Impact of double reading on NI-RADS diagnostic accuracy in reporting oral squamous cell carcinoma surveillance imaging – a single-center study

Objectives: The Neck Imaging Reporting and Data System (NI-RADS) is an increasingly utilized risk stratification tool for imaging surveillance after treatment for head and neck cancer. This study aims to measure the impact of supervision by subspecialized radiologists on diagnostic accuracy of NI-RADS when initial reading is performed by residents. Methods: 150 CT and MRI datasets were initially read by two trained residents, and then supervised by two subspecialized radiologists. Recurrence rates by NI-RADS category were calculated, and receiver operating characteristic (ROC) curves were plotted. After dichotomization of the NI-RADS system (category 1 vs categories 2 + 3+4 and categories 1 + 2 vs 3 + 4), sensitivity, specificity, positive and negative predictive value were calculated. Results: 26% of the reports were modified by the supervising radiologists. Area under the curve of ROC plots values of the supervision session were higher than those of the initial reading session for both the primary site (0.89 vs 0.86) and the neck (0.94 vs 0.91), but the difference was not statistically significant. For dichotomized NI-RADS category assignments, differences between the initial reading and the supervision session were statistically significant regarding specificity and PPV for the primary site (1 + 2 vs 3 + 4 and 1 vs 2 + 3+4) or even for both sites combined (1 vs 2 + 3+4). Conclusion: NI-RADS enables trained resident radiologists to report surveillance imaging in patients with treated oral squamous cell carcinoma with high discriminatory power. Additional supervision by a subspecialized head and neck radiologist particularly improves specificity of radiological reports

Reliability of NI-RADS criteria in the interpretation of contrast-enhanced magnetic resonance imaging considering the potential role of diffusion-weighted imaging

Objectives: To assess inter- and intrareader agreement of the Neck Imaging Reporting and Data System (NI-RADS) used in contrast-enhanced magnetic resonance imaging (MRI) including analysis of diffusion-weighted imaging (DWI), which is currently not part of the NI-RADS criteria. Methods: This retrospective study included anonymized surveillance contrast-enhanced MRI datasets of 104 patients treated for different head and neck cancers. Three radiologists experienced in head and neck imaging reported findings for the primary site and the neck using NI-RADS criteria in a first step and evaluated DWI sequences for the primary site in a second step. Thirty randomly selected imaging datasets were again presented to the readers. Kappa statistics and observed agreement (A(o)) were calculated. Results: Interreader agreement across all MRI datasets was moderate (kappa(Fleiss) = 0.53) for NI-RADS categories assigned to the primary site, substantial for NI-RADS categories of the neck (kappa(Fleiss) = 0.67), and almost perfect for DWI of the primary site (kappa(Fleiss) = 0.83). Interreader agreement for the primary site was particularly low in cases of cancer recurrence (kappa(Fleiss) = 0.35) and when categories 2a, 2b, and 3 were combined (kappa(Fleiss) = 0.30). Intrareader agreement was considerably lower for NI-RADS categories of the primary site (range A(o) = 53.3-70.0%) than for NI-RADS categories of the neck (range A(o) = 83.3-90.0%) and DWI of the primary site (range A(o) = 93.3-100.0%). Conclusion: Interreader agreement of NI-RADS for reporting contrast-enhanced MRI findings is acceptable for the neck but limited for the primary site. Here, DWI has the potential to serve as a reliable additional criterion

Dynamic evolution of the sofosbuvir-associated variant A1343V in HEV-infected patients under concomitant sofosbuvir-ribavirin treatment

Background & Aims: In the absence of a hepatitis E virus (HEV)-specific antiviral treatment, sofosbuvir has recently been shown to have antiviral activity against HEV in vivo. However, a variant, A1343V, that is strongly associated with viral relapse impedes treatment success. In this study, we investigated the occurrence of variants during sofosbuvir and ribavirin treatment in vivo and assessed the sensitivity of resistance-associated variants to concurrent treatment in cell culture. Methods: Two patients with chronic HEV infection that did not clear infection under ribavirin treatment were subsequently treated with a combination of sofosbuvir and ribavirin. We determined response to treatment by measuring liver enzymes and viral load in blood and stool. Moreover, we analyzed viral evolution using polymerase-targeted high-throughput sequencing and assessed replication fitness of resistance-associated variants using a HEV replicon system. Results: Combination treatment was successful in decreasing viral load towards the limit of quantification. However, during treatment sustained virological response was not achieved. Variants associated with sofosbuvir or ribavirin treatment emerged during treatment, including A1343V and G1634R. Moreover, A1343V, as a single or double mutation with G1634R, was associated with sofosbuvir resistance during concomitant treatment in vitro. Conclusions: These results highlight the importance of variant profiling during antiviral treatment of patients with chronic infection. Understanding how intra-host viral evolution impedes treatment success will help guide the design of next-generation antivirals. Impact and implications: The lack of hepatitis E virus (HEV)-specific antivirals to treat chronic infection remains a serious health burden. Although ribavirin, interferon and sofosbuvir have been reported as anti-HEV drugs, not all patients are eligible for treatment or clear infection, since resistant-associated variants can rapidly emerge. In this study, we analyzed the efficacy of sofosbuvir and ribavirin combination treatment in terms of HEV suppression, the emergence of resistance-associated variants and their ability to escape treatment inhibition in vitro. Our results provide novel insights into evolutionary dynamics of HEV during treatment and thus will help guide the design of next-generation antivirals

Comparison of the Translational Potential of Human Mesenchymal Progenitor Cells from Different Bone Entities for Autologous 3D Bioprinted Bone Grafts

Reconstruction of segmental bone defects by autologous bone grafting is still the standard of care but presents challenges including anatomical availability and potential donor site morbidity. The process of 3D bioprinting, the application of 3D printing for direct fabrication of living tissue, opens new possibilities for highly personalized tissue implants, making it an appealing alternative to autologous bone grafts. One of the most crucial hurdles for the clinical application of 3D bioprinting is the choice of a suitable cell source, which should be minimally invasive, with high osteogenic potential, with fast, easy expansion. In this study, mesenchymal progenitor cells were isolated from clinically relevant human bone biopsy sites (explant cultures from alveolar bone, iliac crest and fibula; bone marrow aspirates; and periosteal bone shaving from the mastoid) and 3D bioprinted using projection-based stereolithography. Printed constructs were cultivated for 28 days and analyzed regarding their osteogenic potential by assessing viability, mineralization, and gene expression. While viability levels of all cell sources were comparable over the course of the cultivation, cells obtained by periosteal bone shaving showed higher mineralization of the print matrix, with gene expression data suggesting advanced osteogenic differentiation. These results indicate that periosteum-derived cells represent a highly promising cell source for translational bioprinting of bone tissue given their superior osteogenic potential as well as their minimally invasive obtainability