2.Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions
Md Jakir HOSSAIN ; Michael D. KENDIG ; Meg E. LETTON ; Margaret J. MORRIS ; Ria ARNOLD
Diabetes & Metabolism Journal 2022;46(2):198-221
Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.
3.Assessment of Suspected Malignancy or Infectionin Immunocompromised Patients After Solid Organ Transplantationby 18FFDG PET/CT and 18FFDG PET/MRI
Nika GUBERINA ; Anja GÄCKLER ; Johannes GRUENEISEN ; Axel WETTER ; Oliver WITZKE ; Ken HERRMANN ; Christoph RISCHPLER ; Wolfgang FENDLER ; Lale UMUTLU ; Lino Morris SAWICKI ; Michael FORSTING ; Hana ROHN
Korean Journal of Nuclear Medicine 2020;54(4):183-191
Purpose:
To study the value of 2-deoxy-2-[18F]fluoro-D-glucose([18F]FDG) positron emission tomography/computed tomography(PET/CT) and [18F]FDG positron emission tomography/magnetic resonance imaging (PET/MRI) in assessing immunocompromisedpatients with suspected malignancy or infection.
Methods:
[18F]FDG-PET/CT and [18F]FDG-PET/MRI examinations of patients who were immunocompromised after receivinglung, heart, pancreas, kidney, liver, or combined kidney-liver transplants were analyzed in this retrospective study. Patientsunderwent whole-body hybrid-imaging because of clinical signs of malignancy and/or infection. Findings were assessed bymolecular features ([18F]FDG-uptake) and morphological changes. The final diagnosis, which was arrived at after review ofclinical, laboratory, and histopathologic analyses and follow-up imaging studies, served as the reference standard.
Results:
Altogether, (i) 28 contrast-enhanced [18F]FDG-PET/CT scans (CE-PET/CT), (ii) 33 non-contrast [18F]FDG-PET/CTscans (NC-PET/CT), and (iii) 18 [18F]FDG-PET/MRI scans were included. Additionally, 12/62 patients underwent follow-upPET imaging to rule out vital tumor ormetabolic active inflammatory processes. CE-PET/CT exhibited 94.4%sensitivity, 80.0%specificity, 89.5% positive predictive value (PPV), 88.9% negative predictive value (NPV), and 89.3% accuracy with regard tothe reference standard. NC-PET/CT exhibited 91.3% sensitivity, 80.0% specificity, 91.3% PPV, 80.0% NPV, and 87.9% accuracy. PET/MRI exhibited 88.6% sensitivity, 99.2% specificity, 99.6% PPV, 81.3% NPV, and 94.4% accuracy. ExactMcNemar statistical test (one-sided) showed significant difference between the CT-/MR-component alone and the integratedPET/CT and PET/MRI for diagnosis of malignancy or infection (p value < 0.001). Radiation exposure was 4- to 7-fold higherwith PET/CT than with PET/MRI.
Conclusion
For immunocompromised patients with clinically unresolved symptoms, to rule out vital tumor manifestations ormetabolic active inflammation, [18F]FDG-PET/MRI, CE-[18F]FDG-PET/CT, and NC-[18F]FDG-PET/CT exhibit excellent performancein diagnosing malignancy or infection. The main strength of PET/MRI is its considerably lower level of radiationexposure than that associated with PET/CT.