Adiponectin stimulates cholesterol efflux in macrophages and low adiponectin may in part contribute to disturbed reverse cholesterol transport in type 2 diabetes. Monocytes express high levels of annexin A6 that could inhibit cholesterol efflux and it was investigated whether the atheroprotective effects of adiponectin are accompanied by changes in annexin A6 levels. Adiponectin reduces annexin A6 protein whereas mRNA levels are not affected. Adiponectin-mediated activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and AMP-activated protein kinase (AMPK) does not account for reduced annexin A6 expression. Further, fatty acids and lipopolysaccharide that are elevated in obesity do not influence annexin A6 protein levels. Annexin A6 in monocytes from overweight probands or type 2 diabetic patients is significantly elevated compared to monocytes of normal-weight controls. Monocytic annexin A6 positively correlates with body mass index and negatively with systemic adiponectin of the blood donors. Therefore, the current study demonstrates that adiponectin reduces annexin A6 in monocytes and thereby may enhance cholesterol efflux. In agreement with these in vitro finding an increase of monocytic annexin A6 in type 2 diabetes monocytes was observed.
AMP-Activated Protein Kinases/metabolism ; Adiponectin/*pharmacology ; Animals ; Annexin A6/genetics/*metabolism ; Body Mass Index ; CHO Cells ; Case-Control Studies ; Cell Culture Techniques ; Cholesterol/metabolism ; Cricetinae ; Cricetulus ; Diabetes Mellitus, Type 2/*blood ; Down-Regulation/*drug effects ; Electrophoresis, Polyacrylamide Gel ; Humans ; Immunoblotting ; Male ; Middle Aged ; Monocytes/*metabolism ; Obesity/*blood ; PPAR alpha/metabolism ; RNA, Messenger/metabolism ; Recombinant Proteins/pharmacology ; Reverse Transcriptase Polymerase Chain Reaction

Background: and Purpose Prolonged electrocardiography (ECG)-monitoring in stroke patients improves the detection of paroxysmal atrial fibrillation (pAF). However, most randomized studies only had short follow-up. We aimed to provide 3-year follow-up data for AF detection and stroke recurrence risk. Methods:
We randomized 402 patients aged ≥60 years with acute ischemic strokes without AF to either enhanced and prolonged monitoring (EPM; 3×10-day Holter-ECG-monitoring) or standard-of-care (≥24 hours ECG-monitoring). The endpoint of the current analysis was AF within 36 months analyzed by intention to treat. Long-term follow-up was performed for 36 months. Results:
Two hundred and seventy-four patients (80%) participated in the extended follow-up (median duration of follow-up was 36 months [interquartile range, 12 to 36]). During the first 6 months, more AF was documented in the EPM arm compared to the control arm (13.5% vs. 5.1%; 95% confidence interval, 2.9% to 14.4%; P=0.004). During months 6 to 36, AF was less detected in the EPM intervention arm than in the control arm (2.0% vs. 7.3%; 95% confidence interval, 0.7% to 9.9%; P=0.028). Overall, the detection rate of AF within 36 months was numerically higher within the EPM group (15.0% vs. 11.1%, P=0.30). Numerically less patients in the EPM arm had recurrent ischemic strokes (5.5% vs. 9.1%, P=0.18), transient ischemic attacks (3.0% vs. 4.5%, P=0.44) or died (4.5% vs. 6.6%, P=0.37). Conclusions
Enhanced and prolonged ECG monitoring increased AF detection during the first six months, but there was significantly more clinical AF during months 6 to 36 observed in the usual-care arm. This suggests that EPM leads to an earlier detection of clinically relevant AF.

Purpose: PASylation® offers the ability to systematically tune and optimize the pharmacokinetics of protein tracers for molecularimaging. Here we report the first clinical translation of a PASylated Fab fragment (89Zr∙Df-HER2-Fab-PAS200) for the molecularimaging of tumor-related HER2 expression. Methods: A patient with HER2-positive metastatic breast cancer received 37 MBq of 89Zr∙Df-HER2-Fab-PAS200 at a total massdose of 70 μg. PET/CT was carried out 6, 24, and 45 h after injection, followed by image analysis of biodistribution, normalorgan uptake, and lesion targeting. Results: Images show a biodistribution typical for protein tracers, characterized by a prominent blood pool 6 h p.i., whichdecreased over time. Lesions were detectable as early as 24 h p.i. 89Zr∙Df-HER2-Fab-PAS200 was tolerated well. Conclusion This study demonstrates that a PASylated Fab tracer shows appropriate blood clearance to allow sensitive visualizationof small tumor lesions in a clinical setting.

Background/Aims: Endosonography is associated with a long learning curve. We aimed to assess variables that may influence the diagnostic outcomes in endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) of solid pancreatic tumors regarding the level of endoscopists' experience. Methods: Consecutive patients undergoing EUS-guided puncture of solid pancreatic tumors (eight endosonographers, including six trainees) were prospectively enrolled. An experienced endosonographer was defined as having performed at least 250 EUS examinations, including 75 FNA/Bs. The final diagnosis was determined by cytopathology, histopathology, or clinical followup. Results: In total, 283 EUS-FNA/Bs of solid pancreatic tumors (75.6% malignant) in 239 patients (median age 69 years, 57.6% males) were enrolled. Trainees performed 149/283 (52.7%) of the interventions. Accuracy and sensitivity for detecting malignancy were significantly higher in the expert group than in the trainee group (85.8% vs 73.2%, p=0.01 and 82.5% vs 68.4%, p=0.02). Solid lesions evaluated by an expert using FNB needles showed the best odds for a correct diagnosis (odds ratio, 3.07; 95% confidence interval, 1.15 to 8.23; p=0.02). More experienced endoscopists achieved better accuracy in sampling via the transduodenal approach (86.7% vs 68.5%, p<0.001), in the sampling of malignant lesions (82.5 vs 68.4, p=0.02), and in the sampling of lesions located in the pancreatic head (86.1 vs 69.1, p=0.02). In cases involving these factors, we observed a moderate improvement in the diagnostic accuracy after 40 attempts. Conclusions Transduodenal approach, pancreatic head lesions, and malignancy were recognized as the most important clinical factors affecting the learning curve in EUS-FNA/B of solid pancreatic lesions.