Safety and efficacy of combined dilation/stenting of venous abnormalities, including complete obstructions, during lead extractions in patients with congenital heart disease.

INTRODUCTION: Management of transvenous leads in patients with congenital heart disease (CHD) can be complicated by venous obstructions and residual shunts. We present our experience performing concurrent lead extraction and dilation/stenting of venous pathways, including patients with complete venous obstruction. METHODS: All cases of concurrent lead extraction and recanalization of vena cavae/baffles between 2017 and 2021 at Boston Children's Hospital were retrospectively included and reviewed for safety and efficacy. RESULTS: Eight patients, 4 female, median 38.5 years of age (range 16.7-49 years) and 81.6 kg weight (range 41.3-97.8 kg) at time of procedure were included. All patients had CHD, a majority (n = 7) having transposition of the great arteries palliated via atrial switch. All leads were removed in their entirety, with most patients having two leads extracted (n = 7). Median lead dwell time was 13.8 years (range 3.6-35.3 years). Three patients had complete obstructions, three required stenting of their innominate veins and three required recanalization of their femoral vessels. Median procedure time was 9.8 h (range 5.4-12.8 h). Complications included blood transfusion (n = 2), arrhythmia (n = 3), pleural effusion (n = 1), and pressure ulcer (n = 1). There were no cardiac perforations, venous tears, or deaths. CONCLUSION: Lead extraction along with dilation and stenting of venous anomalies, though long in duration, proved effective with minimal complications. This combined procedure can safely and effectively resolve complete obstructions secondary to transvenous leads.

Predictors of Serious Adverse Events and High-Level Cardiorespiratory Support in Patients Undergoing Transcatheter Pulmonary Vein Interventions.

Patients with pulmonary vein stenosis (PVS) often require frequent transcatheter pulmonary vein (PV) interventions for management of restenosis. Predictors of serious adverse events (AEs) and need for high-level cardiorespiratory support (mechanical ventilation, vasoactive support, and/or extracorporeal membrane oxygenation) 48 h after transcatheter PV interventions have not been reported. This is a single-center retrospective cohort analysis of patients with PVS who underwent transcatheter PV interventions from 3/1/2014 to 12/31/2021. Univariate and multivariable analyses were performed using generalized estimating equations to account for within-patient correlation. 240 patients underwent 841 catheterizations involving PV interventions (median 2 catheterizations per patient [1,3]). At least one serious AE was reported in 100 (12%) cases, the most common of which were pulmonary hemorrhage (n = 20) and arrhythmia (n = 17). There were 14 severe/catastrophic AEs (1.7% of cases) including three strokes and one patient death. On multivariable analysis, age less than 6 months, low systemic arterial saturation (< 95% in patients with biventricular [BiV] physiology, < 78% in single ventricle [SV] physiology), and severely elevated mean PA pressure (≥ 45 mmHg in BiV, ≥ 17 mmHg in SV) were associated with SAEs. Age less than 1 year, hospitalization prior to catheterization, and moderate-severe RV dysfunction were associated with high-level support after catheterization. Serious AEs during transcatheter PV interventions in patients with PVS are common, although major events such as stroke or death are uncommon. Younger patients and those with abnormal hemodynamics are more likely to experience serious AEs and require high-level cardiorespiratory support after catheterization.

The Need for Surgery After Vascular or Cardiac Trauma, or Technical Adverse Events in the Congenital Cardiac Catheterization Laboratory.

Data on the frequency and outcome of surgical interventions as a result of adverse events (AE) encountered in the pediatric and congenital cardiac catheterization laboratory are limited. This study analyzes the outcomes of specific types of AE that are most likely to require immediate surgical intervention. Data from the C3PO registry were analyzed to identify specific types of significant vascular/cardiac trauma or technical adverse events (stent/device/coil embolization/migration). The relationship between these AE and an "adverse outcome" (defined as either surgery, ECMO, or death) were analyzed. Between 01/2014 and 12/2017, 25,731 cases were entered into the C3PO registry. Vascular or cardiac trauma were observed in 92 cases (0.36% cases in C3PO), and technical adverse events were observed in 176 cases (0.68% cases in C3PO). The two highest procedure type risk categories (PREDIC3T) accounted for 61% of the cases in the cardiac/vascular trauma cohort, and 34% in the technical AE cohort. For vascular/cardiac trauma, 24 (26%) had an adverse outcome, with ECMO in 8 (9%), surgery in 19 (20%), and death in 9 (10%). For technical AE 25 (14%) had an adverse outcome, with ECMO in 3 (2%), surgery in 23 (13%), and death in 3 (2%). Survival after cardiac surgery secondary to an AE was 68% for cardiac/vascular trauma, and 96% for technical adverse events. RF perforation of the pulmonary valve was the procedure most likely to result in cardiac/vascular trauma (10%), with 57% of those having an adverse outcome. Atrial septal interventions accounted for 29% of all adverse outcomes in the cardiac/vascular trauma cohort. Non-elective or emergent cases were associated with a significantly higher incidence of an adverse outcome for both, cardiac/vascular trauma (OR 7.1) and technical adverse events (OR 2.7). Surgery within the last 30 days was associated with a significantly higher incidence of an adverse outcome for cardiac/vascular trauma only (OR 4.2). Significant cardiac/vascular trauma or stent/device/coil embolization/migration are rare, but high consequence AE. With appropriate surgical and ECMO backup, a high survival can be achieved. The potential need for and impact of immediate surgical backup seems to be higher for cardiac/vascular trauma (in particular after specific case types), than for device/coil migration/embolization, and as such case specific backup arrangements are required.

Does single-visit root canal treatment of permanent teeth provide more benefit than a multiple-visit approach?

DATA SOURCES: Cochrane Oral Health's Trials Register, Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE Ovid, Embase Ovid. STUDY SELECTION: Randomised controlled trials and quasi-randomised controlled trials were included. POPULATION: Participants aged ≥ 10 with a permanent tooth possessing a completely formed apex and without resorption; Intervention: Root canal treatment (RoCT) carried out in a single visit; Comparison: RoCT carried out over multiple visits; Outcome: Primary outcome was treatment success (retention of tooth or radiographic evidence of healing), with secondary outcomes investigating post-operative symptoms (pain, swelling, sinus tract formation). DATA EXTRACTION AND SYNTHESIS: Standard Cochrane methods to assess internal validity were used. The Robins 1 tool (for quasi randomised controlled trials) or risk of bias (RoB) 1 tool (for randomised controlled trials) were used to assess RoB whereby a judgement was assigned as 'low', 'high' or 'unclear'. GRADE (GRADEpro GDT software) was used to assess certainty of evidence for each outcome. The certainty of evidence was defined as high, moderate, low or very low, having no downgrade, downgrade of one level, downgrade of two levels and downgrade of three or more levels, respectively. Of the various subgroups investigated to determine their relevance, only pretreatment conditions (vital teeth versus necrotic teeth) and endodontic technique (manual versus mechanical instrumentation) were available for subgroup analysis. The Cochrane's test for heterogeneity and I2 test were used to assess the variation in treatment effects. A random-effects model was used to combine risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data. Sensitivity analysis was performed for each outcome, excluding studies at overall high or unclear RoB. RESULTS: Forty-seven studies were included in the meta-analysis and internal validity assessment, with 5693 teeth analysed. Ten studies were found to have a low RoB, 17 with a high RoB and 20 with an unclear RoB. No evidence was identified suggesting a difference between treatment carried out in a single visit compared to a multiple visits approach for the primary outcome measure, but there was very low certainty about the findings (RR 0.46, 95% confidence interval (CI) 0.09 to 2.50; I 2 = 0%; 2 studies, 402 teeth). No evidence was identified suggesting a difference between treatment carried out in a single visit compared to multiple visits with regards to radiological failure (RR 0.93, 95% CI: 0.81 to 1.07; I 2 = 0%; 13 studies, 1505 teeth; moderate-certainty evidence), participants reporting pain up to 72 h post obturation (RR 0.97, 95% CI: 0.81 to 1.16; I 2 = 70%; 12 studies, 1329 teeth; low-certainty evidence), pain for 72 h post obturation (MD 0.26, 95% CI: -4.76 to 5.29; I 2 = 98%; 12 studies, 1258 teeth; low-certainty evidence) or pain at 1 week post obturation (RR 1.05, 95% CI: 0.67 to 1.67; I2 = 61%; 9 studies, 1139 teeth; very low-certainty evidence). Similarly, no evidence was identified to prove that there was a difference between treatment carried out in a single visit compared to multiple visits with regards to swelling or flare-up (RR 0.56 95% CI: 0.16-1.92; I 2 = 0%; 6 studies; 605 teeth; very low-certainty evidence), analgesic use (RR 1.25 95% CI: 0.75-2.09; I 2 = 36%; 6 studies, 540 teeth; very low-certainty evidence) and sinus tract or fistula presence (RR 1.00, 95% CI: 0.24-4.28; I 2 = 0%; 5 studies, 650 teeth; very low-certainty evidence). Interestingly, however, there was evidence to show that more participants reported pain after 1 week following RoCT completed in a single visit, compared to those in multiple visit groups (RR 1.55, 95% CI: 1.14-2.09; I 2 = 18%; 5 studies, 638 teeth; moderate-certainty evidence). Subgroup analysis showed there was an increase in post-treatment pain after 1 week for RoCT carried out in a single visit on vital teeth (RR 2.16, 95% CI: 1.39-3.36; I 2 = 0%; 2 studies, 316 teeth), and with the use of mechanical instrumentation (RR 1.80, 95% CI: 1.10-2.92; I 2 = 56%; 2 studies, 278 teeth). CONCLUSIONS: The current evidence shows that RoCT carried out in a single visit is no more effective than RoCT carried out over multiple visits; after 12 months, there is no difference in pain or complications with either approach. However, single visit RoCT has been shown to have increased post-operative pain after 1 week compared to RoCT completed over multiple visits.

ICU Admission Tool for Congenital Heart Catheterization (iCATCH): A Predictive Model for High Level Post-Catheterization Care and Patient Management.

OBJECTIVES: Currently, there are no prediction tools available to identify patients at risk of needing high-complexity care following cardiac catheterization for congenital heart disease. We sought to develop a method to predict the likelihood a patient will require intensive care level resources following elective cardiac catheterization. DESIGN: Prospective single-center study capturing important patient and procedural characteristics for predicting discharge to the ICU. Characteristics significant at the 0.10 level in the derivation dataset (July 1, 2017 to December 31, 2019) were considered for inclusion in the final multivariable logistic regression model. The model was validated in the testing dataset (January 1, 2020 to December 31, 2020). The novel pre-procedure cardiac status (PCS) feature, collection started in January 2019, was assessed separately in the final model using the 2019 through 2020 dataset. SETTING: Tertiary pediatric heart center. PATIENTS: All elective cases coming from home or non-ICU who underwent a cardiac catheterization from July 2017 to December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 2,192 cases were recorded in the derivation dataset, of which 11% of patients ( n = 245) were admitted to the ICU, while 64% ( n = 1,413) were admitted to a medical unit and 24% ( n = 534) were discharged home. In multivariable analysis, the following predictors were identified: 1) weight less than 5 kg and 5-9.9 kg, 2) presence of systemic illness, 3) recent cardiac intervention less than 90 days, and 4) ICU Admission Tool for Congenital Heart Catheterization case type risk categories (1-5), with C -statistics of 0.79 and 0.76 in the derivation and testing cohorts, respectively. The addition of the PCS feature fit into the final model resulted in a C -statistic of 0.79. CONCLUSIONS: The creation of a validated pre-procedural risk prediction model for ICU admission following congenital cardiac catheterization using a large volume, single-center, academic institution will improve resource allocation and prediction of capacity needs for this complex patient population.

Interpreting Quality Improvement When Introducing New Technology: A Collaborative Experience in ASD Device Closures.

The objective of this study was to evaluate the impact of the regular introduction of new technologies into interventional cardiac catheterization procedures, in this case new atrial septal defect (ASD) closure devices, while conducting a multi-center collaborative initiative to reduce radiation usage during all procedures. Data were collected prospectively by 8 C3PO institutions between January 1, 2014 and December 31, 2017 for ASD device closure procedures in the cardiac catheterization lab during a quality improvement (QI) initiative aimed at reducing patient radiation exposure. Radiation exposure was measured in dose area product per body weight (µGy*m2/kg). Use of proposed practice change strategies at the beginning and end of the QI intervention period was assessed. Radiation exposure was summarized by institution and by initial type of device used for closure. This study included 602 ASD device closures. Without changes in patient characteristics, total fluoroscopy duration, or number of digital acquisitions, median radiation exposure decreased from 37 DAP/kg to 14 DAP/kg from 2014 to 2017. While all individual centers decreased overall median DAP/kg, the use of novel devices for ASD closure correlated with a temporary period of worsening institutional radiation exposure and increased fluoroscopy time. The introduction of new ASD closure devices resulted in increased radiation exposure during a QI project designed to reduce radiation exposure. Therefore, outcome assessment must be contextualized in QI projects, hospital evaluation, and public reporting, to acknowledge the expected variation during innovation and introduction of novel therapies.

Shape and texture-based radiomics signature on CT effectively discriminates benign from malignant renal masses.

OBJECTIVES: Using a radiomics framework to quantitatively analyze tumor shape and texture features in three dimensions, we tested its ability to objectively and robustly distinguish between benign and malignant renal masses. We assessed the relative contributions of shape and texture metrics separately and together in the prediction model. MATERIALS AND METHODS: Computed tomography (CT) images of 735 patients with 539 malignant and 196 benign masses were segmented in this retrospective study. Thirty-three shape and 760 texture metrics were calculated per tumor. Tumor classification models using shape, texture, and both metrics were built using random forest and AdaBoost with tenfold cross-validation. Sensitivity analyses on five sub-cohorts with respect to the acquisition phase were conducted. Additional sensitivity analyses after multiple imputation were also conducted. Model performance was assessed using AUC. RESULTS: Random forest classifier showed shape metrics featuring within the top 10% performing metrics regardless of phase, attaining the highest variable importance in the corticomedullary phase. Convex hull perimeter ratio is a consistently high-performing shape feature. Shape metrics alone achieved an AUC ranging 0.64-0.68 across multiple classifiers, compared with 0.67-0.75 and 0.68-0.75 achieved by texture-only and combined models, respectively. CONCLUSION: Shape metrics alone attain high prediction performance and high variable importance in the combined model, while being independent of the acquisition phase (unlike texture). Shape analysis therefore should not be overlooked in its potential to distinguish benign from malignant tumors, and future radiomics platforms powered by machine learning should harness both shape and texture metrics. KEY POINTS: • Current radiomics research is heavily weighted towards texture analysis, but quantitative shape metrics should not be ignored in their potential to distinguish benign from malignant renal tumors. • Shape metrics alone can attain high prediction performance and demonstrate high variable importance in the combined shape and texture radiomics model. • Any future radiomics platform powered by machine learning should harness both shape and texture metrics, especially since tumor shape (unlike texture) is independent of the acquisition phase and more robust from the imaging variations.

Provision of COVID-19 Convalescent Plasma in a Resource-Constrained State.

BACKGROUND: Arkansas is a rural state of 3 million people. It is ranked fifth for poverty nationally. The first case of coronavirus disease 2019 (COVID-19) in Arkansas occurred on 11 March 2020. Since then, approximately 8% of all Arkansans have tested positive. Given the resource limitations of Arkansas, COVID-19 convalescent plasma (CCP) was explored as a potentially lifesaving, therapeutic option. Therefore, the Arkansas Initiative for Convalescent Plasma was developed to ensure that every Arkansan has access to this therapy. STUDY DESIGN AND METHOD: This brief report describes the statewide collaborative response from hospitals, blood collectors, and the Arkansas Department of Health (ADH) to ensure that CCP was available in a resource-limited state. RESULTS: Early contact tracing by ADH identified individuals who had come into contact with "patient zero" in early March. Within the first week, 32 patients tested positive for COVID-19. The first set of CCP collections occurred on 9 April 2020. Donors had to be triaged carefully in the initial period, as many had recently resolved their symptoms. From our first collections, with appropriate resource and inventory management, we collected sufficient CCP to provide the requested number of units for every patient treated with CCP in Arkansas. CONCLUSIONS: The Arkansas Initiative, a statewide effort to ensure CCP for every patient in a resource-limited state, required careful coordination among key players. Collaboration and resource management was crucial to meet the demand of CCP products and potentially save lives.

Patient-Specific Organ and Effective Dose Estimates in Adult Oncologic CT.

OBJECTIVE. Patient-specific organ and effective dose provides essential information for CT protocol optimization. However, such information is not readily available in the scan records. The purpose of this study was to develop a method to obtain accurate examination- and patient-specific organ and effective dose estimates by use of available scan data and patient body size information for a large cohort of patients. MATERIALS AND METHODS. The data were randomly collected for 1200 patients who underwent CT in a 2-year period. Physical characteristics of the patients and CT technique were processed as inputs for the dose estimator. Organ and effective doses were estimated by use of the inputs and computational human phantoms matched to patients on the basis of sex and effective diameter. Size-based ratios were applied to correct for patient-phantom body size differences. RESULTS. Patients received a mean of 59.9 mGy to the lens of the eye per brain scan, 10.1 mGy to the thyroid per chest scan, 17.5 mGy to the liver per abdomen and pelvis scan, and 19.0 mGy to the liver per body scan. A factor of 2 difference in dose estimates was observed between patients of various habitus. CONCLUSION. Examination- and patient-specific organ and effective doses were estimated for 1200 adult oncology patients undergoing CT. The dose conversion factors calculated facilitate rapid organ and effective dose estimation in clinics. Compared with nonspecific dose estimation methods, patient dose estimations with data specific to the patient and examination can differ by a factor of 2.

Patient-adapted organ absorbed dose and effective dose estimates in pediatric 18F-FDG positron emission tomography/computed tomography studies.

BACKGROUND: Organ absorbed doses and effective doses can be used to compare radiation exposure among medical imaging procedures, compare alternative imaging options, and guide dose optimization efforts. Individual dose estimates are important for relatively radiosensitive patient populations such as children and for radiosensitive organs such as the eye lens. Software-based dose calculation methods conveniently calculate organ dose using patient-adjusted and examination-specific inputs. METHODS: Organ absorbed doses and effective doses were calculated for 429 pediatric 18F-FDG PET-CT patients. Patient-adjusted and scan-specific information was extracted from the electronic medical record and scanner dose-monitoring software. The VirtualDose and OLINDA/EXM (version 2.0) programs, respectively, were used to calculate the CT and the radiopharmaceutical organ absorbed doses and effective doses. Patients were grouped according to age at the time of the scan as follows: less than 1 year old, 1 to 5 years old, 6 to 10 years old, 11 to 15 years old, and 16 to 17 years old. RESULTS: The mean (+/- standard deviation, range) total PET plus CT effective dose was 14.5 (1.9, 11.2-22.3) mSv. The mean (+/- standard deviation, range) PET effective dose was 8.1 (1.2, 5.7-16.5) mSv. The mean (+/- standard deviation, range) CT effective dose was 6.4 (1.8, 2.9-14.7) mSv. The five organs with highest PET dose were: Urinary bladder, heart, liver, lungs, and brain. The five organs with highest CT dose were: Thymus, thyroid, kidneys, eye lens, and gonads. CONCLUSIONS: Organ and effective dose for both the CT and PET components can be estimated with actual patient and scan data using commercial software. Doses calculated using software generally agree with those calculated using dose conversion factors, although some organ doses were found to be appreciably different. Software-based dose calculation methods allow patient-adjusted dose factors. The effort to gather the needed patient data is justified by the resulting value of the characterization of patient-adjusted dosimetry.

Telehealth Intervention Programs for Seniors: An Observational Study of a Community-Embedded Health Monitoring Initiative.

Background:Chronic disease in older adults is estimated to account for 84% of annual health care spending in the United States, with many preventable costs expected to rise as the population continues to age.Introduction:Telehealth Intervention Programs for Seniors (TIPS) is a community-embedded program targeting low-income older adults, providing weekly assessment of vital signs and subjective wellness, and wrap-around aging services.Materials and Methods:TIPS recruited 765 volunteers over 55 years, who were Medicaid and/or Medicare eligible. Data were collected from 2014 to 2016 [median enrollment 343 days (105-435)] using 12 TIPS sites. This observational study evaluated the efficacy of TIPS by measuring within-subject changes in self-reported hospital visits and <30-day readmissions, before and during TIPS participation. Data of 617 participants (median age 74.3; interquartile range 16) were analyzed.Results:Self-reported hospital visits were reduced by 28.9% (p = 0.0013). Medicare participants benefited the most, with a 50% (p < 0.0001) reduction in hospital visits, and a 75.5% (p = 0.017) reduction in <30-day readmissions. Multivariate analysis revealed that participants (1) Medicaid-registered (odds ratio [OR] = 2.72, 95% confidence interval [CI] 0.392-1.611), (2) reporting feeling unwell (OR = 1.33, 95% CI 0.118-0.459), and (3) living alone (OR = 2.34, 95% CI 0.115-1.592) were significantly more likely than other participants to experience a hospital visit.Discussion:TIPS demonstrates that community-embedded health services can reduce rates of hospital visits in older adults.Conclusion:The success of TIPS highlights the potential of successfully deployed remote patient-monitoring initiatives in reducing the utilization of costly health services.

Radiation Risk Categories in Cardiac Catheterization for Congenital Heart Disease: A Tool to Aid in the Evaluation of Radiation Outcomes.

To stratify diverse procedure types into categories with similar radiation exposure in cardiac catheterization for congenital heart disease. Radiation exposures for a comprehensive list of specific procedure types and stratification of outcomes based on radiation risk are not currently available. Data between January 2014 and December 2015 were collected on all cases performed at sites participating in C3PO-QI (Congenital Cardiac Catheterization Outcomes Project-Quality Improvement Initiative) and 9 centers were included. Using expert consensus, 40 unique procedure types were defined by diagnostic characteristics or the intervention(s) performed, and dose area product (DAP) per kilogram of body weight (µGy × m2/kg) was summarized. Using empiric and consensus methods, three radiation risk categories were created. A total of 11,735 cases were included for analysis. Thirteen (n = 7918) procedure types with median DAP/kg < 100 were categorized in the low radiation exposure category (median DAP/kg 39). The medium exposure category (n = 1807) consisted of 16 procedure types with median DAP/kg values ranging 100 to < 200 (overall median DAP/kg 131). Finally, the high radiation exposure category (n = 1073) consisted of 11 procedure types with median DAP/kg ≥ 200 (overall median DAP/kg of 231). The radiation exposure risk categories created in this multi-center dataset are a critical step towards the development of a robust risk adjustment methodology for radiation exposure in catheterization for congenital heart disease.

Modulating ryanodine receptors with dantrolene attenuates neuronopathic phenotype in Gaucher disease mice.

Neuronopathic Gaucher disease (nGD) manifests as severe neurological symptoms in patients with no effective treatment available. Ryanodine receptors (Ryrs) are a family of calcium release channels on intracellular stores. The goal of this study is to determine if Ryrs are potential targets for nGD treatment. A nGD cell model (CBE-N2a) was created by inhibiting acid ß-glucosidase (GCase) in N2a cells with conduritol B epoxide (CBE). Enhanced cytosolic calcium in CBE-N2a cells was blocked by either ryanodine or dantrolene, antagonists of Ryrs and by Genz-161, a glucosylceramide synthase inhibitor, suggesting substrate-mediated ER-calcium efflux occurs through ryanodine receptors. In the brain of a nGD (4L;C*) mouse model, expression of Ryrs was normal at 13 days of age, but significantly decreased below the wild type level in end-stage 4L;C* brains at 40 days. Treatment with dantrolene in 4L;C* mice starting at postnatal day 5 delayed neurological pathology and prolonged survival. Compared to untreated 4L;C* mice, dantrolene treatment significantly improved gait, reduced LC3-II levels, improved mitochondrial ATP production and reduced inflammation in the brain. Dantrolene treatment partially normalized Ryr expression and its potential regulators, CAMK IV and calmodulin. Furthermore, dantrolene treatment increased residual mutant GCase activity in 4L;C* brains. These data demonstrate that modulating Ryrs has neuroprotective effects in nGD through mechanisms that protect the mitochondria, autophagy, Ryr expression and enhance GCase activity. This study suggests that calcium signalling stabilization, e.g. with dantrolene, could be a potential disease modifying therapy for nGD.

Ecotoxicity responses of the freshwater cnidarian Hydra attenuata to 11 rare earth elements.

Lanthanides are the major family of rare earth elements (REEs) owing to the essential properties these metallic species provide in diverse fields of today's world economy. They are now being mined and produced as never before. This raises new environmental concerns in terms of their expected future discharges notably to aquatic systems. Interspecies studies of their ecotoxicity are sparse and effects on aquatic life are still poorly understood. Absence of such information for cnidarians, an ecologically relevant freshwater community, thus prompted the present research on REEs toxicity using Hydra attenuata as our animal model. Lethal and sublethal ecotoxicity data generated with the 11 REEs displayed LC50 values ranging from 0.21 to 0.77 mg L-1and EC50 values ranging from 0.02 to 0.27 mg L-1, thereby confirming the inherent sensitivity of Hydra to REE exposure at environmentally relevant concentrations. Additionally, two properties of REEs were shown to modulate Hydra (sub)lethal toxicity (LC50 and EC50) which decreases with increasing atomic number and with decreasing ionic radius. Compared to studies carried out with different taxonomic groups, Hydra toxicity responses to REEs proved to be among the most sensitive, along with those of other invertebrate species (i.e., Daphnia magna, Ceriodaphnia dubia, Hyalella azteca), suggesting that members of this community are likely more at risk to eventual REE discharges in aquatic environments. Demonstrated Hydra sensitivity to REE exposure strongly justifies their future use in toxicity testing battery approaches to evaluate liquid samples suspected of harbouring REEs.

A comparison of pediatric and adult CT organ dose estimation methods.

BACKGROUND: Computed Tomography (CT) contributes up to 50% of the medical exposure to the United States population. Children are considered to be at higher risk of developing radiation-induced tumors due to the young age of exposure and increased tissue radiosensitivity. Organ dose estimation is essential for pediatric and adult patient cancer risk assessment. The objective of this study is to validate the VirtualDose software in comparison to currently available software and methods for pediatric and adult CT organ dose estimation. METHODS: Five age groups of pediatric patients and adult patients were simulated by three organ dose estimators. Head, chest, abdomen-pelvis, and chest-abdomen-pelvis CT scans were simulated, and doses to organs both inside and outside the scan range were compared. For adults, VirtualDose was compared against ImPACT and CT-Expo. For pediatric patients, VirtualDose was compared to CT-Expo and compared to size-based methods from literature. Pediatric to adult effective dose ratios were also calculated with VirtualDose, and were compared with the ranges of effective dose ratios provided in ImPACT. RESULTS: In-field organs see less than 60% difference in dose between dose estimators. For organs outside scan range or distributed organs, a five times' difference can occur. VirtualDose agrees with the size-based methods within 20% difference for the organs investigated. Between VirtualDose and ImPACT, the pediatric to adult ratios for effective dose are compared, and less than 21% difference is observed for chest scan while more than 40% difference is observed for head-neck scan and abdomen-pelvis scan. For pediatric patients, 2 cm scan range change can lead to a five times dose difference in partially scanned organs. CONCLUSIONS: VirtualDose is validated against CT-Expo and ImPACT with relatively small discrepancies in dose for organs inside scan range, while large discrepancies in dose are observed for organs outside scan range. Patient-specific organ dose estimation is possible using the size-based methods, and VirtualDose agrees with size-based method for the organs investigated. Careful range selection for CT protocols is necessary for organ dose optimization for pediatric and adult patients.

Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK.

The multifunctional AMPK-activated protein kinase (AMPK) is an evolutionarily conserved energy sensor that plays an important role in cell proliferation, growth, and survival. It remains unclear whether AMPK functions as a tumor suppressor or a contextual oncogene. This is because although on one hand active AMPK inhibits mammalian target of rapamycin (mTOR) and lipogenesis--two crucial arms of cancer growth--AMPK also ensures viability by metabolic reprogramming in cancer cells. AMPK activation by two indirect AMPK agonists AICAR and metformin (now in over 50 clinical trials on cancer) has been correlated with reduced cancer cell proliferation and viability. Surprisingly, we found that compared with normal tissue, AMPK is constitutively activated in both human and mouse gliomas. Therefore, we questioned whether the antiproliferative actions of AICAR and metformin are AMPK independent. Both AMPK agonists inhibited proliferation, but through unique AMPK-independent mechanisms and both reduced tumor growth in vivo independent of AMPK. Importantly, A769662, a direct AMPK activator, had no effect on proliferation, uncoupling high AMPK activity from inhibition of proliferation. Metformin directly inhibited mTOR by enhancing PRAS40's association with RAPTOR, whereas AICAR blocked the cell cycle through proteasomal degradation of the G2M phosphatase cdc25c. Together, our results suggest that although AICAR and metformin are potent AMPK-independent antiproliferative agents, physiological AMPK activation in glioma may be a response mechanism to metabolic stress and anticancer agents.

Results of a 10-year survey of workload for 10 treatment vaults at a high-throughput comprehensive cancer center.

The workload for shielding purposes of modern linear accelerators (linacs) consists of primary and scatter radiation which depends on the dose delivered to isocenter (cGy) and leakage radiation which depends on the monitor units (MUs). In this study, we report on the workload for 10 treatment vaults in terms of dose to isocenter (cGy), monitor units delivered (MUs), number of treatment sessions (Txs), as well as, use factors (U) and modulation factors (CI) for different treatment techniques. The survey was performed for the years between 2006 and 2015 and included 16 treatment machines which represent different generations of Varian linear accelerators (6EX, 600C, 2100C, 2100EX, and TrueBeam) operating at different electron and x-ray energies (6, 9, 12, 16 and 20 MeV electrons and, 6 and 15 MV x-rays). An institutional review board (IRB) approval was acquired to perform this study. Data regarding patient workload, dose to isocenter, number of monitor units delivered, beam energies, gantry angles, and treatment techniques were exported from an ARIA treatment management system (Varian Medical Systems, Palo Alto, Ca.) into Excel spreadsheets and data analysis was performed in Matlab. The average (± std-dev) number of treatment sessions, dose to isocenter, and number of monitor units delivered per week per machine in 2006 was 119 ± 39 Txs, (300 ± 116) × 102 cGys, and (78 ± 28) × 103 MUs respectively. In contrast, the workload in 2015 was 112 ± 40 Txs, (337 ± 124) × 102 cGys, and (111 ± 46) × 103 MUs. 60% of the workload (cGy) was delivered using 6 MV and 30% using 15 MV while the remaining 10% was delivered using electron beams. The modulation factors (MU/cGy) for IMRT and VMAT were 5.0 (± 3.4) and 4.6 (± 1.6) respectively. Use factors using 90° gantry angle intervals were equally distributed (~0.25) but varied considerably among different treatment techniques. The workload, in terms of dose to isocenter (cGy) and subsequently monitor units (MUs), has been steadily increasing over the past decade. This increase can be attributed to increased use of high dose hypo-fractionated regimens (SBRT, SRS) and the increase in use of IMRT and VMAT, which require higher MUs per cGy as compared to more conventional treatment (3DCRT). Meanwhile, the patient workload in terms of treatment sessions per week remained relatively constant. The findings of this report show that variables used for shielding purposes still fall within the recommendation of NCRP Report 151.

Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice.

Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid ß-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies implicate a pathogenic link between Gaucher and neurodegenerative diseases. The aggregation and inclusion bodies of α-synuclein with ubiquitin are present in the brains of Gaucher disease patients and mouse models. Indirect evidence of ß-amyloid pathology promoting α-synuclein fibrillation supports these pathogenic proteins as a common feature in neurodegenerative diseases. Here, multiple proteins are implicated in the pathogenesis of chronic neuronopathic Gaucher disease (nGD). Immunohistochemical and biochemical analyses showed significant amounts of ß-amyloid and amyloid precursor protein (APP) aggregates in the cortex, hippocampus, stratum and substantia nigra of the nGD mice. APP aggregates were in neuronal cells and colocalized with α-synuclein signals. A majority of APP co-localized with the mitochondrial markers TOM40 and Cox IV; a small portion co-localized with the autophagy proteins, P62/LC3, and the lysosomal marker, LAMP1. In cultured wild-type brain cortical neural cells, the GCase-irreversible inhibitor, conduritol B epoxide (CBE), reproduced the APP/α-synuclein aggregation and the accumulation of GC/GS. Ultrastructural studies showed numerous larger-sized and electron-dense mitochondria in nGD cerebral cortical neural cells. Significant reductions of mitochondrial adenosine triphosphate production and oxygen consumption (28-40%) were detected in nGD brains and in CBE-treated neural cells. These studies implicate defective GCase function and GC/GS accumulation as risk factors for mitochondrial dysfunction and the multi-proteinopathies (α-synuclein-, APP- and Aß-aggregates) in nGD.

Wastewater Treatment Works (WwTW) as a Source of Microplastics in the Aquatic Environment.

Municipal effluent discharged from wastewater treatment works (WwTW) is suspected to be a significant contributor of microplastics (MP) to the environment as many personal care products contain plastic microbeads. A secondary WwTW (population equivalent 650 000) was sampled for microplastics at different stages of the treatment process to ascertain at what stage in the treatment process the MP are being removed. The influent contained on average 15.70 (±5.23) MP·L(-1). This was reduced to 0.25 (±0.04) MP·L(-1) in the final effluent, a decrease of 98.41%. Despite this large reduction we calculate that this WwTW is releasing 65 million microplastics into the receiving water every day. A significant proportion of the microplastic accumulated in and was removed during the grease removal stage (19.67 (±4.51) MP/2.5 g), it was only in the grease that the much publicised microbeads were found. This study shows that despite the efficient removal rates of MP achieved by this modern treatment plant when dealing with such a large volume of effluent even a modest amount of microplastics being released per liter of effluent could result in significant amounts of microplastics entering the environment. This is the first study to describe in detail the fate of microplastics during the wastewater treatment process.

Radiation dosimetry of 18F-FDG PET/CT: incorporating exam-specific parameters in dose estimates.

BACKGROUND: Whole body fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is the standard of care in oncologic diagnosis and staging, and patient radiation dose must be well understood to balance exam benefits with the risk from radiation exposure. Although reference PET/CT patient doses are available, the potential for widely varying total dose prompts evaluation of clinic-specific patient dose. The aims of this study were to use exam-specific information to characterize the radiation dosimetry of PET/CT exams that used two different CT techniques for adult oncology patients and evaluate the practicality of employing an exam-specific approach to dose estimation. METHODS: Whole body PET/CT scans from two sets of consecutive adult patients were retrospectively reviewed. One set received a PET scan with a standard registration CT and the other a PET scan with a diagnostic quality CT. PET dose was calculated by modifying the standard reference phantoms in OLINDA/EXM 1.1 with patient-specific organ mass. CT dose was calculated using patient-specific data in ImPACT. International Commission on Radiological Protection publication 103 tissue weighting coefficients were used for effective dose. RESULTS: One hundred eighty three adult scans were evaluated (95 men, 88 women). The mean patient-specific effective dose from a mean injected 18F-FDG activity of 450 ± 32 MBq was 9.0 ± 1.6 mSv. For all standard PET/CT patients, mean effective mAs was 39 ± 11 mAs, mean CT effective dose was 5.0 ± 1.0 mSv and mean total effective dose was 14 ± 1.3 mSv. For all diagnostic PET/CT patients, mean effective mAs was 120 ± 51 mAs, mean CT effective dose was 15.4 ± 5.0 mSv and mean total effective dose was 24.4 ± 4.3 mSv. The five organs receiving the highest organ equivalent doses in all exams were bladder, heart, brain, liver and lungs. CONCLUSIONS: Patient-specific parameters optimize the patient dosimetry utilized in the medical justification of whole body PET/CT referrals and optimization of PET and CT acquisition parameters. Incorporating patient-specific data into dose estimates is a worthwhile effort for characterizing patient dose, and the specific dosimetric information assists in the justification of risk and optimization of PET/CT.