, and Hasan A. Zaidi

OBJECTIVE

Sports injuries are known to present a high risk of spinal trauma. The authors hypothesized that different sports predispose participants to different injuries and injury severities.

METHODS

The authors conducted a retrospective cohort analysis of adult patients who experienced a sports-related traumatic spinal injury (TSI), including spinal fractures and spinal cord injuries (SCIs), encoded within the National Trauma Data Bank from 2011 through 2014. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were estimated.

RESULTS

The authors included 12,031 cases of TSI, which represented 15% of all sports-related trauma. The majority of patients with TSI were male (82%), and the median age was 48 years (interquartile range 32–57 years). The most frequent mechanisms of injury in this database were cycling injuries (81%), skiing and snowboarding accidents (12%), aquatic sports injuries (3%), and contact sports (3%). Spinal surgery was required during initial hospitalization for 9.1% of patients with TSI.

Compared to non-TSI sports-related trauma, TSIs were associated with an average 2.3-day increase in length of stay (95% CI 2.1–2.4; p < 0.001) and discharge to or with rehabilitative services (adjusted OR 2.6, 95% CI 2.4–2.7; p < 0.001). Among sports injuries, TSIs were the cause of discharge to or with rehabilitative services in 32% of cases. SCI was present in 15% of cases with TSI. Within sports-related TSIs, the rate of SCI was 13% for cycling injuries compared to 41% and 49% for contact sports and aquatic sports injuries, respectively. Patients experiencing SCI had a longer length of stay (7.0 days longer; 95% CI 6.7–7.3) and a higher likelihood of adverse discharge disposition (adjusted OR 9.69, 95% CI 8.72–10.77) compared to patients with TSI but without SCI.

CONCLUSIONS

Of patients with sports-related trauma discharged to rehabilitation, one-third had TSIs. Cycling injuries were the most common cause, suggesting that policies to make cycling safer may reduce TSI.