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Background: Direct oral anticoagulant (DOAC) use presents a challenge to all providers involved in emergency care of patients since widely accepted laboratory tests to assess the level of anticoagulation for such medications are lacking. Viscoelastic tests such as thromboelastography (TEG) tests are increasingly used throughout major trauma centers to help guide resuscitation efforts in patients presenting with trauma and/or hemorrhagic shock., Objective: The primary outcome compared TEG parameters between emergency department trauma patients reporting DOAC therapy and known normal TEG parameter values. The secondary outcome evaluated patients who reported time of last known DOAC dose within a preferred time frame of <12 h for once daily dosing DOAC therapy or < 6 h for twice daily dosing DOAC therapy., Methods: This single-center, retrospective cohort study assessed TEG values in patients receiving DOAC therapy and compared these to institution TEG ranges considered normal. TEG values of reaction time (R time), kinetics (K), alpha angle (AA), maximum amplitude (MA), and percent lysis in 30 min (LY30) were collected for patients reporting DOAC therapy., Results: 40 patients were included in this study. 19 patients reported apixaban therapy and 21 reported rivaroxaban therapy. 5 (12.5%) patients had an elevated R time and 1 (2.5%) patient had a reduced MA. All other TEG values did not suggest hypocoagulability. For the secondary outcome assessing patients reporting last known dose within the preferred time frame, only the R time was elevated in 2 (14.3%) patients. Lastly, in a subgroup analysis of patients with elevated low-molecular-weight heparin (LMWH) orAnti- Xa levels, the R time was the only parameter affected in 25% of patients., Conclusion: TEG values were typically not affected by rivaroxaban or apixaban use in an emergency department trauma population suggesting that TEG is not sensitive for Xa inhibitor detection and should not be relied upon for assessing anticoagulation in such settings., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The Asian tiger mosquito Aedes albopictus is globally expanding and has become the main vector for human arboviruses in Europe. With limited antiviral drugs and vaccines available, vector control is the primary approach to prevent mosquito-borne diseases. A reliable and accurate DNA sequence of the Ae. albopictus genome is essential to develop new approaches that involve genetic manipulation of mosquitoes., Results: We use long-read sequencing methods and modern scaffolding techniques (PacBio, 10X, and Hi-C) to produce AalbF2, a dramatically improved assembly of the Ae. albopictus genome. AalbF2 reveals widespread viral insertions, novel microRNAs and piRNA clusters, the sex-determining locus, and new immunity genes, and enables genome-wide studies of geographically diverse Ae. albopictus populations and analyses of the developmental and stage-dependent network of expression data. Additionally, we build the first physical map for this species with 75% of the assembled genome anchored to the chromosomes., Conclusion: The AalbF2 genome assembly represents the most up-to-date collective knowledge of the Ae. albopictus genome. These resources represent a foundation to improve understanding of the adaptation potential and the epidemiological relevance of this species and foster the development of innovative control measures.

Background and Purpose: While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus., Materials and Methods: We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations., Results: During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively)., Conclusions: In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance, including the use, in pediatric patients, of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most important, a patient should not be deprived of a well-indicated contrasted MR examination., (© 2016 by American Journal of Neuroradiology.)

Background: With advances in the understanding of histopathology on outcome, accurate meningioma grading becomes critical and drives treatment selection. The 2000 and 2007 WHO schema greatly increased the proportion of grade II meningiomas. Although associations with progression-free survival (PFS) and overall survival (OS) have been independently validated, interobserver concordance has not been formally assessed., Methods: Once mature, NRG Oncology RTOG-0539 will report PFS and OS in variably treated low-, intermediate-, and high-risk cohorts. We address concordance of histopathologic assessment between enrolling institutions and central review, performed by a single pathologist (AP), who is also involved in developing current WHO criteria., Results: The trial included 170 evaluable patients, 2 of whom had 2 eligible pathology reviews from different surgeries, resulting in 172 cases for analysis. Upon central review, 76 cases were categorized as WHO grade I, 71 as grade II, and 25 as grade III. Concordance for tumor grade was 87.2%. Among patients with WHO grades I, II, and III meningioma, respective concordance rates were 93.0%, 87.8%, and 93.6% (P values < .0001). Moderate to substantial agreement was encountered for individual grading criteria and were highest for brain invasion, ≥20 mitoses/10 high-powered field [HPF], and spontaneous necrosis, and lowest for small cells, sheeting, and ≥4 mitoses/10 HPF. In comparison, published concordance for gliomas in clinical trials have ranged from 8%-74%., Conclusion: Our data suggest that current meningioma classification and grading are at least as objective and reproducible as for gliomas. Nevertheless, reproducibility remains suboptimal. Further improvements may be anticipated with education and clarification of subjective criteria, although development of biomarkers may be the most promising strategy., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Object: The objective of this study was to examine radiation dose distributions created by 2 competing radiosurgery modalities for treating multiple brain metastases: single-isocenter volumetric modulated arc radiosurgery (VMAS) and Gamma Knife Perfexion (GKP). In addition, the effectiveness of multiple radiosurgery quality metrics was evaluated and compared between these advanced treatment modalities., Methods: Seven anonymized MRI data sets, each showing 2-5 metastases, were used to create plans on each system. The GammaPlan (version 10.1) program was used for planning of GKP. A neurosurgeon contoured the volumes to be treated, and no planning target volume expansion was used. A prescription dose coverage of ≥ 99% was achieved for each tumor volume. The Philips Pinnacle (version 9.2) program was used for planning of VMAS, using the SmartArc optimization algorithm for delivery on a Varian iX linear accelerator. Contours were transferred from GammaPlan, and again no planning target volume expansion was used. Between 2 and 5 arcs with table angles of 90°-270° were used. Again, a V100% of ≥ 99% was achieved for each tumor volume. After planning, the MRI scans, tumor volumes, and dose information from each plan were exported according to the Digital Imaging and Communications in Medicine standard to the VelocityAI program for analysis. Brain dose-volume histograms (DVHs) for normal brain tissues were generated, and the volume of these tissues receiving 20%-90% of the prescription dose was tabulated. Finally, the prescription isodose to tumor volume ratio (PITV; Shaw et al., 1993), conformity index (CI; Paddick, 2000), gradient index (GI, Paddick and Lippitz, 2006), and conformity/gradient index (CGI, Wagner et al. 2003) were calculated for each plan. Both the PITV and CI have ideal values of 1, while the GI and CGI have ideal values of lowest and highest achievable, respectively., Results: The DVHs consistently showed that with VMAS a higher amount of normal brain tissues received each dose level than with GKP. These increases were largest for lower isodose levels, with the volumes of normal brain that received 20%-50% and 60%-90% of the prescription dose showing average increases of 403% and 227%, respectively. Prescription isodose conformality showed only minor differences between the 2 modalities. Radiosurgery quality metrics including measures of the dose gradient (GI and CGI) indicated that the GKP plan was superior in each case, with respective average GI and CGI values of 3.04 and 57.75 for GKP and of 10.22 and 10.85 for VMAS. Metrics evaluating prescription isodose conformality alone differed only slightly between the modalities. Average respective PITV and CI values were 2.13 and 0.53 for GKP and 2.27 and 0.51 for VMAS., Conclusions: Stereotactic radiosurgery plans for the treatment of multiple metastases with VMAS delivered significantly more dose to the normal brain tissues than plans for GKP. Radiosurgery quality metrics including a measure of the dose gradient are better suited to providing contrast between modern radiosurgery treatment platforms.

Purpose: To evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local control (LC), disease-free survival (DFS) and/or overall survival (OS)., Material and Methods: A retrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpostat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest., Results: The records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a median survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with statistically significantly inferior LC (p = 0.035) and inferior DFS (p = 0.011) for patients with mean Point A dose of > 80 Gy. Insufficient evidence existed to conclude an association with OS., Conclusions: LDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC.

Summary: Wilms tumor relapses are infrequent, occurring in approximately 15% of favorable histology patients. Very few cases of late recurrent relapse exist in the literature. Long-term survival after autologous stem cell rescue ranges from 40% to 73%, but there are very few reports of patients transplanted in their third complete response. We report a late recurrent relapse of Wilms tumor successfully treated with high-dose chemotherapy and autologous stem cell rescue in his third complete response who remains disease free 15 months posttransplant.

Pseudomonas syringae pv. tomato strain DC3000 (PtoDC3000) is one of the most intensively studied bacterial plant pathogens today. Here we report a thorough investigation into PtoDC3000 and close relatives isolated from Antirrhinum majus (snapdragon), Apium graveolens (celery), and Solanaceae and Brassicaceae species. Multilocus sequence typing (MLST) was used to resolve the precise phylogenetic relationship between isolates and to determine the importance of recombination in their evolution. MLST data were correlated with an analysis of the locus coding for the type III secreted (T3S) effector AvrPto1 to investigate the role of recombination in the evolution of effector repertoires. Host range tests were performed to determine if closely related isolates from different plants have different host ranges. It was found that PtoDC3000 is located in the same phylogenetic cluster as isolates from several Brassicaceae and Solanaceae species and that these isolates have a relatively wide host range that includes tomato, Arabidopsis thaliana, and cauliflower. All other analyzed tomato isolates from three different continents form a distinct cluster and are pathogenic only on tomato. Therefore, PtoDC3000 is a very unusual tomato isolate. Several recombination breakpoints were detected within sequenced gene fragments, and population genetic tests indicate that recombination contributed more than mutation to the variation between isolates. Moreover, recombination may play an important role in the reassortment of T3S effectors between strains. The data are finally discussed from a taxonomic standpoint, and P. syringae pv. tomato is proposed to be divided into two pathovars.

The bacterial plant pathogen Pseudomonas syringae injects a large repertoire of effector proteins into plant cells using a type III secretion apparatus. Effectors can trigger or suppress defences in a host-dependent fashion. Host defences are often accompanied by programmed cell death, while interference with defences is sometimes associated with cell death suppression. We previously predicted the effector repertoire of the sequenced bean pathogen P. syringae pv. syringae (Psy) B728a using bioinformatics. Here we show that PsyB728a is also pathogenic on the model plant species Nicotiana benthamiana (tobacco). We confirm our effector predictions and clone the nearly complete PsyB728a effector repertoire. We find effectors to have different cell death-modulating activities and distinct roles during the infection of the susceptible bean and tobacco hosts. Unexpectedly, we do not find a strict correlation between cell death-eliciting and defence-eliciting activity and between cell death-suppressing activity and defence-interfering activity. Furthermore, we find several effectors with quantitative avirulence activities on their susceptible hosts, but with growth-promoting effects on Arabidopsis thaliana, a species on which PsyB728a does not cause disease. We conclude that P. syringae strains may have evolved large effector repertoires to extend their host ranges or increase their survival on various unrelated plant species.

Objective: To review the cumulative experience of 10 institutions in treating recurrent malignant gliomas with the brachytherapy device, GliaSite Radiation Therapy System., Methods: The patient population consisted of 95 patients with recurrent grade 3 or 4 gliomas, a median age of 51 years, and a median Karnofsky performance status score of 80. All patients had previously undergone resection and had received external beam radiotherapy as part of their initial treatment. After recurrence, each patient underwent maximal surgical debulking of their recurrent lesion and placement of an expandable balloon catheter (GliaSite) in the tumor cavity. The balloon was afterloaded with liquid I (Iotrex) to deliver a median dose of 60 Gy to an average depth of 1 cm with a median dose rate of 52.3 Gy/hr. Patients were carefully followed with serial magnetic resonance imaging and monthly examinations for tumor progression, side effects, and survival., Results: The median survival for all patients, measured from date of GliaSite placement, was 36.3 weeks with an estimated 1 year survival of 31.1%. The median survival was 35.9 weeks for patients with an initial diagnosis of glioblastoma multiforme and 43.6 weeks for those with non- glioblastoma multiforme malignant gliomas. Analysis of the influence of various individual prognostic factors on patient survival demonstrated that only Karnofsky performance status significantly predicted for improved survival. There were three cases of pathologically documented radiation necrosis., Conclusion: Reirradiation of malignant gliomas with the GliaSite Radiation Therapy System after reresection seems to provide a modest survival benefit above what would be expected from surgery alone. This report not only confirms the initial results of the feasibility study but provides evidence that similar outcomes can be obtained outside of a clinical trial.

Two pregnant patients received radiation therapy, one for the treatment of mediastinal Hodgkin's lymphoma and the other for a head and neck squamous cell carcinoma. The fetuses were both protected by additional shielding which reduced the unshielded exposure of the first fetus by 20-40%, and that of the second by 20-60%. The first child received an estimated maximum dose of 42 cGy, the second a maximum dose of 9 cGy. Treatment details are reported and a review of the literature that addresses the possible irradiation-induced side effects at low doses is included.

Cutaneous manifestations of sarcoidosis frequently respond to medical management. Occasionally, however, this problem will reappear with the discontinuation of medication and ultimately result in the scarring and disfigurement of the patient's skin. Such a patient was treated with radiation therapy and had considerable improvement in her acute disease.

Desmoid tumors developed on the toes of a young woman with idiopathic multicentric osteolysis (IMO) after amputation of the toenails. A summary of IMO is given, and a review of literature for the etiologic factors of desmoid tumors is added.

We have been pleased with our initial experience in an evolving program. As newer surgical and radiotherapy techniques have become available, the role of radiosurgery has been and will continue to be modified. As more commercially available systems have been marketed, the availability will become more widespread. A battery of residents in neurosurgery and radiation oncology trained in these technologies will provide leadership and future directions of this therapy.

Background: We present and discuss the successful treatment of pleuropulmonary blastoma metastatic to the brain using a multimodality regimen with surgery, high-dose chemotherapy and radiation therapy., Procedure: A 3-year-old boy referred to our institution with bilateral pulmonary cysts was diagnosed with pleuropulmonary blastoma (PPB). Initial treatment included surgery and multiagent chemotherapy with vincristine, dactinomycin, cyclophosphamide, cisplatin, and doxorubicin. One year after the completion of therapy, his PPB recurred as an intracerebral metastasis, and required further treatment with a multimodality salvage regimen. The child was successfully treated with a subtotal surgical resection, followed by high-dose cyclophosphamide, and radiation therapy. He is now disease-free 24 months later., Results: Intracerebral metastases of PPB have been a uniformly fatal complication of this tumor. Postsurgical chemotherapy and radiation therapy appear to have contributed to the prolonged survival and potential for cure in our patient., Conclusions: The use of this multimodality regimen may be warranted in other patients with recurrent PPB metastatic to the brain.

In a multidisciplinary approach to the treatment of malignant melanoma, the role of radiation therapy is often relegated to one of minor importance. There is a supporting body of scientific literature that shows a relative radioresistance of melanoma when compared with other malignancies. Others have disputed the notion of resistance and have recommended radiation in a number of clinical settings including not only palliation but also in the primary management of melanoma. This article reviews the current and historical literature to better define the current role of radiation in a multidisciplinary approach for cancer management.

Treatment of anal epidermoid carcinoma by radiation and chemotherapy does offer an excellent opportunity to maintain quality of life. No patient in this series suffered long-term complications; and all have maintained rectal, anal, and sexual function. Patients with early stage lesions (AJC I-II) are most amenable to anus conserving therapy for epidermoid cancer of the anus. The success rate is markedly diminished in patients having more advanced disease, with patients possessing AJC stage III and VI disease presenting major problems. The possibility of post operative radiation therapy is markedly compromised by preoperative radiation therapy. Clinical surveillance and early recognition of these lesions by primary physicians can now offer patients with lesser stage cancer of this type excellent opportunity for organ preservation therapy. For those patients presenting with Stage III and VI carcinoma of the anus the aforementioned problems should be addressed and discussed before initiating conservative therapy.

Two months after a complete response to doxorubicin hydrochloride and cyclophosphamide administered for systemic effects, with the disappearance of pulmonary and pleural metastases from adenoid cystic carcinoma of salivary origin, a patient experienced symptomatic choroidal metastasis with no other evidence of active disease. Irradiation produced complete disappearance of the choroidal metastasis and restoration of visual acuity. The literature is reviewed, and the unusual nature of this metastasis is discussed.