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.
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Saksham Gupta, Wenya Linda Bi, and Ian F. Dunn
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.
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.
Blake M. Hauser, Saksham Gupta, Tejas S. Athni, David J. Segar, Ravindra Uppaluri, and Omar Arnaout
BACKGROUND
Intracranial epidermoid cysts are benign, slow-growing malformations that most commonly arise at the skull base. Maximizing resection of the cyst contents and the capsule reduces long-term recurrence but can be made difficult by cyst wall adherence to critical neurovascular structures. Expanded endonasal approaches (EEAs) offer an alternative to traditional open transcranial approaches for accessible epidermoid cysts. In this case report, the authors demonstrate a transclival EEA for a large, ventral brainstem epidermoid cyst.
OBSERVATIONS
A 41-year-old woman who presented with progressive headaches, diplopia, malaise, and fatigue was found to have a 4.7-cm midline, ventral brainstem epidermoid cyst. She underwent an expanded endonasal transclival approach that exposed the brainstem from the level of the dorsum sella to the tip of the basion. A near-total resection was completed with removal of all cyst contents and most of the capsular wall. Reconstruction was completed with Duragen, an autologous fat graft, and a nasoseptal flap. Postoperatively, she had a partial left cranial nerve VI palsy that remained stable 8 weeks after surgery.
LESSONS
The expanded endoscopic transclival approach can facilitate effective resection of midline, ventral epidermoid cysts.
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.
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.
Samantha E. Hoffman, Saksham Gupta, Matthew O’Connor, Casey A. Jarvis, Maryann Zhao, Blake M. Hauser, Joshua D. Bernstock, Shayna Murphy, Siobhan M. Raftery, Karen Lane, E. Antonio Chiocca, and Omar Arnaout
OBJECTIVE
The authors created a postoperative postanesthesia care unit (PACU) pathway to bypass routine intensive care unit (ICU) admissions of patients undergoing routine craniotomies, to improve ICU resource utilization and reduce overall hospital costs and lengths of stay while maintaining quality of care and patient satisfaction. In the present study, the authors evaluated this novel PACU-to-floor clinical pathway for a subset of patients undergoing craniotomy with a case time under 5 hours and blood loss under 500 ml.
METHODS
A single-institution retrospective cohort study was performed to compare 202 patients enrolled in the PACU-to-floor pathway and 193 historical controls who would have met pathway inclusion criteria. The pathway cohort consisted of all adult supratentorial brain tumor cases from the second half of January 2021 to the end of January 2022 that met the study inclusion criteria. Control cases were selected from the beginning of January 2020 to halfway through January 2021. The authors also discuss common themes of similar previously published pathways and the logistical and clinical barriers overcome for successful PACU pathway implementation.
RESULTS
Pathway enrollees had a median age of 61 years (IQR 49–69 years) and 53% were female. Age, sex, pathology, and American Society of Anesthesiologists physical status distributions were similar between pathway and control patients (p > 0.05). Most of the pathway cases (96%) were performed on weekdays, and 31% had start times before noon. Nineteen percent of pathway patients had 30-day readmissions, most frequently for headache (16%) and syncope (10%), whereas 18% of control patients had 30-day readmissions (p = 0.897). The average time to MRI was 6 hours faster for pathway patients (p < 0.001) and the time to inpatient physical therapy and/or occupational therapy evaluation was 4.1 hours faster (p = 0.046). The average total length of stay was 0.7 days shorter for pathway patients (p = 0.02). A home discharge occurred in 86% of pathway cases compared to 81% of controls (p = 0.225). The average total hospitalization charges were $13,448 lower for pathway patients, representing a 7.4% decrease (p = 0.0012, adjusted model). Seven pathway cases were escalated to the ICU postoperatively because of attending physician preference (2 cases), agitation (1 case), and new postoperative neurological deficits (4 cases), resulting in a 96.5% rate of successful discharge from the pathway. In bypassing the ICU, critical care resource utilization was improved by releasing 0.95 ICU days per patient, or 185 ICU days across the cohort.
CONCLUSIONS
The featured PACU-to-floor pathway reduces the stay of postoperative craniotomy patients and does not increase the risk of early hospital readmission.
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.
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.
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.
