Abstract Introduction: A test that detects cancer signal across multiple cancer types and predicts signal (tissue) origin (SO) could aid in more efficient diagnostic workup and shorten time to cancer diagnosis in individuals with signs and symptoms.Methods: The Circulating Cell-free Genome Atlas (CCGA; NCT02889978) study is a prospective, longitudinal, multicenter, case-control study to develop and validate a multi-cancer detection test. The 2nd CCGA substudy utilized a targeted methylation-based cell-free DNA assay and machine learning algorithm and included assessment of test performance (sensitivity and SO prediction accuracy) in a subgroup of participants with clinically presenting cancers (CPCs) that were undiagnosed prior to blood draw. Specificity was assessed in the noncancer group and subgroups with confounding (nonmalignant) conditions (CCs; eg, cirrhosis) and noncancer participants enrolled in hematology clinics (HCs).Results: Specificity was 99.5% (95% confidence interval: 98.2-99.9%; 396/398), 93.8% (71.7-99.7%; 15/16), and 99.3% (96.0-100.0%; 136/137) for the noncancer group, CCs subgroup, and HCs subgroup, respectively. Overall sensitivity among those with CPCs was 66.4% (62.2-70.3%; 344/518). Sensitivity of cancer signal detection increased with increasing clinical stage (Table). SO prediction accuracy was 91.7% (88.3-94.3%; 300/327) among CPC participants with cancers detected, excluding those with multiple or unknown primaries. The test demonstrated prognostic value as detected cancer participants had worse survival probability than those not detected. Conclusions: This multi-cancer detection test detected cancer signals and predicted SO in individuals with CPCs with high specificity. These findings support further clinical development of this multi-cancer detection test that could accelerate the diagnostic resolution of symptomatic cancers. Table. Sensitivity by Clinical Stage Across Cancer Type in Clinically Presenting CancersClinical StagePositive Test/Total Cancer; Sensitivity (95% CI)All*344/518; 66.4% (62.2-70.3%)I33/122; 27.0% (20.0-35.5%)II60/102; 58.8% (49.1-67.9%)III103/121; 85.1% (77.7-90.4%)IV136/147; 92.5% (87.1-95.8%)Not expected to be staged9/21; 42.9% (24.5-63.5%)Non-informative2/4; 50.0% (15.0-85.0%)CI, confidence interval.*One participant who had a positive test result had multiple primaries with clinical stage I and not-expected-to-be-staged. Citation Format: Alan H. Bryce, Minetta C. Liu, Michael V. Seiden, David D. Thiel, Donald Richards, Carlos Becerra, Kathryn N. Kurtzman, Xiaoji Chen, Tony Wu, Quan Zhang, Jingjing Gao, Nan Zhang, Earl Hubbell, Arash Jamshidi, Eric T. Fung, Eric A. Klein. Performance of a cell-free DNA-based multi-cancer detection test as a tool for diagnostic resolution of symptomatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB058.
Distribution, management and outcomes of AMI according to principal diagnosis priority during inpatient admission
Abstract Introduction Enoxaparin, a low molecular weight heparin, has been proven to safely and effectively prevent venous thromboembolism (VTE) in acutely ill patients. Burn patients may be particularly vulnerable to the occurrence of a VTE due to prolonged immobility, frequent operating room procedures, and low flow states. Treatment of acute VTE is associated with a direct medical cost of $12000-$15000 and subsequent complications increase costs to $18000 to $23000 per case. Current institutional protocol for initiation of enoxaparin an all burn adult patients is 40 mg administered subcutaneously every 12 hours. Anti-Xa levels are used to monitor anticoagulation prophylaxis, with 0.3–0.5 U/mL recognized as the prophylactic range. Doses are subsequently modified in 10 mg increments to achieve goal prophylaxis anti-Xa levels. The purpose of this study was to evaluate current practice (CP) and assess if the implementation of a published enoxaparin dosing algorithm could minimize delay in achieving anticoagulation prophylaxis. Methods A retrospective chart review was performed of 94 adult burn patients. The doses and time required to reach goal prophylaxis anti-Xa levels using current practice (CP) were compared to the predicted algorithm dose (AD). The number of dose adjustments and the number of days needed for adjustments for CP were documented. Charges related for laboratory determinations and medication administration were calculated. Results Of the 94 patients reviewed, the average age was 47 years, the majority were male (74%), mean actual weight 92 kilograms and mean TBSA 15.7%. The most common mechanism of injury was flash/flame (63%) with 18% suffering an inhalation injury. On average, using CP, it took 9.3 days to get to goal prophylaxis anti-Xa levels, with a mean of 2.86 anti-Xa lab tests needed and an average prophylactic dose of 55.5 mg. A total of 360 labs draws were performed and 74% were timed correctly. The CP average starting dose was lower than the AD 40 mg versus 45 mg (p < .0001). If the algorithm had been used the number of dosing adjustments would have been 25% less. The algorithm overestimated the starting dose in only 2.1% of the population. The average charges until goal was met for enoxaparin were $2,933 and $787 for anti-Xa levels. Conclusions This study demonstrates increased clinical efficacy and cost-effectiveness for an algorithm driven enoxaparin dosing regimen for burn patients. Prospective study with larger patient numbers is warranted.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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AbstractObjective Video recording and video recognition (VR) with computer vision have become widely used in many aspects of modern life. Hospitals have employed VR technology for security purposes, however, despite the growing number of studies showing the feasibility of VR software for physiologic monitoring or detection of patient movement, its use in the intensive care unit (ICU) in real-time is sparse and the perception of this novel technology is unknown. The objective of this study is to understand the attitudes of providers, patients, and patient's families toward using VR in the ICU.Design A 10-question survey instrument was used and distributed into two groups of participants: clinicians (MDs, advance practice providers, registered nurses), patients and families (adult patients and patients' relatives). Questions were specifically worded and section for free text-comments created to elicit respondents' thoughts and attitudes on potential issues and barriers toward implementation of VR in the ICU.Setting The survey was conducted at Mayo Clinic in Minnesota and Florida.Results A total of 233 clinicians' and 50 patients' surveys were collected. Both cohorts favored VR under specific circumstances (e.g., invasive intervention and diagnostic manipulation). Acceptable reasons for VR usage according to clinicians were anticipated positive impact on patient safety (70%), and diagnostic suggestions and decision support (51%). A minority of providers was concerned that artificial intelligence (AI) would replace their job (14%) or erode professional skills (28%). The potential use of VR in lawsuits (81% clinicians) and privacy breaches (59% patients) were major areas of concern. Further identified barriers were lack of trust for AI, deterioration of the patient–clinician rapport. Patients agreed with VR unless it does not reduce nursing care or record sensitive scenarios.Conclusion The survey provides valuable information on the acceptance of VR cameras in the critical care setting including an overview of real concerns and attitudes toward the use of VR technology in the ICU.
Computer automation for physics chart check should be adopted in clinic to replace manual chart checking for radiotherapy
PurposeAccurate radiation dosimetry in radiobiological experiments is crucial for preclinical research in advancement of cancer treatment. Vendors of cell irradiators often perform calibration for end‐users. However, calibration accuracy remains unclear due to missing detailed information on calibration equipment and procedures. In this study, we report our findings of a vender miscalibration of the radiation output and our investigation on the root cause of the discrepancy.MethodsIndependent calibration verification for a commercial preclinical orthovoltage irradiator was conducted. Initially, in the absence of ionization chambers calibrated at kV energy, radiochromic films (EBT3) was first calibrated at MV energy. Energy correction factors from literature were used to create an in‐house kV dosimetry system. The miscalibration identified with the in‐house kV EBT3 dosimetry was later confirmed by ADCL calibrated ionization chambers (Exradin A1SL and PTW 30013) at kV energy. Ionization chambers were suspended in‐air following TG‐61 recommendation for output calibration. To investigate the root cause of the miscalibration, additional measurements were performed with ionization chambers placed on the shelf. A validated Monte Carlo simulation code was also used to investigate the impact of placing the ionization chamber on the shelf instead of suspending it in air during the vendor‐performed calibration process.ResultsUp to a 6% dosimetry error was observed when comparing the vendor calibrated output of the preclinical irradiator with our independent calibration check. Further investigation showed incorrect setups in the vendor’s calibration procedure which may result in dose errors up to 11% from the backscatter of the shelf board during calibration, and up to 5% from omitting temperature and pressure corrections to ionization chamber readings.ConclusionOur study revealed large dose calibration errors caused by incorrect setup and the omission of temperature/pressure correction in the vendor’s calibration procedure. The findings also highlighted the importance of performing an independent check of the dose calibration for preclinical kV irradiators. More absolute dosimetry training is needed for both vendors and end users for establishing accurate absolute dosimetry.
A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS