A Universal Approach to Eliminate Antigenic Properties of Alpha-Gliadin Peptides in Celiac Disease

Celiac disease is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins, including the α-gliadins. It has been shown that α-gliadins harbor several major epitopes involved in the disease pathogenesis. A major step towards elimination of gluten toxicity for celiac disease patients would thus be the elimination of such epitopes from α-gliadins. We have analyzed over 3,000 expressed α-gliadin sequences from 11 bread wheat cultivars to determine whether they encode for peptides potentially involved in celiac disease. All identified epitope variants were synthesized as peptides and tested for binding to the disease-associated HLA-DQ2 and HLA-DQ8 molecules and for recognition by patient-derived α-gliadin specific T cell clones. Several specific naturally occurring amino acid substitutions were identified for each of the α-gliadin derived peptides involved in celiac disease that eliminate the antigenic properties of the epitope variants. Finally, we provide proof of principle at the peptide level that through the systematic introduction of such naturally occurring variations α-gliadins genes can be generated that no longer encode antigenic peptides. This forms a crucial step in the development of strategies to modify gluten genes in wheat so that it becomes safe for celiac disease patients. It also provides the information to design and introduce safe gluten genes in other cereals, which would exhibit improved quality while remaining safe for consumption by celiac disease patients

Uncomplicated 90Y Selective Internal Radio Therapy in a Patient With Hepatocellular Carcinoma After Arterial and Portal Vein Embolizations

Selective internal radio therapy (SIRT) with90Y-glass microspheres was performed in a cirrhotic patient with hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage C) after arterial coil embolization for treatment of intratumoral hemorrhage and planned preoperative right portal vein embolization. Three technetium99mTc macro-albumin-aggregate injections were needed to optimize intralesional uptake without extrahepatic deposition. The consecutive SIRT treatment was uncomplicated with a remarkable result

Diagnostic performance of PET/computed tomography versus PET/MRI and diffusion-weighted imaging in the N- and M-staging of breast cancer patients

Objective To provide a systematic review regarding the diagnostic performance of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) and diffusion-weighted imaging (DWI) compared to 18F-FDG PET/computed tomography (CT) focused on nodal and distant staging in breast cancer patients. Methods ThePubMedandEmbasedatabases were searched for relevant publications until April 2020. Two independent reviewers searched for eligible articles based on predefined in- and exclusion criteria, assessed quality and extracted data. Results Eleven eligible studies were selected from 561 publications identified by the search. In seven studies, PET/CT was compared with PET/MRI, and in five, PET/CT with DWI. Significantly higher sensitivity for PET/MRI compared to PET/CT in a lesion-based analysis was reported for all lesions together (77% versus 89%) in one study, osseous metastases (69-99% versus 92-98%) in two studies and hepatic metastases (70-75% versus 80-100%) in one study. Moreover, PET/MRI revealed a significantly higher amount of osseous metastases (90 versus 141) than PET/CT. PET/CT is associated with a statistically higher specificity than PET/MRI in the lesion detection of all lesions together (98% versus 96%) and of osseous metastases (100% versus 95%), both in one study. None of the reviewed studies reported significant differences between PET/CT and DWI for any of the evaluated sites. There is a trend toward higher specificity for PET/CT. Conclusion In general, there is a trend toward higher sensitivity and lower specificity of PET/MRI when compared to PET/CT. Results on the diagnostic performance of DWI are conflicting. Rather than evaluating it separate, it seems to have complementary value when combined with other MR sequences

Imaging of osteomyelitis with FDG PET-MR

Osteomyelitis is an inflammatory process accompanied by bone destruction, and is caused by microorganism infection. The infection can be limited to a single portion of the bone or can involve several compartments such as marrow, cortex, periosteum and the surrounding soft tissue. Osteomyelitis can be (1) spread locally from a focal source of infection, (2) secondary to vascular insufficiency, or (3) caused by hematogenous spread of the microorganism from a different source. For osteomyelitis in the extremities, the most common pathogen is Staphylococcus aureus. In skull-base osteomyelitis (SBO) it is Pseudomonas aeruginosa (50–90% of cases) [1]. Osteomyelitis of the skull base most often occurs as a complication of otitis externa, and can be categorized within the first category of focal infections. However, it is perceived as a special case due to the severe complications that can arise, given the location. The bacterial infection causes bone erosions, and uses fascial planes and venous sinuses for distant tissue invasion. It then can progress and spread to the surrounding osseous and soft tissues via the skull base

Imaging of osteomyelitis with FDG PET-MR

Osteomyelitis is an inflammatory process accompanied by bone destruction, and is caused by microorganism infection. The infection can be limited to a single portion of the bone or can involve several compartments such as marrow, cortex, periosteum and the surrounding soft tissue. Osteomyelitis can be (1) spread locally from a focal source of infection, (2) secondary to vascular insufficiency, or (3) caused by hematogenous spread of the microorganism from a different source. For osteomyelitis in the extremities, the most common pathogen is Staphylococcus aureus. In skull-base osteomyelitis (SBO) it is Pseudomonas aeruginosa (50–90% of cases) [1]. Osteomyelitis of the skull base most often occurs as a complication of otitis externa, and can be categorized within the first category of focal infections. However, it is perceived as a special case due to the severe complications that can arise, given the location. The bacterial infection causes bone erosions, and uses fascial planes and venous sinuses for distant tissue invasion. It then can progress and spread to the surrounding osseous and soft tissues via the skull base

The Use of 18F-FET-PET-MRI in Neuro-Oncology: The Best of Both Worlds-A Narrative Review

Gliomas are the most frequent primary tumors of the brain. They can be divided into grade II-IV astrocytomas and grade II-III oligodendrogliomas, based on their histomolecular profile. The prognosis and treatment is highly dependent on grade and well-identified prognostic and/or predictive molecular markers. Multi-parametric MRI, including diffusion weighted imaging, perfusion, and MR spectroscopy, showed increasing value in the non-invasive characterization of specific molecular subsets of gliomas. Radiolabeled amino-acid analogues, such as 18F-FET, have also been proven valuable in glioma imaging. These tracers not only contribute in the diagnostic process by detecting areas of dedifferentiation in diffuse gliomas, but this technique is also valuable in the follow-up of gliomas, as it can differentiate pseudo-progression from real tumor progression. Since multi-parametric MRI and 18F-FET PET are complementary imaging techniques, there may be a synergistic role for PET-MRI imaging in the neuro-oncological imaging of primary brain tumors. This could be of value for both primary staging, as well as during treatment and follow-up