Accounting for contact network uncertainty in epidemic inferences.

When modeling the dynamics of infectious disease, the incorporation of contact network information allows for the capture of the non-randomness and heterogeneity of realistic contact patterns. Oftentimes, it is assumed that the underlying contact pattern is known with perfect certainty. However, in realistic settings, the observed data often serves as an imperfect proxy of the actual contact patterns in the population. Furthermore, the epidemic in the real world are often not fully observed; event times such as infection and recovery times may be missing. In order to conduct accurate inferences on parameters of contagion spread, it is crucial to incorporate these sources of uncertainty. In this paper, we propose the use of Mixture Density Network compressed ABC (MDN-ABC) to learn informative summary statistics for the available data. This method will allow for Bayesian inference on the epidemic parameters of a contagious process, while accounting for imperfect observations on the epidemic and the contact network. We will demonstrate the use of this method on simulated epidemics and networks, and extend this framework to analyze the spread of Tattoo Skin Disease (TSD) among bottlenose dolphins in Shark Bay, Australia.

Flexible Bayesian inference on partially observed epidemics.

Individual-based models of contagious processes are useful for predicting epidemic trajectories and informing intervention strategies. In such models, the incorporation of contact network information can capture the non-randomness and heterogeneity of realistic contact dynamics. In this article, we consider Bayesian inference on the spreading parameters of an SIR contagion on a known, static network, where information regarding individual disease status is known only from a series of tests (positive or negative disease status). When the contagion model is complex or information such as infection and removal times is missing, the posterior distribution can be difficult to sample from. Previous work has considered the use of Approximate Bayesian Computation (ABC), which allows for simulation-based Bayesian inference on complex models. However, ABC methods usually require the user to select reasonable summary statistics. Here, we consider an inference scheme based on the Mixture Density Network compressed ABC, which minimizes the expected posterior entropy in order to learn informative summary statistics. This allows us to conduct Bayesian inference on the parameters of a partially observed contagious process while also circumventing the need for manual summary statistic selection. This methodology can be extended to incorporate additional simulation complexities, including behavioural change after positive tests or false test results.

A week in the life of the human brain: stable states punctuated by chaotic transitions.

Many important neurocognitive states, such as performing natural activities and fluctuations of arousal, shift over minutes-to-hours in the real-world. We harnessed 3-12 days of continuous multi-electrode intracranial recordings in twenty humans during natural behavior (socializing, using digital devices, sleeping, etc.) to study real-world neurodynamics. Applying deep learning with dynamical systems approaches revealed that brain networks formed consistent stable states that predicted behavior and physiology. Changes in behavior were associated with bursts of rapid neural fluctuations where brain networks chaotically explored many configurations before settling into new states. These trajectories traversed an hourglass-shaped structure anchored around a set of networks that slowly tracked levels of outward awareness related to wake-sleep stages, and a central attractor corresponding to default mode network activation. These findings indicate ways our brains use rapid, chaotic transitions that coalesce into neurocognitive states slowly fluctuating around a stabilizing central equilibrium to balance flexibility and stability during real-world behavior.

Flexible Bayesian Inference on Partially Observed Epidemics.

Individual-based models of contagious processes are useful for predicting epidemic trajectories and informing intervention strategies. In such models, the incorporation of contact network information can capture the non-randomness and heterogeneity of realistic contact dynamics. In this paper, we consider Bayesian inference on the spreading parameters of an SIR contagion on a known, static network, where information regarding individual disease status is known only from a series of tests (positive or negative disease status). When the contagion model is complex or information such as infection and removal times is missing, the posterior distribution can be difficult to sample from. Previous work has considered the use of Approximate Bayesian Computation (ABC), which allows for simulation-based Bayesian inference on complex models. However, ABC methods usually require the user to select reasonable summary statistics. Here, we consider an inference scheme based on the Mixture Density Network compressed ABC (MDN-ABC), which minimizes the expected posterior entropy in order to learn informative summary statistics. This allows us to conduct Bayesian inference on the parameters of a partially observed contagious process while also circumventing the need for manual summary statistic selection. This methodology can be extended to incorporate additional simulation complexities, including behavioral change after positive tests or false test results.

Leveraging Contact Network Information in Clustered Randomized Studies of Contagion Processes.

In a randomized study, leveraging covariates related to the outcome (e.g. disease status) may produce less variable estimates of the effect of exposure. For contagion processes operating on a contact network, transmission can only occur through ties that connect affected and unaffected individuals; the outcome of such a process is known to depend intimately on the structure of the network. In this paper, we investigate the use of contact network features as efficiency covariates in exposure effect estimation. Using augmented generalized estimating equations (GEE), we estimate how gains in efficiency depend on the network structure and spread of the contagious agent or behavior. We apply this approach to simulated randomized trials using a stochastic compartmental contagion model on a collection of model-based contact networks and compare the bias, power, and variance of the estimated exposure effects using an assortment of network covariate adjustment strategies. We also demonstrate the use of network-augmented GEEs on a clustered randomized trial evaluating the effects of wastewater monitoring on COVID-19 cases in residential buildings at the the University of California San Diego.

Quantification of new intracerebral lesions on diffusion-weighted magnetic resonance imaging after transcarotid artery revascularization for treatment of carotid artery stenosis.

Objective: Transcarotid artery revascularization (TCAR) has been used with increasing prevalence for treatment of carotid artery stenosis. TCAR holds potential benefits over traditional carotid endarterectomy (CEA) or transfemoral carotid artery stenting by its nature of being less invasive than CEA but more neuroprotective than transfemoral carotid artery stenting. The purpose of this pilot study is to evaluate the effectiveness of the neuroprotection system of TCAR with flow reversal by quantifying the incidence and degree of new intracerebral lesions using diffusion-weighted magnetic resonance imaging (DW-MRI). This study is the first to evaluate these findings in a real-world, high-risk cohort, who would have been excluded from the ROADSTER and ENROUTE transcarotid neuroprotection system DW-MRI studies. Methods: Patients undergoing unilateral TCAR for symptomatic or asymptomatic severe internal carotid artery disease were eligible and prospectively enrolled in the study. All patients had high risk features, including comorbidities or medications, which excluded them from industry-sponsored DW-MRI trials. Patients underwent a preoperative DW-MRI to obtain a baseline intracerebral evaluation within 1 week of the scheduled surgery. The follow-up DW-MRI occurred within 48 hours postoperatively. The primary outcome was new, acute postoperative lesion(s) identified on DW-MRI. Secondary outcomes include any major stroke, myocardial infarction, or death during hospitalization. Results: Five consecutive patients underwent TCAR with preoperative and postoperative imaging. All five patients were on dual antiplatelet therapy before their procedure and verified to be therapeutic on these agents. All patients underwent a right-sided TCAR and three were symptomatic as the indication for their procedure. All five patients demonstrated chronic lesions on the preoperative DW-MRI. Technical success was achieved in all five patients, with one operative complication involving a dissection of the common carotid at the access site, which was stented using the TCAR system. Postoperative DW-MRI did not identify any new intracerebral lesions in any patient following the procedure. No patient had a stroke, myocardial infarction, or death during hospitalization. Conclusions: In this real-world, high-risk cohort, TCAR was completed with no evidence of new, postoperative DW-MRI lesions. These data further demonstrate that TCAR with flow reversal is an effective neuroprotective strategy for carotid revascularization. Further study is warranted to evaluate DW-MRI differences between TCAR and CEA.

Opioid-Sparing Effects of the Bupivacaine Pleural Catheter in Surgical Decompression of the Thoracic Outlet.

BACKGROUND: Rib resection in thoracic outlet decompression can result in significant postoperative pain requiring high levels of opioid medications. We evaluated the impact of a bupivacaine infusing pleural catheter on postoperative pain and opioid usage in patients undergoing rib resection for thoracic outlet syndrome. We hypothesized that delivery of local anesthetic via the pleural catheter would improve postoperative pain control compared to standard multimodal analgesia, and that the use of the catheter would decrease opioid use during the index hospitalization and prescriptions for opioid pain medications at discharge. METHODS: We conducted a single-center retrospective cohort study of 26 patients who underwent rib resection for thoracic outlet decompression. Primary outcome was opioid consumption during the index hospitalization, measured in morphine milligram equivalents (MME). Secondary outcomes were MME prescribed at discharge and pain scores during the index hospitalization before and after the pleural drain and pleural catheter were removed. RESULTS: Patients in the bupivacaine infusion pleural catheter group (n = 11) had significantly lower MME usage during the index hospitalization (22.5 [1.9, 65.6] vs. 119.8 [76.5, 167.4]), and significantly lower MME prescribed at discharge (0 [0, 37.5] vs. 225 [183, 315]), compared to standard multimodal analgesia in controls (n = 15). Only 3 patients in the bupivacaine pleural catheter group were discharged with any opioid prescriptions (27%), compared to 14 patients in the control group (93%). There was no difference in postoperative pain scores between groups before or after removal of the pleural drain, which was placed in all cases (P = 0.31 and P = 0.76, respectively). CONCLUSIONS: Intraoperative placement of a bupivacaine infusion pleural catheter significantly reduced opioid use during the index hospitalization and opioid prescribing at discharge. Anesthetic infusion pleural catheters should be the treatment modality of choice for postoperative pain management in patients undergoing thoracic outlet decompression.

Changes in intraoperative aortic strain as detected by ultrasound elastography in patients following abdominal endovascular aneurysm repair.

Objective: Predicting success after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) relies on measurements of aneurysm sac regression. However, in the absence of regression, morphometric analysis alone is insufficient to reliably predict the successful remodeling of AAAs after EVAR. Biomechanical parameters, such as pressure-normalized principal strain, might provide useful information in the post-EVAR AAA assessment. Our objective was to assess the feasibility of our novel ultrasound elastography (USE) technique to detect changes in the aortic wall principal strain in patients who had undergone EVAR and determine the temporal nature of the biomechanical changes in the aorta. Methods: USE images were obtained from patients undergoing elective EVAR intraoperatively, immediately before and after endograft implantation, and at their 30-day follow-up. The maximal mean principal strain ( ε ρ + ¯ ) for each scan was assessed using our novel technique, which uses a finite element mesh to track the frame-to-frame displacements of the aortic wall over one cardiac cycle. The ε ρ + ¯ in the user-defined aortic wall was then divided by the pulse pressure at the time of the scan to produce a pressure-normalized strain measurement ( ε ρ + ¯ /PP), a surrogate for tissue stiffness. Paired t tests were used to compare the pre- and postoperative ε ρ + ¯ /PP and the postoperative and 30-day ε ρ + ¯ /PP. Patient 30-day sac regression and endoleak data were collected by a review of 30-day follow-up computed tomography scans. Results: USE analysis of the data from 12 patients demonstrated a significant reduction in aortic wall ε ρ + ¯ /PP (average, 0.191% ± 0.09%/kPa vs 0.087% ± 0.04%/kPa; P = .002) immediately after graft implantation, with a nonsignificant change in the ε ρ + ¯ /PP (0.091% ± 0.04%/kPa vs 0.102% ± 0.05%/kPa; P = .47) from postoperatively to 30-day follow-up. This represents an average 46.5% reduction after stent placement, with a nonsignificant 18.1% increase at 30-day follow-up. All the patients showed sac stability, except for two patients who had demonstrated 7.3-mm and 6.8-mm sac regressions. Conclusions: Our analysis has demonstrated that the presented USE technique is a feasible method for detecting significant reductions in aortic ε ρ + ¯ /PP intraoperatively after EVAR. We found that patients undergoing EVAR will experience large reductions in the ε ρ + ¯ /PP intraoperatively after graft implantation, with stabilization found at their 30-day follow-up. These preliminary data have shown that an intraoperative ε ρ + ¯ /PP reduction could be a promising correlate of post-EVAR aneurysm remodeling. Our results have also suggested that endograft design likely plays a large role in determining the aneurysm biomechanical changes immediately after implantation.

Deep brain stimulation for parkinson's disease induces spontaneous cortical hypersynchrony in extended motor and cognitive networks.

The mechanism of action of deep brain stimulation (DBS) to the basal ganglia for Parkinson's disease remains unclear. Studies have shown that DBS decreases pathological beta hypersynchrony between the basal ganglia and motor cortex. However, little is known about DBS's effects on long range corticocortical synchronization. Here, we use machine learning combined with graph theory to compare resting-state cortical connectivity between the off and on-stimulation states and to healthy controls. We found that turning DBS on increased high beta and gamma band synchrony (26 to 50 Hz) in a cortical circuit spanning the motor, occipitoparietal, middle temporal, and prefrontal cortices. The synchrony in this network was greater in DBS on relative to both DBS off and controls, with no significant difference between DBS off and controls. Turning DBS on also increased network efficiency and strength and subnetwork modularity relative to both DBS off and controls in the beta and gamma band. Thus, unlike DBS's subcortical normalization of pathological basal ganglia activity, it introduces greater synchrony relative to healthy controls in cortical circuitry that includes both motor and non-motor systems. This increased high beta/gamma synchronization may reflect compensatory mechanisms related to DBS's clinical benefits, as well as undesirable non-motor side effects.

The 27 Facial Sutures: Timing and Clinical Consequences of Closure.

SUMMARY: Facial sutures contribute significantly to postnatal facial development, but their potential role in craniofacial disease is understudied. Since interest in their development and physiology peaked in the mid-twentieth century, facial sutures have not garnered nearly the same clinical research interest as calvarial sutures or cranial base endochondral articulations. In addition to reinforcing the complex structure of the facial skeleton, facial sutures absorb mechanical stress and generally remain patent into and beyond adolescence, as they mediate growth and refine the shape of facial bones. However, premature closure of these sites of postnatal osteogenesis leads to disrupted growth vectors and consequent dysmorphologies. Although abnormality in individual sutures results in isolated facial deformities, we posit that generalized abnormality across multiple sutures may be involved in complex craniofacial conditions such as syndromic craniosynostosis. In this work, the authors comprehensively review 27 key facial sutures, including physiologic maturation and closure, contributions to postnatal facial development, and clinical consequences of premature closure.

Rapidly Extensive Recurrence of Esophageal Neuroendocrine Carcinoma After Complete Pathologic Response to Definitive Chemoradiation.

Primary esophageal neuroendocrine carcinoma is a rare, aggressive malignancy lacking evidence-based treatment guidelines. The timing and nature of relapse after successful treatment of locoregional disease are not well characterized. We report a patient lacking risk factors for esophageal cancer who rapidly developed extensive disease recurrence 4 months after achieving complete pathologic response to nonsurgical treatment. Although optimal survival for early stage nonmetastatic disease is achieved by esophagectomy with adjuvant therapy, definitive chemotherapy is also appropriate for late stage nonmetastatic patients. There are presently no protocols for maintenance therapy. We highlight complex treatment considerations for this rare malignancy.

Edge Density Imaging Identifies White Matter Biomarkers of Late-Life Obesity and Cognition.

Alzheimer disease (AD) and obesity are related to disruptions in the white matter (WM) connectome. We examined the link between the WM connectome and obesity and AD through edge-density imaging/index (EDI), a tractography-based method that characterizes the anatomical embedding of tractography connections. A total of 60 participants, 30 known to convert from normal cognition or mild-cognitive impairment to AD within a minimum of 24 months of follow up, were selected from the Alzheimer disease Neuroimaging Initiative (ADNI). Diffusion-weighted MR images from the baseline scans were used to extract fractional anisotropy (FA) and EDI maps that were subsequently averaged using deterministic WM tractography based on the Desikan-Killiany atlas. Multiple linear and logistic regression analysis were used to identify the weighted sum of tract-specific FA or EDI indices that maximized correlation to body-mass-index (BMI) or conversion to AD. Participants from the Open Access Series of Imaging Studies (OASIS) were used as an independent validation for the BMI findings. The edge-density rich, periventricular, commissural and projection fibers were among the most important WM tracts linking BMI to FA as well as to EDI. WM fibers that contributed significantly to the regression model related to BMI overlapped with those that predicted conversion; specifically in the frontopontine, corticostriatal, and optic radiation pathways. These results were replicated by testing the tract-specific coefficients found using ADNI in the OASIS-4 dataset. WM mapping with EDI enables identification of an abnormal connectome implicated in both obesity and conversion to AD.

Facial Suture Pathology in Syndromic Craniosynostosis: Human and Animal Studies.

BACKGROUND: Facial deformities in syndromic craniosynostosis are not only functionally, psychosocially, and aesthetically impairing but also notoriously challenging to reconstruct. Whether facial suture synostosis plays a significant role in the pathogenesis of these deformities is inadequately studied in human patients. METHODS: The MEDLINE database was queried using a methodologically generated search term inventory. Article inclusion was adjudicated by 2 authors after independent review. Articles provided insight into facial suture involvement in either syndromic craniosynostosis patients or animal models of disease. RESULTS: Comprehensive review yielded 19 relevant articles meeting inclusion criteria. Mid-20th century craniofacial biologists characterized how patent facial sutures are essential for normal postnatal facial development. They also posited that premature ossification disrupts growth vectors, causing significant dysmorphologies. Recently, facial suture synostosis was found to cause midfacial deformities independent of cranial base pathology in mouse models of syndromic craniosynostosis. Few recent studies have begun exploring facial suture involvement in patients, and although they have paved the way for future research, they bear significant limitations. CONCLUSIONS: The hypothesis that facial suture synostosis acts in conjunction with cranial base pathology to produce the prominent, multifocal facial deformities in syndromic craniosynostosis may fundamentally alter surgical management and warrants further investigation. Methodically evaluating the literature, this review synthesizes all basic science and human clinical research thus far on the role of facial sutures in syndromic craniosynostosis and elucidates important topics for future research. We ultimately identify the need for rigorous imaging studies that longitudinally evaluate facial osteology across patients with various craniosynostosis syndromes.

A Reappraisal of CT Angiography Derived Duplex Ultrasound Velocity Criteria With a Comparison to Digital Subtraction Angiography in Patients With Carotid Artery Stenosis.

BACKGROUND: Traditionally, carotid duplex ultrasound (CDUS) velocity criteria have been derived from angiography. Recent studies support a shift toward computed tomography angiography (CTA) derived velocity criteria; however, they lack a comparison to angiography. The purposes of this study are to validate CTA derived measurements with digital subtraction angiography (DSA) and to update our previous CTA-derived velocity criteria for 50% and 80% stenosis. METHODS: All patients between 2010 and 2019 who underwent CDUS and a neck CTA within 6 months were identified for a retrospective review. Vessel diameter and corresponding CDUS data were recorded. Additional DSA measurements were recorded for a subset of patients. Data from this cohort were added to a previously reported deidentified data set from patients between 2000 and 2009. Receiver operating characteristic (ROC) curves were generated to determine optimal velocity thresholds. Spearman rank correlation was used to correlate measurements obtained by CTA to those obtained by DSA. RESULTS: A total of 1139 vessels from 636 patients were analyzed. ROC analysis to identify ≥ 50% stenosis resulted in optimized thresholds of 143 cm/sec, 46.2 cm/sec, and 2.15 for peak systolic velocity (PSV), end-diastolic velocity (EDV), and PSV to common carotid artery PSV ratio (PSVR), respectively. ROC analysis to identify ≥ 80% stenosis resulted in optimized thresholds of 319 cm/sec, 87.2 cm/sec, and 3.49 for PSV, EDV, and PSVR, respectively. The degree of carotid artery stenosis for a subset of 124 vessels on CTA correlated well with that of DSA (ρ = 0.89, P< 0.0001). CONCLUSIONS: These data demonstrate a high correlation between measurements obtained on CTA and DSA while forming reliable CTA-derived CDUS velocity criteria.

Postoperative Admission of Adult Craniotomy Patients to the Neuroscience Ward Reduces Length of Stay and Cost.

BACKGROUND: The neurointensive care unit (NICU) has traditionally been the default recovery unit after elective craniotomies. OBJECTIVE: To assess whether admitting adult patients without significant comorbidities to the neuroscience ward (NW) instead of NICU for recovery resulted in similar clinical outcome while reducing length of stay (LOS) and hospitalization cost. METHODS: We retrospectively analyzed the clinical and cost data of adult patients undergoing supratentorial craniotomy at a university hospital within a 5-yr period who had a LOS less than 7 d. We compared those admitted to the NICU for 1 night of recovery versus those directly admitted to the NW. RESULTS: The NICU and NW groups included 340 and 209 patients, respectively, and were comparable in terms of age, ethnicity, overall health, and expected LOS. NW admissions had shorter LOS (3.046 vs 3.586 d, P < .001), and independently predicted shorter LOS in multivariate analysis. While the NICU group had longer surgeries (6.8 vs 6.4 h), there was no statistically significant difference in the cost of surgery. The NW group was associated with reduced hospitalization cost by $3193 per admission on average (P < .001). Clinically, there were no statistically significant differences in the rate of return to Operating Room, Emergency Department readmission, or hospital readmission within 30 d. CONCLUSION: Admitting adult craniotomy patients without significant comorbidities, who are expected to have short LOS, to NW was associated with reduced LOS and total cost of admission, without significant differences in postoperative clinical outcome.

Oral Flora and Perioperative Antimicrobial Interventions in Cleft Palate Surgery: A Review of the Literature.

BACKGROUND: The role of perioperative antibiotics in cleft palate remains a topic of debate. Advocates stress their importance in preventing local and systemic infections and decreasing the incidence of oronasal fistula formation. However, few studies to date have directly evaluated the role of antibiotics and other antimicrobial measures in cleft palate surgery. OBJECTIVE: The aim of this review is to evaluate the evidence surrounding the use of perioperative antibiotics and other antimicrobial interventions in cleft palate surgery. Additionally, we review the literature on the oral flora unique to the cleft palate patient population. METHODS: This was accomplished utilizing PubMed, Medline, and the Cochrane Library with MeSH and generic terms. Articles were selected based on predefined inclusion and exclusion criteria. RESULTS: This review highlights the lack of higher level evidence on perioperative antibiotic use and other antimicrobial interventions in cleft palatoplasty and calls for further research on the matter. CONCLUSIONS: The literature appears to support the use of preoperative antibiotics for cleft palatoplasty, but the benefits of prolonged postoperative antibiotic use remain questionable.

Effect of Cross-Sex Hormone Therapy on Venous Thromboembolism Risk in Male-to-Female Gender-Affirming Surgery.

Individuals with gender dysphoria often seek medical interventions, such as hormone treatment and surgery, to live as their identified gender. Cross-sex hormone therapy typically consists of various estrogen formulations which confer varying risks of venous thromboembolism (VTE). Currently, there is no standard practice by surgeons regarding the preoperative gender-affirming surgery (GAS) hormone regimen of male-to-female (MTF) patients to minimize thromboembolic postoperative complications. The aim of this review is to examine the current literature on VTE occurring in MTF transgender patients on cross-sex hormone therapy (CSHT) when undergoing various gender-affirming surgeries-facial feminization surgery (FFS), top surgery (TS), and bottom surgery (BS)-to understand how evidence-based recommendations regarding perioperative hormone regimens can be established to improve clinical outcomes. Within the past 25 years, 7 published studies have examined the incidence of VTE in MTF patients undergoing GAS procedures. Two of these articles examined MTF patients undergoing FFS, 1 article reported a patient who had undergone BS and FFS during the same hospitalization, and the remaining 4 articles investigated VTE risk in BS. Our review supports that plastic surgeons who perform GAS are divided on their preferred CSHT protocols, with some requiring patients to suspend their CSHT weeks before surgery and others allowing patients to continue CSHT through the day of surgery. Three of the 7 studies detailed a CSHT perioperative regimen which instructed patients to suspend CSHT sometime before surgery; 1 study tapered CSHT to lower levels before surgery; the remaining 3 studies did not specify a CSHT perioperative regimen. This review highlights the paucity of data failing to support that continuing CSHT through GAS elevates VTE risk. We conclude that in the absence of definitive VTE risk factors (e.g., smoking, clotting disorders, or malignancy), surgeons may engage MTF patients in joint decision-making process to determine the most optimal perioperative CSHT management plan on a case-by-case basis. Future studies are warranted to evaluate VTE risk based on patient age, type of surgery, operating time, prophylactic measures, follow-up time, and CSHT perioperative regimens.

Diagnostic Value of Molecular Testing in Sonographically Suspicious Thyroid Nodules.

OBJECTIVE: Molecular testing can refine the diagnosis for the 20% of thyroid fine-needle aspiration biopsies that have indeterminate cytology. We assessed the diagnostic accuracy of molecular testing based on ultrasound risk classification. METHODS: This retrospective cohort study analyzed all thyroid nodules with indeterminate cytology at an academic US medical center (2012-2016). All indeterminate nodules underwent reflexive molecular testing with the Afirma Gene Expression Classifier (GEC). Radiologists performed blinded reviews to categorize each nodule according to the American Thyroid Association (ATA) ultrasound classification and the American College of Radiology Thyroid Imaging, Reporting and Data System. GEC results and diagnostic performance were compared across ultrasound risk categories. RESULTS: Of 297 nodules, histopathology confirmed malignancy in 65 (22%). Nodules by ATA classification were 8% high suspicion, 44% intermediate, and 48% low/very low suspicion. A suspicious GEC result was more likely in ATA high-suspicion nodules (81%) than in nodules of all other ATA categories (57%; P = .04). The positive predictive value (PPV) of GEC remained consistent across ultrasound categories (ATA high suspicion, 64% vs all other ATA categories, 48%; P = .39). The ATA high-suspicion category had higher specificity than a suspicious GEC result (93% vs 51%; P < .01). A suspicious GEC result did not increase specificity for the ATA high-suspicion category. CONCLUSION: The PPV of molecular testing remained consistent across ultrasound risk categories. However, a suspicious GEC result was very likely in ATA high-suspicion nodules and did not improve specificity in this sonographic category.

Connectome mapping with edge density imaging differentiates pediatric mild traumatic brain injury from typically developing controls: proof of concept.

BACKGROUND: Although acute neurologic impairment might be transient, other long-term effects can be observed with mild traumatic brain injury. However, when pediatric patients with mild traumatic brain injury present for medical care, conventional imaging with CT and MR imaging often does not reveal abnormalities. OBJECTIVE: To determine whether edge density imaging can separate pediatric mild traumatic brain injury from typically developing controls. MATERIALS AND METHODS: Subjects were recruited as part of the "Therapeutic Resources for Attention Improvement using Neuroimaging in Traumatic Brain Injury" (TRAIN-TBI) study. We included 24 adolescents (χ=14.1 years of age, σ=1.6 years, range 10-16 years), 14 with mild traumatic brain injury (TBI) and 10 typically developing controls. Neurocognitive assessments included the pediatric version of the California Verbal Learning Test (CVLT) and the Attention Network Task (ANT). Diffusion MR imaging was acquired on a 3-tesla (T) scanner. Edge density images were computed utilizing fiber tractography. Principal component analysis (PCA) and support vector machines (SVM) were used in an exploratory analysis to separate mild TBI and control groups. The diagnostic accuracy of edge density imaging, neurocognitive tests, and fractional anisotropy (FA) from diffusion tensor imaging (DTI) was computed with two-sample t-tests and receiver operating characteristic (ROC) metrics. RESULTS: Support vector machine-principal component analysis of edge density imaging maps identified three white matter regions distinguishing pediatric mild TBI from controls. The bilateral tapetum, sagittal stratum, and callosal splenium identified mild TBI subjects with sensitivity of 79% and specificity of 100%. Accuracy from the area under the ROC curve (AUC) was 94%. Neurocognitive testing provided an AUC of 61% (CVLT) and 71% (ANT). Fractional anisotropy yielded an AUC of 48%. CONCLUSION: In this proof-of-concept study, we show that edge density imaging is a new form of connectome mapping that provides better diagnostic delineation between pediatric mild TBI and healthy controls than DTI or neurocognitive assessments of memory or attention.