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Kathrin Kahnert,1 Rudolf A Jörres,2 Tanja Lucke,2 Franziska C Trudzinski,3 Pontus Mertsch,1 Christiane Bickert,1 Joachim H Ficker,4 Jürgen Behr,1 Robert Bals,5 Henrik Watz,6 Tobias Welte,7 Claus F Vogelmeier,8 Peter Alter8 On behalf of COSYCONET Study Group1Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; 3Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany; 4Department of Respiratory Medicine, Nürnberg General Hospital, Paracelsus Medical University, Nürnberg, Germany; 5Department of Internal Medicine V - Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany; 6Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 7Clinic for Pneumology, Hannover Medical School, Member of the German Center for Lung Research (DZL), Hannover, Germany; 8Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg (UMR), Germany, Member of the German Center for Lung Research (DZL), Marburg, GermanyCorrespondence: Kathrin KahnertDepartment of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, GermanyTel +49 89 4400 52590Fax +49 89 4400 54905Email kathrin.kahnert@med.uni-muenchen.deBackground: Patients with chronic obstructive pulmonary disease (COPD) often have osteoporosis and diabetes as comorbid conditions. Anti-diabetic medication, including metformin, has protective effects on osteoporosis in experimental studies. We therefore studied whether patients with COPD receiving anti-diabetic medication had a lower osteoporosis prevalence in a large COPD cohort, COSYCONET.Methods: Assessment of osteoporosis was based on patients’ reports of physician-based diagnoses and the presence of disease-specific medication. The predictive value of physical characteristics, lung function, comorbidities, cardiovascular medication, and the use of anti-inflammatory diabetes medication, including metformin, sulfonylureas, glinides or DPP4I, was evaluated using logistic regression analysis. ClinicalTrials.gov: NCT01245933.Results: In total, 2222 patients were eligible for analysis (863 [39%] female, mean age 65 y), 515 of whom had higher symptoms and exacerbations (Global Initiative for Chronic Obstructive Lung Disease group D). Osteoporosis was present in 15.8% of the overall cohort, and in 24.1% of GOLD D patients. Regression analyses identified the following as associated with osteoporosis (p < 0.05): female sex, higher age, lower body-mass index, asthma, higher air trapping, oral steroids, and cardiovascular medication. Although oral anti-diabetic medication was overall not associated with a lower prevalence of osteoporosis (p = 0.131), anti-inflammatory anti-diabetic medication (p = 0.009) and metformin-containing therapy (p = 0.039) were. This was driven by GOLD D patients.Conclusion: In a large COPD cohort, anti-inflammatory diabetes therapy, including metformin, was associated with a lower prevalence of osteoporosis, especially in patients with higher symptoms and exacerbations. These findings suggest a protective effect of common anti-diabetic medication on osteoporosis, possibly as a result of attenuated systemic inflammation.Keywords: chronic obstructive pulmonary disease, oral corticosteroids, inhaled corticosteroids, anti-inflammatory, metformin, diabetes

Adaptive atrioventricular (AV)-shortening algorithms have achieved QRS duration (QRSd) narrowing in traditional cardiac resynchronization therapy (CRT) patients. Multipoint pacing (MPP) has also demonstrated benefit in this population. An additional site of activation via intrinsic conduction of the septum may further contribute to CRT; however, the incorporation of all strategies together has yet to be explored. We therefore developed and tested a method combining MPP-CRT and controlled septal contribution to create a multifuse pacing (MFP) technique, establishing four ventricular activation sites for CRT patients using measurements from intracardiac electrograms (EGMs) and incorporating an AV-delay shortening algorithm (SyncAV™; Abbott Laboratories, Chicago, IL, USA) to narrow the QRSd. Patients in sinus rhythm with an AV conduction time of less than 350 ms were included in this analysis and were further stratified by strictly defined left bundle branch block (sLBBB) or nonspecific intraventricular conduction delay (IVCD). EGM-based measurements to determine the QRS septal onset to right ventricular (RV) time (SRAT) and the left ventricular (LV) to RV pacing conduction time were collected and applied to a formula to facilitate MFP. QRSd was compared between before and after programming. A total of 22 patients (19 men and three women) with similar baseline characteristics were compared (all values in mean ± standard deviation). The overall baseline QRSd of 153.31 ± 24.60 ms was decreased to 115.31 ± 16.31 ms after MFP programming (p < 0.0001). The measured SRAT was 59.40 ± 28.49 ms, resulting in a negative AV offset of -20.0 ± 24.97 ms. Patients in the sLBBB group (n = 7) were aged 67.8 ± 13.3 years and had a QRSd of 168.85 ± 27.29 ms that decreased to 113 ± 16.69 ms for a reduction of 55.42 ± 19.3 ms or 32.1% (p = 0.0003). In the IVCD group (n = 15), the baseline QRSd of 146.06 ± 20.29 ms was decreased to 116 ± 16.66 ms for a reduction of 30.07 ± 16.41 ms or 20.62% (p = 0.0001). When comparing the sLBBB and IVCD groups, the sLBBB group was favored by a reduction of 25.35 ms (p = 0.00046). Ultimately, MFP achieved statistically significant reductions in QRSd in all patients tested in this analysis. The benefit was also significantly better in the sLBBB group as compared with in the IVCD group., Competing Interests: Dr. Corbisiero has received honoraria for speaking from Boston Scientific and Abbott Laboratories. Mr. Muller is an employee of Abbott Laboratories. The other authors report no conflicts of interest for the published content., (Copyright: © 2021 Innovations in Cardiac Rhythm Management.)

Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin. About 50% of patients with STS experience relapse and more than 30% will die within 10 years after diagnosis. In this study we investigated circulating free DNA (cfDNA) and tumor-specific genetic alterations therein (circulating tumor DNA, ctDNA) as diagnostic biomarkers. Plasma concentrations and fragmentation of cfDNA was analyzed with quantitative PCR. Patients with STS (n = 64) had significantly higher plasma concentrations and increased fragmentation of cfDNA when compared to patients in complete remission (n = 19) and healthy controls (n = 41) (p < 0.01 and p < 0.001). Due to overlapping values between patients with STS and controls, the sensitivity and specificity of these assays is limited. Sensitive assays to detect genomic alterations in cfDNA of synovial sarcomas (t(X;18)), myxoid liposarcomas (t(12;16) and TERT C228T promoter mutation) and well-differentiated/de-differentiated liposarcomas (MDM2 amplifications) were established. ctDNA was quantified in nine liposarcoma patients during the course of their treatment. Levels of breakpoint t(12;16) and TERT C228T ctDNA correlated with the clinical course and tumor burden in patients with myxoid liposarcomas (n = 4). ctDNA could detect minimal residual disease and tumor recurrence. In contrast, detection of MDM2 amplifications was not sensitive enough to detect tumors in patients with well-differentiated/de-differentiated liposarcomas (n = 5). Genotyping of cfDNA for tumor specific genetic alterations is a feasible and promising approach for monitoring tumor activity in patients with myxoid liposarcomas. Detection of ctDNA during follow-up examinations despite negative standard imaging studies might warrant more sensitive imaging (e.g. PET-CT) or closer follow-up intervals to timely localize and treat recurrences., (© 2019 UICC.)