AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype.

BACKGROUND: Kidney involvement is a feature of COVID-19 and it can be severe in Black patients. Previous research linked increased susceptibility to collapsing glomerulopathy, including in patients with HIV-associated nephropathy, to apo L1 (APOL1) variants that are more common in those of African descent. METHODS: To investigate genetic, histopathologic, and molecular features in six Black patients with COVID-19 presenting with AKI and de novo nephrotic-range proteinuria, we obtained biopsied kidney tissue, which was examined by in situ hybridization for viral detection and by NanoString for COVID-19 and acute tubular injury-associated genes. We also collected peripheral blood for APOL1 genotyping. RESULTS: This case series included six Black patients with COVID-19 (four men, two women), mean age 55 years. At biopsy day, mean serum creatinine was 6.5 mg/dl and mean urine protein-creatinine ratio was 11.5 g. Kidney biopsy specimens showed collapsing glomerulopathy, extensive foot process effacement, and focal/diffuse acute tubular injury. Three patients had endothelial reticular aggregates. We found no evidence of viral particles or SARS-CoV-2 RNA. NanoString showed elevated chemokine gene expression and changes in expression of genes associated with acute tubular injury compared with controls. All six patients had an APOL1 high-risk genotype. Five patients needed dialysis (two of whom died); one partially recovered without dialysis. CONCLUSIONS: Collapsing glomerulopathy in Black patients with COVID-19 was associated with high-risk APOL1 variants. We found no direct viral infection in the kidneys, suggesting a possible alternative mechanism: a "two-hit" combination of genetic predisposition and cytokine-mediated host response to SARS-CoV-2 infection. Given this entity's resemblance with HIV-associated nephropathy, we propose the term COVID-19-associated nephropathy to describe it.

Assessment of Response to Transcatheter Arterial Chemoembolization with Doxorubicin-eluting Microspheres: Tumor Biology and Hepatocellular Carcinoma Recurrence in a 5-year Transplant Cohort.

Purpose To assess response to transcatheter arterial chemoembolization (TACE) based on immune markers and tumor biology in patients with hepatocellular carcinoma (HCC) who were bridged to liver transplantation, and to produce an optimized pretransplantation model for posttransplantation recurrence risk. Materials and Methods In this institutional review board-approved HIPAA-compliant retrospective analysis, 93 consecutive patients (73 male, 20 female; mean age, 59.6 years; age range, 23-72 years) underwent TACE with doxorubicin-eluting microspheres (DEB) (hereafter, DEB-TACE) and subsequently underwent transplantation over a 5-year period from July 7, 2011, to May 16, 2016. DEB-TACE response was based on modified Response Evaluation Criteria in Solid Tumors. Imaging responses and posttransplantation recurrence were compared with demographics, liver function, basic immune markers, treatment dose, and tumor morphology. Treatment response and recurrence were analyzed with uni- and multivariate statistics, as well as internal validation and propensity score matching of factors known to affect recurrence to assess independent effects of DEB-TACE response on recurrence. Results Low-grade tumors (grade 0, 1, or 2) demonstrated a favorable long-term treatment response in 87% of patients (complete response, 49%; partial response, 38%; stable disease [SD] or local disease progression [DP], 13%) versus 33% of high-grade tumors (grade 3 or 4) (complete response, 0%; partial response, 33%; SD or DP, 67%) (P < .001). Of the 93 patients who underwent treatment, 82 were followed-up after transplantation (mean duration, 757 days). Recurrence occurred in seven (9%) patients (mean time after transplantation, 635 days). Poor response to DEB-TACE (SD or DP) was present in 86% of cases and accounted for 35% of all patients with SD or DP (P < .001). By using only variables routinely available prior to liver transplantation, a validated model of posttransplantation recurrence risk was produced with a concordance statistic of 0.83. The validated model shows sensitivity of 83.6%, specificity of 82.6%, and negative predictive value of 98.4%, which are pessimistic estimates. Conclusion Response to DEB-TACE is correlated with tumor biology and patients at risk for posttransplantation recurrence, and it may be associated with HCC recurrence after liver transplantation. © RSNA, 2017 Online supplemental material is available for this article.

Evaluation of pancreatic allografts with sonography.

OBJECTIVES: The purposes of this study were to develop a protocol for evaluating pancreas allografts, to describe a method for successfully studying pancreatic transplants, and to determine whether the resistive index (RI) of the splenic artery is a useful differentiator between complications. METHODS: We retrospectively analyzed clinical, surgical, procedural, and radiologic reports in 51 consecutive patients undergoing 182 sonographic examinations during a 4.5-year period. Complications included splenic vein thrombosis, rejection, and pancreatitis. We obtained RIs in normal and complication groups and performed mixed model regression methods and receiver operating characteristic analysis. RESULTS: The mean RI ± SD for normal transplants was 0.65 ± 0.09; for splenic vein thrombosis, 0.76 ± 0.09; after resolution of splenic vein thrombosis, 0.73 ± 0.09; during rejection, 0.94 ± 0.09; after successful treatment of rejection, 0.74 ± 0.09; for pancreatitis, 0.83 ± 0.09; and for fluid collections, 0.66 ± 0.09. There was a statistically significant difference (P < .05) between normal transplants and splenic vein thrombosis (P = .0003), rejection (P < .0001), and pancreatitis (P = .04). A significant difference was also seen between rejection and successful treatment thereof (P < .0001). CONCLUSIONS: We developed a protocol that allowed us to successfully evaluate 96% of the pancreatic allografts studied. Furthermore, our data show that the RI can be used as a therapeutic guide. When the RI is less than 0.65, the risk of vascular abnormalities is very low; however, fluid collections may be present. When greater than 0.75, splenic vein thrombosis, pancreatitis, or rejection should be suspected. When greater than 0.9, rejection must be seriously considered.

A cloud-based platform to predict wind pressure coefficients on buildings.

Natural ventilation (NV) is a key passive strategy to design energy-efficient buildings and improve indoor air quality. Therefore, accurate modeling of the NV effects is a basic requirement to include this technique during the building design process. However, there is an important lack of wind pressure coefficients (C p ) data, essential input parameters for NV models. Besides this, there are no simple but still reliable tools to predict C p data on buildings with arbitrary shapes and surrounding conditions, which means a significant limitation to NV modeling in real applications. For this reason, the present contribution proposes a novel cloud-based platform to predict wind pressure coefficients on buildings. The platform comprises a set of tools for performing fully unattended computational fluid dynamics (CFD) simulations of the atmospheric boundary layer and getting reliable C p data for actual scenarios. CFD-expert decisions throughout the entire workflow are implemented to automatize the generation of the computational domain, the meshing procedure, the solution stage, and the post-processing of the results. To evaluate the performance of the platform, an exhaustive validation against wind tunnel experimental data is carried out for a wide range of case studies. These include buildings with openings, balconies, irregular floor-plans, and surrounding urban environments. The C p results are in close agreement with experimental data, reducing 60%-77% the prediction error on the openings regarding the EnergyPlus software. The platform introduced shows being a reliable and practical C p data source for NV modeling in real building design scenarios. Electronic Supplementary Material ESM: The appendix is available in the online version of this article at 10.1007/s12273-021-0881-9.

A Multiscale Approach for the Numerical Simulation of Turbulent Flows with Droplets.

A multiscale approach for the detailed simulation of water droplets dispersed in a turbulent airflow is presented. The multiscale procedure combines a novel representative volume element (RVE) with the Pseudo Direct Numerical Simulation (P-DNS) method. The solution at the coarse-scale relies on a synthetic model, constructed using precomputed offline RVE simulations and an alternating digital tree, to characterize the non-linear dynamic response at the fine-scale. A set of numerical experiments for a wide range of volume fractions, particle distribution sizes, and external shear forces in the RVE are carried out. Quantitative results of the statistically stationary turbulent state are obtained, and the turbulence modulation phenomenon due to the presence of droplets is discussed. The developed synthetic model is then employed to solve global scale simulations of flows with airborne droplets via the P-DNS method. Improved predictions are obtained for flow conditions where turbulence modulation is noticeable.

Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression.

Ischemic stroke triggers lipid peroxidation and neuronal injury. Docosahexaenoic acid released from membrane phospholipids during brain ischemia is a major source of lipid peroxides. Leukocyte infiltration and pro-inflammatory gene expression also contribute to stroke damage. In this study using lipidomic analysis, we have identified stereospecific messengers from docosahexaenoate-oxygenation pathways in a mouse stroke model. Aspirin, widely used to prevent cerebrovascular disease, activates an additional pathway, which includes the 17R-resolvins. The newly discovered brain messenger 10,17S-docosatriene potently inhibited leukocyte infiltration, NFkappaB, and cyclooxygenase-2 induction in experimental stroke and elicited neuroprotection. In addition, in neural cells in culture, this lipid messenger also inhibited both interleukin 1-beta-induced NFkappaB activation and cyclooxygenase-2 expression. Thus, the specific novel bioactive docosanoids generated in vivo counteract leukocyte-mediated injury as well as pro-inflammatory gene induction. These results challenge the view that docosahexaenoate only participates in brain damage and demonstrate that this fatty acid is also the endogenous precursor to a neuroprotective signaling response to ischemia-reperfusion.