Cycle threshold values and SARS-CoV-2: Relationship to demographic characteristics and disease severity.

Cycle threshold (Ct), or the number of cycles required to amplify viral RNA to a detectable level, provides an estimate of viral load. Previous studies have demonstrated mixed results in regard to the association between SARS-CoV-2 Ct from real-time reverse transcriptase PCR (rRT-PCR) testing to patient outcomes, and there is less data on the relationship between Ct and patient characteristics. This was a retrospective study of 256 patients tested at a tertiary care emergency department from March to July 2020 via nasopharyngeal rRT-PCR testing utilizing the Abbott M2000 SARS-CoV-2 assay. Kruskal-Wallis, univariable, and multivariable logistic regression were used where appropriate for analysis. There were no significant differences in Ct value by demographic characteristics including age, sex, race, or ethnicity. Ct increased with time since symptom onset (p < 0.001), and increasing Ct was associated with increased odds of severe disease (odds ratio: 1.05, 95% confidence interval: 1.0-1.11). Ct was not found to be associated with patient demographic characteristics and increasing Ct was found to be associated with increased odds of severe disease. Continued study will allow us to better comprehend the complex factors that contribute to the risk for severe outcomes due to SARS-CoV-2 infection.

Diagnostic stewardship to improve patient outcomes and healthcare-associated infection (HAI) metrics.

Diagnostic stewardship seeks to improve ordering, collection, performance, and reporting of tests. Test results play an important role in reportable HAIs. The inclusion of HAIs in public reporting and pay for performance programs has highlighted the value of diagnostic stewardship as part of infection prevention initiatives. Inappropriate testing should be discouraged, and approaches that seek to alter testing solely to impact a reportable metric should be avoided. HAI definitions should be further adapted to new testing technologies, with focus on actionable and clinically relevant test results that will improve patient care.

Effecting the culture: Impact of changing urinalysis with reflex to culture criteria on culture rates and outcomes.

OBJECTIVE: To evaluate the impact of changes to urinalysis with reflex to culture (UARC) reflex criteria on culture performance and clinical decision outcomes. DESIGN: Retrospective study utilizing interrupted time series analysis from December 2018 to November 2020. Primary outcomes were measures of culture performance. Secondary outcomes were rates of antimicrobial prescription for suspected urinary tract infection (UTI) and catheter-associated urinary tract infection (CAUTI). We also assessed harmful events related to antimicrobial prescription for all causes and UTI, UTI symptoms, and sepsis. SETTING: A 415-bed, academic, tertiary-care, medical center. PATIENTS: Hospitalized adult patients with urine testing performed. INTERVENTION: UARC reflex criteria were changed on October 22, 2019, from ≥5×109/L white blood cells (WBCs) or trace leukocyte esterase or positive nitrite units on urinalysis to only ≥15×109/L WBCs. RESULTS: The study included 11,322 unique UARC tests. We detected a significant decrease in the rate of urine cultures performed from UARC after the intervention (32.5-8.7 cultures per 1,000 patient days; P < .001), with improved diagnostic efficacy (ie, culture positivity increased from 34.8% to 62.1%). CAUTI rates did not change. We detected a significant decrease in antimicrobial prescription rates (P = .05), this was primarily driven by preintervention changes. One case of sepsis occurred secondary to a missed UTI, and UTIs were rarely missed after the intervention. CONCLUSIONS: Implementation of a stricter UARC reflex criterion was associated with a decrease in culture rates with improved diagnostic efficacy without significant adverse events. Continued education is needed to change antimicrobial prescribing practices.

Impact of provider-selected indication requirement on urine test utilization and positivity.

Objective: To evaluate the impact of the addition of an indication specification requirement to isolated urine-culture ordering on testing utilization. Design: Retrospective study utilizing interrupted time series analysis with negative binomial regression. The preintervention period was October 1, 2018-November 11, 2019, and the postintervention period was November 12, 2019-October 31, 2020. The primary outcome was isolated culture rate per 1,000 patient days. Secondary outcomes were the proportion of all urine tests ordered as isolated urine culture and culture positivity. An exploratory analysis assessed the appropriateness of selected testing indications. Setting: A 415-bed, urban, academic medical center. Patients: Adult patients with urine testing performed during hospital admission. In total, 1,494 unique isolated urine-culture orders were included in the analysis. Interventions: On November 12, 2019, the laboratory order interface was changed to require the ordering provider to select an indication for isolated urine culture. Results: Isolated urine-culture rates did not significantly change after the intervention (11.2-7.8 cultures per 1,000 patient days; P = .17) nor did culture positivity (26.9% vs 26.8%). Most ordering providers left the indication for testing blank, and of those charts reviewed, 67% did not have a documented condition for which isolated urine culture was the most appropriate initial test. Conclusions: The addition of an order-specification requirement for isolated urine-culture testing did not significantly affect ordering practices. The test remains overused as the initial diagnostic evaluation for a suspected urinary tract infection. Further provider education and continued changes in provider workflow are needed to achieve lasting change in practice.

Technical note: Toward implementation of MR-guided radiation therapy for laryngeal cancer with healthy volunteer imaging and a custom MR-CT larynx phantom.

PURPOSE: Internal motion of the larynx can cause normal tissue toxicity and/or tumor underdosage during radiotherapy. MR-guided radiation therapy (MRgRT) provides improved soft-tissue contrast for patient setup and real-time gating of radiation based on cine imaging of tumor motion, potentially making it an advantageous modality for laryngeal treatments. However, there are potential concerns regarding the small target size, proximity to heterogeneous tissue interfaces in the airway that may cause dosimetric errors in the presence of the magnetic field, and uncertainty about the ability of MR-linear accelerator (MR-Linac) systems to visualize and track laryngeal motion. To date, there have been no reports of the use of MRgRT for laryngeal treatments. METHODS: A healthy volunteer was imaged on a ViewRay MRIdian MR-Linac. Organs-at-risk and a laryngeal pseudo target were contoured and used to generate a stereotactic body radiotherapy plan. A custom phantom was created using 3D-printing based on structures delineated on the volunteer images to construct an enclosure containing the target and airway anatomy, with a gap for radiochromic film, and filled with gelatin . The treatment plan was mapped onto the phantom and delivered dose assessed on radiochromic film with global normalization and a 10% dose threshold. A cine MR of the volunteer was acquired to assess the magnitude of larynx motion with speaking and swallowing, and system's ability to gate radiation. RESULTS: A clinically acceptable laryngeal treatment plan and larynx phantom that was MR and computed tomography-visible were successfully created. The delivered dose had good agreement with the treatment plan with a gamma passing rate of 96.5% (3%/2 mm). The MR-Linac was able to visualize, track, and gate larynx motion. CONCLUSIONS: The MRgRT workflow for laryngeal treatments was assessed and performed in preparation for clinical implementation on the MR-Linac, demonstrating that it is feasible to treat laryngeal cancer patients on the MR-Linac.

First Do No Harm: Moving Beyond Universal Preprocedural Testing for COVID-19.

Preprocedural testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was introduced early in the pandemic in an effort to protect health care workers, direct appropriate use of personal protective equipment (PPE), and improve patient outcomes. In light of our appreciation for the efficacy of PPE and the nuances associated with interpretation of polymerase chain reaction testing for SARS-CoV-2, particularly as community transmission decreases, we call for a re-evaluation of universal preprocedural testing. We propose a transition to a patient-centered approach, focusing on testing patients whose outcomes would be improved by a delayed procedure in the event of a positive test and a greater reliance on appropriate PPE rather than preprocedural test results. We recommend that a community infection rate threshold be set at which point preprocedural testing is discontinued, understanding that there is an inflection point at which testing downsides outweigh the benefits.

Use of a healthy volunteer imaging program to optimize clinical implementation of stereotactic MR-guided adaptive radiotherapy.

PURPOSE: MR-linacs (MRLs) have enabled the use of stereotactic magnetic resonance (MR) guided online adaptive radiotherapy (SMART) across many cancers. As data emerges to support SMART, uncertainty remains regarding optimal technical parameters, such as optimal patient positioning, immobilization, image quality, and contouring protocols. Prior to clinical implementation of SMART, we conducted a prospective study in healthy volunteers (HVs) to determine optimal technical parameters and to develop and practice a multidisciplinary SMART workflow. METHODS: HVs 18 years or older were eligible to participate in this IRB-approved study. Using a 0.35 T MRL, simulated adaptive treatments were performed by a multi-disciplinary treatment team in HVs. For each scan, image quality parameters were assessed on a 5-point scale (5 = extremely high, 1 = extremely poor). Adaptive recontouring times were compared between HVs and subsequent clinical cases with a t-test. RESULTS: 18 simulated treatments were performed in HVs on MRL. Mean parameters for visibility of target, visibility of nearby organs, and overall image quality were 4.58, 4.62, and 4.62, respectively (range of 4-5 for all measures). In HVs, mean ART was 15.7 min (range 4-35), comparable to mean of 16.1 (range 7-33) in the clinical cases (p = 0.8963). Using HV cases, optimal simulation and contouring guidelines were developed across a range of disease sites and have since been implemented clinically. CONCLUSIONS: Prior to clinical implementation of SMART, scans of HVs on an MRL resulted in acceptable image quality and target visibility across a range of organs with similar ARTs to clinical SMART. We continue to utilize HV scans prior to clinical implementation of SMART in new disease sites and to further optimize target tracking and immobilization. Further study is needed to determine the optimal duration of HV scanning prior to clinical implementation.

A unique short-chain dehydrogenase/reductase in Arabidopsis glucose signaling and abscisic acid biosynthesis and functions.

Glc has hormone-like functions and controls many vital processes through mostly unknown mechanisms in plants. We report here on the molecular cloning of GLUCOSE INSENSITIVE1 (GIN1) and ABSCISIC ACID DEFICIENT2 (ABA2) which encodes a unique Arabidopsis short-chain dehydrogenase/reductase (SDR1) that functions as a molecular link between nutrient signaling and plant hormone biosynthesis. SDR1 is related to SDR superfamily members involved in retinoid and steroid hormone biosynthesis in mammals and sex determination in maize. Glc antagonizes ethylene signaling by activating ABA2/GIN1 and other abscisic acid (ABA) biosynthesis and signaling genes, which requires Glc and ABA synergistically. Analyses of aba2/gin1 null mutants define dual functions of endogenous ABA in inhibiting the postgermination developmental switch modulated by distinct Glc and osmotic signals and in promoting organ and body size and fertility in the absence of severe stress. SDR1 is sufficient for the multistep conversion of plastid- and carotenoid-derived xanthoxin to abscisic aldehyde in the cytosol. The surprisingly restricted spatial and temporal expression of SDR1 suggests the dynamic mobilization of ABA precursors and/or ABA.