The Impact of Mammographic, Radiologist, and Patient Factors on the Likelihood of Probably Benign (BI-RADS 3) Assessment at Diagnostic Mammography.

OBJECTIVE: To evaluate the association of mammographic, radiologist, and patient factors on BI-RADS 3 assessment at diagnostic mammography in patients recalled from screening mammography. METHODS: This Institutional Review Board-approved retrospective study of consecutive unique diagnostic mammography examinations in asymptomatic patients recalled from screening mammography March 5, 2014, to December 31, 2019, was conducted in a single large United States health care institution. Mammographic features (mass, calcification, distortion, asymmetry), breast density, prior examination, and BI-RADS assessment were extracted from reports by natural language processing. Patient age, race, and ethnicity were extracted from the electronic health record. Radiologist years in practice, recall rate, and number of interpreted diagnostic mammograms were calculated. A mixed effect logistic regression model evaluated factors associated with likelihood of BI-RADS 3 compared with other BI-RADS assessments. RESULTS: A total of 12 080 diagnostic mammography examinations were performed during the study period, yielding 2010 (16.6%) BI-RADS 3 and 10 070 (83.4%) other BI-RADS assessments. Asymmetry (odds ratio [OR] = 6.49, P <.001) and calcification (OR = 5.59, P <.001) were associated with increased likelihood of BI-RADS 3 assessment; distortion (OR = 0.20, P <.001), dense breast parenchyma (OR = 0.82, P <.001), prior examination (OR = 0.63, P = .01), and increasing patient age (OR = 0.99, P <.001) were associated with decreased likelihood. Mass, patient race or ethnicity, and radiologist factors were not significantly associated with BI-RADS 3 assessment. Malignancy rate for BI-RADS 3 lesions was 1.6%. CONCLUSION: Asymmetry and calcifications had an increased likelihood of BI-RADS 3 assessment at diagnostic evaluation with low likelihood of malignancy, while radiologist features had no association.

Actionability of Recommendations for Additional Imaging in Head and Neck Radiology.

PURPOSE: The aims of this study were to measure the actionability of recommendations for additional imaging (RAIs) in head and neck CT and MRI, for which there is a near complete absence of best practices or guidelines; to identify the most common recommendations; and to assess radiologist factors associated with actionability. METHODS: All head and neck CT and MRI radiology reports across a multi-institution, multipractice health care system from June 1, 2021, to May 31, 2022, were retrospectively reviewed. The actionability of RAIs was scored using a validated taxonomy. The most common RAIs were identified. Actionability association with radiologist factors (gender, years out of training, fellowship training, practice type) and with trainees was measured using a mixed-effects model. RESULTS: Two hundred nine radiologists generated 60,543 reports, of which 7.2% (n = 4,382) contained RAIs. Only 3.9% of RAIs (170 of 4,382) were actionable. More than 60% of RAIs were for eight examinations: thyroid ultrasound (14.1%), neck CT (12.6%), brain MRI (6.9%), chest CT (6.5%), neck CT angiography (5.5%), temporal bone CT (5.3%), temporal bone MRI (5.2%), and pituitary MRI (4.6%). Radiologists >23 years out of training (odds ratio, 0.39; 95% confidence interval, 0.15-1.02; P = .05) and community radiologists (odds ratio, 0.53; 95% confidence interval, 0.22-1.31; P = .17) had substantially lower estimated odds of making actionable RAIs than radiologists <7 years out of training and academic radiologists, respectively. CONCLUSIONS: The studied radiologists rarely made actionable RAIs, which makes it difficult to identify and track clinically necessary RAIs to timely performance. Multifaceted quality improvement initiatives including peer comparisons, clinical decision support at the time of reporting, and the development of evidence-based best practices, may help improve tracking and timely performance of clinically necessary RAIs.

Recommendations for Additional Imaging on Head and Neck Imaging Examinations: Interradiologist Variation and Associated Factors.

BACKGROUND. A paucity of relevant guidelines may lead to pronounced variation among radiologists in issuing recommendations for additional imaging (RAI) for head and neck imaging. OBJECTIVE. The purpose of this article was to explore associations of RAI for head and neck imaging examinations with examination, patient, and radiologist factors and to assess the role of individual radiologist-specific behavior in issuing such RAI. METHODS. This retrospective study included 39,200 patients (median age, 58 years; 21,855 women, 17,315 men, 30 with missing sex information) who underwent 39,200 head and neck CT or MRI examinations, interpreted by 61 radiologists, from June 1, 2021, through May 31, 2022. A natural language processing (NLP) tool with manual review of NLP results was used to identify RAI in report impressions. Interradiologist variation in RAI rates was assessed. A generalized mixed-effects model was used to assess associations between RAI and examination, patient, and radiologist factors. RESULTS. A total of 2943 (7.5%) reports contained RAI. Individual radiologist RAI rates ranged from 0.8% to 22.0% (median, 7.1%; IQR, 5.2-10.2%), representing a 27.5-fold difference between minimum and a maximum values and 1.8-fold difference between 25th and 75th percentiles. In multivariable analysis, RAI likelihood was higher for CTA than for CT examinations (OR, 1.32), for examinations that included a trainee in report generation (OR, 1.23), and for patients with self-identified race of Black or African American versus White (OR, 1.25); was lower for male than female patients (OR, 0.90); and was associated with increasing patient age (OR, 1.09 per decade) and inversely associated with radiologist years since training (OR, 0.90 per 5 years). The model accounted for 10.9% of the likelihood of RAI. Of explainable likelihood of RAI, 25.7% was attributable to examination, patient, and radiologist factors; 74.3% was attributable to radiologist-specific behavior. CONCLUSION. Interradiologist variation in RAI rates for head and neck imaging was substantial. RAI appear to be more substantially associated with individual radiologist-specific behavior than with measurable systemic factors. CLINICAL IMPACT. Quality improvement initiatives, incorporating best practices for incidental findings management, may help reduce radiologist preference-sensitive decision-making in issuing RAI for head and neck imaging and associated care variation.

Utility of Patient-Reported Risk Factors for Identifying Advanced Chronic Kidney Disease Before Outpatient CT: Comparison With Recent ACR/NKF Consensus Criteria.

BACKGROUND. Practices vary for screening patients for risk of renal dysfunction before administration of iodinated contrast medium. A 2020 American College of Radiology/National Kidney Foundation (ACR/NKF) consensus statement provided streamlined screening criteria. OBJECTIVE. The purpose of this study was to assess the yield of patient-reported risk factors for identifying estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 before outpatient CT. METHODS. This retrospective study was performed at a health system that implemented an electronic screening form for patients to complete before outpatient CT encounters to report undergoing dialysis, taking cancer-treating medications, having kidney disease, undergoing prior kidney surgery, having diabetes mellitus treated with medication, having hypertension treated with medication, or having multiple myeloma. Patients with any risk factor were required to undergo eGFR testing before CT. Of 44,708 patients completing the form from June 1, 2020, through February 28, 2021, 10,256 patients (5315 men, 4941 women; mean age, 66.8 ± 11.9 [SD] years; range, 21-98 years) underwent eGFR testing on the day of CT. Multivariable regression analysis for predicting reduced eGFR was performed. Findings were compared with those from theoretic use of the ACR/NKF criteria. RESULTS. Same-day testing yielded eGFR less than 30 mL/min/1.73 m2 in 1.4% (144/10,256) of patients. The only significant independent predictors of low eGFR were dialysis (odds ratio [OR], 203.30], kidney disease (OR, 12.55), and diabetes mellitus treated with medication (OR, 2.44). If the ACR/NKF criteria (only kidney disease, defined as dialysis, kidney disease, or prior kidney surgery) had been followed as a trigger for eGFR testing, the number of patients needing testing would have decreased 89.7%, from 10,256 to 1059; yield would have increased to 7.2% (76/1059); and 47.2% (68/144) of patients with low eGFR would have been missed. If the ACR/NKF criteria had been followed but diabetes mellitus been considered a required rather than an optional criterion, the number of patients needing testing would have decreased 77.1%, to 2353; yield would have increased to 4.0% (95/2353); and 34.0% (49/144) of patients with low eGFR would have been missed. CONCLUSION. Using patient-reported risk factors resulted in frequent eGFR testing but low yield of low eGFR. Commonly applied risk factors were not independently associated with low eGFR. CLINICAL IMPACT. Application of ACR/NKF criteria would substantially reduce eGFR testing, but patients with renal dysfunction would be missed. The statement should consider omitting kidney surgery as a trigger for eGFR testing and including diabetes mellitus as a required trigger.

The clinical significance of histone deacetylase-8 in human breast cancer.

Recent studies have shown that the histone deacetylase-8 (HDAC8), as one of the HDACs, regulates the expression and activity of various genes involved in cancer initiation and progression. The HDAC8 plays an epigenetic role to dysregulate expressions or to interact with transcription factors. Most researchers had focused on the HDAC 1-3 and 6, but today the HDAC8 isotype is a promising target in cancer therapy. Different studies, on breast cancer (BC) cells, have recently shown the HDAC8 overexpression and suggested its oncogenic potential. It seems that the HDAC8 could be a novel and promising target in breast cancer treatment. Some studies on BC demonstrated therapeutic properties of the inhibitors of HDAC8 such as suberoylanilide hydroxamic acid (SAHA), Trichostatin A, valproic acid, sodium butyrate, 1,3,4 oxadiazole with alanine hybrid [(R)-2-amino-N-((5-phenyl-1,3,4-oxadiazol-2-yl) methyl) propanamide (10b)], N-(2-Hydroxyphenyl)-2propylpentanamide (compound 2) and PCI-34051. In this review, we highlight the role and existing inhibitors of HDAC8 in BC pathogenesis and therapy.

Predicting severity and prognosis in Parkinson's disease from brain microstructure and connectivity.

OBJECTIVES: Investigating biomarkers to demonstrate progression of Parkinson's disease (PD) is of high priority. We investigated the association of brain structural properties with progression of clinical outcomes and their ability to differentiate clinical subtypes of PD. METHODS: A comprehensive set of clinical features was evaluated at baseline and 4.5-year follow-up for 144 de-novo PD patients from the Parkinson's Progression Markers Initiative. We created a global composite outcome (GCO) by combining z-scores of non-motor and motor symptoms, motor signs, overall activities of daily living and global cognition, as a single numeric indicator of prognosis. We classified patients into three subtypes based on multi-domain clinical criteria: 'mild motor-predominant', 'intermediate' and 'diffuse-malignant'. We analyzed diffusion-weighted scans at the early drug-naïve stage and extracted fractional anisotropy and mean diffusivity (MD) of basal ganglia and cortical sub-regions. Then, we employed graph theory to calculate network properties and used network-based statistic to investigate our primary hypothesis. RESULTS: Baseline MD of globus pallidus was associated with worsening of motor severity, cognition, and GCO after 4.5 years of follow-up. Connectivity disruption at baseline was correlated with decline in cognition, and increase in GCO. Baseline MD of nucleus accumbens, globus pallidus and basal-ganglia were linked to clinical subtypes at 4.5-year of follow-up. Disruption in sub-cortical networks associated with being subtyped as 'diffuse-malignant' versus 'mild motor-predominant' after 4.5 years. CONCLUSIONS: Diffusion imaging analysis at the early de-novo stage of PD was able to differentiate clinical sub-types of PD after 4.5 years and was highly associated with future clinical outcomes of PD.

Activation of ATP-sensitive K-channel promotes the anticonvulsant properties of cannabinoid receptor agonist through mitochondrial ATP level reduction.

Cannabinoid receptor (CBR) agonist could act as a protective agent against seizure susceptibility in animal models of epilepsy. Studies have shown that potassium channels could play a key role in ameliorating neuronal excitability. In this study, we attempted to evaluate how CBRs and Adenosine Tri-Phosphate (ATP)-sensitive potassium channels collaborate to affect seizure susceptibility by changing the clonic seizure threshold (CST). We used male Naval Medical Research Institute (NMRI) mice and treated them with the following drugs: cromakalim (a potassium channel opener, 10 µg/kg), glibenclamide (a potassium channel blocker, 0.03 and 1 mg/kg), 0.5 mg/kg of AM-251 (a selective CB1 antagonist), AM-630 (a selective CB2 antagonist), and 0.5, 3, and 10 mg/kg of WIN 55,212-2 (a nonselective agonist of CBRs); and CST was appraised after each type of administration. Also, we evaluated the ATP level of the hippocampus in each treatment to clarify the interaction between the cannabinoid system and potassium channel. Our results showed that administration of WIN 55,212-2 at 10 mg/kg significantly increased CST (P < 0.001). This change could be reversed by using AM-251(P < 0.001) but not AM-630. Also, either cromakalim (10 µg/kg) or glibenclamide (0.03 and 1 mg/kg) could not significantly affect the CST. In addition, glibenclamide (1 mg/kg) could reverse the anticonvulsant effect of WIN 55,212-2 (10 mg/kg) on CST (P < 0.001). However, the anticonvulsant effect was observed when cromakalim (10 µg/kg) was added to WIN 55,212-2 at its subeffective dose (3 mg/kg) in comparison to single-treated animals. Interestingly, we observed that CB1 agonist could significantly decrease ATP level. In conclusion, CB1 agonist accomplishes at least a part of its anticonvulsant actions through ATP-sensitive potassium channels, probably by decreasing the mitochondrial ATP level to open the potassium channel to induce its anticonvulsant effect.