ACR Appropriateness Criteria® Management of Uterine Fibroids: 2023 Update.

Uterine fibroids are the most common benign tumor in women of reproductive age and can present with symptoms including bleeding, bulk related symptoms, and infertility. Several treatment options are available for the management of uterine fibroids, including medical management, minimally invasive therapies such as uterine artery embolization and MR-guided focused ultrasound ablation, and surgical interventions ranging from laparoscopic myomectomy to open hysterectomy. Given this wide range of therapeutic interventions, it is important to understand the data supporting these interventions and to be able to apply it in different clinical settings. This document provides a summary of recent trials supporting various therapies for uterine fibroids, including recent evidence for MR-guided focused ultrasound ablation and a detailed discussion of fertility outcomes in myomectomy and uterine fibroid embolization. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Development of Next-Generation COVID-19 Vaccines: BARDA Supported Phase 2b Study Designs.

In response to the COVID-19 pandemic, vaccines were quickly and successfully developed and deployed, saving millions of lives globally. While first generation vaccines are safe and effective in preventing disease caused by SARSCoV-2, next-generation vaccines have the potential to improve efficacy and safety. Vaccines delivered by a mucosal route may elicit greater protective immunity at respiratory surfaces thereby reducing transmission. Inclusion of viral antigens in addition to the spike protein may enhance protection against emerging variants of concern. Next-generation vaccine platforms with a new mechanism of action may necessitate efficacy trials to fulfill regulatory requirements. The Biomedical Advanced Research and Development Authority (BARDA) will be supporting Phase 2b clinical trials of candidate next-generation vaccines. The primary endpoint will be improved efficacy in terms of symptomatic disease relative to a currently approved COVID-19 vaccine. In this paper, we discuss the planned endpoints and potential challenges to this complex program.

Acute toxicity of total ammonia to Macrobrachium rosenbergii postlarvae at different salinity levels.

Nitrogen compounds, particularly ammonium, nitrite and nitrate, are a major problem in shrimp production systems. These compounds can accumulate in the aquatic environment and reach harmful or even lethal levels. Thus, monitoring the levels of nitrogenous compounds such as ammonia and studying their effects on the animals are essential. One tool used for this purpose is acute toxicity testing based on the evaluation of LC50 values. Furthermore, tools that can help improve the performance of aquatic organisms in culture are needed. The present study aimed to evaluate the effect of salinity on the toxicity of total ammonia to postlarvae of the freshwater prawn Macrobrachium rosenbergii. For this purpose, acute toxicity testing (LC50-96h) was performed using 540 postlarvae with a mean weight of 0.13 g and a mean total length of 2.47 cm, divided into 54 experimental units of two liters each. A completely randomized design in a 3×6 factorial scheme was used, combining three salinities (0, 5, and 10 g.L-1) and six total ammonia concentrations (0, 8, 16, 32, 64, and 128 mg.L-1), with three replicates per combination. The LC50 values for M. rosenbergii postlarvae at 24, 48, 72, and 96 h and their respective confidence intervals (95%) were estimated using the trimmed Spearman-Karber method. The results showed that salinities of 5 or 10 g.L-1 did not reduce the acute toxicity of total ammonia.

Pulmonary interstitial lymphography: A prospective trial with potential impact on stereotactic ablative radiotherapy planning for early-stage lung cancer.

This prospective feasibility trial investigated pulmonary interstitial lymphography to identify thoracic primary nodal drainage (PND). A post-hoc analysis of nodal recurrences was compared with PND for patients with early-stage lung cancer; larger studies are needed to establish correlation. Exploratory PND-inclusive stereotactic ablative radiotherapy plans were assessed for dosimetric feasibility.

Effect of temperature on embryonic development and first exogenous feeding of goldfish Carassius auratus (Linnaeus, 1758).

Goldfish or Kinguio is a widely marketed species worldwide due to the ornamental market. There is some lack of acknowledgment of the production of the species under specific climatic conditions. To evaluate the effect of temperature on embryonic development and the first exogenous feeding of goldfish, an experiment was proposed. Fifteen incubators, organized in five treatments (18, 22, 26, 30, and 34 °C) with three replications each, were used to keep the fertilized goldfish eggs until the first exogenous feeding of the larvae. The main development events were observed to understand the possible effects of these temperatures on embryos and larvae of the species. Temperature influences embryo development and the time of first exogenous feeding of goldfish. The temperature of 34 °C was lethal to the species causing 100% of anomalies in the embryos and larvae. The experiment data allow us to conclude that the species presents a maximum thermal limit during embryogenesis, and these data are important to the aquaculture industry and to understand the effect of climate changes on goldfish. The data obtained in this experiment will assist in the management of invasive species and production of the species (aquaculture).

From Acceptable to Superlative: Scaling a Technologist Coaching Intervention to Improve Image Quality.

OBJECTIVE: To explore factors influencing the expansion of the peer-based technologist Coaching Model Program (CMP) from its origins in mammography and ultrasound to all imaging modalities at a single tertiary academic medical center. METHODS: After success in mammography and ultrasound, efforts to expand the CMP across all Stanford Radiology modalities commenced in September 2020. From February to April 2021 as lead coaches piloted the program in these novel modalities, an implementation science team designed and conducted semistructured stakeholder interviews and took observational notes at learning collaborative meetings. Data were analyzed using inductive-deductive approaches informed by two implementation science frameworks. RESULTS: Twenty-seven interviews were collected across modalities with radiologists (n = 5), managers (n = 6), coaches (n = 11), and technologists (n = 5) and analyzed with observational notes from six learning meetings with 25 to 40 recurrent participants. The number of technologists, the complexity of examinations, or the existence of standardized auditing criteria for each modality influenced CMP adaptations. Facilitators underlying program expansion included cross-modality learning collaborative, thoughtful pairing of coach and technologist, flexibility in feedback frequency and format, radiologist engagement, and staged rollout. Barriers included lack of protected coaching time, lack of pre-existing audit criteria for some modalities, and the need for privacy of auditing and feedback data. DISCUSSION: Adaptations to each radiology modality and communication of these learnings were key to disseminating the existing CMP to new modalities across the entire department. An intermodality learning collaborative can facilitate the dissemination of evidence-based practices across modalities.

Consumo alimentario en mujeres embarazadas, mujeres que dan de lactar y niños de 0 a 5 años. Centros de salud ciudad de La Paz - área urbana, 2018 / Food consumption in pregnant women, breastfeeding women and children from 0 to 5 years old. La Paz city health centers - urban area, 2018

OBJETIVO: Determinar el consumo de alimentos en mujeres embarazadas, mujeres que dan de lactar y niños de 0 a 5 años, atendidos en Centros de Salud de Primer Nivel en la ciudad de La Paz en el mes de septiembre de 2018. MATERIAL Y MÉTODOS: Estudió transversal descriptivo correlacional en 126 mujeres embarazadas, 120 mujeres que dan de lactar, 105 niños de 0 a 5 meses y 117 niños de 6 a 60 meses, que asistieron a consulta en Centros de Salud. Se aplicó el método de Recordatorio de 24 Horas (R24H) para determinar el consumo de alimentos, método antropométrico para la evaluación nutricional. RESULTADOS: La ingesta promedio en mujeres embarazadas 1999 kcal y mujeres que dan de lactar 1943 Kcal, es menor a la recomendada; inadecuada en grasas, calcio y zinc; suficiente en proteínas, hidratos de carbono, vitaminas A y C; el hierro es deficiente en embarazadas. Los niveles de adecuación de la dieta en niños de 6 a 23 meses en calcio 88,3%, hierro 75%. De 24 a 60 meses en: calorías 86,3%, grasas 46,9% y zinc 50,6%. CONCLUSIONES: El consumo promedio observado en mujeres y niños es inferior a las recomendaciones nutricionales. El estado nutricional no corresponde al exceso o déficit en la ingesta. La ingesta deficiente de micronutrientes, es debida al consumo insuficiente de verduras y frutas.

Monitoring Sarcoma Response to Immune Checkpoint Inhibition and Local Cryotherapy with Circulating Tumor DNA Analysis.

PURPOSE: Immune checkpoint inhibition has led to promising responses in soft tissue sarcomas (STS), but the majority of patients do not respond and biomarkers of response will be crucial. Local ablative therapies may augment systemic responses to immunotherapy. We evaluated circulating tumor DNA (ctDNA) as a biomarker of response in patients treated on a trial combining immunotherapy with local cryotherapy for advanced STS. PATIENTS AND METHODS: We enrolled 30 patients with unresectable or metastatic STS to a phase II clinical trial. Patients received ipilimumab and nivolumab for four doses followed by nivolumab alone with cryoablation performed between cycles 1 and 2. The primary endpoint was objective response rate (ORR) by 14 weeks. Personalized ctDNA analysis using bespoke panels was performed on blood samples collected prior to each immunotherapy cycle. RESULTS: ctDNA was detected in at least one sample for 96% of patients. Pretreatment ctDNA allele fraction was negatively associated with treatment response, progression-free survival (PFS), and overall survival (OS). ctDNA increased in 90% of patients from pretreatment to postcryotherapy, and patients with a subsequent decrease in ctDNA or undetectable ctDNA after cryotherapy had significantly better PFS. Of the 27 evaluable patients, the ORR was 4% by RECIST and 11% by irRECIST. Median PFS and OS were 2.7 and 12.0 months, respectively. No new safety signals were observed. CONCLUSIONS: ctDNA represents a promising biomarker for monitoring response to treatment in patients with advanced STS, warranting future prospective studies. Combining cryotherapy and immune checkpoint inhibitors did not increase the response rate of STS to immunotherapy.

Current State of Peer Learning in Radiology: A Survey of ACR Members.

PURPOSE: Peer learning (PL) programs seek to improve upon the limitations of score-based peer review and incorporate modern approaches to improve patient care. The aim of this study was to further understand the landscape of PL among members of the ACR in the first quarter of 2022. METHODS: Members of the ACR were surveyed to evaluate the incidence, current practices, perceptions, and outcomes of PL in radiology practice. The survey was administered via e-mail to 20,850 ACR members. The demographic and practice characteristics of the 1,153 respondents (6%) were similar to those of the ACR radiologist membership and correspond to a normal distribution of the population of radiologists and can therefore be described as representative of that population. Therefore, the error range for the results from this survey is ±2.9% at a 95% confidence level. RESULTS: Among the total sample, 610 respondents (53%) currently use PL, and 334 (29%) do not. Users of PL are younger (mode age ranges, 45-54 years for users and 55-64 years for nonusers; P < .01), more likely to be female (29% vs 23%, P < .05), and more likely to practice in urban settings (52% vs 40%, P = .0002). Users of PL feel that it supports an improved culture of safety and wellness (543 of 610 [89%]) and fosters continuous improvement initiatives (523 of 610 [86%]). Users of PL are more likely than nonusers to identify learning opportunities from routine clinical practice (83% vs 50%, P < .00001), engage in programming inclusive of more team members, and implement more practice improvement projects (P < .00001). PL users' net promoter score of 65% strongly suggests that users of PL are highly likely to recommend the program to colleagues. CONCLUSIONS: Radiologists across a breadth of radiology practices are engaged in PL activities, which are perceived to align with emerging principles of improving health care and enhance culture, quality, and engagement.

Diagnostic Performance of Anti-dsDNA Tests by Indirect Immunofluorescence and Enzyme-linked Immunosorbent Assay in Patients with Systemic Lupus Erythematosus.

BACKGROUND: Several laboratory techniques for anti double-stranded (ds) DNA detection in systemic lupus erythematosus (SLE) are available, with variable diagnostic performance. We aimed to evaluate anti-dsDNA's diagnostic performance by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (EIA). METHODS: We conducted a single-center retrospective (2015 to 2020) study. Patients with anti-dsDNA tests by IIF and EIA were included. We evaluated the indications, applications, concordance, positive predictive value (PPV) of anti-dsDNA to confirm SLE diagnosis or flares, and associations of disease manifestations with positivity with each technique. RESULTS: A total of 1368 reports of anti-dsDNA tests by IIF and EIA and the corresponding medical records of the patients were analyzed. The main indication for anti-dsDNA testing was to help in the diagnosis of SLE in 890 (65%) of the samples, and the main application after obtaining the results was SLE exclusion in 782 (57.2%) cases. The combination with the highest frequency was the negativity result by both techniques in 801 (58.5%) cases (Cohen kappa 0.57). Both methods were positive in 300 patients with SLE (Cohen kappa 0.42). The PPVs of anti-dsDNA tests to confirm diagnosis/flare was 79.64% (95% CI, 75.35-83.35) by EIA, 78.75% (95% CI, 74.27-82.62) by IIF, and 82% (95% CI, 77.26-85.93) when both were positive. CONCLUSIONS: Anti-dsDNA detection by IIF and EIA are complementary and may indicate different clinical patterns in patients with SLE. The detection of anti-dsDNA antibodies by both techniques has a higher PPV than either separately for confirming SLE diagnosis or flares. These results highlight the need for evaluating both methods in clinical practice.

Is There a Role for Coronary Calcium in Patients With Diabetes?

In the primary prevention of atherosclerotic cardiovascular disease (ASCVD), a significant portion of high-risk patients have diabetes. Two decades ago, patients with or without cardiovascular disease were identified as having coronary heart disease (CHD) risk equivalents because prospective studies showed that they were at risk for future CHD events equivalent to that of patients with established CHD. Thus, for patients with CHD, cholesterol guidelines recommended that patients with diabetes should be treated routinely with statins. However, recently, the treatment of diabetes has been greatly improved, and the risk for ASCVD has decreased. For this reason, it may be appropriate to re-evaluate the recommendations for routine use of statins in patients with diabetes. One of the major advances in the risk assessment for ASCVD is the introduction of coronary artery calcium measurement. This report will examine the role of coronary artery calcium scanning for the decision to initiate statin therapy in the primary prevention for patients with diabetes.

Statin therapy for primary prevention in men: What is the role for coronary artery calcium?

Current cholesterol guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) base statin treatment decisions on multiple risk factor algorithms (e.g., Pooled Cohort Equations [PCEs]). By available PCEs, most older middle-aged men are statin eligible. But several studies cast doubt on predictive accuracy of available PCEs for ASCVD risk assessment. Recent studies suggest that accuracy can be improved by measurement of coronary artery calcium (CAC). This method has the advantage of identifying men at low risk in whom statin therapy can be delayed for several years, provided they are monitored periodically for progression of CAC. Thus, there are two approaches to statin therapy in men ≥ 55 years: first all men could be treated routinely, or second, treatment can be based on the extent of coronary calcium. The latter could allow a sizable fraction of men to avoid treatment for several years or indefinitely. Whether with initial CAC scan or with periodic rescanning, a CAC score ≥ 100 Agatston units is high enough to warrant statin therapy. In otherwise high-risk men (e.g., diabetes, severe hypercholesterolemia, 10-year risk by PCE ≥ 20%), a statin is generally indicated without the need for CAC; but in special cases, CAC measurement may aid in treatment decisions.

Damaging variants in FOXI3 cause microtia and craniofacial microsomia.

PURPOSE: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown. METHODS: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro. RESULTS: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3. CONCLUSION: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.

ACR Appropriateness Criteria® Management of Liver Cancer: 2022 Update.

The treatment and management of hepatic malignancies can be complex because it encompasses a variety of primary and metastatic malignancies and an assortment of local and systemic treatment options. When to use each of these treatments is critical to ensure the most appropriate care for patients. Interventional radiologists have a key role to play in the delivery of a variety of liver directed treatments including percutaneous ablation, transarterial embolization with bland embolic particles alone, transarterial chemoembolization (TACE) with injection of a chemotherapeutic emulsion, and transarterial radioembolization (TARE). Based on 9 clinical variants, the appropriateness of each treatment is described in this document. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

The strawberry-derived permeation enhancer pelargonidin enables oral protein delivery.

Although patients generally prefer oral drug delivery to injections, low permeability of the gastrointestinal tract makes this method impossible for most biomacromolecules. One potential solution is codelivery of macromolecules, including therapeutic proteins or nucleic acids, with intestinal permeation enhancers; however, enhancer use has been limited clinically by modest efficacy and toxicity concerns surrounding long-term administration. Here, we hypothesized that plant-based foods, which are well tolerated by the gastrointestinal tract, may contain compounds that enable oral macromolecular absorption without causing adverse effects. Upon testing more than 100 fruits, vegetables, and herbs, we identified strawberry and its red pigment, pelargonidin, as potent, well-tolerated enhancers of intestinal permeability. In mice, an oral capsule formulation comprising pelargonidin and a 1 U/kg dose of insulin reduced blood glucose levels for over 4 h, with bioactivity exceeding 100% relative to subcutaneous injection. Effects were reversible within 2 h and associated with actin and tight junction rearrangement. Furthermore, daily dosing of mice with pelargonidin for 1 mo resulted in no detectable side effects, including weight loss, tissue damage, or inflammatory responses. These data suggest that pelargonidin is an exceptionally effective enhancer of oral protein uptake that may be safe for routine pharmaceutical use.

Putting "ME" into measurement: Adapting self-report health measures for use with individuals with intellectual disability.

BACKGROUND: Self-report is important for measuring health outcomes; however, most research in intellectual disability (ID) relies on proxy report. The lack of cognitively accessible measures is one barrier to accurate self-reporting by individuals with ID. AIMS: This paper describes the process of adapting self-report measures of health status, health-related quality of life, and environment for use by individuals with ID and presents evidence on their usability (accessibility), usefulness (independent self-report), and reliability (internal consistency and test-retest). METHODS AND PROCEDURES: We used an inclusive research approach, in which we collaborated with adults with ID to revise, cognitively test, and pilot test cognitively accessible self-report measures. Technology supported the independent completion of measures. We assessed usability, usefulness, and reliability of these measures in 41 adults with ID. OUTCOMES AND RESULTS: The resulting measures are useful (independently completed) and usable (elicit a range of responses), with modest reliability (internal consistency and test-retest). CONCLUSIONS AND IMPLICATIONS: Self- report by adults with ID is feasible. A key element of this measure adaptation process was engaging adults with ID. More research is needed to understand the reliability and validity of the adapted measures and the characteristics of the population for whom they are most usable.

Chemometric optimisation of enzymatic hydrolysis of beechwood xylan to target desired xylooligosaccharides.

Generation of specific xylooligosaccharides (XOS) is attractive to the pharmaceutical and food industries due to the importance of their structure upon their application. This study used chemometrics to develop a comprehensive computational modelling set to predict the parameters maximising the generation of the desired XOS during enzymatic hydrolysis. The evaluated parameters included pH, temperature, substrate concentration, enzyme dosage and reaction time. A Box-Behnken design was combined with response surface methodology to develop the models. High-performance anion-exchange chromatography coupled with triple-quadrupole mass spectrometry (HPAEC-QqQ-MS) allowed the identification of 22 XOS within beechwood xylan hydrolysates. These data were used to validate the developed models and demonstrated their accuracy in predicting the parameters maximising the generation of the desired XOS. The maximum yields for X2-X6 were 314.2 ± 1.2, 76.6 ± 4.5, 38.4 ± 0.4, 17.8 ± 0.7, and 5.3 ± 0.2 mg/g xylan, respectively. These values map closely to the model predicted values 311.7, 92.6, 43.0, 16.3, and 4.9 mg/g xylan, respectively.

Prevalence and significance of risk enhancing biomarkers in the United States population at intermediate risk for atherosclerotic disease.

BACKGROUND: Pooled cohort equations (PCEs) estimate 10-year risk for atherosclerotic cardiovascular disease (ASCVD) in US adults. One use is to guide statin eligibility. However, PCEs risk estimate is inaccurate in some US subpopulations. OBJECTIVE: Recent cholesterol guidelines proposed addition of risk enhancing factors to improve risk assessment for selection of statin therapy. This study examines frequencies of several risk enhancing biomarkers in NHANES subjects at intermediate risk (7.5 -<20% 10-year risk for ASCVD) and considers how they may be used to better assess risk for individuals. METHODS: Prevalence of the following biomarkers were determined; elevations in apolipoprotein B-containing lipoproteins, i.e., LDL cholesterol (LDL-C) (160-189 mg/dL), non-HDL-cholesterol (non-HDL-C) (190-219 mg/dL), or total apolipoprotein B (apoB) (≥ 130 mg/dL), serum triglyceride (≥175 mg/dL), hemoglobin A1c (5.7-6.4%), high sensitivity C-reactive protein (2-10 mg/L), and waist circumference ≥ 102 cm, and abnormal estimated glomerular filtration rate (15 - ≤ 60 mg/min/1.73 m2). RESULTS: 25% of NHANES population had intermediate risk. In this subpopulation, 85% had ≥ 1 biomarkers-similarly in women and men-with a third having ≥3 abnormal markers. Frequencies were not age-related, except in those 40-49 years, in whom > 40% had ≥3 abnormal biomarkers. It made little difference whether LDL-C, non-HDL-C or apoB was used as the atherogenic lipoprotein. CONCLUSION: Three or more enhancing risk factors in intermediate risk subjects can complement PCE-estimated 10-year risk and guide the patient-provider discussion toward use of lipid-lowering medication. Future research is needed to integrate risk estimates by PCE and multiple risk enhancers.