Incidence of Contrast-Associated Acute Kidney Injury in Renal-Competent COVID-19 Patients Undergoing Computed Chest Angiography.

PURPOSE: COVID-19 infection poses a significant risk of both renal injury and pulmonary embolism, producing a clinical challenge, as the criterion standard examination for pulmonary embolism, computed tomography angiography (CTA), requires the use of nephrotoxic iodinated contrast agents.Our investigation evaluated whether symptomatic COVID-19-positive patients without laboratory evidence of renal impairment are at increased risk for developing contrast-associated acute kidney injury (CA-AKI). METHOD: All COVID-19-positive patients undergoing noncontrast chest computed tomography and CTA at an apex tertiary medical center between March 1 and December 10, 2020, were retrospectively evaluated. A total of 258 renal-competent (estimated glomerular filtration rate >30) patients with baseline and 48- to 72-hour postexamination creatinine measurements were identified and analyzed for incidence of acute kidney injury (AKI) meeting the criteria for CA-AKI. RESULTS: Twenty-five of 191 patients undergoing CTA (13.1%) and 9 of the 67 undergoing noncontrast computed tomography (13.4%) experienced creatinine increases meeting the criteria for CA-AKI. Univariate and multivariate analyses accounting for known AKI risk factors revealed no correlation between iodinated contrast administration and the incidence AKI meeting the criteria for CA-AKI (univariable odds ratio, 0.97 [95% confidence interval, 0.43-2.20]; multivariable odds ratio, 0.97 [95% confidence interval, 0.40-2.36]). CONCLUSIONS: Renal-competent COVID-19 patients undergoing chest CTA may not have an increased risk of AKI. Additional studies are needed to confirm this preliminary finding.

p16 immunohistochemistry for primary tumor detection in HPV-positive squamous cell carcinoma of unknown primary.

PURPOSE: To examine the potential benefit of reevaluation of original slides and p16 immunohistochemistry (IHC) of tonsillectomy specimens for primary tumor identification in cases of human papillomavirus (HPV) positive squamous cell carcinoma (SCC) of the head and neck of unknown primary. MATERIALS AND METHODS: Through a retrospective review, we identified all patients 18 or older who presented at our institution from 2003 to 2015 with histologically confirmed HPV-positive SCC in a cervical lymph node with unidentified primary tumor after initial workup. For patients for whom specimens were available, an expert head and neck pathologist re-reviewed original hematoxylin and eosin (H&E) slides to confirm absence of tumor and performed p16 IHC and deep sectioning of tissue blocks to identify potential tumor foci. RESULTS: Among 735 patient records assessed, 80 were HPV-positive SCC with unknown primary, 28 of which did not have a primary tumor identified, and 20 with original specimens available. Upon re-review of 103 original H&E slides, invasive SCC was identified for 2 patients. Deep sectioning and p16 IHC did not identify additional primary tumors. CONCLUSION: Re-review of original slides by an expert head and neck pathologist, but not p16 staining or deeper H&E sections, was able to identify additional tumors.

Brg1 determines urothelial cell fate during ureter development.

Developing and adult ureters express the epigenetic regulator Brg1, but the role of Brg1 in ureter development is not well understood. We conditionally ablated Brg1 in the developing ureter using Hoxb7-Cre and found that Brg1 expression is upstream of p63, Pparγ, and sonic hedgehog (Shh) expression in the ureteral epithelium. In addition, epithelial stratification in the basal cells required Brg1-dependent p63 expression, whereas terminal differentiation of the umbrella cells required Brg1-dependent Pparγ expression. Furthermore, the loss of ureteric Brg1 resulted in failure of Shh expression, which correlated with reduced smooth muscle cell development and hydroureter. Taken together, we conclude that Brg1 expression unifies three aspects of ureter development: maintenance of the basal cell population, guidance for terminal differentiation of urothelial cells, and proper investment of ureteral smooth muscle cells.

The Terminator mouse is a diphtheria toxin-receptor knock-in mouse strain for rapid and efficient enrichment of desired cell lineages.

Biomedical research often requires primary cultures of specific cell types, which are challenging to obtain at high purity in a reproducible manner. Here we engineered the murine Rosa26 locus by introducing the diphtheria toxin receptor flanked by loxP sites. The resultant strain was nicknamed the Terminator mouse. This approach results in diphtheria toxin-receptor expression in all non-Cre expressing cell types, making these cells susceptible to diphtheria toxin exposure. In primary cultures of kidney cells derived from the Terminator mouse, over 99.99% of cells were dead within 72 h of diphtheria toxin treatment. After crossing the Terminator with the podocin-Cre (podocyte specific) mouse or the Ggt-Cre (proximal tubule specific) mouse, diphtheria toxin treatment killed non-Cre expressing cells but spared podocytes and proximal tubule cells, respectively, enriching the primary cultures to over 99% purity, based on both western blotting and immunostaining of marker proteins. Thus, the Terminator mouse can be a useful tool to selectively and reproducibly obtain even low-abundant cell types at high quantity and purity.

Increased tubular proliferation as an adaptive response to glomerular albuminuria.

Renal tubular atrophy accompanies many proteinuric renal diseases, suggesting that glomerular proteinuria injures the tubules. However, local or systemic inflammation and filtration of abnormal proteins known to directly injure tubules are also present in many of these diseases and animal models; therefore, whether glomerular proteinuria directly causes tubular injury is unknown. Here, we examined the renal response to proteinuria induced by selective podocyte loss. We generated mice that express the diphtheria toxin receptor exclusively in podocytes, allowing reproducible dose-dependent, specific ablation of podocytes by administering diphtheria toxin. Ablation of <20% of podocytes resulted in profound albuminuria that resolved over 1-2 weeks after the re-establishment of normal podocyte morphology. Immediately after the onset of albuminuria, proximal tubule cells underwent a transient burst of proliferation without evidence of tubular damage or increased apoptosis, resulting in an increase in total tubular cell numbers. The proliferative response coincided with detection of the growth factor Gas6 in the urine and phosphorylation of the Gas6 receptor Axl in the apical membrane of renal tubular cells. In contrast, ablation of >40% of podocytes led to progressive glomerulosclerosis, profound tubular injury, and renal failure. These data suggest that glomerular proteinuria in the absence of severe structural glomerular injury activates tubular proliferation, potentially as an adaptive response to minimize the loss of filtered proteins.

Leadership Titles in Radiology: Usage of Non-Inclusive Terminology among Academic Radiology Departments and Societies.

RATIONALE AND OBJECTIVES: To characterize the use of gender-specific (chairman) and non-inclusive terminology (chief) to describe departmental and divisional/sectional leadership within academic radiology department and radiological society websites. METHODS: From a total of 157 unique institutions identified, we gathered a list of 123 departments with functioning websites. We screened for use of "chairman" and "chief" on departmental home pages, welcome messages, faculty listings, and residency program pages, noting location on websites, and alternative terms, if present. We also assessed for use of "chairman" through a list of 14 radiological society websites. The overall usage of these terms was determined and the relationships between geographic region, faculty gender, and use of terminology were assessed. RESULTS: "Chairman" is common among radiology department websites, with 42.1% (51/121) of websites using the term at least once. Usage of "chairman" was higher in departments whose chairs were men (OR 4.32, 95% CI: 1.36-13.69) and lower in those located in the Midwest (versus Northeast, OR 0.34, 95% CI: 0.12-0.96). Use of "chief" is extremely common among departments listing divisional leadership, at 82.7% (67/81). Alternative terms used included "chair," "head," "chairperson," and "director." Among departments, the proportion of women in leadership roles is low, representing 19.7% (22/122) of chairs and 31.1% (272/874) of other leadership. Radiological societies were unlikely to use "chairman," with only one website using the term. CONCLUSION: Use of "chairman" and "chief" is frequent among academic radiology departments. Further efforts should be made to assess the usage of non-inclusive terminology and its potential impact within academic radiology departments.

Patient Race/Ethnicity and Diagnostic Imaging Utilization in the Emergency Department: A Systematic Review.

PURPOSE: Diagnostic imaging often is a critical contributor to clinical decision making in the emergency department (ED). Racial and ethnic disparities are widely reported in many aspects of health care, and several recent studies have reported a link between patient race/ethnicity and receipt of imaging in the ED. METHODS: The authors conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching three databases (PubMed, Embase, and the Cochrane Library) through July 2020 using keywords related to diagnostic imaging, race/ethnicity, and the ED setting, including both adult and pediatric populations and excluding studies that did not control for the important confounders of disease severity and insurance status. RESULTS: The search strategy identified 7,313 articles, of which 5,668 underwent title and abstract screening and 238 full-text review, leaving 42 articles meeting the inclusion criteria. Studies were predominately conducted in the United States (41), split between adult (13) and pediatric (17) populations or both (12), and spread across a variety of topics, mostly focusing on specific anatomic regions or disease processes. Most studies (30 of 42 [71.4%]) reported an association between Black, African American, Hispanic, or nonwhite race/ethnicity and decreased receipt of imaging. CONCLUSIONS: Despite heterogeneity among studies, patient race/ethnicity is linked with receipt of diagnostic imaging in the ED. The strength and directionality of this association may differ by specific subpopulation and disease process, and more efforts to understand potential underlying factors are needed.

Intraoperative Radiographic Assessment of Bone Resection Margins During Mandibulectomy: A Case Series.

BACKGROUND AND PURPOSE: Mandibulectomy remains the treatment of choice for oral cavity squamous cell carcinoma with infiltration of bone and for benign tumors with full mandibular thickness involvement. Although bone resection margins are critical for patient outcomes, intraoperative immediate bone margins assessment is inadequate, and few alternative options have been described. The purpose of this study was to describe the use of an existing intraoperative radiographic system for objective determination of bone resection margins during mandibulectomy. METHODS: We conducted a retrospective case series of all patients at the Greater Baltimore Medical Center who underwent mandibulectomy and received intraoperative Faxitron radiography from January 1, 2016, to March 1, 2019. Patient characteristics including age, sex, diagnosis, tumor location, clinical and pathologic stage, procedure performed, and bone resection margins were reviewed. RESULTS: A total of 10 patients underwent mandibulectomy with intraoperative radiography. Nine (90%) received surgery for squamous cell carcinoma, with 1 (10%) for ameloblastoma. Out of those with squamous cell carcinoma, tumor location varied, and all were clinically stage T4. Final pathologic margins were negative in all cases (10/10), though in 2 cases, close margins were assessed intraoperatively, leading to further resection or change in operative plan. CONCLUSION: Intraoperative radiographic assessment of bone resection margins is a promising technique, though further validation is required.

CT angiography of abdomen and pelvis in critically ill COVID-19 patients: imaging findings and correlation with the CT chest score.

PURPOSE: To assess the spectrum of computed tomography angiogram (CTA) abdominal and pelvic findings in critically ill COVID-19 patients and investigate correlation with CT chest scores. METHODS: An IRB approved retrospective study of CTA of the chest, abdomen and pelvis between dates March 1st to September 15th, 2020 was performed in the hospitalized COVID-19 positive patients. CTA studies of solely the chest were excluded. Medical record review was performed to note patient demographics, CTA scan details and coagulation profile. CTA findings were reviewed to record vascular and non-vascular findings. CT chest was reviewed to calculate CT chest score. Logistic regression analyses were performed to correlate CT chest scores with odds of vascular and other abdomen-pelvis findings. A p < 0.05 was considered statistically significant. RESULTS: A total of 45 consecutive hospitalized COVID-19 positive patients with 61 years mean age and M:F (2:1) gender ratio were evaluated, out of which majority 68.9% (n = 31) had CTA chest, abdomen and pelvis. The most common vascular findings were hematoma 46.7% (n = 21), active extravasation 24.4% (n = 11) and vascular occlusion 17.8% (n = 8). Higher CT chest scores were significantly associated with hematoma/extravasation (OR 1.19, 95% CI 1.07-1.34, p < 0.01). The most common non-vascular abdomen-pelvis findings were seen in organs gallbladder 20% (n = 9), liver 20% (n = 9) followed by kidney 15.6% (n = 7). Higher CT chest scores were significantly associated with bowel findings (OR 1.28, 95% CI 1.01-1.63, p < 0.05) and cholestasis (OR 13.3, 95% CI 1.28-138.9, p < 0.05). CONCLUSION: Patients with moderate to severe COVID-19 pneumonia have significantly higher rate of vascular complications in the abdomen and pelvis.

Ultrasound Studies of COVID-19-Positive Patients and Patient Under Investigation: Pandemic Experience of Body Imaging Division at a Tertiary Medical Center.

ABSTRACT: This retrospective study shares our departmental experience of screening of ultrasound (US) requests, triaging of studies, and abbreviated US protocols implemented during the COVID-19 pandemic. For US studies requested in April and May 2020, the following data were collected: type of study, indication, COVID-19 status (positive or patient under investigation [PUI]), decision to perform study, US findings, and location of patient. A total of 196 US studies in 150 patients were included. The median age of patients was 60 years (female: 46.7% [70/150]). At the time of study request, 83 patients (55.3%) were COVID-19-positive and 67 (44.7%) were PUI, of which 8 (11.9%) tested positive after waiting for test result. The most frequently requested study was venous extremity Doppler (51%), followed by right upper quadrant (20.4%), renal (11.7%), and liver duplex (6.6%). After radiologist screening and triage of US requests, 156 studies were performed (79.6%), 15 were postponed until COVID test result (7.6%), and 40 were not performed after discussion with ordering provider (20.4%). Notably, 40.1% of studies performed on COVID-19-positive patients yielded pathological findings, most frequently deep venous thrombosis (18.1%), medical renal disease (7.6%), and gall bladder sludge (5.7%). Abbreviated US protocols were used in 29.4% of studies. In conclusion, US study screening and triage played an important role to optimize care of COVID-19 patients and PUIs.

Glia initiate brain assembly through noncanonical Chimaerin-Furin axon guidance in C. elegans.

Brain assembly is hypothesized to begin when pioneer axons extend over non-neuronal cells, forming tracts guiding follower axons. Yet pioneer-neuron identities, their guidance substrates, and their interactions are not well understood. Here, using time-lapse embryonic imaging, genetics, protein-interaction, and functional studies, we uncover the early events of C. elegans brain assembly. We demonstrate that C. elegans glia are key for assembly initiation, guiding pioneer and follower axons using distinct signals. Pioneer sublateral neurons, with unique growth properties, anatomy, and innervation, cooperate with glia to mediate follower-axon guidance. We further identify a Chimaerin (CHIN-1)- Furin (KPC-1) double-mutant that severely disrupts assembly. CHIN-1 and KPC-1 function noncanonically, in glia and pioneer neurons, for guidance-cue trafficking. We exploit this bottleneck to define roles for glial Netrin and Semaphorin in pioneer- and follower-axon guidance, respectively, and for glial and pioneer-neuron Flamingo (CELSR) in follower-axon navigation. Taken together, our studies reveal previously undescribed glial roles in pioneer-axon guidance, suggesting conserved principles of brain assembly.

Six innexins contribute to electrical coupling of C. elegans body-wall muscle.

C. elegans body-wall muscle cells are electrically coupled through gap junctions. Previous studies suggest that UNC-9 is an important, but not the only, innexin mediating the electrical coupling. Here we analyzed junctional current (I j ) for mutants of additional innexins to identify the remaining innexin(s) important to the coupling. The results suggest that a total of six innexins contribute to the coupling, including UNC-9, INX-1, INX-10, INX-11, INX-16, and INX-18. The I j deficiency in each mutant was rescued completely by expressing the corresponding wild-type innexin specifically in muscle, suggesting that the innexins function cell-autonomously. Comparisons of I j between various single, double, and triple mutants suggest that the six innexins probably form two distinct populations of gap junctions with one population consisting of UNC-9 and INX-18 and the other consisting of the remaining four innexins. Consistent with their roles in muscle electrical coupling, five of the six innexins showed punctate localization at muscle intercellular junctions when expressed as GFP- or epitope-tagged proteins, and muscle expression was detected for four of them when assessed by expressing GFP under the control of innexin promoters. The results may serve as a solid foundation for further explorations of structural and functional properties of gap junctions in C. elegans body-wall muscle.