Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention.

The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies including ground-glass opacities, interstitial fibrosis, congested alveoli, and became moribund. Lung tissues from these mice and bronchoalveolar lavage and lung tissues from patients with COVID-19 showed elevated levels of hyaluronic acid (HA), HA-family members, an inflammatory signature, and immune cell infiltration. 4-methylumbelliferone (4-MU), an oral drug for biliary-spasm treatment, inhibits HA-synthesis. At the human equivalent dose, 4-MU prevented/inhibited COVID-19-like pathologies and long-term morbidity; 4-MU and metabolites accumulated in mice lungs. Therefore, these versatile SARS-COV-2 ribo-oligonucleotide oropharyngeal models recapitulate COVID-19 pathology, with HA as its critical mediator and 4-MU as a potential therapeutic for COVID-19.

Analysis of Low Appropriateness Score Exam Trends in Decision Support-based Radiology Order Entry System.

PURPOSE: Awareness of imaging utilization increased after implementation of Radiology Order Entry with decision support systems (ROE-DS). Our hypothesis is few exams with low Clinical Appropriateness Score (CAS) on ROE-DS are performed. Clinical indications of exams with CAS less than 3 (9-point scale) were re-reviewed and reports analyzed. MATERIALS AND METHODS: Structured Query Language-based query retrieved exams with CAS less than 3 in ROE-DS from January 2007 to December 2011. Reasons provided by physicians for ordering these exams and reports of exams performed were analyzed. For each indication, number of exams ordered and performed was calculated. Statistical significance was assessed using Student's t test and χ2 analysis (P < .05). RESULTS: From 445,984 exams, 12,615 exams (2.8%) had CAS less than 3, and 7,956 exams (63%) were performed. Reasons for ordering of 12,615 low CAS exams were as follows: Requests by physician specialists without further explanation (4,516 = 35.8%), notation of special clinical circumstances (2,877 = 22.8%), requests by nonphysician staff without further explanation (1,383 = 10.9%), absence of suspected finding on previous modality (1,099 = 8.7%), patient preference (737 = 5.8%), and requests based on radiologists' recommendations (706 = 5.6%). Difference between male and female (male < female) preferences for low CAS exams was statistically significant (P < .01). Imaging outcome was highest for extremity MRI cases (66.7%; P < .01). CONCLUSION: Less than 3% of exams ordered had low CAS and about two-thirds of these were performed. Most common indication for ordering these exams was physician specialist request based on opinion of medical necessity without specification. Extremity MRI constituted the highest positive findings for low CAS exams performed.

Imaging Practice Patterns: Referral Network Analysis of a Single State of Origination.

PURPOSE: The aim of this study was to examine the referral pattern of imaging studies requested in a single state compared with the potential location of interpretation. METHODS: Analysis of Medicare patients in a DocGraph data set was performed to identify sequential different physician services claims for the same patient for which the second claim was for services provided by a radiologist. RESULTS: In the 2011 Medicare population, radiology referrals from physicians practicing in Georgia resulted in 76.5% of radiology interpretations by radiologists inside the state of Georgia. The states bordering Georgia accounted for 11.6% of interpretations in the Georgia market. The remaining interpretations were distributed throughout the remainder of the country. CONCLUSIONS: A significant proportion of routine imaging interpretation occurs outside the state in which an examination is performed. Additional studies are needed to identify complex drivers of imaging referral patterns, such as patient geographic location and demographics, radiologist workforce distribution, contractual obligations, and social relationships.

BK Nephritis and Venous Thrombosis in Renal Transplant Recipient Detected by 111In Leukocyte Imaging.

Three months after deceased donor kidney transplant, a patient who presented with proteinuric renal dysfunction and fever of undetermined origin was found to have BK viruria by quantitative polymerase chain reaction analysis. An ¹¹¹In leukocyte scan showed increased renal transplant uptake consistent with nephritis and linear uptake in the knee. Venous duplex ultrasound revealed acute occlusive thrombosis in the superficial right lesser saphenous vein in the area of increased radiolabeled leukocyte uptake. This ¹¹¹In leukocyte scan performed for fever of undetermined origin demonstrated findings of BK nephritis in a renal transplant patient and associated acute venous thrombosis related to leukocyte colonization.