Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Extranodal extension of tumour on histopathology is known to be a negative prognostic factor in head and neck cancer. Compelling evidence suggests that extranodal extension detected on radiological imaging is also a negative prognostic factor. Furthermore, if imaging detected extranodal extension could be identified reliably before the start of treatment, it could be used to guide treatment selection, as patients might be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy (surgery, chemotherapy, and radiotherapy together). There are many aspects of imaging detected extranodal extension that remain unresolved or are without consensus, such as the criteria to best diagnose them and the associated terminology. The Head and Neck Cancer International Group conducted a five-round modified Delphi process with a group of 18 international radiology experts, representing 14 national clinical research groups. We generated consensus recommendations on the terminology and diagnostic criteria for imaging detected extranodal extension to harmonise clinical practice and research. These recommendations have been endorsed by 19 national and international organisations, representing 34 countries. We propose a new classification system to aid diagnosis, which was supported by most of the participating experts over existing systems, and which will require validation in the future. Additionally, we have created an online educational resource for grading imaging detected extranodal extensions.

Dyrk1a gene dosage in glutamatergic neurons has key effects in cognitive deficits observed in mouse models of MRD7 and Down syndrome.

Perturbation of the excitation/inhibition (E/I) balance leads to neurodevelopmental diseases including to autism spectrum disorders, intellectual disability, and epilepsy. Loss-of-function mutations in the DYRK1A gene, located on human chromosome 21 (Hsa21,) lead to an intellectual disability syndrome associated with microcephaly, epilepsy, and autistic troubles. Overexpression of DYRK1A, on the other hand, has been linked with learning and memory defects observed in people with Down syndrome (DS). Dyrk1a is expressed in both glutamatergic and GABAergic neurons, but its impact on each neuronal population has not yet been elucidated. Here we investigated the impact of Dyrk1a gene copy number variation in glutamatergic neurons using a conditional knockout allele of Dyrk1a crossed with the Tg(Camk2-Cre)4Gsc transgenic mouse. We explored this genetic modification in homozygotes, heterozygotes and combined with the Dp(16Lipi-Zbtb21)1Yey trisomic mouse model to unravel the consequence of Dyrk1a dosage from 0 to 3, to understand its role in normal physiology, and in MRD7 and DS. Overall, Dyrk1a dosage in postnatal glutamatergic neurons did not impact locomotor activity, working memory or epileptic susceptibility, but revealed that Dyrk1a is involved in long-term explicit memory. Molecular analyses pointed at a deregulation of transcriptional activity through immediate early genes and a role of DYRK1A at the glutamatergic post-synapse by deregulating and interacting with key post-synaptic proteins implicated in mechanism leading to long-term enhanced synaptic plasticity. Altogether, our work gives important information to understand the action of DYRK1A inhibitors and have a better therapeutic approach.

The Quantification of Radiation Fibrosis Using Clinically Indicated Magnetic Resonance Imaging for Head and Neck Cancer Patients.

Currently, no objective method exists to measure the extent of fibrosis in swallowing musculature in head and neck cancer (HNC) patients. We developed and psychometrically tested a method of quantifying fibrosis volume using magnetic resonance imaging (MRI). The overall aim of this study was to determine if clinical MRI is a reliable tool to measure fibrosis of the pharyngeal musculature in patients with HNC managed with RT and to assess its potential to capture changes in fibrosis over time. Eligible participants were adults with HNC treated with radiation therapy (RT) who received minimally two MRIs and videofluoroscopic swallow (VFS) studies from baseline (pre-RT) up to 1-year post-RT. Two neuroradiologists independently contoured fibrosis volume in batches from MRIs using Vitrea™. Sufficient inter-rater reliability was set at Intraclass Correlation Coefficient (ICC) > 0.75. Two speech-language pathologists independently rated VFSs for swallowing impairment using standardized scales, with discrepancies resolved by consensus. MRI and VFS scores were correlated using Spearman's rank coefficient. Participants included 42 adults (male = 33); mean age 59 (SD = 8.8). ICC (95% Confidence Interval) for fibrosis volume was 0.34 (0, 0.76) for batch one and 0.43 (0, 0.82) for batch two. Consensus meetings were held after each batch. Sufficient reliability was reached by batch three (ICC = 0.95 (0.79, 0.99)). Fibrosis volume increased significantly from 3 to 12 months (mean change = 1.28 mL (SD = 5.21), p = 0.006), as did pharyngeal impairment from baseline to 12 months (mean score change = 3.05 (SD = 3.02), p = 0.003). Fibrosis volume moderately correlated with pharyngeal impairment at 3 and 12 months (0.49, p = 0.004 and 0.59, p = 0.005, respectively). We demonstrated a reliable measure of fibrosis volume in swallowing musculature from existing clinical MRIs and identified that larger fibrosis volume was associated with worse swallowing function. The reliable capture of fibrosis volume offers a pragmatic method for early detection of fibrosis and concomitant dysphagia.

Genetic Mapping of APP and Amyloid-ß Biology Modulation by Trisomy 21.

Individuals who have Down syndrome (DS) frequently develop early onset Alzheimer's disease (AD), a neurodegenerative condition caused by the buildup of aggregated amyloid-ß (Aß) and tau proteins in the brain. Aß is produced by amyloid precursor protein (APP), a gene located on chromosome 21. People who have DS have three copies of chromosome 21 and thus also an additional copy of APP; this genetic change drives the early development of AD in these individuals. Here we use a combination of next-generation mouse models of DS (Tc1, Dp3Tyb, Dp(10)2Yey and Dp(17)3Yey) and a knockin mouse model of Aß accumulation (AppNL-F ) to determine how chromosome 21 genes, other than APP, modulate APP/Aß in the brain when in three copies. Using both male and female mice, we demonstrate that three copies of other chromosome 21 genes are sufficient to partially ameliorate Aß accumulation in the brain. We go on to identify a subregion of chromosome 21 that contains the gene(s) causing this decrease in Aß accumulation and investigate the role of two lead candidate genes, Dyrk1a and Bace2 Thus, an additional copy of chromosome 21 genes, other than APP, can modulate APP/Aß in the brain under physiological conditions. This work provides critical mechanistic insight into the development of disease and an explanation for the typically later age of onset of dementia in people who have AD in DS, compared with those who have familial AD caused by triplication of APP SIGNIFICANCE STATEMENT Trisomy of chromosome 21 is a commonly occurring genetic risk factor for early-onset Alzheimer's disease (AD), which has been previously attributed to people with Down syndrome having three copies of the amyloid precursor protein (APP) gene, which is encoded on chromosome 21. However, we have shown that an extra copy of other chromosome 21 genes modifies AD-like phenotypes independently of APP copy number (Wiseman et al., 2018; Tosh et al., 2021). Here, we use a mapping approach to narrow down the genetic cause of the modulation of pathology, demonstrating that gene(s) on chromosome 21 decrease Aß accumulation in the brain, independently of alterations to full-length APP or C-terminal fragment abundance and that just 38 genes are sufficient to cause this.

Clinical presentation and outcome of human papillomavirus-positive nasopharyngeal carcinoma in a North American cohort.

BACKGROUND: The objective of this study was to describe the clinical presentation and outcomes of human papillomavirus (HPV)-positive nasopharyngeal cancer (NPC) versus Epstein-Barr virus (EBV)-positive NPC and HPV-positive oropharyngeal cancer (OPC). METHODS: Clinical characteristics and presenting signs/symptoms were compared between patients who had viral-related NPC versus viral-related OPC treated with intensity-modulated radiotherapy from 2005 to 2020 and who were matched 1:1 (by tumor and lymph node categories, smoking, age, sex, histology, and year of diagnosis). Locoregional control (LRC), distant control (DC), and overall survival (OS) were compared using the 2005-2018 cohort to maintain 2 years of minimum follow-up. Multivariable analysis was used to evaluate the cohort effect. RESULTS: Similar to HPV-positive OPC (n = 1531), HPV-positive NPC (n = 29) occurred mostly in White patients compared with EBV-positive NPC (n = 422; 86% vs. 15%; p < .001). Primary tumor volumes were larger in HPV-positive NPC versus EBV-positive NPC (median volume, 51 vs. 23 cm3 ; p = .002), with marginally more Level IB nodal involvement. More patients with HPV-positive NPC complained of local pain (38% vs. 3%; p = .002). The median follow-up for the 2005-2018 cohort was 5.3 years. Patients who had HPV-positive NPC (n = 20) had rates of 3-year LRC (95% vs. 90%; p = .360), DC (75% vs. 87%; p = .188), and OS (84% vs. 89%; p = .311) similar to the rates in those who had EBV-positive NPC (n = 374). Patients who had HPV-positive NPC also had rates of LRC (95% vs. 94%; p = .709) and OS (84% vs. 87%; p = .440) similar to the rates in those who had HPV-positive OPC (n = 1287). The DC rate was lower in patients who had HPV-positive disease (75% vs. 90%; p = .046), but the difference became nonsignificant (p = .220) when the analysis was adjusted for tumor and lymph node categories, smoking, and chemotherapy. CONCLUSIONS: HPV-positive NPC and EBV-positive NPC seem to be mutually exclusive diseases. Patients who have HPV-positive NPC have greater local symptom burden and larger primary tumors but have similar outcomes compared with patients who have EBV-positive NPC or HPV-positive OPC.

Defect Engineering of Graphene to Modulate pH Response of Graphene Devices.

Graphene-based pH sensors are a robust, durable, sensitive, and scalable approach for the sensitive detection of pH in various environments. However, the mechanisms through which graphene responds to pH variations are not well-understood yet. This study provides a new look into the surface science of graphene-based pH sensors to address the existing gaps and inconsistencies among the literature concerning sensing response, the role of defects, and surface/solution interactions. Herein, we demonstrate the dependence of the sensing response on the defect density level of graphene, measured by Raman spectroscopy. At the crossover point (ID/IG = 0.35), two countervailing mechanisms balance each other out, separating two regions where either a surface defect induced (negative slope) or a double layer induced (positive slope) response dominates. For ratios above 0.35, the pH-dependent induction of charges at surface functional groups (both pH-sensitive and nonsensitive groups) dominates the device response. Below a ratio of 0.35, the response is dominated by the modulation of charge carriers in the graphene due to the electric double layer formed from the interaction between the graphene surface and the electrolyte solution. Selective functionalization of the surface was utilized to uncover the dominant acid-base interactions of carboxyl and amine groups at low pH while hydroxyl groups control the high pH range sensitivity. The overall pH-sensing characteristics of the graphene will be determined by the balance of these two mechanisms.

Elevated ocular VEMP responses in the absence of a superior semicircular canal dehiscence.

BACKGROUND: Vestibular evoked myogenic potentials (VEMPs) have an accepted role in the diagnosis of the superior semicircular canal dehiscence (SSCD) syndrome. The current impression is that ocular VEMPs (oVEMPs) are more sensitive than cervical VEMPs (cVEMPs) for detecting a SSCD and that oVEMP testing in response to air conducted sound provides an excellent screening test without risk of radiation exposure from computerized tomography (CT). AIMS/OBJECTIVES: To report on patients with elevated oVEMP amplitudes but without evidence for a SSCD on multiplanar CT imaging. MATERIAL AND METHODS: Retrospective chart review of all patients referred for vestibular function testing to our department. Patients with oVEMP peak-to-peak amplitudes ≥17 µν without evidence for a SSCD on imaging were evaluated. RESULTS: 26 patients had oVEMP peak-to-peak amplitudes ≥17 µν with no evidence of a SSCD on imaging. The most common diagnosis was Meniere's disease in those identified. CONCLUSION AND SIGNIFICANCE: oVEMPs can provide false positive results for diagnosis of a SSCD and an elevated oVEMP amplitude in itself is insufficient for diagnosis of a SSCD.

Clinical outcomes and transfusion management following intracranial hemorrhage in patients with acute leukemia.

BACKGROUND: There is little evidence to guide management of patients with acute leukemia and intracranial hemorrhage (ICH). Predictors of long-term outcome following ICH are unknown. STUDY DESIGN AND METHODS: This study included adult patients with acute leukemia and ICH over an 8-year period. The primary outcome was data regarding 90-day mortality. Secondary outcomes included data related to the proportion of patients receiving post-remission therapy and predictors of 90-day mortality. RESULTS: ICH occurred in 101 patients; 12 patients died within 72 hours. For the 89 others, 90-day mortality was 40%. Of 43 patients who received induction, 30 achieved remission and 26 received post-remission therapy. Older age (p = 0.03) and higher white count (p = 0.02) at the time of ICH were predictive of inferior survival. During 90-day follow-up, median platelet count was 37 x 109 /L (0-1526 x 109 /L). Lower platelet count during follow-up was predictive of 90-day mortality (p = <0.01). Twenty-one percent of platelet transfusions were provided when the platelet count was less than 10 x 109 /L, 54% between 10 and 29 x 109 /L, and 25% greater than 30 x 109 /L. New or progressive ICH occurred in 23 patients. There was no difference in the median platelet transfusion trigger between patients who had new or progressive ICH and those who did not. CONCLUSION: In patients with acute leukemia, survival following ICH is poor. Older age and higher white count is associated with increased mortality, perhaps reflecting higher risk disease. Following ICH in acute leukemia platelet transfusions do not appear to alter the risk of progressive bleeding or mortality.

Preoperative Computed Tomography Changes Surgical Management for Clinically Low-Risk Well-Differentiated Thyroid Cancer.

BACKGROUND: In the current guidelines for differentiated thyroid cancer (DTC), computed tomography (CT) of the neck has a limited role. The authors hypothesized that adding CT to the workup of clinically low-risk DTC size 4 cm or smaller changes the surgical management for a portion of patients due to detection of clinically significant lymph node metastases not located by ultrasound of the neck. METHODS: A prospective cohort of DTC patients at an academic referral center between 2012 and 2016 was reviewed. All the patients with fine-needle aspiration cytopathology results suspicious for malignancy or malignant tumor (Bethesda category 5 or 6, respectively) underwent CT before surgery. Clinically low-risk DTC patients were selected if they had a tumor diameter of 4 cm or less and no evidence for local invasion or suspicious lymph nodes seen on ultrasound. Outcomes focused on alteration of the surgical plan based on CT and correlation with pathology. RESULTS: The CT findings for 25 (22.5%) of 111 patients with clinically low-risk DTC led to a change in surgical management. Of these 25 patients, 16 (14.4% of the entire cohort) benefited due to the removal of clinically significant lymph node disease not seen on ultrasound. Categorization of the group that had a change in management showed that 6 (85.7%) of 7 lateral neck dissections and 10 (55.6%) of 18 central neck dissections (CND) harbored metastatic nodes larger than 2 mm. CONCLUSIONS: In the group with clinically low-risk DTC, CT changed surgical management for a substantial number of the patients with clinically significant nodal disease not detected by ultrasound. This highlights the fact that in certain practice settings, adding CT to the preoperative staging may be favorable for the detection of nodal metastasis.

Ultrasound Is Superior to Palpation in Identifying the Cricothyroid Membrane in Subjects with Poorly Defined Neck Landmarks: A Randomized Clinical Trial.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Success of a cricothyrotomy is dependent on accurate identification of the cricothyroid membrane. The objective of this study was to compare the accuracy of ultrasonography versus external palpation in localizing the cricothyroid membrane. METHODS: In total, 223 subjects with abnormal neck anatomy who were scheduled for neck computed-tomography scan at University Health Network hospitals in Toronto, Canada, were randomized into two groups: external palpation and ultrasound. The localization points of the cricothyroid membrane determined by ultrasonography or external palpation were compared to the reference midpoint (computed-tomography point) of the cricothyroid membrane by a radiologist who was blinded to group allocation. Primary outcome was the accuracy in identification of the cricothyroid membrane, which was measured by digital ruler in millimeters from the computed-tomography point to the ultrasound point or external-palpation point. Success was defined as the proportion of accurate attempts within a 5-mm distance from the computed-tomography point to the ultrasound point or external-palpation point. RESULTS: The percentage of accurate attempts was 10-fold greater in the ultrasound than external-palpation group (81% vs. 8%; 95% CI, 63.6 to 81.3%; P < 0.0001). The mean (SD) distance measured from the external-palpation to computed-tomography point was five-fold greater than the ultrasound to the computed-tomography point (16.6 ± 7.5 vs. 3.4 ± 3.3 mm; 95% CI, 11.67 to 14.70; P < 0.0001). Analysis demonstrated that the risk ratio of inaccurate localization of the cricothyroid membrane was 9.14-fold greater with the external palpation than with the ultrasound (P < 0.0001). There were no adverse events observed. CONCLUSIONS: In subjects with poorly defined neck landmarks, ultrasonography is more accurate than external palpation in localizing the cricothyroid membrane.

Cerebral venous thrombosis: state of the art diagnosis and management.

PURPOSE: This review article aims to discuss the pathophysiology, clinical presentation, and neuroimaging of cerebral venous thrombosis (CVT). Different approaches for diagnosis of CVT, including CT/CTV, MRI/MRV, and US will be discussed and the reader will become acquainted with imaging findings as well as limitations of each modality. Lastly, this exhibit will review the standard of care for CVT treatment and emerging endovascular options. METHODS: A literature search using PubMed and the MEDLINE subengine was completed using the terms "cerebral venous thrombosis," "stroke," and "imaging." Studies reporting on the workup, imaging characteristics, clinical history, and management of patients with CVT were included. RESULTS: The presentation of CVT is often non-specific and requires a high index of clinical suspicion. Signs of CVT on NECT can be divided into indirect signs (edema, parenchymal hemorrhage, subarachnoid hemorrhage, and rarely subdural hematomas) and less commonly direct signs (visualization of dense thrombus within a vein or within the cerebral venous sinuses). Confirmation is performed with CTV, directly demonstrating the thrombus as a filling defect, or MRI/MRV, which also provides superior characterization of parenchymal abnormalities. General pitfalls and anatomic variants will also be discussed. Lastly, endovascular management options including thrombolysis and mechanical thrombectomy are discussed. CONCLUSIONS: CVT is a relatively uncommon phenomenon and frequently overlooked at initial presentation. Familiarity with imaging features and diagnostic work-up of CVT will help in providing timely diagnosis and therapy which can significantly improve outcome and diminish the risk of acute and long-term complications, optimizing patient care.

Low-Energy Virtual Monochromatic Dual-Energy Computed Tomography Images for the Evaluation of Head and Neck Squamous Cell Carcinoma: A Study of Tumor Visibility Compared With Single-Energy Computed Tomography and User Acceptance.

OBJECTIVE: Dual-energy computed tomography (CT) 40-keV virtual monochromatic images (VMIs) have been reported to improve visualization of head and neck squamous cell carcinoma, but a direct comparison to single-energy CT (SECT) is lacking, and there is debate regarding subjective user preference. We compared 40-keV VMIs with SECT and performed a subjective evaluation of their utility and acceptability for clinical use. METHODS: A total of 60 dual-energy CT and 60 SECT scans from 2 different institutions were evaluated. Tumor conspicuity was evaluated objectively using absolute and relative attenuation and subjectively by 3 head and neck specialists and 3 general radiologists. RESULTS: Tumors had significantly higher absolute and relative attenuation on 40-keV VMIs (P < 0.0001). Subjectively, the 40-keV VMIs improved visualization, with substantial (κ, 0.61-0.80) to almost perfect (κ, 0.81-1) interrater agreements. CONCLUSIONS: The 40-keV VMIs improve tumor visibility objectively and subjectively both by head and neck specialists and general radiologists.

Is Ultrasound a Valid and Reliable Imaging Modality for Airway Evaluation?: An Observational Computed Tomographic Validation Study Using Submandibular Scanning of the Mouth and Oropharynx.

OBJECTIVES: Ultrasound (US) imaging of the airway may be useful in predicting difficulty of airway management (DAM); but its use is limited by lack of proof of its validity and reliability. We sought to validate US imaging of the airway by comparison to CT-scan, and to assess its inter- and intra-observer reliability. We used submandibular sonographic imaging of the mouth and oropharynx to examine how well the ratio of tongue thickness to oral cavity height correlates with the ratio of tongue volume to oral cavity volume, an established tomographic measure of DAM. METHODS: A cohort of 34 patients undergoing CT-scan was recruited. Study standardized assessments included CT-measured ratios of tongue volume to oropharyngeal cavity volume; tongue thickness to oral cavity height; and US-measured ratio of tongue thickness to oral cavity height. Two sonographers independently performed US imaging of the airway before and after CT-scan. RESULTS: Our findings indicate that the US-measured ratio of tongue thickness to oral cavity height highly correlates with the CT-measured ratio of tongue volume to oral cavity volume. US measurements also demonstrated strong inter- and intra-observer reliability. CONCLUSIONS: This study suggests that US is a valid and reliable tool for imaging the oral and oropharyngeal parts of the airway, as well as for measuring the volumetric relationship between the tongue and oral cavity, and may therefore be a useful predictor of DAM.

Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study.

BACKGROUND: Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) aimed to develop a TNM classification specific to HPV+ oropharyngeal cancer. METHODS: The ICON-S study included patients with non-metastatic oropharyngeal cancer from seven cancer centres located across Europe and North America; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients' HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status. We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory training cohort to assess relevance within the ICON-S classification. FINDINGS: Of 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III, and IVA (respectively; 88% [95% CI 74-100]; 82% [71-95]; 84% [79-89]; and 81% [79-83]; global p=0·25) but was lower for stage IVB (60% [53-68]; p<0·0001). 5-year overall survival did not differ among N0 (80% [95% CI 73-87]), N1-N2a (87% [83-90]), and N2b (83% [80-86]) subsets, but was significantly lower for those with N3 disease (59% [51-69]; p<0·0001). Stage classifications derived by RPA and AHR models were ranked according to survival performance, and AHR-New was ranked first, followed by AHR-Orig, RPA, and 7th edition TNM. AHR-New was selected as the proposed ICON-S stage classification. Because 5-year overall survival was similar for patients classed as T4a and T4b, T4 is no longer subdivided in the re-termed ICON-S T categories. Since 5-year overall survival was similar among N1, N2a, and N2b, we re-termed the 7th edition N categories as follows: ICON-S N0, no lymph nodes; ICON-S N1, ipsilateral lymph nodes; ICON-S N2, bilateral or contralateral lymph nodes; and ICON-S N3, lymph nodes larger than 6 cm. This resembles the N classification of nasopharyngeal carcinoma but without a lower neck lymph node variable. The proposed ICON-S classification is stage I (T1-T2N0-N1), stage II (T1-T2N2 or T3N0-N2), and stage III (T4 or N3). Metastatic disease (M1) is classified as ICON-S stage IV. In an exploratory training cohort (n=702), lower lymph node neck involvement had a significant effect on survival in ICON-S stage III but had no effect in ICON-S stage I and II and was not significant as an independent factor. Overall survival was similar for patients with fewer than five lymph nodes and those with five or more lymph nodes, within all ICON-S stages. INTERPRETATION: Our proposed ICON-S staging system for HPV+ oropharyngeal cancer is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification. FUNDING: None.

Venous vascular malformation of the floor of mouth masquerading as a dermoid tumor.

Venous vascular malformations (VVMs) are described as abnormal post-capillary lesions which exhibit low flow. These are typically malleable and may grow with endocrine fluctuations. A VVM that mimics the classic appearance of dermoid tumor on imaging has never been reported. We encountered a 43-year-old woman with intermittent dysphagia relating to a firm submandibular mass. Physical exam and cross-sectional imaging revealed features consistent with variant dermoid cyst. However, catheter angiography eventually demonstrated a VVM which possessed vessels of variable size and partial thrombosis. We report the case and propose that catheter angiography remains important in cases where vascular malformation is considered.

Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group.

The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.

Excitation/inhibition balance and learning are modified by Dyrk1a gene dosage.

Cognitive deficits in Down syndrome (DS) have been linked to increased synaptic inhibition, leading to an imbalance of excitation/inhibition (E/I). Various mouse models and studies from human brains have implicated an HSA21 gene, the serine/threonine kinase DYRK1A, as a candidate for inducing cognitive dysfunction. Here, consequences of alterations in Dyrk1a dosage were assessed in mouse models with varying copy numbers of Dyrk1a: mBACtgDyrk1a, Ts65Dn and Dp(16)1Yey (with 3 gene copies) and Dyrk1a(+/-) (one functional copy). Molecular (i.e. immunoblotting/immunohistochemistry) and behavioral analyses (e.g., rotarod, Morris water maze, Y-maze) were performed in mBACtgDyrk1a mice. Increased expression of DYRK1A in mBACtgDyrk1a induced molecular alterations in synaptic plasticity pathways, particularly expression changes in GABAergic and glutaminergic related proteins. Similar alterations were observed in models with partial trisomy of MMU16, Ts65Dn and Dp(16)1Yey, and were reversed in the Dyrk1a(+/-) model. Dyrk1a overexpression produced an increased number and signal intensity of GAD67 positive neurons, indicating enhanced inhibition pathways in three different models: mBACtgDyrk1a, hYACtgDyrk1a and Dp(16)1Yey. Functionally, Dyrk1a overexpression protected mice from PTZ-induced seizures related to GABAergic neuron plasticity. Our study shows that DYRK1A overexpression affects pathways involved in synaptogenesis and synaptic plasticity and influences E/I balance toward inhibition. Inhibition of DYRK1A activity offers a therapeutic target for DS, but its inhibition/activation may also be relevant for other psychiatric diseases with E/I balance alterations.

Enhancing targeted tumor treatment by near IR light-activatable photodynamic-photothermal synergistic therapy.

For several decades, cancer has been one of the most life-threatening diseases. For enhancing anticancer efficiency with minimum side effects, combination therapy is envisioned. The current manuscript reports for the first time the development of a methylene blue (MB) bound nanoplatform, which is capable of delivering targeted diagnostic and combined synergistic photothermal and photodynamic treatment of cancer. Experimental data found that, once the nanoparticle binds with the target cell surface, it can detect LNCaP human prostate cancer cell selectively using fluorescence imaging. Our result shows that the therapeutic actions can be controlled with external NIR light. No cytotoxicity was observed in the absence of NIR light. Targeted photodynamic and photothermal treatment using 785 nm NIR light indicates that the multimodal treatment enhances the possibility of destroying LNCaP prostate cancer cells in vitro dramatically. We discuss the operating principle for the targeted imaging and possible mechanisms for combined therapeutic actions. Our experimental data show that NIR light activated combined therapy for cancer may become a highly effective treatment procedure in clinical settings.