. Background. The adipocytokine adiponectin has been proposed to play important roles in the regulation of energy homeostasis, insulin sensitivity and shows anti‐inflammatory properties. Aim. In this study we investigated the role of circulating adiponectin in different chronic liver diseases, its regulation by systemic anti‐tumour necrosis factor (TNF)‐α treatment and its hepatic metabolism. Patients and methods. Plasma adiponectin levels were determined in 87 patients with liver cirrhosis of different aetiologies, seven patients with alcoholic steatohepatitis undergoing systemic anti‐TNF‐α treatment, in 11 patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt implantation and in 21 healthy controls. Results. Adiponectin levels were significantly higher in all subjects with liver cirrhosis of different aetiologies when compared with healthy controls and increased dependent on Child‐Pugh classification. In subjects with alcoholic steatohepatitis, systemic anti‐TNF‐α treatment caused a significant decrease in circulating adiponectin. Adiponectin concentrations were similar in portal, hepatic and peripheral veins. No correlation between adiponectin levels and insulin resistance was found in any patient group. Conclusions. Our data suggest that circulating adiponectin is increased in liver cirrhosis independent of the aetiology of liver disease. We suggest that high adiponectin levels in chronic liver disease might reflect one of the body's anti‐inflammatory mechanisms in chronic liver diseases.
The prevalence of gout has increased in recent decades. Several clinical studies have demonstrated an association between gout and coronary heart disease, but direct cardiovascular imaging of monosodium urate (MSU) deposits by using dual-energy computed tomography (DECT) has not been reported to date. OBJECTIVE To compare coronary calcium score and cardiovascular MSU deposits detected by DECT in patients with gout and controls. DESIGN, SETTING, AND PARTICIPANTS This prospective Health Insurance Portability and Accountability Act-compliant study included patients with gout and controls who presented to a rheumatologic clinic from January 1, 2017, to November 1, 2018. All consecutive patients underwent DECT to assess coronary calcium score and MSU deposits in aorta and coronary arteries. In addition, cadavers were assessed by DECT for cardiovascular MSU deposits and verified by polarizing microscope. Analysis began in January 2017. MAIN OUTCOMES AND MEASURES Detection rate of cardiovascular MSU deposits using DECT in patients with gout and control group patients without a previous history of gout or inflammatory rheumatic diseases. RESULTS A total of 59 patients with gout (mean [SD] age, 59 [5.7] years; range, 47-89 years), 47 controls (mean [SD] age, 70 [10.4] years; range, 44-86 years), and 6 cadavers (mean [SD] age at death, 76 [17] years; range, 56-95 years) were analyzed. The frequency of cardiovascular MSU deposits was higher among patients with gout (51 [86.4%]) compared with controls (7 [14.9%]) (χ 2 = 17.68, P < .001), as well as coronary MSU deposits among patients with gout (19 [32.2%]) vs controls (2 [4.3%]) (χ 2 = 8.97, P = .003). Coronary calcium score was significantly higher among patients with gout (900 Agatston units [AU]; 95% CI, 589-1211) compared with controls (263 AU; 95% CI, 76-451; P = .001) and also significantly higher among 58 individuals with cardiovascular MSU deposits (950 AU; 95% CI, 639-1261) compared with 48 individuals without MSU deposits (217 AU; 95% CI, 37-397; P < .001). Among 6 cadavers, 3 showed cardiovascular MSU deposits, which were verified by polarizing light microscope.CONCLUSION AND RELEVANCE Dual-energy computed tomography demonstrates cardiovascular MSU deposits, as confirmed by polarized light microscopy. Cardiovascular MSU deposits were detected by DECT significantly more often in patients with gout compared with controls and were associated with higher coronary calcium score. This new modality may be of importance in gout population being at risk from cardiovascular disease.
Introduction: Gastrin Releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a 68 Ga-labelled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumours ('MITIGATE') (grant agreement number 602306) in patients with oligometastatic gastrointestinal stromal tumors (GIST). Materials and methods:The main objectives were evaluation of safety, biodistribution, dosimetry and preliminary tumor targeting of 68 Ga-NeoBOMB1 in patients with advanced TKI-treated GIST using PET/CT. Six patients with histologically confirmed GIST and unresectable primary or metastases undergoing an extended protocol for detailed pharmacokinetic analysis were included. 68 Ga-NeoBOMB1 was prepared using a kit procedure with a licensed 68 Ge/ 68 Ga generator. 3 MBq/kg body-weight were injected intravenously and safety parameters were assessed. PET/CT included dynamic imaging at 5 min, 11 min and 19 min as well as static imaging at 1, 2 and 3-4 h p.i. for dosimetry calculations. Venous blood samples and urine were collected for pharmacokinetics. Tumor targeting was assessed on a per-lesion and perpatient basis.Results: 68 Ga-NeoBOMB1 (50 µg) was prepared with high radiochemical purity (yield >97%). Patients received 174 ± 28 MBq of the radiotracer, which was well tolerated in all patients over a follow-up period of 4 weeks. Dosimetry calculations revealed a mean adsorbed effective dose of 0.029 ± 0.06 mSv/MBq with highest organ dose to the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life was 27.3 min with primarily renal clearance (mean 25.7 ± 5.4% of injected dose 4h p.i.). Plasma metabolite analyses revealed high stability, metabolites were only detected in the urine. In three patients a significant uptake with increasing maximum standard uptake values (SUVmax at 2h p.i.: 4.3 to 25.9) over time was found in tumor lesions. Conclusion:This Phase I/IIa study provides safety data for 68 Ga-NeoBOMB1, a promising radiopharmaceutical for targeting GRPR-expressing tumors. Safety profiles and pharmacokinetics are suitable for PET imaging and absorbed dose estimates are comparable to other 68 Ga-labelled radiopharmaceuticals used in clinical routine.
Volumetric analysis after endovascular repair of Stanford type B dissection shows optimal technical outcome in the stented segment, whereas the false lumen in the segment immediately adjacent to the stent-graft seems to be a vulnerable area. Extension of clot formation beyond the endograft seems to be no reliable predictor of outcome.
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