OBJECT The majority of growing and/or symptomatic peripheral nerve tumors are schwannomas and neurofibromas. They are almost always benign and can usually be resected while minimizing motor and ...sensory deficits if approached with the proper expertise and techniques. Intraoperative electrophysiological stimulation and recording techniques allow the surgeon to map the surface of the tumor in an effort to identify and thus avoid damaging functioning nerve fibers. Recently, MR diffusion tensor imaging (DTI) techniques have permitted the visualization of axons, because of their anisotropic properties, in peripheral nerves. The object of this study was to compare the distribution of nerve fibers as revealed by direct electrical stimulation with that seen on preoperative MR DTI. METHODS The authors conducted a retrospective chart review of patients with a peripheral nerve or nerve root tumor between March 2012 and January 2014. Diffusion tensor imaging and intraoperative data had been prospectively collected for patients with peripheral nerve tumors that were resected. Preoperative identification of the nerve fiber location in relation to the nerve tumor surface as seen on DTI studies was compared with the nerve fiber's intraoperative localization using electrophysiological stimulation and recordings. RESULTS In 23 patients eligible for study there was good correlation between nerve fiber location on DTI and its anatomical location seen intraoperatively. Diffusion tensor imaging demonstrated the relationship of nerve fibers relative to the tumor with 95.7% sensitivity, 66.7% specificity, 75% positive predictive value, and 93.8% negative predictive value. CONCLUSIONS Preoperative DTI techniques are useful in helping the peripheral nerve surgeon to both determine the risks involved in resecting a nerve tumor and plan the safest surgical approach.
In this study, we sought to determine the accuracy of a computer algorithm that automatically assesses head computed tomography (CT) studies in patients with suspected traumatic brain injury (TBI) ...for features of intracranial hemorrhage and mass effect, employing a neuroradiologist's interpretation as the gold standard. To this end, we designed a suite of computer algorithms that evaluates in a fully automated fashion the presence of intracranial blood and/or mass effect based on the following CT findings: (1) presence or absence of a subdural or epidural hematoma, (2) presence or absence of subarachnoid hemorrhage, (3) presence or absence of an intraparenchymal hematoma, (4) presence or absence of clinically significant midline shift (>or=5 mm), and (5) normal, partly effaced, or completely effaced basal cisterns. The algorithm displays abnormal findings as color overlays on the original head CT images, and calculates the volume of each type of blood collection, the midline shift, and the volume of the basal cisterns, based on the above-described features. Thresholds and parameters yielding optimal accuracy of the computer algorithm were determined using a development sample of 33 selected, nonconsecutive patients. The software was then applied to a validation sample of 250 consecutive patients evaluated for suspicion of acute TBI at our institution in 2006-2007. Software detection of the presence of at least one noncontrast CT (NCT) feature of acute TBI demonstrated high sensitivity of 98% and high negative predictive value (NPV) of 99%. There was actually only one false negative case, where a very subtle subdural hematoma, extending exclusively along the falx, was diagnosed by the neuroradiologist, while the case was considered as normal by the computer algorithm. The software was excellent at detecting the presence of mass effect and intracranial hemorrhage, but showed some disagreements with the neuroradiologist in quantifying the degree of mass effect and characterizing the type of intracranial hemorrhage. In summary, we have developed a fully automated computer algorithm that demonstrated excellent sensitivity for acute intracranial hemorrhage and clinically significant midline shift, while maintaining intermediate specificity. Further studies are required to evaluate the potential favorable impact of this software on facilitating workflow and improving diagnostic accuracy when used as a screening aid by physicians with different levels of experience.
•Emergency department toxicology screen (tox+) is an indicator of active substance use.•Tox+ confounds neurologic assessment and is a risk factor for poor outcomes after TBI.•Tox+ is associated with ...prior substance use history and prior TBIs.•Tox+ is associated with increased hospital admissions in CT-negative TBI.•Tox+ is associated with PTSD and psychiatric symptoms at 6-months postinjury.
Substance use is commonly associated with traumatic brain injury (TBI). We investigate associations between active substance use, peri-injury factors, and outcome after TBI across three U.S. Level I trauma centers. TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) with Marshall computed tomography (CT) score 1–3, no neurosurgical procedure/operation, and admission urine toxicology screen (tox+/−) were extracted. Associations between tox+/−, comorbidities, hospital variables, and six-month functional (GOSE) and neuropsychiatric (PCL-C, BSI18, RPQ-13, SWLS) outcomes were analyzed. Multivariable regression was performed for associations significant on univariate analysis with odds ratios (mOR) presented. Significance assessed at p < 0.05. In 133 subjects, tox+/tox− were 29.1%/72.9%. Tox+ was younger (35.5/43.6-years, p = 0.018), trended toward male sex (80.6%/63.9%, p = 0.067), was associated with history of seizures (27.8%/10.3%, p = 0.012), self-reported substance use (44.4%/17.5%, p = 0.001), prior TBI (58.8%/34.1%, p = 0.009), GCS < 15 (69.4%/48.4%, p = 0.031) and blood alcohol level >0.08-mg/dl (55.6%/30.8%, p = 0.022). In CT-negative subjects, tox+ was associated with increased hospital admission (95.7%/66.7%, p = 0.034). At six-months, tox+ was associated with screening positive for post-traumatic stress disorder (PCL-C: 40.0%/15.9%; mOR = 8.24, p = 0.022) and psychiatric symptoms (BSI18: 40.0%/14.3%, mOR = 11.06, p = 0.023). Active substance use in TBI may confound GCS assessment, triage to higher level of care, and be associated with increased six-month neuropsychiatric symptoms. Substance use screening should be integrated into standard emergency/acute care TBI protocols to optimize management and resource utilization. Clinicians should be vigilant in providing education, counselling, and follow-up for TBI patients with substance use.
Intracranial pressure (ICP) is the pressure within the intracranial space. Intracranial hypotension is a clinical syndrome in which low cerebrospinal fluid volume (CSF) results in orthostatic ...headache. Severe cases can result in nausea, vomiting, photophobia, and, rarely, decreased level of consciousness and coma. CSF opening pressure can be within the normal range in spontaneous intracranial hypotension. Imaging tests therefore play a key and decisive role in the diagnosis, as well as treatment, of intracranial hypotension. Intracranial hypertension occurs in a chronic form known as idiopathic intracranial hypertension, as well as in a large variety of neurologic and systemic disorders. Symptoms include headache, nausea and vomiting, blurred vision, and in severe cases, altered level of consciousness that can progress to coma and death. Direct measurements of CSF pressure through lumbar puncture (in idiopathic intracranial hypotension) or invasive ICP monitoring (in acute intracranial hypertension) are the key diagnostic tests. Imaging is used primarily to determine treatable causes of increased ICP, to assess for impending brain herniation, and to evaluate ventricular size.
Standard statistical practice used for determining the relative importance of competing causes of disease typically relies on ad hoc methods, often byproducts of machine learning procedures (stepwise ...regression, random forest, etc.). Causal inference framework and data-adaptive methods may help to tailor parameters to match the clinical question and free one from arbitrary modeling assumptions. Our focus is on implementations of such semiparametric methods for a variable importance measure (VIM). We propose a fully automated procedure for VIM based on collaborative targeted maximum likelihood estimation (cTMLE), a method that optimizes the estimate of an association in the presence of potentially numerous competing causes. We applied the approach to data collected from traumatic brain injury patients, specifically a prospective, observational study including three US Level-1 trauma centers. The primary outcome was a disability score (Glasgow Outcome Scale - Extended (GOSE)) collected three months post-injury. We identified clinically important predictors among a set of risk factors using a variable importance analysis based on targeted maximum likelihood estimators (TMLE) and on cTMLE. Via a parametric bootstrap, we demonstrate that the latter procedure has the potential for robust automated estimation of variable importance measures based upon machine-learning algorithms. The cTMLE estimator was associated with substantially less positivity bias as compared to TMLE and larger coverage of the 95% CI. This study confirms the power of an automated cTMLE procedure that can target model selection via machine learning to estimate VIMs in complicated, high-dimensional data.
Background
Contemporary data of peripheral T‐cell lymphoma (PTCL) and natural‐killer/T‐cell lymphoma (NKTL) patients treated with ifosfamide, carboplatin and etoposide (ICE) are limited.
Aims
We ...performed a retrospective analysis to estimate outcomes of ICE‐treated PTCL and NKTL patients at three tertiary cancer centres in Singapore.
Methods and Results
Patients were identified through lymphoma databases from National Cancer Centre Singapore (NCCS), National University Hospital, Singapore (NUHS), and Singapore General Hospital (SGH). Responses and survival outcomes were determined from electronic medical records. A total of 75 patients with a median age of 50 were included. ICE was used as first‐line treatment in 14 patients (19%) and as subsequent lines of treatment in 61 patients (81%). The overall response rates (ORR) for all patients was 63% (40% complete response CR). The ORR and CR in the first line were 86% and 64% respectively. At a median follow‐up duration of 71.0 months, the median progression‐free (PFS) and overall survival (OS) for all patients were 4.4 months (95%CI, 2.7–6.0) and 16 months (95%CI, 8.3–45.4) respectively.
Conclusion
In summary, ICE showed high ORR but poor PFS in relapsed/refractory PTCL and NKTL. ORR of ICE in the first line setting appears better than real‐world CHOP data and warrants further study.
Abstract
Older adults have the highest incidence of traumatic brain injury globally. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of age and ...time post-injury. Several reports have suggested lower accuracy for blood-based biomarkers in older adults, and there is a paucity of data beyond day-1 post-injury. Our aims were to investigate age-related differences in diagnostic accuracy and 2-week evolution of four leading candidate blood-based traumatic brain injury biomarkers—plasma glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, S100 calcium binding protein B and neuron-specific enolase—among participants in the 18-site prospective cohort study Transforming Research And Clinical Knowledge in Traumatic Brain Injury. Day-1 biomarker data were available for 2602 participants including 2151 patients with traumatic brain injury, 242 orthopedic trauma controls and 209 healthy controls. Participants were stratified into 3 age categories (young: 17–39 years, middle-aged: 40–64 years, older: 65–90 years). We investigated age-stratified biomarker levels and biomarker discriminative abilities across three diagnostic groups: head CT-positive/negative; traumatic brain injury/orthopedic controls; and traumatic brain injury/healthy controls. The difference in day-1 glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1 and neuron-specific enolase levels across most diagnostic groups was significantly smaller for older versus younger adults, resulting in a narrower range within which a traumatic brain injury diagnosis may be discriminated in older adults. Despite this, day-1 glial fibrillary acidic protein had good to excellent performance across all age-categories for discriminating all three diagnostic groups (area under the curve 0.84–0.96; lower limit of 95% confidence intervals all >0.78). Day-1 S100 calcium-binding protein B and ubiquitin carboxy-terminal hydrolase L1 showed good discrimination of CT-positive versus negative only among adults under age 40 years within 6 hours of injury. Longitudinal blood-based biomarker data were available for 522 hospitalized patients with traumatic brain injury and 24 hospitalized orthopaedic controls. Glial fibrillary acidic protein levels maintained good to excellent discrimination across diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients only. In conclusion, the blood-based glial fibrillary acidic protein assay tested here has good to excellent performance across all age-categories for discriminating key traumatic brain injury diagnostic groups to at least 3 days post-injury in this trauma centre cohort. The addition of a blood-based diagnostic to the evaluation of traumatic brain injury, including geriatric traumatic brain injury, has potential to streamline diagnosis.
Gardner et al. report that blood-based glial fibrillary acidic protein level has good-excellent discrimination across key traumatic brain injury diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients.
Graphical Abstract
Graphical abstract
The aim of this study was to evaluate microarray technology in the detection of micrometastases of head and neck squamous cell carcinoma (HNSCC) in muscle tissue. Three hundred SCCVII tumor cells ...were injected intramuscularly into the right flank of ten C3H/Km mice. One week later, the animals were euthanized and the muscle tissue was taken out. Histology (H&E staining), microarray and reverse transcriptase polymerase chain reaction analysis (RT-PCR) of the tissue was performed. Histology showed a few tumor cells between the muscle fibers. Microarray technology showed the different gene expression pattern of the muscle tissue with micrometastases in comparison to normal muscle tissue. Only genes with a fold change difference of 10 or greater were considered. Gene expression analysis revealed changes in the expression levels of 91 genes of micrometastases in muscle tissue. RT-PCR confirmed gene up-regulation. Significant differences in gene expression between micrometastases in muscle tissue and pure muscle tissue were found. The genes found to be up-regulated could be used to detect micrometastases in muscle tissue.
•Day-of-injury blood alcohol level (BAL) from 107mTBI patients with negative brain CT.•BAL≥80-mg/dl (U.S. legal limit) vs. BAL<80-mg/dl cohorts for comparative analysis.•Higher BAL associated with ...decreased GCS score and increased LOC duration.•BAL≥80-mg/dl associated with higher odds of impaired six-month functional recovery.•BAL≥80-mg/dl associated with decreased six-month nonverbal processing speed.
The relationship between blood alcohol level (BAL) and mild traumatic brain injury (mTBI) remains in need of improved characterization. Adult patients suffering mTBI without intracranial pathology on computed tomography (CT) from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with emergency department (ED) Glasgow Coma Scale (GCS) 13–15 and recorded blood alcohol level (BAL) were extracted. BAL≥80-mg/dl was set as proxy for excessive use. Multivariable regression was performed for patients with six-month Glasgow Outcome Scale-Extended (GOSE; functional recovery) and Wechsler Adult Intelligence Scale Processing Speed Index Composite Score (WAIS-PSI; nonverbal processing speed), using BAL≥80-mg/dl and <80-mg/dl cohorts, adjusting for demographic/injury factors. Overall, 107 patients were aged 42.7±16.8-years, 67.3%-male, and 80.4%-Caucasian; 65.4% had BAL=0-mg/dl, 4.6% BAL<80-mg/dl, and 30.0% BAL≥80-mg/dl (range 100–440-mg/dl). BAL differed across loss of consciousness (LOC; none: median 0-mg/dl interquartile range (IQR) 0–0, <30-min: 0-mg/dl 0–43, ≥30-min: 224-mg/dl 50–269, unknown: 108-mg/dl 0–232; p=0.002). GCS<15 associated with higher BAL (19-mg/dl 0–204 vs. 0-mg/dl 0–20; p=0.013). On univariate analysis, BAL≥80-mg/dl associated with less-than-full functional recovery (GOSE≤7; 38.1% vs. 11.5%; p=0.025) and lower WAIS-PSI (92.4±12.7, 30th-percentile vs. 105.1±11.7, 63rd-percentile; p<0.001). On multivariable regression BAL≥80-mg/dl demonstrated an odds ratio of 8.05 (95% CI 1.35–47.92; p=0.022) for GOSE≤7 and an adjusted mean decrease of 8.88-points (95% CI 0.67–17.09; p=0.035) on WAIS-PSI. Day-of-injury BAL>80-mg/dl after uncomplicated mTBI was associated with decreased GCS score and prolongation of reported LOC. BAL may be a biomarker for impaired return to baseline function and decreased nonverbal processing speed at six-months postinjury. Future confirmatory studies are needed.
Objective: To investigate the clinical management and medical follow-up of patients with mild traumatic brain injury (mTBI) presenting to emergency departments (EDs). Methods: Overall, 168 adult ...patients with mTBI from the prospective, multicentre Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study with Glasgow Coma Scale (GCS) 13-15, no polytrauma and alive at six months were included. Predictors for hospital admission, three-month follow-up referral and six-month functional disability (Glasgow Outcome Scale-Extended (GOSE) ≤ 6) were analysed using multivariable regression. Results: Overall, 48% were admitted to hospital, 22% received three-month referral and 27% reported six-month functional disability. Intracranial pathology on ED head computed tomography (multivariable odds ratio (OR) = 81.08, 95% confidence interval (CI) 10.28-639.36) and amnesia (>30-minutes: OR = 5.27 1.75-15.87; unknown duration: OR = 4.43 1.26-15.62) predicted hospital admission. Older age (per-year OR = 1.03 1.01-1.05) predicted three-month referral, while part-time/unemployment predicted lack of referral (OR = 0.17 0.06-0.50). GCS < 15 (OR = 2.46 1.05-5.78) and prior history of seizures (OR = 3.62 1.21-10.89) predicted six-month functional disability, while increased education (per-year OR = 0.86 0.76-0.97) was protective. Conclusions: Clinical factors modulate triage to admission, while demographic/socioeconomic elements modulate follow-up care acquisition; six-month functional disability associates with both clinical and demographic/socioeconomic variables. Improving triage to acute and outpatient care requires further investigation to optimize resource allocation and outcome after mTBI.
ClinicalTrials.gov registration: NCT01565551
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