Search

To identify the clinical findings available at the time of hospitalization from the emergency department that are associated with deterioration within 24 hours.A retrospective case-control study.A pediatric hospital in Ottawa, ON, Canada.Children less than 18 years old who were hospitalized via the emergency department between January 1, 2008, and December 31, 2012. Cases (n = 98) had an unplanned admission to the PICU or unexpected death on the hospital ward within 24 hours of hospitalization and controls (n = 196) did not.None.Ninety-eight children (53% boys; mean age 63.2 mo) required early unplanned admission to the PICU. Multivariable conditional logistic regression resulted in a model with five predictors reaching statistical significance: higher triage acuity score (odds ratio, 4.1; 95% CI, 1.7-10.2), tachypnea in the emergency department (odds ratio, 4.6; 95% CI, 1.8-11.8), tachycardia in the emergency department (odds ratio, 2.6; 95% CI, 1.1-6.5), PICU consultation in the emergency department (odds ratio, 8.0; 95% CI, 1.1-57.7), and admission to a ward not typical for age and/or diagnosis (odds ratio, 4.5; 95% CI, 1.7-11.6).We have identified risk factors that should be included as potential predictor variables in future large, prospective studies to derive and validate a weighted scoring system to identify hospitalized children at high risk of early clinical deterioration.

We sought to determine whether significantly displaced Lisfranc injuries had a higher rate of loss of reduction after fixation compared to those with low displacement. Forty-five patients who had fixation of an acute Lisfranc injury from 2005 to 2014 were retrospectively reviewed. All patients underwent subsequent hardware removal at 3 to 15 months after their index procedure. Radiographs were reviewed from the time of injury, 2 weeks, and 6 months postoperative. Lisfranc joint reduction was assessed using criteria previously described in the literature and graded as malreduced if displacement was >2 mm. We used a cutoff of 4 mm for high initial displacement. Those patients with ≥4 mm of initial displacement did not have an increased rate of loss of reduction after hardware removal compared to those patients with Levels of Evidence: Prognostic study, Level II: Retrospective

BACKGROUND Head and neck squamous cell carcinoma of unknown primary site (HNSCCUP) is a diagnostic challenge. Identification of an ultraviolet (UV) light-related DNA damage signature using next-generation sequencing (NGS) can classify the primary site of origin as cutaneous. METHODS A 62-year-old male was seen with 2 months of left neck swelling. He was a lifetime nonsmoker but had a history of cutaneous squamous cell carcinoma (SCC) of the left helix. He was also found to have left hilar adenopathy. He had a p16-negative HNSCCUP on fine needle aspiration (FNA) biopsy of the left neck. RESULTS NGS of the FNA specimen revealed a high number of somatic mutations that were mostly C to T transitions, indicating a UV mutation signature and confirming the diagnosis of cutaneous SCC. CONCLUSIONS Identification of a UV DNA damage signature with NGS distinguishes HNSCCUP of cutaneous vs mucosal or other squamous cell carcinoma origin.

As of 2007, an estimated 62% of individual bankruptcy filings in the United States were a direct result of costs borne from medical treatment following illness or injury, up from 46% in 2001. This pressing issue is only getting worse and is in need of relief. In this work, we consider the potential of a relatively recent, and rapidly growing, phenomenon to mitigate the problem: online crowdfunding for medical expenses, wherein patients reach out to their social network for monetary support via online platforms that facilitate the process. On the surface, medical crowdfunding holds the potential to address insurance gaps and to help those burdened by medical debt. However, recent questions have arisen in the healthcare literature around fairness and equity in the distribution of funds. Consistent with the notion of digital divide, many have raised concerns that the individuals most likely to benefit from these services are not the individuals who are most in need. Accordingly, we first seek to establish the effect of this novel phenomenon on a key indicator of financial distress: rates of personal bankruptcy. We then explore heterogeneity in patterns of funding solicitation and acquisition, to assess the presence inequalities across patient populations. We leverage proprietary data from a large medical crowdfunding platform based in the United States, which we combine with county records of personal bankruptcy filings. We report evidence that greater success amongst medical crowdfunding campaigns does translate into a reduction in personal bankruptcy filings. Subsequently, we report analyses which revealed evidence consistent with the presence of a digital divide. Specifically, we report evidence that disadvantaged groups are systematically more likely to launch medical crowdfunding campaigns, yet conditional on campaign launch, garner systematically less in funding. We discuss the implications for the literature on the digital divide, as well as implications for practice and policy.

BACKGROUND Surgery is the mainstay of meningioma treatment, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. DNA methylation profiling, copy number variants (CNVs), exome sequencing, and RNA sequencing have improved understanding of meningioma biology, but have not superseded histologic grading, or revealed biomarkers for radiotherapy responses. To address these unmet needs, we optimized and validated a targeted gene expression biomarker predicting meningioma outcomes and responses to radiotherapy. METHODS Targeted gene expression profiling was performed on a discovery cohort of 173 meningiomas (median follow-up 8.1 years) and a validation cohort of 331 meningiomas (median follow-up 6.1 years) treated with surgery (n=504) and postoperative radiotherapy (n=73) at independent, international institutions (70% WHO grade 1, 24% WHO grade 2, 6% WHO grade 3). Optimized targeted gene expression models predicting clinical outcomes (34 genes) or radiotherapy responses (12 genes) were developed from the discovery cohort, and compared to histologic and molecular classification systems by performing DNA methylation profiling, CNV analysis, exome sequencing, and RNA sequencing on the same meningiomas. RESULTS Targeted gene expression profiling achieved a concordance-index of 0.75 ± 0.03 (SEM) for local freedom from recurrence (LFFR) and 0.72 ± 0.03 for overall survival (OS) in the validation cohort, outperforming WHO grade (5-year LFFR delta-AUC 0.15, 95% CI 0.076-0.229, p=0.001) and DNA methylation grouping (delta-AUC 0.075, 95% CI 0.006-0.130, p=0.01) for LFFR, disease-specific survival, and OS. The biomarker was independently prognostic after accounting for WHO grade, extent of resection, primary versus recurrent presentation, CNV status, DNA methylation group, and Ki67 labeling index, and identified meningiomas benefiting from radiotherapy (interaction p-value=0.0008), suggesting postoperative radiotherapy could be refined in 30.2% of cases. CONCLUSIONS Targeted gene expression profiling of 504 meningiomas improves discrimination of meningioma local recurrence, disease-specific survival, and overall survival, and predicts radiotherapy responses.

2007 Background: Improvements in risk stratification of meningioma are needed to guide post-operative management and application of adjuvant therapy. Although profiling of DNA methylation, copy number variants (CNVs), RNA sequencing, and exome sequencing have better elucidated meningioma biology, these approaches have not revealed clinically tractable biomarkers for radiotherapy responses. In this study, we develop and validate a targeted gene expression biomarker to predict meningioma outcomes and benefit from radiotherapy. Methods: Targeted gene expression profiling was performed on a development set of 173 meningiomas (median follow-up 8.1 years) and a validation set of 331 consecutive meningiomas (median follow-up 6.1 years) treated at independent institutions (70% WHO grade 1, 24% WHO grade 2, 6% WHO grade 3). All patients underwent surgery (n = 504) with or without postoperative radiotherapy (n = 73 with radiation). Regularized Cox regression within the development set resulted in a continuous gene expression risk score for local freedom from recurrence (LFFR). The model (34 genes and 7 housekeeping genes) and thresholds for low, intermediate, and high-risk scores were locked and applied to the validation set. Results: The gene expression risk score outperformed WHO grade (validation 5-year LFFR delta-AUC 0.15, 95% CI 0.076-0.229, p = 0.001) and DNA methylation grouping (delta-AUC 0.075, 95% CI 0.006-0.130, p = 0.01) for LFFR, disease-specific survival, and OS, achieving a negative predictive value for recurrence at 5-years of 93.2%. The biomarker reclassified 35.8% of WHO grade 1 tumors as intermediate or high risk (5-year LFFR/OS 62%/79%), and 18.3% of WHO grade 2-3 tumors as low risk (5-year LFFR/OS 78%/100%). The biomarker was independently prognostic after accounting for WHO grade, extent of resection, primary versus recurrent presentation, CNV status, DNA methylation group, and Ki67 labeling index, and was predictive for LFFR after postoperative radiotherapy, with a hazard ratio of 0.41 for intermediate to high risk propensity-matched meningiomas (95% CI 0.2-0.9, p = 0.0002) versus 0.79 for low risk meningiomas (95% CI 0.1-8.8, p = 0.5182). Conclusions: Targeted gene expression profiling of 504 meningiomas resulted in a biomarker which improved discrimination of meningioma local recurrence, disease-specific survival, and overall survival, and also predicted benefit from radiotherapy.

e14049 Background: Ratios of differential blood counts (hematological indices, HI) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSL), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HI could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HI were calculated at three time-points: baseline (pre-steroid), pre-chemoimmunotherapy (post-steroid) and post-chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan-Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan-Meier analysis to generate a decision-tree prognostic model, the NNI-NCCS score. Results: A total of 75 patients who received chemoimmunotherapy were included in the final analysis. For NLR, OS was longer with higher pre-chemoimmunotherapy (post-steroid) NLR (dichotomized at NLR≥4.0, HR 0.42, 95% CI: 0.21-0.83, p = 0.01) only. For platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), OS was better for lower post-chemoimmunotherapy PLR (dichotomized at PLR≥241, HR 2.27, 95% CI: 1.00 to 5.18, p = 0.05) and lower pre-chemoimmunotherapy (post-steroid) LMR (dichotomized at LMR ≥25.7, HR 2.17, 95% CI: 1.10 to 4.31, p = 0.03) respectively only. Decision-tree model using age ≤70, post-steroid NLR > 4.0, and pre-steroid (baseline) NLR < 2.5 divided patients into three risk categories – low, medium, high – and achieved good accuracy (area-under-curve of 0.78), with good calibration (Brier score: 0.16) for predicting 2-year overall survival. Conclusions: We found that post-steroid NLR, when considered together with baseline NLR, has prognostic value, and incorporation into a prognostic model allowed accurate and well-calibrated stratification into three risk groups.

Title III, codified at Title 18 USC \S\S 2510-2521, allows for federal and state law enforcement interceptions of wire, oral, or electronic communications, which requires obtaining a court order. For the two parallel court systems in the United States, however, the operational standard being followed by law enforcement agencies may differ. This paper compares the outcomes from wiretap orders authorized by the federal and the state courts. Guided by an economic model of criminal behavior, we show that arrests and convictions increase in wiretap intensity (at a diminishing rate), but federal orders reach the peak point faster than state orders so. We do not find cross effects between the two layers of wiretap orders.

Background: Controversy exists in the treatment of adolescent proximal humerus fractures as patients reach skeletal maturity. No universally agreed upon treatment algorithm currently exists for this population. Purpose: The purpose of this study is to determine risk factors that may pre-dispose a patient to have surgical treatment over non-operative treatment. Methods: This is an IRB approved multi-center retrospective cohort study of adolescent proximal humerus fractures treated by three pediatric orthopaedic surgeons at three academic hospitals. Adolescent was defined at ages 12-17. Variables analyzed include age, weight, mechanism of injury, treatment, associated injury, Neer-Horowitz (NH)grade, neck-shaft angle of the AP, axillary lateral and scapular Y view. Two-sample T-test was used to analyze continuous variables and categorical variables were analyzed using Chi-square test. Results: A total of 76 patients met inclusion criteria. 38.2% of patients received operative management. 28/76 (37%) fractures were classified as NH1, 22/76 (29%) as NH2, 12/76 (16%) as NH3 and 14/76(18%) as NH4. 4% of NH1, 17% of NH2, 100% of NH3, and 100% of NH4 fractures were treated operatively (p1/3 displaced (NH3,4), the latter group had operative intervention more often (83% vs 4%) with risk ratio (RR) of 9.23 (PConclusion: At the time of injury, factors that predispose an adolescent patient with a proximal humerus fracture to operative intervention are increased age, greater fracture displacement, pedestrian struck mechanism and being polytraumatized. These findings suggest that higher energy mechanisms of injury are predictive factors for operative intervention in adolescent proximal humerus fractures.

Artificial intelligence (AI) is beginning to transform IMRT treatment planning for head and neck patients. However, the complexity and novelty of AI algorithms make them susceptible to misuse by researchers and clinicians. Understanding nuances of new technologies could serve to mitigate potential clinical implementation pitfalls. This article is intended to facilitate integration of AI into the radiotherapy clinic by providing an overview of AI algorithms, including support vector machines (SVMs), random forests (RF), gradient boosting (GB), and several variations of deep learning. This document describes current AI algorithms that have been applied to head and neck IMRT planning and identifies rapidly growing branches of AI in industry that have potential applications to head and neck cancer patients receiving IMRT. AI algorithms have great clinical potential if used correctly but can also cause harm if misused, so it is important to raise the level of AI competence within radiation oncology so that the benefits can be realized in a controlled and safe manner.

PURPOSE Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven. PATIENTS AND METHODS In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI). RESULTS Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( P = .04). For IMRT, 2-year PFS was 87.6% ( P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( P = .56). CONCLUSION The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.

Objective To determine whether timing of CGM initiation offering low glucose suspend (LGS) affects CGM adherence in children and youth starting insulin pump therapy. Methods A 5-site RCT of pump-naive subjects (aged 5-18 years) with type 1 diabetes (T1D) for at least 1 year compared simultaneous pump and CGM initiation offering LGS vs. standard pump therapy with CGM initiation delayed for 6 months. Primary outcome was CGM adherence (hours per 28 days) (MiniMed™ Paradigm™ Veo™ system; CareLink™ Pro software) over 6 months after CGM initiation. Secondary outcome HbA1c was measured centrally. Linear mixed-models and ordinary least squares models were fitted to estimate effect of intervention, and covariates baseline age, T1D duration, HbA1c, gender, ethnicity, hypoglycemia history, clinical site, and association between CGM adherence and HbA1c. Results The trial randomized 144/152 (95%) eligible subjects. Baseline mean age was 11.5±3.3(SD) years, T1D duration 3.4±3.1 years, and HbA1c 7.9±0.9%. Six months after CGM initiation, adjusted mean difference in CGM adherence was 62.4 hours per 28 days greater in the Simultaneous Group compared to Delayed Group (p=0.007). There was no difference in mean HbA1c at 6 months. However, for each 100 hours of CGM use per 28-day period, HbA1c was 0.39% (95% CI 0.10% to 0.69%) lower. Higher CGM adherence was associated with reduced time with glucose >10 mmol/L (p Conclusion CGM adherence was higher after 6 months when initiated at same time as pump therapy compared to starting CGM 6 months after pump therapy. Greater CGM adherence was associated with improved HbA1c. This article is protected by copyright. All rights reserved.

Background/aimsThe association between the development of cystoid macular oedema (CMO) following uneventful cataract surgery and prostaglandin analogue (PGA) therapy has not been fully determined. The study aim was to investigate whether discontinuation of PGA therapy following uneventful cataract surgery affected the incidence of postoperative CMO.MethodsA prospective randomised controlled trial of 62 eyes of 62 participants with ocular hypertension (OH) or primary open angle glaucoma (POAG) treated with PGAs prior to cataract surgery. Participants were randomised to continue with PGA therapy after cataract surgery (CPGA) (n=31) or to discontinue PGA therapy (n=31). The primary outcome measure was the development of CMO at 1-month postoperatively, determined by a masked observer assessment of optical coherence tomography scans. The secondary outcome measure was change from baseline intraocular pressure (IOP).ResultsThe incidence of CMO was identical in both groups at 12.9% (4 of 31 eyes) at the 1-month postoperative visit (OR 1.000; 95% CI 0.227 to 4.415). At 1-month postoperatively, the IOP was significantly lower in the CPGA group compared with baseline IOP.ConclusionContinuation of PGA therapy following uneventful cataract surgery in eyes with normal macular morphology did not increase the incidence of CMO. Continuation of PGA therapy significantly reduced IOP at 1-month postoperatively suggesting that, when indicated, it might be beneficial to continue PGA therapy in patients with POAG or OH after uneventful cataract surgery in the absence of other risk factors for developing CMO.

Emerging evidence suggests that chronic exposure to aristolochic acids (AAs) is one of the etiological pathways leading to chronic kidney disease (CKD). Due to the traditional practice of herbal medicine and AA-containing plants being used extensively as medicinal herbs, over 100 million East Asians are estimated to be at risk of AA poisoning. Given that the chronic nephrotoxicity of AAs only manifests itself after decades of exposure, early diagnosis of AA exposure could allow for timely intervention and disease risk reduction. However, an early detection method is not yet available, and diagnosis can only be established at the end stage of CKD. The goal of this study was to develop a highly sensitive and selective method to quantitate protein adducts of aristolochic acid I (AAI) as a biomarker of AA exposure. The method entails the release of protein-bound aristolactam I (ALI) by heat-assisted alkaline hydrolysis, extraction of ALI, addition of internal standard, and quantitation by liquid chromatography-tandem mass spectrometric analysis. Accuracy and precision of the method were critically evaluated using a synthetic ALI-containing glutathione adduct. The validated method was subsequently used to detect dose-dependent formation of ALI-protein adducts in human serum albumin exposed to AAI and in proteins isolated from the tissues and sera of AAI-exposed rats. Our time-dependent study showed that ALI-protein adducts remained detectable in rats even at 28 days postdosing. It is anticipated that the developed method will fill the technical gap in diagnosing AA intoxication and facilitate the biomonitoring of human exposures to AAs.

The entire liquid-film dryout process in a vertical two-phase annular flow is characterized experimentally, from inception to completion. Experiments are conducted using saturated R245fa at high vapor qualities in a heated rectangular channel with a hydraulic diameter of 18 mm and an aspect ratio of 1/3. The walls of the test section are made of glass coated with fluorine-doped tin oxide (FTO). Heat fluxes up to 50 kW/m 2 are generated at the inner surface of the window by passing an electrical current through the FTO coating. Instantaneous pressure and temperature in the test section, temperature on the outer wall of the test section, liquid-film thickness, and high-speed videos are recorded simultaneously during the dryout events. In addition, the state (wet or dry) of the heated surface is measured using a non-invasive laser reflectance technique at high sampling rate (2000 Hz) and over long periods of time ( > 1000 s). The laser reflectance measurement is used to calculate the time-averaged dry fraction, f d r y , which is the fraction of time that the wall is dry during intermittent cycles of dryout and rewet. Data show that cyclic dryout starts before the critical heat flux (CHF) is reached. The dryout heat flux (DHF), which marks the onset of dryout, is typically 90% of the CHF, except at very high quality ( x > 0.95 ), where it can be as low as 50% of CHF. For all the investigated mass fluxes, CHF, where the heat transfer coefficient peaks, occurs consistently at f d r y ≈ 0.05. Further insight into the liquid-film behavior at the onset of dryout is obtained by combining analyses of high-speed videos, time-resolved liquid-film thickness signals, and statistics about the duration of and time between dryout events. The rewetting process is driven by disturbance waves. In the wake of disturbance waves, the liquid film is almost stationary. Calculations of the characteristic time it takes for this stationary film to evaporate predict well the characteristic time during dryout events measured with the laser reflectance method.

With increasing ecommerce penetration, it is believed that consumers are spending more shopping time online and away from physical stores. This brings to question the role of physical stores in an increasingly digitized landscape and whether they remain relevant. The measurement of the impact of physical stores has been characterized by the difficulty of attributing the increase in online sales to customers seeing and experiencing products showcased in physical stores, as this information is not typically observed and captured. Should physical stores remain valuable in the digital age, which products should be showcased in stores? In this study, we attempt to shed light on these questions using a quasi-experiment, taking place through a nationwide retailer that expanded its physical presence during the study period. This work distinguishes from past studies in that it studies purchasing behavior in the underexplored Chinese market. Through a ``triple-differences'' framework, we provide a more direct evidence on the effect of the physical channel on online sales outcomes. We find that online sales for products showcased in physical stores increase for both high and low involvement products, suggesting that two possible mechanisms are at work in driving the online sales of showcased products.

Objectives: The Timing of Initiation of Continuous Glucose Monitoring in Established Pediatric Diabetes (CGM TIME) Trial is a multicenter, randomized controlled trial in children with type 1 diabetes, comparing simultaneous pump and CGM with CGM initiation 6 months later (Paradigm, Veo, Enlite Sensor, Medtronic Canada). This study addresses the ability of SOCRATES (Stages Of Change Readiness And Treatment Eagerness Scale) to classify children and parents into distinct motivational stages and identify the stages’ association with glycated hemoglobin (A1C) at trial entry and outcomes 6 months after CGM initiation. Methods: Ninety-eight of 99 eligible children 10 to 18 years of age and 137 of 141 eligible parents completed SOCRATES at trial entry and 6 months later. Parent-child agreement for motivational stage was determined by weighted kappa. Linear regression was used to examine association between motivational stage and i) A1C at trial entry and ii) change in A1C and CGM adherence 6 months after CGM initiation. Results: More than 87% of children and 88% of parents were classified into distinct motivational stages, with weak parent-child agreement. At trial entry, motivational stage was associated with A1C, which was 1.02% higher for children in the Action stage than in the Precontemplation stage (p

BACKGROUND Meningioma treatments are limited due to incomplete understanding of meningioma biology. To address this, we performed multiplatform molecular profiling on 565 meningiomas with comprehensive clinical data to define genomic drivers and identify therapeutic vulnerabilities. METHODS DNA methylation profiling was performed on meningiomas from UCSF (n=200, discovery) and Hong Kong University (n=365, validation). Median follow-up was 5.6 years, and there were 388/142/35 WHO grade I/II/III meningiomas. Copy number variants (CNVs) were calculated for all meningiomas, and RNA sequencing was performed on UCSF meningiomas. Cell type deconvolution, metagenomics, CRISPR, and pharmacology were used for mechanistic and functional validation. RESULTS Unsupervised hierarchical clustering of differentially methylated DNA probes revealed that meningiomas were comprised of 3 epigenetic subgroups associated with good, intermediate, and poor outcomes, with representation from all WHO grades in each subgroup. Meningiomas from the subgroup with the best outcomes (52% WHO grade I) were distinguished by recurrent gain of Chr5. Meningiomas from the subgroup with intermediate outcomes (31% WHO grade II) were distinguished by genomic stability, enrichment of innate immune genes, and immune infiltration in the setting of endogenous retroviral gene re-expression, a mechanism of immune recruitment. The most aggressive subgroup of meningiomas (57% WHO grade III) was distinguished by genomic instability, including recurrent loss of Chr22q harboring NF2, and decreased immune infiltration. Consistently, NF2 suppression in primary meningioma cells derived from immunogenic meningiomas decreased expression of innate immune genes critical for immune recruitment, suggesting a novel immunostimulatory function of NF2. The most aggressive subgroup of meningiomas were further distinguished by activation of the mitogenic FOXM1 transcriptional program, and recurrent loss of Chr9p harboring CDKN2A/B, which rendered primary meningioma cells from this subgroup susceptible to CDK4/6 inhibitors. CONCLUSIONS Meningiomas are comprised of 3 epigenetic subgroups defined by genetic mechanisms driving immune infiltration in the tumor microenvironment and meningioma cell proliferation.

The prognostic significance of bone invasion in oral cavity squamous cell carcinoma (OCSCC) after accounting for tumor size, nodal spread, and surgical margins is controversial. The aim of this study is to determine whether patients with pT4aN0 oral cavity squamous cell carcinoma with bone invasion have improved overall and disease-free survival with adjuvant treatment.We conducted a retrospective review of medical records from 64 patients with stage pT4aN0 due to mandibular involvement who underwent surgery from 2000 to 2020. Kaplan-Meier analysis compared disease-free survival and overall survival between groups who underwent surgery only versus surgery and adjuvant therapy. The prognostic impact of adjuvant therapy was assessed using multivariate analysis and reported as hazard ratios.There were no statistically significant differences in clinicopathologic features or mean follow-up between patients who received surgery only and patients who received surgery with RT/CCRT (radiotherapy/concurrent chemoradiation therapy). 5-year disease-free (42.5% versus 65.9%, p = 0.02) and overall survival (43.6% versus 69.0%, p = 0.014) were improved in groups who received surgery and RT/CCRT. Regression analysis controlling for clinicopathologic characteristics, including tumor size, identified radiation as an independent predictor of improved disease-free survival (HR: 0.04, p 0.001) and overall survival (HR: 0.10, p 0.001).Adjuvant RT/CCRT in patients with pT4N0 OCSCC with mandibular bone involvement is associated with improved disease-free and overall survival. This association was significant regardless of tumor pathologic features such as size or margin status. These findings may help guide physicians in counseling patients regarding risks and benefits of adjuvant RT/CCRT and inform practice guidelines.

The formation of covalently bound DNA-protein crosslinks (DPCs) is linked to the pathophysiology of cancers and many other degenerative diseases. Knowledge of the proteins that were frequently involved in forming DPCs will improve our understanding of the etiological mechanism of diseases and facilitate the establishment of preventive measures and treatment methods. By using SDS-PAGE and nano-LC coupled Orbitrap LC-MS/MS analyses, we identified, for the first time, that the major DNA-cross-linked proteins in HeLa cells exposed to a methylating agent (methylmethanesulfonate) or hydroxyl free radicals are transcription-associated proteins. In particular, histone H2B3B and poly(rC) binding protein 2 were identified as the most frequent DPC-forming proteins.

Author(s): Wu, Susan Y; Yee, Emily; Chan, Jason W; Chapman, Christopher H; Boreta, Lauren; Braunstein, Steve E | Abstract: PurposeUrgent indications for palliative radiation therapy (RT) include malignant spinal cord compression, symptomatic brain metastases, pain, airway obstruction, and bleeding. Data on the timing of palliative RT in the inpatient setting are limited. We report our experience with inpatient palliative RT at a tertiary academic center and evaluate the effect of a dedicated inpatient palliative RT nurse practitioner (NP) on treatment timelines.Methods and materialsWe performed a retrospective, single-institution review of 219 inpatients consulted for RT to sites of metastatic disease between May 2012 and May 2018. We compared time-to-treatment intervals before and after integrating an NP for palliative RT in Augustn2017.ResultsThe median age of the 219 patients receiving RT was 61 years (interquartile range [IQR], 51-69 years). The most frequent indications were symptomatic brain metastases (73 patients [33%]), pain (61 patients [28%]), and cord/cauda compression (48 patients [22%]). The median time from consultation request to consult was 1 day (IQR, 0-2 days), and the median time from consultation request to first RT fraction was 3 days (IQR, 2-6 days). The median time from consultation request to RT was shorter for cord compression (2 [IQR, 1-4] days) than for pain (5 [IQR, 2-7] days) (P = .001) or symptomatic brain metastases (3 [IQR, 1-6] days; P = .037). With an NP, patients were more likely to undergo same-day consultation and simulation (75% vs 60%; P = .045), which was associated with shorter median duration from consultation to initiation of RT (1 [IQR, 0-3] days vs 4 [IQR, 2-7] days; P l.001). After the integration of an NP for palliative RT, patients had a higher median Karnofsky Performance Score (70 [IQR, 60-80] vs 50 [IQR, 40-60]; P l .001) and were more likely to complete their prescribed RT course (93% vs 82%; P = .05).ConclusionsTime from consultation request to RT is necessarily short for urgent inpatient palliative RT. Advanced practice providers may facilitate and potentially expedite treatment, with significantly shorter times to treatment among patients who undergo same-day consultation and simulation.

Objective: To validate the accuracy and safety of the Canadian Syncope Risk Score (CSRS) for patients presenting with syncope. Methods: Single centre prospective observational study in Brisbane, Australia. Adults presenting to the ED with syncope within the last 24 h were recruited after applying exclusion criteria. Study was conducted over 1 year, from March 2018 to March 2019. Thirty-day serious adverse events (SAE) were reported based on the original derivation study and standardised outcome reporting for syncope. Individual patient CSRS was calculated and correlated with 30-day SAE and disposition status from ED. Results: Two hundred and eighty-three patients were recruited to the study. Average age was 55.6 years (SD 22.7 years), 37.1% being male with a 39.9% admission rate. Thirty-day SAE occurred in seven patients (2.5%) and no recorded deaths. The CSRS performed with a sensitivity of 71.4% (95% confidence interval [CI] 30.3–94.9%), specificity 72.8% (95% CI 67.1–77.9%) for a threshold score of 1 or higher. Conclusion: Syncope patients in our study were predominantly very low to low risk (72%). The prevalence of 30-day SAE was low, majority occurring following hospital discharge. Sensitivity estimates for CSRS was lower than the derivation study but lacked robustness with wide CIs because of a small sample size and number of events observed. However, the CSRS did not miss any clinically relevant outcomes in low risk patients making it potentially useful in aiding their disposition. Larger validation studies in Australia are encouraged to further test the diagnostic accuracy of the CSRS.

FDT (IEC62453) is a technology which allows integration of devices and networks to engineering tools, e.g. for industrial control systems (ICS) and asset management systems. This paper introduces the latest FDT3 (FDT version 3) technical specification which enables the FDT IIoT Server™ (FITS™) concept. FDT3 addresses end user requirements (total platform independence, support of fieldbus protocols, centralized DTM repository, NAMUR Open Architecture). This paper provides an overview of the FITServer and its components, including OPC UA Server and a web server, and how to get started with FITS development with FITServer Common Components.

Instantaneous temperature measurements at the interface between a solid wall and a thin, unsteady liquid film are performed using thermoreflectance, a nonintrusive optical technique with high temporal resolution. A laser beam is directed at a wall–liquid interface, and the intensity of the light reflected at that interface is measured by a photodiode. The intensity of the reflected light varies with the index of refraction of the liquid at the wall. The index of refraction is a function of temperature, which enables the instantaneous measurement of the wall temperature. In the presence of thin liquid films, reflections from the liquid–vapor interface at the free surface of the film generate noise in the measurements. We demonstrate that orienting the laser beam at a large incident angle, close to total internal reflection, minimizes noise from the liquid–vapor interface while increasing the sensitivity of the measurement. The thermoreflectance technique is validated in an unsteady two-phase annular flow. Measurements of temperature fluctuations less than 1 K in amplitude are achieved, with an uncertainty of 0.1 K.

Several recent advances, including the use of robotic devices, have been explored to improve outcomes in total knee arthroplasty (TKA). The TSolution One ® Total Knee Application (THINK Surgical, Inc., Fremont, CA, USA) introduces an active robotic device that supports an open implant platform and CT-based preoperative planning workflow, and requires minimal surgeon intervention for making bone cuts. Our experience was part of a multi-center, prospective, non-randomized trial assessing the safety and effectiveness of this active robotic system for TKA. Each patient underwent a preoperative CT-scan, which was uploaded to proprietary planning software. The surgeon reviewed the software-generated 3D digital model, selected the appropriate implants and generated a final preoperative plan. Intra-operatively, a standard medial parapatellar approach was used. The leg was then rigidly attached to the robot via fixation pins, and registration markers were placed in the tibia and femur. Landmark registration was performed to inform the robot of the knee's position in space and to confirm the robot's ability to execute the preoperative plan. Next, the robot performed femoral and tibial cuts using a cutter in a sequential fashion along a defined cut-path. The robot was then removed from the operative field and the surgeon completed the procedure by removing marginal bone and performing final balancing and implantation in the usual fashion. The TSolution One® Total Knee Application is a computer-assisted device that potentially allows a surgeon to make more accurate cuts and to determine optimal implant position based on the patient's specific anatomy. It is the only active robotic system currently available. In this manuscript, we describe the operative technique and workflow involved in performing this surgery and offer insight on optimizing safety and efficiency as we introduce new technologies to the operating theater. We also present two cases performed by the senior author to further demonstrate technical aspects of the procedure.

BACKGROUND: The requirement for a tracheostomy in children is associated with significant morbidity, mortality, and healthcare utilization. Easy identification of children with tracheostomies would facilitate important research on this population and provide quality improvement initiatives. AIM: The purpose of this study is to determine whether an algorithm of diagnostic and procedural codes can accurately identify children hospitalized with a tracheostomy using routinely collected health data. METHODS: Chart reviews were performed at the Children's Hospital of Eastern Ontario (CHEO) and the London Health Sciences Center (LHSC) to establish a true positive cohort of pediatric patients with tracheostomies admitted between 2008 and 2016. A multidisciplinary team developed algorithms of diagnostic and procedural codes contained within the Canadian Institute for Health Information Discharge Abstract Database. Algorithms were tested and refined against the true-positive and true-negative cohort. The accuracy of the diagnostic codes related to tracheostomy complications was also evaluated. RESULTS: A chart review identified 158 unique children with tracheostomies (77 at CHEO, 81 at LHSC) with 901 individual admissions (401 at CHEO, 507 at LHSC). The best algorithms for identifying children with a tracheostomy had a sensitivity and specificity of more than 99%, a positive predictive value (PPV) of 94.0% and negative predictive value (NPV) of 100%. The algorithm for the identification of tracheostomy-related complications had a sensitivity of 76.7%, a specificity of 65%, PPV of 52.3%, and an NPV of 84.7%. CONCLUSIONS: This study provides an algorithm for the accurate identification of children hospitalized in Canada with a tracheostomy, facilitating population-level epidemiological research and quality improvement initiatives.

OBJECTIVES/HYPOTHESIS Squamous cell carcinoma of the hypopharynx (SCCHP) is associated with worse survival compared to other head and neck subsites. This report quantifies the impact of technological improvements in radiotherapy (RT) on outcomes over 6 decades. METHODS Patients with SCCHP receiving curative-intent treatment between 1962 and 2015 were retrospectively reviewed. Kaplan-Meier analyses of freedom from local recurrence (FFLR), progression-free survival (PFS), and overall survival (OS) were compared across treatment eras and radiation techniques. Multivariable Cox proportional hazards modeling was performed to specify the effect of RT technique. RESULTS One hundred thirty-four patients had a median follow-up of 17 months (IQR = 9-38). There were no differences in staging or use of surgery over time, but use of chemotherapy concurrent with RT increased (P

Oxidative stress is associated with the pathophysiology of many degenerative human diseases, including Alzheimer's disease, atherosclerosis, Parkinson's disease, and cancers. We discovered in our previous study that thioproline (SPro), a proline analogue, is generated in oxidant-exposed cells. With the prior observation that SPro served as an efficient nitrile trapping agent, we tested in this study the hypothesis that this oxidative stress generated cysteine-formaldehyde adduct, SPro, may serve as an antioxidant protecting cells from oxidative stress. Interestingly, results showed that HeLa cells cultured in SPro-supplemented culture media are more tolerant of oxidative stress, indicated by a dosage-dependent increase in cell viability. Investigation of the molecular mechanism of the observed increase in cell tolerance to oxidative stress revealed SPro acting as an effective antioxidant by sacrificial oxidation. Results also showed that SPro had been incorporated into cellular proteins and induced changes in protein expression profiles of treated cells. Despite being yet to determine the participation of individual factors to the observed increase of cell tolerance to oxidative stress, this study sheds light on the potential use of SPro as a dietary supplement for protecting humans from oxidative stress-associated degenerative human diseases.

PURPOSE: To suggest an attention-aware, cycle-consistent generative adversarial network (A-CycleGAN) enhanced with variational autoencoding (VAE) as a superior alternative to current state-of-the-art MR-to-CT image translation methods. MATERIALS AND METHODS: An attention-gating mechanism is incorporated into a discriminator network to encourage a more parsimonious use of network parameters, whereas VAE enhancement enables deeper discrimination architectures without inhibiting model convergence. Findings from 60 patients with head, neck, and brain cancer were used to train and validate A-CycleGAN, and findings from 30 patients were used for the holdout test set and were used to report final evaluation metric results using mean absolute error (MAE) and peak signal-to-noise ratio (PSNR). RESULTS: A-CycleGAN achieved superior results compared with U-Net, a generative adversarial network (GAN), and a cycle-consistent GAN. The A-CycleGAN averages, 95% confidence intervals (CIs), and Wilcoxon signed-rank two-sided test statistics are shown for MAE (19.61 [95% CI: 18.83, 20.39], P = .0104), structure similarity index metric (0.778 [95% CI: 0.758, 0.798], P = .0495), and PSNR (62.35 [95% CI: 61.80, 62.90], P = .0571). CONCLUSION: A-CycleGANs were a superior alternative to state-of-the-art MR-to-CT image translation methods. © RSNA, 2020

Pediatric in-patients with tracheostomy (PIT) are at high risk for clinical deterioration. Medical emergency teams (MET) have been developed to identify high-risk patients. This study compared MET activation rates between PITs and the general ward population. This was a retrospective cohort study conducted at a tertiary pediatric hospital. The primary outcome (MET activation) was obtained from a database. Between 2008 and 2014, the MET activation rate was significantly higher in the PIT group than the general ward population (14 vs. 2.9 per 100 admissions, p

Emerging evidence suggests that aristolochic acids (AA) produced naturally by a common weed Aristolochia clematitis in the cultivation fields is contaminating the food products in Balkan Peninsula and acting as the etiological agent in the development of Balkan endemic nephropathy. In this study, we investigated the combined use of natural anti-oxidative "food additives" and different cooking methods to find a solution for the widespread contamination of AA in food products. The results indicated that the addition of healthy dietary supplements (such as cysteine, glutathione, ascorbic acid, citric acid and magnesium) during cooking, is a highly efficient method in lowering the concentration of AA in the final food products. Because previous observation indicated one of the toxicological mechanisms by which AA exert its toxicity is to induce oxidative stress in internal organs, it is anticipated that these added anti-oxidants will also help to attenuate the nephrotoxicity of AA.

Leptomeningeal metastasis (LM) is a late stage manifestation of advanced breast cancer frequently managed with whole brain radiotherapy (WBRT) and/or intrathecal chemotherapy. A subset of breast cancer patients who undergo stereotactic radiosurgery (SRS) for limited brain metastases (BM) ultimately develop LM. We hypothesized that this subset of high-risk patients may be identified by patient, disease, and/or treatment parameters. Clinical records from 133 breast cancer patients from a single institution who underwent SRS for BM between February 2010 and March 2018 were retrospectively analyzed. Variables including histopathology, BM features, systemic disease burden, and prior treatments were analyzed. Cumulative incidence rates were estimated with death as a competing risk. Dichotomous variable cutoffs were based on the 75th percentile value. In our cohort, 27 (20.3%) patients ultimately developed LM. With a median follow up of 21.2 months after diagnosis of BM, the actuarial rate of LM at 24 months was 15.2% (95% CI, 8.7%-21.7%). Median OS after diagnosis of LM was 7.0 (95% CI, 3.1–15.4) months. There was significantly increased risk of LM with ≥9 vs < 9 BM at BM diagnosis (28.1% vs 10.8% [24-month actuarial risk], subdistribution HR 2.4, p=0.027), and ≥11 vs < 11 cumulative number of BM treated (25.7% vs 11.7% [24-month actuarial risk], subdistribution HR 2.7, p=0.01). Variables not significantly associated with the risk of LM included tumor receptor status (ER, PR, HER2, triple negative), graded prognostic assessment, KPS, extracranial metastases, total BM volume, prior WBRT, or prior surgical resection. Time intervals between SRS treatments immediately preceding LM diagnosis was not significantly different from other time intervals. In conclusion, patients with a larger number of brain metastases at BM diagnosis (≥9) or cumulatively treated (≥11) appear to be at higher risk of developing LM and may benefit from stronger consideration of WBRT, intrathecal chemotherapy, and/or brain-penetrating systemic therapy.

Introduction There is currently no standard of care for the upfront management of patients with mature T cell non-Hodgkin lymphomas (T-NHL). The role of anthracyclines in the treatment of T-NHL remains unclear and is also associated with significant toxicity. CEPP (cyclophosphamide, etoposide, procarbazine, and prednisone), a non-anthracycline regimen, is an effective salvage regimen for relapsed/refractory NHL and has shown a favourable toxicity profile. Since 2005, CEPP has been used in Singapore in the upfront treatment of T-NHL patients either with a contraindication to anthracyclines or at physicians' discretion. Our study aimed to assess the efficacy of CEPP in the upfront treatment of T-NHL. Methods A retrospective study of all patients with newly diagnosed T-NHL treated with CEPP with curative intent from 2005-2021 was undertaken across 2 national cancer centers in Singapore. Outcomes of this population was also compared with a 1:1 control group treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) in the same time period, and matched for age, T-NHL subtype, clinical stage and international prognostic index (IPI). Patient demographics, disease characteristics and clinical outcomes (progression free survival, PFS and overall survival, OS) were evaluated. None of the patients had upfront autologous transplantation. Results We identified 34 patients treated with CEPP who met the inclusion criteria. Clinical characteristics were as follows: Median age was 71 (range 39-85), 24 (71%) were male, 26 (76%) had advanced disease (Stage III-IV) and 21 (62%) had a high intermediate or high risk IPI ( IPI 3, 14 (41%) and IPI 4-5, 21 (21%)). The most common T-NHL subtypes were peripheral T-NHL (PTCL-NOS) not otherwise specified, 11 (32%) as well as angioimmunoblastic T cell lymphoma (AITL), 16 (47%). At a median follow up of 20 months (range 2-197months), the median PFS and OS were 17.6mths and 37.2mths respectively for the CEPP group. 15/34 (44%) CEPP patients have died (8 with lymphoma, 2 from treatment toxicity and 5 from unrelated causes). In the matched control comparison, the 5yr PFS and OS were both similar for patients treated with CEPP compared to patients in the CHOP control group, PFS 30% vs 32%, p= 0.43 and OS 47% vs 52%, p = 0.32, respectively (Figure 1) Conclusion Our findings show that CEPP is a well-tolerated regimen which can cure a proportion of patients with T-NHL even without autologous transplantation consolidation. Outcome of these patients do not seem to be significantly different compared to a similar population treated with standard CHOP. This study supports CEPP as a tolerable treatment option for selected patients who cannot tolerate anthracyclines and as an alternative to CHOP regimen for older patients who are not planned for ASCT. Figure 1 Figure 1. Disclosures Jeyasekharan: Turbine Ltd: Consultancy; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Perkin Elmer: Other: travel funding ; MSD: Consultancy.

PurposeRadiation of the draining lymph node basin remains controversial for Merkel cell carcinoma, particularly in the era of sentinel lymph node biopsy (SLNB).Methods and materialsBased on a 20-year experience using SLNB-guided adjuvant radiation therapy (RT), we conducted a retrospective review of clinically node-negative patients testing 2 hypotheses: (1) whether nodal RT could be safely omitted in SLNB-negative Merkel cell carcinoma and (2) whether the excised primary site should always be radiated. Clinically node-positive patients were excluded.ResultsAmong 57 clinically node-negative patients who underwent SLNB and wide local excision (WLE), 42 (74%) had a negative SLNB, and 15 (26%) had a positive SLNB. At a median follow-up of 43 months (range, 5-182), SLNB-negative patients irradiated to the primary site had improved 4-year disease-specific survival (100% vs 65%, P=.008), local recurrence-free survival (100% vs 76%, P=.009), and distant recurrence-free survival (100% vs 75%, P=.008), but not overall survival (87.5% vs 57.7%, P=.164) compared with SLNB-positive patients receiving comprehensive RT. Among SLNB-negative patients treated with WLE only, 67% (6/9) had a disease relapse, half of which were local relapses (33%).ConclusionsIn this single-institution retrospective review, after negative SLNB and WLE, RT given only to the primary site provided 100% disease control without a need for nodal RT. Among SLNB-negative patients who had WLE, omission of postoperative primary-site RT was associated with 67% cancer relapse, of which half was local.

Background and Objectives Up to one-half of children may use complementary health approaches (CHA). However, current prevalence in North America, variables associated with CHA use and caregiver perceptions of effectiveness are unclear. We aimed to determine the self-reported use of CHA during the previous 12 months in paediatric patients, demographic variables associated with CHA use and perceptions around effectiveness of CHA. Methods A cross-sectional survey study of patients aged between 28 days and 18 years who presented to a large paediatric emergency department was conducted between December 2014 and July 2015. Univariate analysis and multivariate logistic regression were used to examine variables associated with CHA use. Results Of 475 potential participants, 412 (86.7%) responded to the questionnaire, of whom 369 (89.5%) had completed the entire survey. Of these, 61.7% (95% confidence interval [CI] 56.7% to 66.6%) reported using CHA for their child. The most used CHA products were vitamins and minerals (59.2%, 95% CI 52.4% to 65.7%). Among CHA practices, massage (50.0%, 95% CI 15.5% to 30.1%) was most common. Most CHA users perceived effectiveness of the therapy used. Parental education remained statistically significant (P=0.03) in multivariate logistic regression; the odds of CHA use among caregivers with university-level education were 1.65 times higher when compared with those without (95% CI 1.04% to 2.61%). Conclusions CHA use is higher than previously reported in children. Given the high self-reported perceived effectiveness, paediatricians and family physicians should review CHA use with their patients in an open, non-judgmental manner, exploring both perceptions of safety and efficacy.

9059 Background: Immune checkpoint inhibitors (ICIs) have demonstrated limited efficacy in patients (pts) with actionable oncogenic drivers. As a result, pts with the prototypic oncogenic drivers (EGFR and ALK) have purposefully been excluded from many NSCLC ICI trials although ICI is commonly used in combination with chemotherapy for these pts. Data from one randomized trial that included pts with known EGFR and ALK alterations did not show a survival benefit with an ICI plus a platinum doublet. We sought to gain further insight into the role of chemotherapy plus ICI in pts with oncogenic driven tumors. Methods: We conducted a retrospective analysis of pts with oncogenic drivers (EGFR, ALK, ROS1, BRAF, MET, RET, HER2 and KRAS) who were treated with chemotherapy (C) or chemotherapy plus ICI (C+ICI) between 2018 and 2019 at the five University of California (UC) NCI Designated Cancer Centers (UC Irvine, UC Davis, UC Los Angeles, UC San Diego and UC San Francisco). Descriptive statistics were used. Kaplan-Meier plots and confidence intervals summarize PFS and OS in the overall cohort and oncogenic subgroups. Results: 125 pts were identified. Median age 64.1 years; M/F (45%/55%); White/Asian (59%/33%); Current/Former/Never Smokers (4%/39%/57%); PS 0/1/2(22%/68%/10%); prior number of tyrosine kinase inhibitors 0/1/2/ > 3 (46%/23%/19%/11%); Oncogenic driver: EGFR mutations (60%), KRAS mutations (23%), ALK fusions (8%), MET mutations (2.4%), RET fusions (1.6%), ROS1 fusions (1.6%), HER2 mutations (1.6%), and BRAF mutations (0.8%). The table below displays the efficacy outcomes. Conclusions: There was no survival benefit for pts with oncogenic drivers treated with chemotherapy plus an immune checkpoint inhibitor in the overall cohort or any of the subsets. Pts with KRAS mutations treated with C+ICI had a numerically longer median PFS than their counterparts treated with C. Updated data and additional analyses including PD-L1, TMB, co-mutations and toxicity will be presented.[Table: see text]

Aims Self–expanding (SE) valves are characterized with long stent frame design and the radial force of the device exists both in the inflow and outflow level. Therefore, we hypothesized that device success of SE-valves may be influenced by ascending aortic dimensions (AAD). The aim of this study was to determine the influence of AAD on acute device success rates following SE transcatheter aortic valve replacement (TAVR). Methods & Results In 4 centers in the United States and Asia, 214 consecutive patients underwent SE-TAVR. Outcomes were assessed in line with Valve Academic Research Consortium criteria. AAD was defined as the sum of the short and long axis aortic diameter divided by 2. Overall, device success rate was 85.0%. Multivariate analysis revealed that increased AAD (Odds ratio 1.27) and % oversizing (Odds ratio 0.88) were found to be independent predictors of unsuccessful device implantation. The c-statistic of the model for device success was area under the curve 0.79, sensitivity 81.3% and specificity 44.0%. Co-existence of several risk factors was associated with an exponential fall to 64.2% in device success rate. For a large AAD, however, optimally oversized SE-valves (threshold 16.2%) resulted with high device success rates compared to suboptimal oversizing (88.6% vs. 64.2%, p=0.005). Conclusions Larger AAD and smaller degrees of oversizing were confirmed to be the most relevant predictors of unsuccessful device implantation following SE-valve implantations. Optimal oversizing of great significance was noted, particularly that with a large AAD.

Purpose /Objective(s): The outcomes of repeat stereotactic radiosurgery (SRS) after failure of previous SRS are not well established. We report our overall experience using SRS for the retreatment of locally recurrent brain metastases. Methods Patients with brain metastases diagnosed between 2003-2015 who underwent repeat SRS for local tumor progression following prior SRS were identified. Rates of local control, radiation necrosis, and overall survival were analyzed. Factors affecting local failure and radiation necrosis were assessed by Chi-squared test. Results 24 lesions in 22 patients underwent repeat SRS in a single fraction. Median age was 59 years. The median SRS-1 dose was 18 Gy and the median SRS-2 dose was 15.5 Gy. The median SRS-1 target volume was 2.25 cm 3 and the median SRS-2 target volume was 3.30 cm 3. The median follow up from SRS-2 was 8.8 months. The actuarial local control for SRS-2 was 94.1% and 61.1% at 6 and 12 months, respectively. Actuarial radiation necrosis was 9.2% and 9.2% at 6 and 12 months, respectively. Volume of tumor >4 cm 3 correlated with increased risk of local failure (p=0.006) with no local failures recorded with volumes ≤4 cm 3 . SRS-2 dose, cumulative SRS dose, receipt of WBRT, and use of SRS-2 as boost after surgery did not correlate with local failure or radiation necrosis. Median overall survival after SRS-2 was 8.78 months. Conclusion Repeat SRS is feasible for select patients particularly for those with tumor volume ≤4 cm 3 . Further evaluation is needed to establish the most appropriate treatment doses and volumes for this approach.

Environmental pollution caused by the discharge of mutagenic and carcinogenic nitrofurans to the aquatic and soil environment is an emerging public health concern because of the potential in producing drug-resistant microbes and being uptaken by food crops. Using liquid chromatography-tandem mass spectrometry analysis and with spring onion (Allium wakegi Araki) as the plant model, we investigated in this study the plant uptake and accumulation of nitrofuran from a contaminated environment. Our study revealed for the first time high uptake and accumulation rates of nitrofuran in the edible parts of the food crop. Furthermore, results indicated highly efficient plant metabolism of the absorbed nitrofuran within the plant, leading to the formation of genotoxic hydrazine-containing metabolites. The results from this study may disclose a previously unidentified human exposure pathway through contaminated food crops.

Objectives The aim of this study was to evaluate the use of transcatheter heart valves (THV) for the treatment of noncalcific pure native aortic valve regurgitation (NAVR) and failing bioprosthetic surgical heart valves (SHVs) with pure severe aortic regurgitation (AR). Background Limited data are available about the “off-label” use of transcatheter aortic valve replacement (TAVR) to treat pure severe AR. Methods The study population consisted of patients with pure severe AR treated by TAVR at 18 different centers. Study endpoints were device success, early safety, and clinical efficacy at 30 days, as defined by Valve Academic Research Consortium 2 criteria. Results A total of 146 patients were included, 78 patients in the NAVR group and 68 patients in the failing SHV group. In the NAVR group, device success, early safety, and clinical efficacy were 72%, 66%, and 61%, respectively. Device success and clinical efficacy were significantly better with newer generation THVs compared with old-generation THVs (85% vs. 54% and 75% vs. 46%, respectively, p 8%, major vascular or access complication, and moderate to severe AR. In the failing SHV group, device success, early safety, and clinical efficacy were 71%, 90%, and 77%, respectively. Conclusions TAVR for pure NAVR remains a challenging condition, with old-generation THVs being associated with THV embolization and migration and significant paravalvular regurgitation. Newer generation THVs show more promising outcomes. For those patients with severe AR due to failing SHVs, TAVR is a valuable therapeutic option.

Insulin is the most effective blood glucose lowering agent and remains one of the cornerstones of diabetes management. However, many individuals with diabetes are either reluctant to initiate or are nonadherent to their insulin therapy for various reasons, including fear of frequent injections. Technosphere Insulin (TI) is a novel inhaled insulin powder that is approved by the United States Food and Drug Administration for the management of diabetes. The results from 2 phase III clinical trials have shown that TI was noninferior to subcutaneous insulin aspart and superior to inhaled placebo in lowering HbA1c in patients with diabetes mellitus types 1 and 2, respectively. Across both studies, TI appears to be generally well tolerated, with the most common adverse events being hypoglycemia and cough. However, long-term pulmonary safety concerns have not been addressed and additional studies are needed. Overall, TI appears to be a promising noninvasive prandial insulin alternative for individuals with diabetes who are at risk for medication nonadherence due to aversion to frequent injections. This article provides a review of the historical development of TI, its safety and efficacy data, and its advantages and disadvantages over traditional injectable insulins.