Citations

Abstract Purpose Using electrocardiogram (ECG) interpretation as an example of a widely taught diagnostic skill, the authors conducted a systematic review and meta-analysis to demonstrate how research evidence on instruction in diagnosis can be synthesized to facilitate improvement of educational activities (instructional modalities, instructional methods, and interpretation approaches), guide the content and specificity of such activities, and provide direction for research. Method The authors searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, PsycInfo, CINAHL, ERIC, and Web of Science databases through February 21, 2020, for empirical investigations of ECG interpretation training enrolling medical students, residents, or practicing physicians. They appraised study quality with the Medical Education Research Study Quality Instrument and pooled standardized mean differences (SMDs) using random effects meta-analysis. Results Of 1,002 articles identified, 59 were included (enrolling 17,251 participants). Among 10 studies comparing instructional modalities, 8 compared computer-assisted and face-to-face instruction, with pooled SMD 0.23 (95% CI, 0.09, 0.36) indicating a small, statistically significant difference favoring computer-assisted instruction. Among 19 studies comparing instructional methods, 5 evaluated individual versus group training (pooled SMD −0.35 favoring group study [95% CI, −0.06, −0.63]), 4 evaluated peer-led versus faculty-led instruction (pooled SMD 0.38 favoring peer instruction [95% CI, 0.01, 0.74]), and 4 evaluated contrasting ECG features (e.g., QRS width) from 2 or more diagnostic categories versus routine examination of features within a single ECG or diagnosis (pooled SMD 0.23 not significantly favoring contrasting features [95% CI, −0.30, 0.76]). Eight studies compared ECG interpretation approaches, with pooled SMD 0.92 (95% CI, 0.48, 1.37) indicating a large, statistically significant effect favoring more systematic interpretation approaches. Conclusions Some instructional interventions appear to improve learning in ECG interpretation; however, many evidence-based instructional strategies are insufficiently investigated. The findings may have implications for future research and design of training to improve skills in ECG interpretation and other types of visual diagnosis.

Abstract Molecular drivers of metastasis in patients with high-risk localized prostate cancer are poorly understood. Therefore, we aim to study molecular drivers of metastatic progression in patients with high-risk prostate cancer. A retrospective matched case-control study of two clinico-pathologically identical groups of patients with high-risk prostate cancer was undertaken. One group developed metastatic recurrence (n = 19) while the other did not (n = 25). The primary index tumor was identified by a uro-pathologist, followed by DNA and RNA extraction for somatic copy-number aberration (SCNA) analysis and whole-transcriptome gene expression analysis. In vitro and in vivo studies included cell line manipulation and xenograft models. The integrative CNA and gene expression analyses identified an increase in Antizyme Inhibitor 1 (AZIN1) gene expression within a focal amplification of 8q22.3, which was associated with metastatic recurrence of patients with high-risk prostate cancer in four independent cohorts. The effects of AZIN1 knockdown were evaluated, due to its therapeutic potential. AZIN1 knockdown effected proliferation and metastatic potential of prostate cancer cells and xenograft models. RNA sequencing after AZIN1 knockdown in prostate cancer cells revealed upregulation of genes coding for collagen subunits. The observed effect on cell migration after AZIN1 knockdown was mimicked when exposing prostate cancer cells to bio-active molecules deriving from COL4A1 and COL4A2. Our integrated CNA and gene expression analysis of primary high-risk prostate cancer identified the AZIN1 gene as a novel driver of metastatic progression, by altering collagen subunit expression. Future research should further investigate its therapeutic potential in preventing metastatic recurrence. Implications: AZIN1 was identified as driver of metastatic progression in high-risk prostate cancer through matrikine regulation.

11 Background: Six months of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) remains a standard in high-risk stage III patients. Early treatment discontinuation (ETD) could worsen the prognosis. In addition, there is current lack of data on the prognostic impact of early oxaliplatin only discontinuation (EOD). Methods: We studied the prognostic impact of ETD and EOD in patients with stage III CC who participated in 11 relevant clinical trials of the ACCENT and IDEA databases, where patients were planned to receive 6 months of adjuvant fluoropyrimidine plus oxaliplatin (FOLFOX or CAPOX). ETD was defined as discontinuation of treatment before 75% of cycles of chemotherapy. EOD was defined as discontinuation of oxaliplatin only, while continuing the fluoropyrimidine, before 75% of cycles of oxaliplatin. Association between ETD/EOD and overall survival (OS) and disease-free survival (DFS) was assessed by Cox model adjusted for prognostic factors. Results: ETD analysis included 10,444 patients (FOLFOX n = 7,033; CAPOX n = 3,411), with 20.9% of patients with ETD (17.8% with FOLFOX and 27.2% with CAPOX, p < 0.001). Out of 7,243 patients, 18.8% experienced EOD (17.4% FOLFOX versus 21.4% with CAPOX, p < 0.001). Compared to patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, older, with higher ECOG-PS ≥ 1, and in addition for ETD, a Body Mass Index (BMI) < 18.5 kg/m2. In multivariate analyses, ETD was associated with a decrease in DFS and OS in the overall population (HR: 1.40 95%CI 1.23-1.58, p < 0.001 and HR: 1.51 95%CI 1.31-1.74, p < 0.001, respectively). The same pattern was present with FOLFOX and CAPOX regimen, and also in low-risk and high-risk groups for each regimen with the exception of the CAPOX regimen in the low-risk group for DFS and OS. By contrast, EOD was not associated with reduced DFS or OS in the overall population (HR: 1.10 95%CI 0.77-1.58, p = 0.6 and HR: 0.97 95%CI 0.62-1.52, p = 0.9, respectively), in the low-risk group (HR: 0.97 95%CI 0.56-1.66, p = 0.9 and HR: 0.97 95%CI 0.51-1.82, p = 0.9, respectively) and high-risk group (HR: 1.22 95%CI 0.74-2.02, p = 0.4 and HR: 1.05 95%CI 0.53-2.08, p = 0.9, respectively) and for all subgroups of regimen. Conclusions: In patients treated with 6 months of oxaliplatin-based adjuvant chemotherapy for stage III CC, ETD was associated with a decrease in DFS and OS. By contrast, EOD was not significantly associated with poorer outcomes. In case of relevant neurotoxicity during a 6 months schedule, these data are not in favor of continuing oxaliplatin beyond 75% of planned cycles of adjuvant chemotherapy, and demonstrate that fluoropyrimidines remain the cornerstone of adjuvant chemotherapy in localized CC.

AbstractObjectiveQuantifying the degree of dorsal hand atrophy is a challenging endeavor, but often necessary, in both the clinical and the research setting. The aim of this investigation was to create and consecutively validate a 5‐point photonumeric scale for assessment of dorsal hand atrophy.Material and MethodsA medical team created a novel 5‐point photonumeric scale. Twelve international raters were involved in the digital validation, while five raters performed a live validation.ResultsFor the digital validation of the Croma Hand Atrophy Assessment Scale, a total of 72 subjects (58 females, 14 males) with a mean age of 43.0 ± 14.4 years [18–73 years] were assessed. For the live validation, 88 subjects (73 females, 15 males) with a mean age of 45.0 ± 14.1 years [20–73 years] were rated. The results revealed almost perfect intra‐rater (ICC: 0.90 [95% CI: 0.88–0.92]) and inter‐rater agreements (ICC: 0.85 [95% CI: 0.81–0.89] and 0.86 [95% CI:0.82–0.89]) in the digital validation and substantial intra‐rater (ICC: 0.79 [95% CI: 0.75–0.82]) and inter‐rater agreements (ICC: 0.75 [95% CI: 0.68–0.81] and ICC: 0.67 [95% CI: 0.54–0.77]) in the live validation.ConclusionThe created scale to assess dorsal hand atrophy has been shown to provide substantial‐to‐almost perfect agreement in the digital and live validation cycles and reached comparable intra‐rater and inter‐rater agreement to already published and validated scales. It is expected that the created scale will help physicians and researchers in the assessment of hand atrophy in the clinical and research setting in the future.

AbstractModern fluoroscopes used for image guidance have become quite complex. Adding to this complexity are the many regulatory and accreditation requirements that must be fulfilled during acceptance testing of a new unit. Further, some of these acceptance tests have pass/fail criteria, whereas others do not, making acceptance testing a subjective and time‐consuming task. The AAPM Task Group 272 Report spells out the details of tests that are required and gives visibility to some of the tests that while not yet required are recommended as good practice. The organization of the report begins with the most complicated fluoroscopes used in interventional radiology or cardiology and continues with general fluoroscopy and mobile C‐arms. Finally, the appendices of the report provide useful information, an example report form and topics that needed their own section due to the level of detail.

Abstract: The ability of virally suppressive antiretroviral therapy use to extend the life span of people with HIV (PWH) implies that the age of PWH will also increase. Among PWH, extended survival comes at a cost of earlier onset and increased rates of aging-associated comorbidities and geriatric syndromes, with persistent inflammation and immune dysregulation consequent to chronic HIV infection and to antiretroviral therapy use contributing to an overall decrease in health span. The geroscience hypothesis proposes that the root causes of most aging-related chronic diseases and conditions is the aging process itself. Hence, therapeutically targeting fundamental aging processes could have a greater impact on alleviating or delaying aging-associated comorbidities than addressing each disease individually. Extending the geroscience hypothesis to PWH, we speculate that targeting basic mechanisms of aging will improve overall health with age. Clinical features and pathophysiologic mechanisms of chronic diseases in PWH qualitatively resemble those seen in older adults without HIV. Therefore, drugs that target any of the pillars of aging, including metformin, rapamycin, and nicotinamide adenine dinucleotide precursors, may also slow the rate of onset of age-associated comorbidities and geriatric syndromes in PWH. Drugs that selectively induce apoptosis of senescent cells, termed senolytics, may also improve health span among PWH. Preliminary evidence suggests that senescent cell burden is increased in PWH, implying that senescent cells are an excellent therapeutic target for extending health span. Recently initiated clinical trials evaluating senolytics in age-related diseases offer insights into the design and potential implementation of similar trials for PWH.

Background: Novel imaging methods have provided new insights into the layered anatomy of the forehead. This study seeks to critically reevaluate the layered anatomy of the forehead by using ultrasound imaging and cadaveric dissection to provide an accurate anatomical description that can be used to guide safer surgical and minimally invasive frontal procedures. Methods: This study used ultrasound imaging in a sample of 20 volunteers (12 female and eight male volunteers; aged 35.25 ± 4.2 years; body mass index, 24.28 ± 3.5 kg/m2) and cadaveric dissections of 16 body donors (12 female and four male body donors; aged 72.76 ± 9.5 years) to reevaluate the layered anatomy of the forehead. Layer-by-layer dissections and ultrasound-based measurements of the frontal structures guided conclusions. Results: The following layered arrangement was identified: layer 1, skin; layer 2, superficial fatty layer; layer 3, suprafrontalis fascia; layer 4, orbicularis oculi and frontalis muscle (same plane); layer 5, a homogenous layer of fat [preseptal fat (in the upper eyelid), retro-orbicularis fat (deep to the orbicularis oculi muscle), and retro-frontalis fat (deep to the frontalis muscle); layer 6, subfrontalis fascia; layer 7, preperiosteal fat within the prefrontal space in the lower forehead and deep compartments in the upper forehead; and layer 8, periosteum. Conclusions: The results of this study add to the current understanding of the layered arrangement of the forehead. The combination of ultrasound imaging and cadaveric dissections provided evidence for a continuous fatty layer deep to the frontalis muscle.

BackgroundPreferential publication of studies with positive findings can lead to overestimation of diagnostic test accuracy (i.e. publication bias). Understanding the contribution of the editorial process to publication bias could inform interventions to optimize the evidence guiding clinical decisions.Purpose/HypothesisTo evaluate whether accuracy estimates, abstract conclusion positivity, and completeness of abstract reporting are associated with acceptance to radiology conferences and journals.Study TypeMeta‐research.PopulationAbstracts submitted to radiology conferences (European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and International Society for Magnetic Resonance in Medicine (ISMRM)) from 2008 to 2018 and manuscripts submitted to radiology journals (Radiology, Journal of Magnetic Resonance Imaging [JMRI]) from 2017 to 2018. Primary clinical studies evaluating sensitivity and specificity of a diagnostic imaging test in humans with available editorial decisions were included.AssessmentPrimary variables (Youden's index [YI > 0.8 vs. <0.8], abstract conclusion positivity [positive vs. neutral/negative], number of reported items on the Standards for Reporting of Diagnostic Accuracy Studies [STARD] for Abstract guideline) and confounding variables (prospective vs. retrospective/unreported, sample size, study duration, interobserver agreement assessment, subspecialty, modality) were extracted.Statistical TestsMultivariable logistic regression to obtain adjusted odds ratio (OR) as a measure of the association between the primary variables and acceptance by radiology conferences and journals; 95% confidence intervals (CIs) and P‐values were obtained; the threshold for statistical significance was P < 0.05.ResultsA total of 1000 conference abstracts (500 ESGAR and 500 ISMRM) and 1000 journal manuscripts (505 Radiology and 495 JMRI) were included. Conference abstract acceptance was not significantly associated with YI (adjusted OR = 0.97 for YI > 0.8; CI = 0.70–1.35), conclusion positivity (OR = 1.21 for positive conclusions; CI = 0.75–1.90) or STARD for Abstracts adherence (OR = 0.96 per unit increase in reported items; CI = 0.82–1.18). Manuscripts with positive abstract conclusions were less likely to be accepted by radiology journals (OR = 0.45; CI = 0.24–0.86), while YI (OR = 0.85; CI = 0.56–1.29) and STARD for Abstracts adherence (OR = 1.06; CI = 0.87–1.30) showed no significant association. Positive conclusions were present in 86.7% of submitted conference abstracts and 90.2% of journal manuscripts.Data ConclusionDiagnostic test accuracy studies with positive findings were not preferentially accepted by the evaluated radiology conferences or journals.Evidence Level3Technical EfficacyStage 2.

AbstractBackgroundPrior evidence has suggested associations between hearing loss and smaller brain volumes particularly in the temporal lobe where the primary auditory cortex is located, probably due to changes in cortical organization associated with reduced auditory stimulation. Evidence regarding associations of central auditory processing with brain volumes is relatively limited. The study aims to investigate cross‐sectional associations of central auditory processing with brain volumes in older adults.MethodWe studied 587 cognitively normal (Mini‐Mental State Exam ≥23 if high school degree or less and ≥25 if above high school degree) older adults (mean age: 77±4 years, 56% female, 17% black), including 426 with hearing loss from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) baseline (2018‐19), which is an ancillary randomized controlled trial of the Atherosclerosis Risk in Communities (ARIC) Study and 161 with normal hearing, comparable age and cognitive status from the ARIC Visit 6/7 (2016‐17/2018‐19). Brain volumes were measured by magnetic resonance imaging (MRI) scans and were transformed to z‐scores. Central auditory processing was measured by the Quick Speech‐in‐Noise (QuickSIN) test. Total scores range from 0 to 30 with lower scores indicating worse speech‐in‐noise performance. Multivariable‐adjusted linear regression was used to estimate cross‐sectional differences in standardized brain volumes associated with differences in QuickSIN score. Models adjusted for age, sex, race, education, cohort, body mass index, smoking, hypertension, diabetes, stroke, intracranial volume, and pure‐tone average.ResultEvery 5‐point decrease in QuickSIN score (worse performance) was associated with smaller volumes of the temporal lobe (‐0.07SD, 95% CI: ‐0.13, ‐0.01). QuickSIN score was also associated with subregions of the temporal lobe related to auditory processing, memory and emotion, including amygdala (‐0.13SD, 95% CI: ‐0.21, ‐0.04), middle (‐0.08SD, 95% CI: ‐0.15, ‐0.00) and superior temporal gyri (‐0.08SD, 95% CI: ‐0.15, ‐0.01).ConclusionPoorer central auditory processing was associated with smaller temporal lobe volumes, including but not limited to subregions important for auditory processing. The ongoing collection of ACHIEVE data with longitudinal MRI data will facilitate understanding of association between hearing loss and brain atrophy as well as the potential promising effects of hearing treatment in mitigating brain aging.

Patients with decompensated cirrhosis, particularly those with acute‐on‐chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE‐SAFETY randomized, double‐blind, placebo‐controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography–tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan–kynurenine and carnitine beta‐oxidation pathways. An ACLF‐specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan–kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.