Autosomal Dominant Polycystic Kidney Disease: Role of Imaging in Diagnosis and Management.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder with progressive renal function decline, and disease severity is determined based on the type of genetic mutation. The diagnosis is usually established at imaging, primarily at US, and is based on age-dependent criteria and the number of visible cysts. ADPKD is classified into class 1 (typical) and class 2 (atypical) according to the Mayo Clinic Imaging Classification (MCIC) system. Height-adjusted total kidney volume (TKV) has emerged as a predictor of future renal function decline and renal failure in ADPKD, and several methods can be used for estimation. MCIC class 1 ADPKD is further subdivided into five types based on height-adjusted TKV (A, B, C, D, and E). Patients with a larger height-adjusted TKV (ie, MCIC 1C-E) are at high risk for progression to end-stage renal disease and will potentially benefit from vasopressin receptor antagonists, which have been shown to reduce the rate of cyst growth and slow renal function decline. Other renal complications primarily relate to hemorrhage within cysts or cyst infections. Subtraction images are key for assessment of complex cysts when malignancy is suspected, as the presence of protein and blood can limit the assessment for an enhancing component. The radiologist has a central role in establishing a diagnosis, excluding mimics, identifying complications, assessing severity, and predicting future renal failure. Interventional radiologists play a therapeutic role in management of complications by cyst drainage, sclerotherapy, or embolization. © RSNA, 2022 Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Thoracic imaging tests for the diagnosis of COVID-19.

BACKGROUND: Our March 2021 edition of this review showed thoracic imaging computed tomography (CT) to be sensitive and moderately specific in diagnosing COVID-19 pneumonia. This new edition is an update of the review. OBJECTIVES: Our objectives were to evaluate the diagnostic accuracy of thoracic imaging in people with suspected COVID-19; assess the rate of positive imaging in people who had an initial reverse transcriptase polymerase chain reaction (RT-PCR) negative result and a positive RT-PCR result on follow-up; and evaluate the accuracy of thoracic imaging for screening COVID-19 in asymptomatic individuals. The secondary objective was to assess threshold effects of index test positivity on accuracy. SEARCH METHODS: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, The Stephen B. Thacker CDC Library, and repositories of COVID-19 publications through to 17 February 2021. We did not apply any language restrictions. SELECTION CRITERIA: We included diagnostic accuracy studies of all designs, except for case-control, that recruited participants of any age group suspected to have COVID-19. Studies had to assess chest CT, chest X-ray, or ultrasound of the lungs for the diagnosis of COVID-19, use a reference standard that included RT-PCR, and report estimates of test accuracy or provide data from which we could compute estimates. We excluded studies that used imaging as part of the reference standard and studies that excluded participants with normal index test results. DATA COLLECTION AND ANALYSIS: The review authors independently and in duplicate screened articles, extracted data and assessed risk of bias and applicability concerns using QUADAS-2. We presented sensitivity and specificity per study on paired forest plots, and summarized pooled estimates in tables. We used a bivariate meta-analysis model where appropriate. MAIN RESULTS: We included 98 studies in this review. Of these, 94 were included for evaluating the diagnostic accuracy of thoracic imaging in the evaluation of people with suspected COVID-19. Eight studies were included for assessing the rate of positive imaging in individuals with initial RT-PCR negative results and positive RT-PCR results on follow-up, and 10 studies were included for evaluating the accuracy of thoracic imaging for imagining asymptomatic individuals. For all 98 included studies, risk of bias was high or unclear in 52 (53%) studies with respect to participant selection, in 64 (65%) studies with respect to reference standard, in 46 (47%) studies with respect to index test, and in 48 (49%) studies with respect to flow and timing. Concerns about the applicability of the evidence to: participants were high or unclear in eight (8%) studies; index test were high or unclear in seven (7%) studies; and reference standard were high or unclear in seven (7%) studies. Imaging in people with suspected COVID-19 We included 94 studies. Eighty-seven studies evaluated one imaging modality, and seven studies evaluated two imaging modalities. All studies used RT-PCR alone or in combination with other criteria (for example, clinical signs and symptoms, positive contacts) as the reference standard for the diagnosis of COVID-19. For chest CT (69 studies, 28285 participants, 14,342 (51%) cases), sensitivities ranged from 45% to 100%, and specificities from 10% to 99%. The pooled sensitivity of chest CT was 86.9% (95% confidence interval (CI) 83.6 to 89.6), and pooled specificity was 78.3% (95% CI 73.7 to 82.3). Definition for index test positivity was a source of heterogeneity for sensitivity, but not specificity. Reference standard was not a source of heterogeneity. For chest X-ray (17 studies, 8529 participants, 5303 (62%) cases), the sensitivity ranged from 44% to 94% and specificity from 24 to 93%. The pooled sensitivity of chest X-ray was 73.1% (95% CI 64. to -80.5), and pooled specificity was 73.3% (95% CI 61.9 to 82.2). Definition for index test positivity was not found to be a source of heterogeneity. Definition for index test positivity and reference standard were not found to be sources of heterogeneity. For ultrasound of the lungs (15 studies, 2410 participants, 1158 (48%) cases), the sensitivity ranged from 73% to 94% and the specificity ranged from 21% to 98%. The pooled sensitivity of ultrasound was 88.9% (95% CI 84.9 to 92.0), and the pooled specificity was 72.2% (95% CI 58.8 to 82.5). Definition for index test positivity and reference standard were not found to be sources of heterogeneity. Indirect comparisons of modalities evaluated across all 94 studies indicated that chest CT and ultrasound gave higher sensitivity estimates than X-ray (P = 0.0003 and P = 0.001, respectively). Chest CT and ultrasound gave similar sensitivities (P=0.42). All modalities had similar specificities (CT versus X-ray P = 0.36; CT versus ultrasound P = 0.32; X-ray versus ultrasound P = 0.89). Imaging in PCR-negative people who subsequently became positive For rate of positive imaging in individuals with initial RT-PCR negative results, we included 8 studies (7 CT, 1 ultrasound) with a total of 198 participants suspected of having COVID-19, all of whom had a final diagnosis of COVID-19. Most studies (7/8) evaluated CT. Of 177 participants with initially negative RT-PCR who had positive RT-PCR results on follow-up testing, 75.8% (95% CI 45.3 to 92.2) had positive CT findings. Imaging in asymptomatic PCR-positive people For imaging asymptomatic individuals, we included 10 studies (7 CT, 1 X-ray, 2 ultrasound) with a total of 3548 asymptomatic participants, of whom 364 (10%) had a final diagnosis of COVID-19. For chest CT (7 studies, 3134 participants, 315 (10%) cases), the pooled sensitivity was 55.7% (95% CI 35.4 to 74.3) and the pooled specificity was 91.1% (95% CI 82.6 to 95.7). AUTHORS' CONCLUSIONS: Chest CT and ultrasound of the lungs are sensitive and moderately specific in diagnosing COVID-19. Chest X-ray is moderately sensitive and moderately specific in diagnosing COVID-19. Thus, chest CT and ultrasound may have more utility for ruling out COVID-19 than for differentiating SARS-CoV-2 infection from other causes of respiratory illness. The uncertainty resulting from high or unclear risk of bias and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results.

The SGLT2 inhibitor empagliflozin reduces mortality and prevents progression in experimental pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a rare, but progressive and devastating vascular disease with few treatment options to prevent the advancement to right ventricular dysfunction hypertrophy and failure. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion as well as reduces cardiovascular events and mortality in individuals with type 2 diabetes. While empagliflozin has been reported to lower systemic hypertension due to increased diuresis, the effect of empagliflozin on PAH is unknown. We used monocrotaline (MCT)-treated Sprague-Dawley rats to determine if empagliflozin alters PAH-associated outcomes. Compared to vehicle control, daily empagliflozin administration significantly improved survival in rats with severe MCT-induced PAH. Hemodynamic assessments showed that empagliflozin treatment significantly reduced mean pulmonary artery pressure, right ventricular systolic pressure, and increased pulmonary acceleration time. Empagliflozin treatment resulted in reduced right ventricular hypertrophy and fibrosis. Histological and molecular assessments of lung vasculature revealed significantly reduced medial wall thickening and decreased muscularization of pulmonary arterioles after empagliflozin treatment compared to vehicle-treated rats. In summary, SGLT2 inhibition with empagliflozin lowered mortality, reduced right ventricle systolic pressure, and attenuated maladaptive pulmonary remodeling in MCT-induced PAH. Clinical studies evaluating the efficacy of SGLT-2 inhibition should be considered for patients with PAH.

Empagliflozin improves cardiorespiratory fitness in type 2 diabetes: translational implications.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to prevent heart failure and reduce cardiovascular death in patients with type 2 diabetes (T2DM) and cardiovascular disease (CVD). Whether or not SGLT2 inhibitors improve indices of cardiorespiratory fitness (CRF), an independent predictor of mortality in patients with CVD, remains unknown. We evaluated the effects of empagliflozin on indices of CRF in patients with T2DM. Twenty patients with T2DM received either empagliflozin 10 mg or usual care. Baseline and 3- to 6-month post-treatment measurements of CRF were evaluated using cardiopulmonary exercise testing on a cycle ergometer. Treatment with empagliflozin led to an increased peak oxygen consumption (VO2), reduction in VE/VCO2 slope, and improvement in heart rate recovery. Our results suggest that SGLT2 inhibitors may improve markers of CRF in patients with T2DM. This may help provide important clues into the mechanism of benefit of SGLT2 inhibitors in clinical trials and provide a translational framework for the ongoing large studies of SGLT2 inhibitors in the treatment of heart failure.

A global profile of glucose-sensitive endothelial-expressed long non-coding RNAs.

Hyperglycemia-related endothelial dysfunction is believed to be the crux of diabetes-associated micro- and macro-vascular complications. We conducted a systematic transcriptional survey to screen for human endothelial long non-coding RNAs (lncRNAs) regulated by elevated glucose levels. lncRNAs and protein-coding transcripts from human umbilical vein endothelial cells (HUVECs) cultured under high (25 mmol/L) or normal (5 mmol/L) glucose conditions for 24 h were profiled with the Arraystar Human LncRNA Expression Microarray V3.0. Of the 30 586 lncRNAs screened, 100 were significantly upregulated and 186 appreciably downregulated (P < 0.05) in response to high-glucose exposure. In the same HUVEC samples, 133 of the 26 109 mRNAs screened were upregulated and 166 downregulated. Of these 299 differentially expressed mRNAs, 26 were significantly associated with 28 differentially expressed long intergenic non-coding RNAs (P < 0.05). Bioinformatics analyses indicated that the mRNAs most upregulated are primarily enriched in axon guidance signaling pathways; those most downregulated are notably involved in pathways targeting vascular smooth muscle cell contraction, dopaminergic signaling, ubiquitin-mediated proteolysis, and adrenergic signaling. This is the first lncRNA and mRNA transcriptome profile of high-glucose-mediated changes in human endothelial cells. These observations may prove novel insights into novel regulatory molecules and pathways of hyperglycemia-related endothelial dysfunction and, accordingly, diabetes-associated vascular disease.

Dual Energy CT Physics-A Primer for the Emergency Radiologist.

Dual energy CT (DECT) refers to the acquisition of CT images at two energy spectra and can provide information about tissue composition beyond that obtainable by conventional CT. The attenuation of a photon beam varies depends on the atomic number and density of the attenuating material and the energy of the incoming photon beam. This differential attenuation of the beam at varying energy levels forms the basis of DECT imaging and enables separation of materials with different atomic numbers but similar CT attenuation. DECT can be used to detect and quantify materials like iodine, calcium, or uric acid. Several post-processing techniques are available to generate virtual non-contrast images, iodine maps, virtual mono-chromatic images, Mixed or weighted images and material specific images. Although initially the concept of dual energy CT was introduced in 1970, it is only over the past two decades that it has been extensively used in clinical practice owing to advances in CT hardware and post-processing capabilities. There are numerous applications of DECT in Emergency radiology including stroke imaging to differentiate intracranial hemorrhage and contrast staining, diagnosis of pulmonary embolism, characterization of incidentally detected renal and adrenal lesions, to reduce beam and metal hardening artifacts, in identification of uric acid renal stones and in the diagnosis of gout. This review article aims to provide the emergency radiologist with an overview of the physics and basic principles of dual energy CT. In addition, we discuss the types of DECT acquisition and post processing techniques including newer advances such as photon-counting CT followed by a brief discussion on the applications of DECT in Emergency radiology.

Trends in elective and ruptured abdominal aortic aneurysm repair by practice setting in Ontario, Canada, from 2003 to 2016: a population-based time-series analysis.

BACKGROUND: Recent years have seen centralization of vascular surgery services in Ontario. We sought to examine the trends in overall and approach-specific elective and ruptured abdominal aortic aneurysm repair by hospital type (teaching v. community). METHODS: We conducted a population-based time-series analysis of elective and ruptured abdominal aortic aneurysm repairs in Ontario, Canada, from 2003 to 2016. Quarterly cumulative incidences of repairs per 100 000 Ontarians aged 40 years and older were calculated. We fit exponential smoothing models to the data stratified by approach and hospital type to examine repair trends. RESULTS: We identified 19 219 elective and 2722 ruptured repairs between 2003 and 2016. The cumulative incidences of overall elective repair and elective open surgical repair decreased by 1.15% (p = 0.008) and 67% (p < 0.001), respectively, in teaching hospitals and by 23% (p < 0.001) and 60% (p < 0.001), respectively, in community hospitals. The cumulative incidence of elective endovascular repair increased 667% in teaching hospitals (p < 0.001). Elective endovascular repair began in community centres after 2010 and increased to 0.98/100 000 (p < 0.001), resulting in a rebound in overall elective repair in the community. Overall ruptured repairs and ruptured open repairs decreased by 84% (p < 0.001) and 88% (p = 0.002), respectively, at community hospitals. Ruptured endovascular repairs at community hospitals increased from no procedures before 2006 to 0.03/100 000 in 2016 (p = 0.005). INTERPRETATION: There has been substantial uptake of endovascular aortic repair in teaching and community hospitals in Ontario, and community hospital uptake of endovascular repair has begun decentralization of abdominal aortic aneurysm repair. Increased experience and training in endovascular repair and reduced specialized care requirements will probably lead to continued decentralization.

SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus.

Hess et al. quantified circulating aldehyde dehydrogenase-expressing (ALDHhi) cell subsets in people with T2DM given either empagliflozin (EMPA) or placebo. EMPA treatment increased circulating pro-angiogenic CD133+ progenitor cells, decreased pro-inflammatory ALDHhi granulocyte precursors, and increased ALDHhi monocytes with M2 polarization. EMPA treatment improved T2DM-associated "regenerative cell depletion" contributing to enhanced vascular health.