Differentiation of lower limb vasculitis from physiological uptake on FDG PET/CT imaging.

PURPOSES: To analyze the difference of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) uptake between vasculitis and non-vasculitic patients in PET/CT imaging and the factors related to vascular uptake in non-vasculitic patients. To investigate the feasibility of identifying vasculitis of the lower limb and physiological uptake with delayed imaging. PROCEDURES: Among 244 patients who underwent PET/CT examination, imaging features of patients with or without vasculitis were retrospectively analyzed. The factors related to FDG uptake in the lower limb vessels of non-vasculitic patients were analyzed. Another 44 patients with suspected systemic vasculitis in PET/CT were prospectively studied to analyze the efficacy of delayed imaging on differentiating vascular uptake in lower limbs. RESULTS: In PET/CT imaging of patients with vasculitis, involvement of trunk vessels showed segmental or diffuse FDG distribution. Lower limb vascular involvement showed reticular uptake accompanied by nodular or patchy changes. In non-vasculitic patients, vascular uptake mainly showed linear uptake in lower limb vessels and there was no significant difference in uptake degree compared with vasculitis patients. Body weight and interval time were the independent influence factors of vascular uptake in lower limbs of non-vasculitic patients. In delayed imaging, lower limb vasculitis all showed reticular uptake and physiological uptake all showed a linear pattern. ROC analysis showed the change rate of SUVmax (≥ 20%) between early and delayed imaging could delineate physiological vascular uptake with a sensitivity of 100% and specificity of 81.0%. CONCLUSIONS: When PET/CT is used for the diagnosis and classification of vasculitis, the physiological uptake of lower limb vessels may mislead the diagnosis. PET/CT imaging features or delayed imaging improved diagnostic efficacy.

Fluorine-18 labeled fluorodeoxyglucose positron emission tomography/computed tomography used in diagnosing connective tissue diseases in fever of unknown origin/inflammatory of unknown origin patients.

OBJECTIVE: To explore the significance of Fluorine-18 labeled fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in diagnosing connective tissue diseases (CTDs) in fever of unknown origin (FUO) or inflammation of unknown origin (IUO) patients. METHODS: Clinical and image data of 242 consecutive FUO/IUO patients who underwent PET/CT examination and eventually diagnosed CTDs were retrospectively analyzed, including distribution of diseases, clinical characteristics, and PET/CT imaging findings. The role of FDG PET/CT in differential diagnosis of CTDs was evaluated through clinical questionnaire survey. RESULTS: Patients diagnosed as CTDs accounted for 48.1% of FUO/IUO patients. Among them, adult-onset Still's disease was most frequently diagnosed. Other common diseases included systemic vasculitis, undifferentiated connective tissue disease, rheumatoid arthritis, idiopathic inflammatory myopathy, systemic lupus erythematosus, and polymyalgia rheumatica. On FDG PET/CT examination, 97.9% of the patients had positive findings. Inflammatory lesions were detected in 66.5% and non-specific abnormal uptakes were found in 31.4%. Detected lesions distributed consistently with corresponding susceptible organs and tissues in various diseases. Clinical questionnaire results shown that FDG PET/CT excluded malignant tumors, focal infections, or other typical CTDs in 45.5% of the patients; indicated important diagnostic clues or appropriate biopsy sites in 20.6% of patients; and directly suggested the diagnosis of a CTD in 33.1% of patients. CONCLUSION: FDG PET/CT could reveal inflammatory lesions in organs and tissues that reflect the clinical characteristics in different CTDs, thus providing an objective evidence for differential diagnosis, classification, and treatment decision of these diseases. Key Points • FDG PET/CT is a useful tool for differential diagnosing connective tissue diseases among patients with fever of unknown origin/inflammatory of unknown origin.

Inhibitory effect of chlormethiazole on the toxicokinetics of diethylnitrosamine in normal and hepatofibrotic rats.

The effect of chlormethiazole (CMZ) at single and multiple doses on the toxicokinetics of diethylnitrosamine (DEN) was investigated in normal rats and those with DEN-induced liver fibrosis. Twelve rats were treated with DEN (50 mg/kg) alone and in combination with a single dose of CMZ (10, 50, or 100 mg/kg) by intraperitoneal (i.p.) injection. In a multiple dose test, six rats were treated with CMZ (50 mg/kg) for 7 d with addition of DEN (50 mg/kg) on days 1 and 7. Lastly, 12 rats were treated with DEN (50 mg/kg) by i.p. injection twice a week for 4 consecutive weeks, followed by weekly injections for another 8 weeks to build the model of liver fibrosis. Following this induction, the 12 rats were given CMZ (50 mg/kg) combined with DEN (50 mg/kg) to study the inhibitory effect of CMZ on DEN metabolism in hepatofibrotic rats. Serial blood samples were also collected and analyzed by a validated high-performance liquid chromatography (HPLC) method. A single-dose CMZ treatment decreased DEN clearance (CL), prolonged the t1/2, and increased the 'area under the curve' (AUC) for DEN in normal and hepatofibrotic rats relative to rats that did not receive CMZ. Treatment with CMZ for 7 d further prolonged the t1/2 for DEN but did not alter the CL and AUC relative to a single CMZ treatment. These results suggest that CMZ significantly inhibits the metabolism of DEN in normal and hepatofibrotic rats.

CYP3A4/5 Activity Probed with Testosterone and Midazolam: Correlation between Two Substrates at the Microsomal and Enzyme Levels.

Testosterone (TST) and midazolam (MDZ) are widely used as probes to detect CYP3A4/5 activity, but the data acquired with these two substrates do not correlate well at the microsomal level (per milligram of microsomal protein), and the reason is unclear. In this study, CYP3A4/5 activity was probed with TST and MDZ at the microsomal and enzyme levels (per picomole of CYP3A4/5) in 72 human liver samples. Correlation coefficients were lower in Vmax and CLint at the microsomal level, as compared with those at the enzyme level ( Vmax 0.658 vs 0.883; CLint no correlation vs 0.796). Compared with TST, MDZ was found to correlate better with the content of CYP3A4/5 (no correlation vs 0.431) and CYP3A5 (no correlation vs 0.447), and huge variations in enzyme content existed among different genotypes, which explained the lower degree of correlation at the microsomal level. In addition, different genotypes had varying effects on activity at the enzyme level, whereas the difference between activity at the enzyme level probed with TST and that probed with MDZ was not obvious ( P > 0.05), indicating that the effect of gene polymorphisms on correlation between activity probed with these two substrates was limited at the enzyme level. In conclusion, our study demonstrates a high degree of correlation between CYP3A4/5 activity probed with TST and MDZ at the enzyme level but not at the microsomal level and allows us to correctly understand the influence of gene polymorphisms on the correlations.

Effect of Intravitreal Bevacizumab with or without Macular Photocoagulation for Diabetic Macular Edema: A Meta-Analysis.

INTRODUCTION: In this meta-analysis, we aimed to assess the possible benefits of macular photocoagulation (MPC) as an additional treatment with intravitreal bevacizumab (IVB) in patients with diabetic macular edema. METHODS: The studies were identified from three databases: PubMed, Web of Science, and the Cochrane Library. The main outcome measures included change in best-corrected visual acuity (BCVA), differences in central macular thickness (CMT), and adverse events within the follow-up period. The results were pooled using weight mean difference with their corresponding 95% confidence intervals. A fixed or random effects model was employed, depending on the heterogeneity of the inclusion trials. RESULTS: Finally, three randomized controlled trial and two high-quality retrospective studies were identified and included. Changes in CMT at 1, 3, and 6 months did not vary significantly between the IVB-alone group and the IVB with MPC group (P = 0.26, 0.06, and 0.65, respectively). Similarly, changes in BCVA at 1, 3, and 6 months also did not vary significantly between the two groups (P = 0.20, 0.91, and 0.70, respectively). Whereas substantial heterogeneity was detected in the CMT results among these studies, the sensitivity analyses showed Solaiman's study was probably the source of the heterogeneity. No publication bias was detected by funnel plots in this study. CONCLUSION: Results of this meta-analysis showed that the treatments with IVB alone and combined IVB and MPC were similarly effective in improving BCVA and reducing CMT. However, more evidence is needed to evaluate their effects in the long-term periods.