Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy. (Funded by Biotronik; CASTLE-AF ClinicalTrials.gov number, NCT00643188 .).

INTRODUCTION:The prevalence of childhood obesity is increasing with its negative medical and psychosocial consequences. This paper examines the association between body mass index (BMI), motor abilities and leisure habits of 668 children within the CHILT (Children's Health InterventionaL Trial) project. METHOD: A total of 668 children (51.0% boys; 49.0% girls) and their parents were questioned on sport and leisure behaviour of the children. The anthropometric data were measured. Motor abilities were determined by a body gross motor development test for children (Köperkoordinationstest für Kinder; KTK) and a 6-min run. RESULTS: The children were 6.7070.42 y old, 122.7275.36 cm tall and weighed 24.4774.59 kg, the average BMI was 16.1772.27 kg/m 2 . KTK showed an average motor quotient (MQ) of 93.49715.01, the 6-min run an average of 835.247110.87 m. Both tests were inversely correlated with BMI (KTK and BMI r ¼ À0.164 (Po0.001); 6-min run and BMI r ¼ À0.201 (Po0.001)); the group of overweight/obese children showed poorer results than the normal/underweight ones, even after adjustment for gender and age (in each case Po0.001). Children with the greatest extent of exercise achieve the highest MQ (P ¼ 0.035). SUMMARY: Overweight/obesity is associated with a poorer body gross motor development and endurance performance. On the other hand, an active lifestyle is positively correlated with a better gross motor development in first-grade children. Therefore, to prevent the negative consequences of physical inactivity and overweight/obesity early intervention to support exercise and movement is recommended.

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Plasmin-catalyzed cleavage of the vascular endothelial growth factor (VEGF)-A isoform VEGF165 results in loss of its carboxyl-terminal heparin-binding domain and significant loss in its bioactivity. Little is known about the in vivo significance of this process. To investigate the biological relevance of the protease sensitivity of VEGF165 in wound healing we assessed the activity of a VEGF165 mutant resistant to plasmin proteolysis (VEGF165 A111P ) in a genetic mouse model of impaired wound healing (db/db mouse). In the present study we demonstrate that in this mouse model plasmin activity is increased at the wound site. The stability of the mutant VEGF165 was substantially increased in wound tissue lysates in comparison to wild-type VEGF165, thus indicating a prolonged activity of the plasmin-resistant VEGF165 mutant. The db/db delayed healing phenotype could be reversed by topical application of wild-type VEGF165 or VEGF165 A111P . However, resistance of VEGF165 to plasmin cleavage resulted in the increased stability of vascular structures during the late phase of healing due to increased recruitment of perivascular cells and delayed and reduced endothelial cell apoptosis. Our data provide the first indication that plasmin-catalyzed cleavage regulates VEGF165-mediated angiogenesis in vivo. Inactivation of the plasmin cleavage site Arg110/Ala111 may preserve the biological function of VEGF165 in therapeutic angiogenesis under conditions in which proteases are highly active, such as wound repair and inflammation.

Abstract Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for the treatment of adults experiencing an acute episode of aTTP, in conjunction with plasma exchange (PEX) and immunosuppression for a minimum of 30 days after stopping daily PEX. We performed a retrospective, observational analysis on the use of caplacizumab in 60 patients from 29 medical centers in Germany during acute disease management. Caplacizumab led to a rapid normalization of the platelet count (median, 3 days; mean 3.78 days). One patient died after late treatment initiation due to aTTP-associated complications. In 2 patients with initial disease presentation and in 4 additional patients with laboratory signs of an exacerbation or relapse after the initial therapy, PEX-free treatment regimens could be established with overall favorable outcome. Caplacizumab is efficacious in the treatment of aTTP independent of timing and ancillary treatment modalities. Based on this real-world experience and published literature, we propose to administer caplacizumab immediately to all patients with an acute episode of aTTP. Treatment decisions regarding the use of PEX should be based on the severity of the clinical presentation and known risk factors. PEX might be dispensable in some patients.

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Abstract Introduction of the nanobody caplacizumab was shown to be effective in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in the acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and the use of caplacizumab for a minimum of 30 days after stopping daily PEX. This study was a retrospective, observational analysis of the use of caplacizumab in 60 patients from 29 medical centers in Germany. Immunosuppressive treatment led to a rapid normalization of ADAMTS13 activities (calculated median, 21 days). In 35 of 60 patients, ADAMTS13 activities started to normalize before day 30 after PEX; in 11 of 60 patients, the treatment was extended beyond day 30; and in 5 patients, it was extended even beyond day 58 due to persistent autoimmune activity. In 34 of 60 instances, caplacizumab was stopped before day 30 with a favorable outcome whenever ADAMTS13 activities were >10%. In contrast, 11 of 34 patients with ADAMTS13 activities <10% at the time of stopping caplacizumab treatment developed a nonfavorable outcome (disease exacerbation or relapse). In some cases, prolongation of the treatment interval to every other day was feasible and resulted in a sustained reduction of von Willebrand factor activity. ADAMTS13 activity measurements are central for a rapid diagnosis in the acute setting but also to tailor disease management. An ADAMTS13 activity–guided approach seems safe for identifying the individual time point when to stop caplacizumab to prevent overtreatment and undertreatment; this approach will result in significant cost savings without jeopardizing the well-being of patients. In addition, von Willebrand factor activity may serve as a biomarker for drug monitoring.

Juvenile obesity is increasing worldwide. Preventive strategies are warranted. The school-based Children's Health Interventional Trial (the CHILT Project) combines health education and physical activity for children. The effect on obesity and physical performance was studied after four years in 12 primary schools compared with five control schools. Anthropometric data were recorded. Physical performance was measured by a coordination test for children (balancing backwards, one-legged obstacle jumping, lateral jumping, sideways movements) and a 6-min run (endurance). No difference in the prevalence and incidence of overweight and obesity was found between the intervention and control schools before and after the intervention. Remission of overweight was higher in the intervention schools (23.2 vs. 19.2%), but not significant. An increase in coordination related to lateral jumping and balancing backwards was apparent in the intervention schools (30.6, s = 10.8 vs. 26.1, s = 10.8, P = 0.005; 21.8, s = 11.8 vs. 19.4, s = 11.7, P = 0.007), and the increase in endurance performance tended to be higher in intervention schools (100.8, s = 122.7 vs. 92.8, s = 126.0, P = 0.055), adjusted for age, sex, baseline test result, and body mass index at final examination. Therefore, preventive intervention in primary school offers the possibility to improve physical performance in children. The prevalence and incidence of obesity were not affected.