Convection-enhanced delivery for high-grade glioma.

Glioblastoma (GBM) is the most common adult primary malignant brain tumor and is associated with a dire prognosis. Despite multi-modality therapies of surgery, radiation, and chemotherapy, its 5-year survival rate is 6.8%. The presence of the blood-brain barrier (BBB) is one factor that has made GBM difficult to treat. Convection-enhanced delivery (CED) is a modality that bypasses the BBB, which allows the intracranial delivery of therapies that would not otherwise cross the BBB and avoids systemic toxicities. This review will summarize prior and ongoing studies and highlights practical considerations related to clinical care to aid providers caring for a high-grade glioma patient being treated with CED. Although not the main scope of this paper, this review also touches upon relevant technical considerations of using CED, an area still under much development.

Electrographic Seizure Detection by Neuroscience Intensive Care Unit Nurses via Bedside Real-Time Quantitative EEG.

OBJECTIVE: Our primary objective was to determine the performance of real-time neuroscience intensive care unit (neuro-ICU) nurse interpretation of quantitative EEG (qEEG) at the bedside for seizure detection. Secondary objectives included determining nurse time to seizure detection and assessing factors that influenced nurse accuracy. METHODS: Nurses caring for neuro-ICU patients undergoing continuous EEG (cEEG) were trained using a 1-hour qEEG panel (rhythmicity spectrogram and amplitude-integrated EEG) bedside display. Nurses' hourly interpretations were compared with post hoc cEEG review by 2 neurophysiologists as the gold standard. Diagnostic performance, time to seizure detection compared with standard of care (SOC), and effects of other factors on nurse accuracy were calculated. RESULTS: A total of 109 patients and 65 nurses were studied. Eight patients had seizures during the study period (7%). Nurse sensitivity and specificity for the detection of seizures were 74% and 92%, respectively. Mean nurse time to seizure detection was significantly shorter than SOC by 132 minutes (Cox proportional hazard ratio 6.96). Inaccurate nurse interpretation was associated with increased hours monitored and presence of brief rhythmic discharges. CONCLUSIONS: This prospective study of real-time nurse interpretation of qEEG for seizure detection in neuro-ICU patients showed clinically adequate sensitivity and specificity. Time to seizure detection was less than that of SOC. TRIAL REGISTRATION INFORMATION: Clinical trial registration number NCT02082873. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that neuro-ICU nurse interpretation of qEEG detects seizures in adults with a sensitivity of 74% and a specificity of 92% compared with traditional cEEG review.

Primary brain tumor patients admitted to a US intensive care unit: a descriptive analysis.

Purpose: To describe our population of primary brain tumor (PBT) patients, a subgroup of cancer patients whose intensive care unit (ICU) outcomes are understudied. Methods: Retrospective analysis of PBT patients admitted to an ICU between 2013 to 2018 for an unplanned need. Using descriptive analyses, we characterized our population and their outcomes. Results: Fifty-nine PBT patients were analyzed. ICU mortality was 19% (11/59). The most common indication for admission was seizures (n = 16, 27%). Conclusion: Our ICU mortality of PBT patients was comparable to other solid tumor patients and the general ICU population and better than patients with hematological malignancies. Further study of a larger population would inform guidelines for triaging PBT patients who would most benefit from ICU-level care.

Lay abstract Purpose: Data are lacking regarding outcomes of patients with primary brain tumors (PBTs) admitted to an intensive care unit (ICU), which may it difficult for ICU providers to know who of these patients will best benefit from ICU-level care. We aimed to describe our patient population to contribute to the limited data. Methods: We performed a retrospective analysis of critically ill PBT patients in our ICU. Results: Of 59 patients analyzed, ICU mortality was 19% (11/59), and the most common indication for admission was seizures (n = 16, 27%). Conclusion: Our ICU mortality of PBT patients was comparable to other solid tumor patients and the general ICU population and better than patients with hematological malignancies.

Palliative Care Use for Critically Ill Patients With Brain Metastases.

CONTEXT: Critically ill patients with brain metastases (BM) face significant uncertainty regarding prognosis and survival and can benefit from Palliative care (PC). However, research regarding the role of PC in this population is lacking. OBJECTIVES: We sought to compare BM patients admitted to an intensive care unit who received an inpatient PC consult (PC cohort) to those who did not (Usual Care, UC cohort). METHODS: We performed a single-institution retrospective cohort analysis. Our outcome variables were mortality, time from intensive care unit admission to death, disposition, and change in code status. We also evaluated PC's role in complex medical decision making, symptom management and hospice education. RESULTS: PC consult was placed in 31 of 118 (28%) of patients. The overall mortality rates were not statistically different (78.8% vs. 90.3%, P= 0.15, UC vs. PC cohort). Patients in the PC cohort had a shorter time to death, higher rate of death within 30 days of admission, increased rate of discharge to hospice, and increase percentage of code status change to "do not attempt resuscitation" during the admission. The primary services provided by PC were symptom management (n = 21, 67.7%) and assistance in complex medical decision making (n = 20, 64.5%). CONCLUSION: In our patient cohort, PC is an underutilized service that can assist in complex medical decision making and symptom management of critically ill BM patients. Further prospective studies surveying patient, family and provider experiences could better inform the qualitative impact of PC in this unique patient population.

A Triage Model for Interhospital Transfers of Low Risk Intracerebral Hemorrhage Patients.

OBJECTIVES: Intracerebral hemorrhage comprises a large proportion of inter-hospital transfers to comprehensive stroke centers from centers without comprehensive stroke center resources despite lack of mortality benefit and low comprehensive stroke center resource utilization. The subset of patients who derive the most benefit from inter-hospital transfers is unclear. Here, we create a triage model to identify patients who can safely avoid transfer to a comprehensive stroke center. MATERIALS AND METHODS: A retrospective cohort of spontaneous intracerebral hemorrhage patients transferred to our comprehensive stroke center from surrounding centers was used. Patients with early discharge from the Neuroscience Intensive Care Unit without use of comprehensive stroke center resources were identified as low risk, non-utilizers. Variables associated with this designation were used to develop and validate a triage model. RESULTS: The development and replication cohorts comprised 358 and 99 patients respectively, of whom 78 (22%) and 26 (26%) were low risk, non-utilizers. Initial Glasgow Coma Scale and baseline hemorrhage volume were associated with low risk, non-utilizers in multivariate analysis. Initial Glasgow Coma Scale >13, intracerebral hemorrhage volume <15ml, absence of intraventricular hemorrhage, and supratentorial location had an area under curve, specificity, and sensitivity of 0.72, 91.4%, 52.6%, respectively, for identifying low risk, non-utilizers, and 0.75, 84.9%, 65.4%, respectively, in the replication cohort. CONCLUSIONS: Spontaneous intracerebral hemorrhage patients with Glasgow Coma Scale >13, intracerebral hemorrhage volume <15 ml, absence of intraventricular hemorrhage, and supratentorial location might safely avoid inter-hospital transfer to a comprehensive stroke center. Validation in a prospective, multicenter cohort is warranted.

A Trial of Real-Time Electrographic Seizure Detection by Neuro-ICU Nurses Using a Panel of Quantitative EEG Trends.

BACKGROUND: Non-convulsive seizures (NCS) are a common occurrence in the neurologic intensive care unit (Neuro-ICU) and are associated with worse outcomes. Continuous electroencephalogram (cEEG) monitoring is necessary for the detection of NCS; however, delays in interpretation are a barrier to early treatment. Quantitative EEG (qEEG) calculates a time-compressed simplified visual display from raw EEG data. This study aims to evaluate the performance of Neuro-ICU nurses utilizing bedside, real-time qEEG interpretation for detecting recurrent NCS. METHODS: This is a prospective, single-institution study of patients admitted to the Duke Neuro-ICU between 2016 and 2018 who had NCS identified on traditional cEEG review. The accuracy of recurrent seizure detection on hourly qEEG review by bedside Neuro-ICU nurses was compared to the gold standard of cEEG interpretation by two board-certified neurophysiologists. The nurses first received brief qEEG training, individualized for their specific patient. The bedside qEEG display consisted of rhythmicity spectrogram (left and right hemispheres) and amplitude-integrated EEG (left and right hemispheres) in 1-h epochs. RESULTS: Twenty patients were included and 174 1-h qEEG blocks were analyzed. Forty-seven blocks contained seizures (27%). The sensitivity was 85.1% (95% CI 71.1-93.1%), and the specificity was 89.8% (82.8-94.2%) for the detection of seizures for each 1-h block when compared to interpretation of conventional cEEG by two neurophysiologists. The false positive rate was 0.1/h. Hemispheric seizures (> 4 unilateral EEG electrodes) were more likely to be correctly identified by nurses on qEEG than focal seizures (≤ 4 unilateral electrodes) (p = 0.03). CONCLUSIONS: After tailored training sessions, Neuro-ICU nurses demonstrated a good sensitivity for the interpretation of bedside real-time qEEG for the detection of recurrent NCS with a low false positive rate. qEEG is a promising tool that may be used by non-neurophysiologists and may lead to earlier detection of NCS.

Loss of Vestibular Ocular Reflex in Nonconvulsive Status Epilepticus.

BACKGROUND: Electroencephalogram (EEG) findings of generalized periodic discharges (GPDs) with triphasic morphology were introduced as a metabolic phenomenon, but more recently have been associated with epileptic phenomenon. Resolution of EEG findings along with clinical improvement from treatment is diagnostic. The known causes of reversible, isolated loss of OVR include medication toxicity, lead exposure, and thiamine deficiency, but its association with nonconvulsive status epilepticus (NCSE) has never been published. Medication induced loss of OVR resolves after a 24-hour washout period. We report a case of reversible, isolated loss of vestibular ocular reflex (VOR) associated with epileptic phenomenon. METHODS: This is a case report of a single patient. RESULTS: A 74-year-old male with a history of complex partial seizures admitted for a pneumonectomy had a post-operative course complicated by two instances of coma, the latter associated with an isolated loss of VOR. EEG revealed GPDs with triphasic morphology initially interpreted as a metabolic phenomenon. The patient's mental status, exam and EEG findings improved after low dose infusion of propofol for tracheostomy, and he was eventually discharged at baseline neurological function. Due to this response, his coma, loss of VOR and EEG were later interpreted as a consequence of NCSE. CONCLUSION: The interpretation of GPDs with triphasic wave morphology range from metabolic phenomenon to NCSE. NCSE should be highly considered on the differential for encephalopathy regardless of the circumstances. NCSE may be a potential cause of reversible, isolated loss of the VOR and an AED trial in the appropriate clinical context should be considered. This is the first report of loss of VOR possibly associated with NCSE.

Child Neurology: An infant with episodic facial flushing: A rare case and review of congenital harlequin syndrome.

Congenital harlequin syndrome is rare dysautonomia of the face most often reported in adults and rarely in infants and children. It is a diagnosis of exclusion and a seemingly benign condition. We report a case of a 6-month-old girl with episodic unilateral and bilateral facial flushing provoked upon awakening and resolved with sleeping with associated autonomic features consistent with harlequin syndrome. This is followed by a review of cases identified regarding this condition in infants and children.

A Diffuse Leptomeningeal Glioneuronal Tumor Without Diffuse Leptomeningeal Involvement: Detailed Molecular and Clinical Characterization.

Prior to their provisional WHO classification as a distinct entity in 2016, diffuse leptomeningeal glioneuronal tumors (DLGNT) were often regarded as diffuse leptomeningeal presentations of oligodendrogliomas or extraventricular neurocytomas. Their classification as a distinct entity partly relies on their pattern of growth, but DLGNTs without radiological leptomeningeal involvement have been described. In a patient with a DLGNT of the spinal cord without evidence of leptomeningeal involvement, we review in depth the clinical course and the histologic and molecular features of the neoplasm, in the context of other reported cases without diffuse leptomeningeal involvement. Our findings highlight the advantages of molecular analysis in making accurate diagnoses on small spinal tissue samples and underline the need for more long-term clinical follow-up of these rare neoplasms to inform treatment decisions.

Examining Menstrual Tracking to Inform the Design of Personal Informatics Tools.

We consider why and how women track their menstrual cycles, examining their experiences to uncover design opportunities and extend the field's understanding of personal informatics tools. To understand menstrual cycle tracking practices, we collected and analyzed data from three sources: 2,000 reviews of popular menstrual tracking apps, a survey of 687 people, and follow-up interviews with 12 survey respondents. We find that women track their menstrual cycle for varied reasons that include remembering and predicting their period as well as informing conversations with healthcare providers. Participants described six methods of tracking their menstrual cycles, including use of technology, awareness of their premenstrual physiological states, and simply remembering. Although women find apps and calendars helpful, these methods are ineffective when predictions of future menstrual cycles are inaccurate. Designs can create feelings of exclusion for gender and sexual minorities. Existing apps also generally fail to consider life stages that women experience, including young adulthood, pregnancy, and menopause. Our findings encourage expanding the field's conceptions of personal informatics.

Reconsidering the Device in the Drawer: Lapses as a Design Opportunity in Personal Informatics.

People stop using personal tracking tools over time, referred to as the lapsing stage of their tool use. We explore how designs can support people when they lapse in tracking, considering how to design data representations for a person who lapses in Fitbit use. Through a survey of 141 people who had lapsed in using Fitbit, we identified three use patterns and four perspectives on tracking. Participants then viewed seven visual representations of their Fitbit data and seven approaches to framing this data. Participant Fitbit use and perspective on tracking influenced their preference, which we surface in a series of contrasts. Specifically, our findings guide selecting appropriate aggregations from Fitbit use (e.g., aggregate more when someone has less data), choosing an appropriate framing technique from tracking perspective (e.g., ensure framing aligns with how the person feels about tracking), and creating appropriate social comparisons (e.g., portray the person positively compared to peers). We conclude by discussing how these contrasts suggest new designs and opportunities in other tracking domains.

Novel chemotherapeutics and other therapies for treating high-grade glioma.

INTRODUCTION: Despite extensive research, high-grade glioma (HGG) remains a dire diagnosis with no change in the standard of care in almost a decade. However, recent advancements uncovering molecular biomarkers of brain tumors and tumor-specific antigens targeted by immunotherapies provide opportunities for novel personalized treatment regimens to improve survival. AREAS COVERED: In this review, the authors provide a comprehensive overview of recent therapeutic advancements in HGG. Furthermore, they describe new molecular biomarkers and molecular classifications, in addition to updated research on bevacizumab, targeted molecular therapies, immunotherapy and alternative delivery methods that overcome the blood-brain barrier to reach the target tumor tissue. Challenges regarding each therapy are also outlined. The authors also provide some insight into a novel non-chemotherapeutic treatment for malignant glioma, NovoTTFA, as well as a summary of current treatment options for recurrence. EXPERT OPINION: Current research for treating malignant gliomas are paving the path to personalized therapy, including immunotherapy, that involve integrated genomic and histolopathologic data, as well as a multi-modal treatment regimen. Immunotherapy will potentially be the next addition to the current standard of care, specialized to the antigens presented on the tumors. The results of the current trials of multi-antigen vaccines are eagerly anticipated.

A health center controlled network's experience in ambulatory care EHR implementation.

Implementing a full-featured EHR at a community health center is a daunting undertaking. Stakeholder buy-in, contract negotiation, workflow redesign, equipment purchases, preloading charts and trainings are just some of the necessary tasks in managing an implementation. METCHIT, a health center controlled network, used a collaborative approach to implement electronic medical records. This article will cover the experience, benefits and lessons learned by a group of four FQHCs that took a cooperative, mentorship approach to implementation. Since 2005, the four community health centers, Charles B. Wang Community Health Center, Morris Heights Health Center, Settlement Health, and Comprehensive Community Development Corporation, have implemented EHRs at four organizations with multiple sites in diverse neighborhoods in New York City. The collaboration began and grew during this period, aided by a technology grant from HRSA.

In vitro 3D model for human vascularized adipose tissue.

The clinical need for both three-dimensional (3D) soft tissue replacements and in vitro adipose tissue models continues to grow. In this study, we evaluated structural and functional characteristics of an in vitro 3D coculture model of vascularized adipose tissue. Tomato red-infected human adipose tissue-derived mesenchymal stem cells (hASCs) and green fluorescence protein-infected human umbilical vein endothelial cells were cocultured on 3D aqueous-derived silk scaffolds for 2 weeks. Confocal microscopy images demonstrated viability of cocultures and organization of both cell types over time. Endothelial cells aligned with time, and further histological analyses revealed continuous endothelial lumen formation in both differentiated and undifferentiated cocultures. Differentiated adipose cocultures secreted significantly higher levels of leptin than undifferentiated cocultures at 1 and 2 weeks. Additionally, lipid accumulation was demonstrated with Oil Red O staining, where positive staining was higher in the differentiated cocultures. A promising in vitro approach for the vascularization of tissue-engineered adipose tissue, and the ability to vascularize a construct containing hASCs was demonstrated. The strategy outlined provides a basis for the formation of other in vitro vascularized tissues as well as a path forward for the sustainable formation of soft tissue due to the use of slowly degrading silk scaffolds.