Machine Learning to Predict Prostate Artery Embolization Outcomes.

PURPOSE: This study leverages pre-procedural data and machine learning (ML) techniques to predict outcomes at one year following prostate artery embolization (PAE). MATERIALS AND METHODS: This retrospective analysis combines data from the UK-ROPE registry and patients that underwent PAE at our institution between 2012 and 2023. Traditional ML approaches, including linear regression, lasso regression, ridge regression, decision trees and random forests, were used with leave-one-out cross-validation to predict international prostate symptom score (IPSS) at baseline and change at 1 year. Predictors included age, prostate volume, Qmax (maximum urinary flow rate), post-void residual volume, Abrams-Griffiths number (urodynamics score) and baseline IPSS (for change at 1 year). We also independently confirmed our findings using a separate dataset. An interactive digital user interface was developed to facilitate real-time outcome prediction. RESULTS: Complete data were available in 128 patients (66.7 ± 6.9 years). All models predicting IPSS demonstrated reasonable performance, with mean absolute error ranging between 4.9-7.3 for baseline IPSS and 5.2-8.2 for change in IPSS. These numbers represent the differences between the patient-reported and model-predicted IPSS scores. Interestingly, the model error in predicting baseline IPSS (based on objective measures alone) significantly correlated with the change in IPSS at 1-year post-PAE (R2 = 0.2, p < 0.001), forming the basis for our digital user interface. CONCLUSION: This study uses ML methods to predict IPSS improvement at 1 year, integrated into a user-friendly interface for real-time prediction. This tool could be used to counsel patients prior to treatment.

Use of Digital COVID-19 Exposure Notifications at a Large Gathering: Survey Analysis of Public Health Conference Attendees.

BACKGROUND: WA Notify was Washington State's smartphone-based COVID-19 digital exposure notification (EN) tool, which was used to help limit the spread of COVID-19 between November 30, 2020, and May 11, 2023. Following the 2022 Washington State Public Health Association Annual Conference, attendees who had WA Notify activated began receiving ENs alerting them to a possible COVID-19 exposure during the conference. A survey was emailed to all conference attendees to measure WA Notify adoption, mechanisms through which attendees received ENs, and self-reported engagement in protective behaviors postexposure. OBJECTIVE: This study aimed to learn more about the experiences of WA Notify adopters and nonadopters who may have been exposed to COVID-19 at a large group gathering. METHODS: A web-based survey administered through REDCap (Research Electronic Data Capture; Vanderbilt University) was sent to all attendees of the Washington State Public Health Association conference. Self-reported demographic information and characteristics of respondents were summarized. Regression models were used to estimate relative risks to compare WA Notify adoption and testing behaviors between groups. RESULTS: Of the 464 total registered attendees who were sent the survey, 205 (44%) responses were received; 201 eligible attendees were included in this analysis. Of those, 149 (74%) respondents reported having WA Notify activated on their phones at the time of the conference. Among respondents with WA Notify activated, 54% (n=77) reported learning of their potential exposure from a WA Notify EN. Respondents who reported that they did not have WA Notify activated and learned of their potential exposure via the event-wide email from conference organizers were 39% less likely to test for COVID-19 compared to respondents with WA Notify activated who learned of their potential exposure from the email (relative risk 0.61, 95% CI 0.40-0.93; P=.02), and this gap was even larger when compared to respondents who learned of their exposure from a WA Notify EN. The most commonly cited reason for not having WA Notify activated was privacy concerns (n=17, 35%), followed by not wanting to receive ENs (n=6, 12%) and being unaware of WA Notify (n=5, 10%). CONCLUSIONS: Digital EN systems are an important tool to directly and anonymously notify close contacts of potential exposures and provide guidance on the next steps in a timely manner. Given the privacy concerns, there is still a need for increasing transparency surrounding EN technology to increase uptake by the public if this technology were to be used in the future to slow the spread of communicable diseases.

Access to beds for interventional radiology patients: improving patient care.

This review describes the rationale in support of admitting rights for interventional radiologists and presents options for the management of interventional radiology (IR) inpatients. The manuscript also discusses wider aspects of IR involvement in inpatient treatment, such as income and funding for IR services, and the implications for IR as a clinical specialty.

Developing day-case units: imperative for optimal patient care in interventional radiology.

As interventional radiology (IR) treatments have evolved, they have become less invasive, enabling rapid recovery, which expedites ambulation and promotes same-day discharge. As a result of this, a significant proportion of IR elective work can be provided using a day-case service model. Reconfiguration of IR services to increase day-case procedures using a dedicated IR day-case unit (RDU) to facilitate the passage of patients is vital to ensure best medical practice. The aim of this review is to discuss the benefits of day-case IR procedures, the optimal structure of an RDU, and to inform radiologists how to introduce and/or improve day-case IR services in their IR practice.

Trading-off privacy and utility: the Washington State experience assessing the performance of a public health digital exposure notification system for coronavirus disease 2019.

OBJECTIVE: Digital exposure notifications (DEN) systems were an emergency response to the coronavirus disease 2019 (COVID-19) pandemic, harnessing smartphone-based technology to enhance conventional pandemic response strategies such as contact tracing. We identify and describe performance measurement constructs relevant to the implementation of DEN tools: (1) reach (number of users enrolled in the intervention); (2) engagement (utilization of the intervention); and (3) effectiveness in preventing transmissions of COVID-19 (impact of the intervention). We also describe WA State's experience utilizing these constructs to design data-driven evaluation approaches. METHODS: We conducted an environmental scan of DEN documentation and relevant publications. Participation in multidisciplinary collaborative environments facilitated shared learning. Compilation of available data sources and their relevance to implementation and operation workflows were synthesized to develop implementation evaluation constructs. RESULTS: We identified 8 useful performance indicators within reach, engagement, and effectiveness constructs. DISCUSSION: We use implementation science to frame the evaluation of DEN tools by linking the theoretical constructs with the metrics available in the underlying disparate, deidentified, and aggregate data infrastructure. Our challenges in developing meaningful metrics include limited data science competencies in public health, validation of analytic methodologies in the complex and evolving pandemic environment, and the lack of integration with the public health infrastructure. CONCLUSION: Continued collaboration and multidisciplinary consensus activities can improve the utility of DEN tools for future public health emergencies.

Engagement in Protective Behaviors by Digital Exposure Notification Users During the COVID-19 Pandemic, Washington State, January-June 2021.

OBJECTIVES: Smartphone-based digital exposure notification (EN) tools were introduced during the COVID-19 pandemic to supplement strained case investigation and contact tracing efforts. We examined the influence of an EN tool implemented in Washington State, WA Notify, on user engagement in behaviors that protect against COVID-19 transmission. METHODS: From January 25 through June 30, 2021, we administered 2 surveys to WA Notify users who received notification of a possible COVID-19 exposure. The initial survey, sent when users received a notification, focused on intent to engage in protective behaviors. The follow-up survey captured data on self-reported actual engagement in protective behaviors and contact by a public health contact tracer. RESULTS: Of 1507 WA Notify users who completed the initial survey, 40.1% (n = 604) reported intending to seek COVID-19 testing and 67.1% (n = 1011) intended to watch for COVID-19 symptoms. Of 407 respondents to the follow-up survey, 57.5% (n = 234) reported getting tested and 84.3% (n = 343) reported watching for COVID-19 symptoms. Approximately 84% (n = 1266) of respondents to the initial survey received a notification from WA Notify before being reached by public health contact tracers; on follow-up, 42.5% (n = 173) of respondents reported never being contacted by public health. CONCLUSIONS: Our findings suggest that WA Notify users may initiate protective behaviors earlier than nonusers who will not know of an exposure until notified by public health or by a known contact. Digital EN tools may be a valuable addition to existing public health outbreak investigation and response activities.

CCL5 production in lung cancer cells leads to an altered immune microenvironment and promotes tumor development.

Current immunotherapies for lung cancer are only effective in a subset of patients. Identifying tumor-derived factors that facilitate immunosuppression offers the opportunity to develop novel strategies to supplement and improve current therapeutics. We sought to determine whether expression of driver oncogenes in lung cancer cells affects cytokine secretion, alters the local immune environment, and influences lung tumor progression. We demonstrate that oncogenic EGFR and KRAS mutations, which are early events in lung tumourigenesis, can drive cytokine and chemokine production by cancer cells. One of the most prominent changes was in CCL5, which was rapidly induced by KRASG12V or EGFRL858R expression, through MAPK activation. Immunocompetent mice implanted with syngeneic KRAS-mutant lung cancer cells deficient in CCL5 have decreased regulatory T cells (Tregs), evidence of T cell exhaustion, and reduced lung tumor burden, indicating tumor-cell CCL5 production contributes to an immune suppressive environment in the lungs. Furthermore, high CCL5 expression correlates with poor prognosis, immunosuppressive regulatory T cells, and alteration to CD8 effector function in lung adenocarcinoma patients. Our data support targeting CCL5 or CCL5 receptors on immune suppressive cells to prevent formation of an immune suppressive tumor microenvironment that promotes lung cancer progression and immunotherapy insensitivity.

Oral Health in the Population Assessment of Tobacco and Health Study.

Tobacco use is a well-established risk factor for multiple adverse oral conditions. Few nationally representative oral health data sets encompass the current diversity of tobacco and nicotine products. This investigation examines the validity of oral health measures in the Population Assessment of Tobacco and Health (PATH) Study to assess relationships between tobacco use and oral health. Cross-sectional data from PATH Study wave 4 (N = 33,643 US adults, collected 2016-2018) were used to obtain estimates for 6 self-reported oral conditions (e.g., bone loss around teeth, tooth extractions) and compared with analogous estimates from the National Health and Nutrition Examination Survey (NHANES) cycle 2017-2018 (N = 5,856). Within the PATH Study, associations were calculated between tobacco use status and lifetime and past 12-mo experience of adverse oral conditions using survey-weighted multivariable logistic regression. Nationally representative estimates of oral conditions between the PATH Study and NHANES were similar (e.g., ever-experience of bone loss around teeth: PATH Study 15.2%, 95% CI, 14.4%-15.9%; NHANES 16.6%, 95% CI, 14.9%-18.4%). In the PATH Study, combustible tobacco smoking was consistently associated with lifetime and past 12-mo experience of adverse oral health (e.g., exclusive cigarette smoking vs. never tobacco use, adjusted odds ratio [AOR] for loose teeth in past 12 mo: 2.02; 95% CI, 1.52-2.69). Exclusive smokeless tobacco use was associated with greater odds of loose teeth (AOR, 1.93; 95% CI, 1.15-3.26) and lifetime precancerous lesions (AOR, 3.85; 95% CI, 1.73-8.57). Use of other noncigarette products (e.g., pipes) was inconsistently associated with oral health outcomes. PATH Study oral health measures closely align with self-reported measures from NHANES and are internally concurrent. Observed associations with tobacco use and the ability to examine emerging tobacco products support application of PATH Study data in dental research, particularly to examine potential oral health effects of novel tobacco products and longitudinal changes in tobacco use behaviors.

Focal Concerns and Police Decision Making in Sexual Assault Cases: A Systematic Review and Meta-Analysis.

Sexual assault and case attrition at the arrest stage are serious problems in the United States. Focal concerns have increasingly been used to explain police decision making in sexual assault cases. Because of the popularity of the focal concerns perspective and potential to inform evidence-based training, a systematic review and meta-analysis are needed to condense the literature. In this study, we assess the overall strength of the relationship between focal concerns variables and police decisions to arrest in cases of sexual assault. Our assessment of the effects of focal concerns variables on arrest decision making in sexual assault cases followed the systematic review protocols provided by the Campbell Collaboration of Systematic Reviews. Specifically, we used the Campbell Collaboration recommendations to search empirical literature and used meta-analysis to evaluate the size, direction, and strength of the impact of focal concerns variables on arrest decisions. Our search strategy detected 14 eligible studies and 79 effect sizes. The meta-analysis found several robust and statistically significant correlates of arrest. In fact, each focal concerns concept produced at least one robust arrest correlate. Overall, focal concerns offers a strong approach for explaining police decisions in sexual assault cases. Although practical concerns and resource constraints produced the strongest arrest correlates, results show the importance of additional case characteristics in officers' decision to arrest.

WA Notify: the planning and implementation of a Bluetooth exposure notification tool for COVID-19 pandemic response in Washington State.

Bluetooth exposure notification tools for mobile phones have emerged as one way to support public health contact tracing and mitigate the spread of COVID-19. Many states have launched their own versions of these tools. Washington State's exposure notification tool, WA Notify, became available on November 30, 2020, following a one-month Seattle campus pilot at the University of Washington. By the end of April 2021, 25% of the state's population had activated WA Notify, one of the highest adoption rates in the country. Washington State's formation of an Exposure Notification Advisory Committee, early pilot testing, and use of the EN Express system framework were all important factors in its adoption. Continuous monitoring and willingness to make early adjustments such as switching to automated texting of verification codes have also been important for improving the tool's value. Evaluation work is ongoing to determine and quantify WA Notify's effectiveness, timeliness, and accessibility.

Early Epidemiological Evidence of Public Health Value of WA Notify, a Smartphone-based Exposure Notification Tool: Modeling COVID-19 Cases Averted in Washington State

BackgroundSecure and anonymous smartphone-based exposure notification tools are recently developed public health interventions that aim to reduce COVID-19 transmission and supplement traditional public health suriveillance. We assessed the impact of Washington States exposure notification tool, WA Notify, in mitigating the spread of COVID-19 during its first four months of implementation. MethodsDue to the constraints of privacy-preservation, aggregate metrics and disparate data sources were utilized to estimate the number of COVID-19 cases averted based on a modelling approach adapted from Wymant et al (2021) using the following parameters: number of notifications generated; the probability that a notified individual goes on to become a case; expected fraction of transmissions preventable by strict quarantine after notification; actual adherence to quarantine; and expected size of the full transmission chain if a contact had not been notified. ResultsThe model was run on a range of secondary attack rates (5.1%-13.706%) and quarantine effectiveness (53% and 64%). Assuming a 12.085% secondary attack rate and 53% quarantine effectiveness, the model shows that 5,500 cases (central 95% range of sensitivity analyses 2,800-8,200) were averted statewide during the first four months of its implementation. Based on an estimated COVID-19 case fatality of 1.4%, WA Notify saved 40-115 lives during the study period. ConclusionsThese findings demonstrate the value of exposure notification tools as a novel public health intervention to mitigate the spread of COVID-19 in the U.S. As new variants emerge and non-essential travel bans are lifted, exposure notification tools may continue to play a valuable role in limiting the spread of COVID-19.

A retrospective cohort study comparing a novel, spherical, resorbable particle against five established embolic agents for uterine fibroid embolisation.

AIM: To evaluate the effectiveness of a novel, resorbable, spherical embolic agent compared with other established agents, by studying percentage fibroid infarction (the best indicator of long-term symptom improvement) in patients undergoing uterine fibroid embolisation (UFE). MATERIALS AND METHODS: This retrospective cohort study examined six different embolic agents used for fibroid embolisation, including a new gelatin-based, fully resorbable, spherical agent. The primary effectiveness outcomes were magnetic resonance imaging (MRI)-determined dominant fibroid infarct percentage (DF%) and all fibroid percentage infarct (AF%) at 3 months post-embolisation. MRI-determined uterine artery patency rate was the secondary outcome. Chi-squared test (χ2), relative risk (RR) calculation (primary outcomes), and analysis of variance (ANOVA) (secondary outcome) were the statistical tests employed. RESULTS: One hundred and twenty patients were treated with six embolic agents (20 consecutive patients per group, overall mean age 44.8±6.4, initial uterine volume 570±472 ml, dominant fibroid volume 249±324 ml). Fibroid infarctrates were similar between the cohorts with no significant difference between the new gelatin-based resorbable particle and other embolics in either DF% (χ2=3.92, p=0.56) or AF% (χ2=2.83, p=0.73). Complete DF% RR=1.07 (0.90-1.27) and AF% RR=1.09 (0.85-1.41) suggest non-inferiority of the resorbable particle (d=0.67, p<0.05). A favourable uterine artery patency rate was demonstrated for the resorbable particle compared with gelatin slurry (82.5% versus 27.5%, p<0.001 after Bonferroni adjustment). CONCLUSIONS: This new gelatin-based, fully resorbable particle is an effective embolic agent for fibroid embolisation and achieves an infarct rate non-inferior to established embolics.

Outcome choice and definition in systematic reviews leads to few eligible studies included in meta-analyses: a case study.

BACKGROUND: There is broad recognition of the importance of evidence in informing clinical decisions. When information from all studies included in a systematic review ("review") does not contribute to a meta-analysis, decision-makers can be frustrated. Our objectives were to use the field of eyes and vision as a case study and examine the extent to which authors of Cochrane reviews conducted meta-analyses for their review's pre-specified main outcome domain and the reasons that some otherwise eligible studies were not incorporated into meta-analyses. METHODS: We examined all completed systematic reviews published by Cochrane Eyes and Vision, as of August 11, 2017. We extracted information about each review's outcomes and, using an algorithm, categorized one outcome as its "main" outcome. We calculated the percentage of included studies incorporated into meta-analyses for any outcome and for the main outcome. We examined reasons for non-inclusion of studies into the meta-analysis for the main outcome. RESULTS: We identified 175 completed reviews, of which 125 reviews included two or more studies. Across these 125 reviews, the median proportions of studies incorporated into at least one meta-analysis for any outcome and for the main outcome were 74% (interquartile range [IQR] 0-100%) and 28% (IQR 0-71%), respectively. Fifty-one reviews (41%) could not conduct a meta-analysis for the main outcome, mostly because fewer than two included studies measured the outcome (21/51 reviews) or the specific measurements for the outcome were inconsistent (16/51 reviews). CONCLUSIONS: Outcome choice during systematic reviews can lead to few eligible studies included in meta-analyses. Core outcome sets and improved reporting of outcomes can help solve some of these problems.

Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer

Objective@#The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. @*Methods@#We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]). @*Results@#We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43–0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22–1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51–1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers. @*Conclusion@#We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.

Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer

Objective@#The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. @*Methods@#We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]). @*Results@#We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43–0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22–1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51–1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers. @*Conclusion@#We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.

The Systematic Review Data Repository (SRDR): descriptive characteristics of publicly available data and opportunities for research.

BACKGROUND: Conducting systematic reviews ("reviews") requires a great deal of effort and resources. Making data extracted during reviews available publicly could offer many benefits, including reducing unnecessary duplication of effort, standardizing data, supporting analyses to address secondary research questions, and facilitating methodologic research. Funded by the US Agency for Healthcare Research and Quality (AHRQ), the Systematic Review Data Repository (SRDR) is a free, web-based, open-source, data management and archival platform for reviews. Our specific objectives in this paper are to describe (1) the current extent of usage of SRDR and (2) the characteristics of all projects with publicly available data on the SRDR website. METHODS: We examined all projects with data made publicly available through SRDR as of November 12, 2019. We extracted information about the characteristics of these projects. Two investigators extracted and verified the data. RESULTS: SRDR has had 2552 individual user accounts belonging to users from 80 countries. Since SRDR's launch in 2012, data have been made available publicly for 152 of the 735 projects in SRDR (21%), at a rate of 24.5 projects per year, on average. Most projects are in clinical fields (144/152 projects; 95%); most have evaluated interventions (therapeutic or preventive) (109/152; 72%). The most frequent health areas addressed are mental and behavioral disorders (31/152; 20%) and diseases of the eye and ocular adnexa (23/152; 15%). Two-thirds of the projects (104/152; 67%) were funded by AHRQ, and one-sixth (23/152; 15%) are Cochrane reviews. The 152 projects each address a median of 3 research questions (IQR 1-5) and include a median of 70 studies (IQR 20-130). CONCLUSIONS: Until we arrive at a future in which the systematic review and broader research communities are comfortable with the accuracy of automated data extraction, re-use of data extracted by humans has the potential to help reduce redundancy and costs. The 152 projects with publicly available data through SRDR, and the more than 15,000 studies therein, are freely available to researchers and the general public who might be working on similar reviews or updates of reviews or who want access to the data for decision-making, meta-research, or other purposes.

Targeting myeloid-derived suppressor cells in combination with primary mammary tumor resection reduces metastatic growth in the lungs.

BACKGROUND: Solid tumors produce proteins that can induce the accumulation of bone marrow-derived cells in various tissues, and these cells can enhance metastatic tumor growth by several mechanisms. 4T1 murine mammary tumors are known to produce granulocyte colony-stimulating factor (G-CSF) and increase the numbers of immunosuppressive CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs) in tissues such as the spleen and lungs of tumor-bearing mice. While surgical resection of primary tumors decreases MDSC levels in the spleen, the longevity and impact of MDSCs and other immune cells in the lungs after tumor resection have been less studied. METHODS: We used mass cytometry time of flight (CyTOF) and flow cytometry to quantify MDSCs in the spleen, peripheral blood, and lungs of mice bearing orthotopic murine mammary tumors. We also tested the effect of primary tumor resection and/or gemcitabine treatment on the levels of MDSCs, other immune suppressor and effector cells, and metastatic tumor cells in the lungs. RESULTS: We have found that, similar to mice with 4T1 tumors, mice bearing metastatic 4T07 tumors also exhibit accumulation of CD11b+Gr1+ MDSCs in the spleen and lungs, while tissues of mice with non-metastatic 67NR tumors do not contain MDSCs. Mice with orthotopically implanted 4T1 tumors have increased granulocytic (G-) MDSCs, monocytic (M-) MDSCs, macrophages, eosinophils, and NK cells in the lungs. Resection of primary 4T1 tumors decreases G-MDSCs, M-MDSCs, and macrophages in the lungs within 48 h, but significant numbers of functional immunosuppressive G-MDSCs persist in the lungs for 2 weeks after tumor resection, indicative of an environment that can promote metastatic tumor growth. The chemotherapeutic agent gemcitabine depletes G-MDSCs, M-MDSCs, macrophages, and eosinophils in the lungs of 4T1 tumor-bearing mice, and we found that treating mice with gemcitabine after primary tumor resection decreases residual G-MDSCs in the lungs and decreases subsequent metastatic growth. CONCLUSIONS: Our data support the development of therapeutic strategies to target MDSCs and to monitor MDSC levels before and after primary tumor resection to enhance the effectiveness of immune-based therapies and improve the treatment of metastatic breast cancer in the clinic.

A randomized trial provided new evidence on the accuracy and efficiency of traditional vs. electronically annotated abstraction approaches in systematic reviews.

OBJECTIVES: Data Abstraction Assistant (DAA) is a software for linking items abstracted into a data collection form for a systematic review to their locations in a study report. We conducted a randomized cross-over trial that compared DAA-facilitated single-data abstraction plus verification ("DAA verification"), single data abstraction plus verification ("regular verification"), and independent dual data abstraction plus adjudication ("independent abstraction"). STUDY DESIGN AND SETTING: This study is an online randomized cross-over trial with 26 pairs of data abstractors. Each pair abstracted data from six articles, two per approach. Outcomes were the proportion of errors and time taken. RESULTS: Overall proportion of errors was 17% for DAA verification, 16% for regular verification, and 15% for independent abstraction. DAA verification was associated with higher odds of errors when compared with regular verification (adjusted odds ratio [OR] = 1.08; 95% confidence interval [CI]: 0.99-1.17) or independent abstraction (adjusted OR = 1.12; 95% CI: 1.03-1.22). For each article, DAA verification took 20 minutes (95% CI: 1-40) longer than regular verification, but 46 minutes (95% CI: 26 to 66) shorter than independent abstraction. CONCLUSION: Independent abstraction may only be necessary for complex data items. DAA provides an audit trail that is crucial for reproducible research.

Simultaneous proton resonance frequency shift thermometry and T1 measurements using a single reference variable flip angle T1 method.

PURPOSE: Implement simultaneous proton resonance frequency (PRF) shift and T1 measurements with equivalent temporal resolution using a single reference variable flip angle method. This novel method allows for simultaneous thermometry in both aqueous and fatty tissue. METHODS: This method acquires a single reference image at the lower flip angle and all dynamic images at the higher angle. T1 is calculated using a single reference variable flip angle method, which accounts for the reference image temperature remaining constant. Monte Carlo simulations determined the optimal dynamic flip angle for combined PRF and T1 measurements. This method was evaluated in MR-guided focused ultrasound heating experiments using a gelatin phantom and human cadaver breasts. In vivo measurement precision was demonstrated in healthy female volunteers under nonheating conditions. RESULTS: Temperature rise during MR-guided focused ultrasound heating was measured in aqueous tissue with both PRF and T1 . Both measures show good qualitative agreement in both space and time in aqueous tissue. The T1 change due to temperature increase was measured in fat, demonstrating the expected temporal response. The dynamic flip angle that produces optimal SNR for PRF measurements is lower than the optimal angle for T1 measurements, necessitating the selection of a compromise angle. CONCLUSION: The single reference variable flip angle method provides a reliable way to simultaneously measure PRF temperature and T1 change and overcomes PRF's inability to simultaneously monitor temperature in aqueous and adipose tissues. Future work will calibrate T1 change to temperature, enabling real-time temperature in fat and increasing patient safety and treatment efficacy during thermal interventional treatments.

Effect of k-space-weighted image contrast and ultrasound focus size on the accuracy of proton resonance frequency thermometry.

PURPOSE: To construct a predictive model that describes how the duration and symmetry of a k-space-weighted image contrast (KWIC) window affects the temporal resolution of differently sized ultrasound foci when using a pseudo-golden angle stack-of-stars acquisition. METHODS: We performed a modulation analysis of proton resonance frequency temperature measurements to create the temporal modulation transfer function for KWIC windows of different symmetry and temporal duration. We reconstructed simulated ultrasound heating trajectories and stack-of-stars k-space data as well as experimental phantom data using the same trajectories. Images were reconstructed using symmetric and asymmetric KWIC windows of 3 different temporal durations. Simulated results were compared against temporal modulation transfer function predictions, experimental results, and the original simulated temperatures. RESULTS: The temporal modulation transfer function shows that temporal resolution with KWIC reconstructions depend on the object size. The KWIC window duration affected SNR and severity of undersampling artifacts. Accuracy and response delay improved as the KWIC window duration decreased or the size of the heated region within the KWIC plane increased. Precision worsened as the window duration decreased. Using a symmetric window eliminated the response delay to heated region size but introduced a large reconstruction delay. CONCLUSION: The accuracy and precision of proton resonance frequency temperature measurements from a stack-of-stars acquisition using a sliding KWIC window reconstruction are dependent on the size of the KWIC window and the size and shape of the heated region. The temporal modulation transfer function of KWIC reconstructions for any object size can predict the temporal response to changes in signal being acquired, such as temperature and contrast enhancement.