Background Transcatheter mitral valve repair (TMVR) has shown to improve symptoms and functional capacity in patients with severe mitral valve regurgitation (MR). Novel device developments provide the technology to treat patients with complex anatomies and large coaptation gaps. Nevertheless, the question of superiority of one device remains unanswered. We aimed to compare the MitraClip XTR and MitraClip NTR system in a real world setting. Hypothesis TMVR with the MitraClip XTR system is equally effective, but associated with a higher risk of leaflet injury. Methods We retrospectively analyzed peri‐procedural and mid‐term clinical and echocardiographic outcomes of 113 patients treated for severe MR between March 2018 and August 2019 at the University Hospital of Munich. Results Postprocedural MR reduction to ≤2+ was comparable in both groups (XTR: 96.1% vs. NTR: 97.6%, p = .38). There was a significant difference in a composite safety endpoint of periprocedural Major adverse cardiac and cerebrovascular events (MACCE) including leaflet injury between groups (XTR 14.6% vs. NTR 1.7%, 95% CI [2.7, 24.6], p = .012). After a median follow‐up of 8.5 (4.4, 14.0) months, durable reduction of MR was confirmed (XTR: in 91.9% vs. NTR: 96.8%, p = .31) and clinical and symptomatic improvement was comparable in both groups accordingly. Conclusion While efficacy was comparable in both treatment groups, patients treated with the MitraClip XTR systems showed more events of acute leaflet tear and single leaflet device attachment (SLDA). A detailed echocardiographic assessment should be done to identify risk candidates for acute leaflet injury.

Objectives: To describe the published literature on EBM curricula for physicians in training and barriers during curriculum implementation. Methods:We performed a systematic search and review of the medical literature on PubMed, Embase, ERIC, Scopus and Web of Science from the earliest available date until September 4, 2019. Results: We screened 9,042 references and included 29 fulltext studies and 14 meeting abstracts. Eighteen studies had moderate validity, and 6 had high validity. The EBM curricular structure proved highly variable in between studies. The majority of the EBM curricula was longitudinal with different lengths. Only five studies reported using Kern's six-step approach for curriculum development. Twenty-one articles reported on EBM skills and knowledge, and only 5/29 full-text articles used a validated assessment tool. Time was the main barrier to EBM curriculum implementation. All the included studies and abstracts, independent of the EBM curriculum structure or evaluation method used, found an improvement in the residents' attitudes and/or EBM skills and knowledge. Conclusions:The current body of literature available to guide educators in EBM curriculum development is enough to constitute a strong scaffold for developing any EBM curriculum. Given the amount of time and resources needed to develop and implement an EBM curriculum, it is very important to follow the curriculum development steps and use validated assessment tools.

The current implementation of ns-3 provides only synthetic mobility models that disregard the map where the nodes are moving, however, the study of vehicular ad-hoc networks requires the usage of more realistic mobility models. The usage of mobility traces created by traffic simulators such as SUMO is feasible, however, these simulators possess a steep learning curve, which prevents their fruition for most researchers whose research focus and expertise are on the data communication layer.This paper presents a mobility model that generates realistic mobility traces that take into account the underlying maps, while maintaining the ease of usage that characterizes the synthetic mobility models. The module described herein is compared against SUMO and against the ns3::RandomWaypointMobilityModel of network simulator 3, to analyze the trade-off it implements in terms of realism and ease of usage.

BackgroundEnd-stage renal disease (ESRD) is the last stage of chronic kidney disease, mainly caused by type 2 diabetes mellitus and characterized by an increased mortality risk related to cardiovascular disease. Low-dose aspirin (acetylsalicylic acid or ASA) seems to effectively prevent cardiovascular events in patients with ESRD. However, the number of interventional studies in this population remains limited and the mechanisms of aspirin-related bleeding remain poorly understood. Aspirin’s efficacy and safety may be modified by the presence of type 2 diabetes mellitus or platelet hyperreactivity.ObjectiveThe overall objective of this protocol is to (1) evaluate aspirin’s safety and efficacy in reducing the risk of thrombotic events in patients with ESRD on hemodialysis and (2) examine whether aspirin’s efficacy is modified by the presence of type 2 diabetes mellitus or platelet hyperreactivity. Specifically, the primary objective is to compare the 12-month rate of any thrombotic event (cardiac death, nonfatal myocardial infarction, nonfatal stroke, arteriovenous fistula thrombosis) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding in patients treated with aspirin compared to those on placebo. Secondary objectives are to test for effect modification of treatment by the presence of type 2 diabetes mellitus or platelet hyperreactivity and compare the rate of TIMI minor bleeding between treatment groups.MethodsWe developed a protocol for a phase 2 randomized, single-center, placebo-controlled, triple-blind, superiority clinical trial to assess the prophylactic efficacy and safety of aspirin in patients with ESRD and on hemodialysis. It follows the ethical principles of the Declaration of Helsinki of the World Medical Association. A total of 342 participants would be enrolled over 12 months at a large dialysis center. Patients will be randomized in a 1:1 ratio and stratified by presence of type 2 diabetes mellitus and platelet hyperreactivity to receive either oral aspirin (100 mg/d) or placebo for a treatment period of 12 months. An intention-to-treat statistical analysis will be performed.ResultsThe randomized clinical trial will be performed after approval by the ethical committee of the participating center and registration at ClinicalTrials.gov.ConclusionsWe provide a protocol for a randomized controlled trial to evaluate the safety and efficacy of treatment with aspirin to reduce the risk of thrombotic events. In addition, such a study would further our understanding of the mechanism of aspirin-related bleeding and help identify subgroups of best-responders and patients with a higher risk of adverse events.Registered Report IdentifierRR1-10.2196/10516

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Functional perturbations of the cohesin complex with subsequent changes in chromatin structure and replication are reported in a multitude of cancers including acute myeloid leukemia (AML). Mutations of its STAG2 subunit may predict unfavorable risk as recognized by the 2022 European Leukemia Net recommendations, but the underlying evidence is limited by small sample sizes and conflicting observations regarding clinical outcomes, as well as scarce information on other cohesion complex subunits. We retrospectively analyzed data from a multi-center cohort of 1615 intensively treated AML patients and identified distinct co-mutational patters for mutations of STAG2, which were associated with normal karyotypes (NK) and concomitant mutations in IDH2, RUNX1, BCOR, ASXL1, and SRSF2. Mutated RAD21 was associated with NK, mutated EZH2, KRAS, CBL, and NPM1. Patients harboring mutated STAG2 were older and presented with decreased white blood cell, bone marrow and peripheral blood blast counts. Overall, neither mutated STAG2, RAD21, SMC1A nor SMC3 displayed any significant, independent effect on clinical outcomes defined as complete remission, event-free, relapse-free or overall survival. However, we found almost complete mutual exclusivity of genetic alterations of individual cohesin subunits. This mutual exclusivity may be the basis for therapeutic strategies via synthetic lethality in cohesin mutated AML.

Background: Carriers of variations in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2△) are at high risk for severe pulmonary arterial hypertension (PAH+). Aim:To define the clinical and hemodynamic phenotype of BMPR2△/PAH+ patients. Methods:We performed a systematic review encompassing observational data from January 2000 to July 2019 about BMPR2△ and confirmed PAH diagnosis. According to international clinical guidelines, we aimed to determine the clinical and hemodynamic phenotype of BMPR2△/PAH+. We also explored functional assessment and risk stratification. PROSPERO ID CRD42019124324. Results:We included 54 reports with 6,668 PAH+ patients, 1,220 were BMPR2△/PAH+ with an allele frequency within studies ranging from 8.8% to 24.9%. Female sex was predominant, and age at diagnosis ranged from 32.2 to 46.2 years. We observed the occurrence of BMPR2△ across all PAH clinical classifications, except for schistosomiasis. BMPR2△ correlated with severity signs and symptoms in PAH, poor functional class, severe pulmonary hypertension with elevated pulmonary vascular resistance, and low cardiac index and output. The clinical and hemodynamic missing data ranged between 28%-49% and 50%-65%, respectively. Conclusion:BMPR2△/PAH+ present a phenotype with high mortality risk. The clinical triad of dyspnea, syncope, and hemoptysis could suggest BMPR2△/PAH+. However, poor clinical and hemodynamic characterization hinders translating the benefits of genomic analyses to the clinical setting.

BackgroundKidney transplantation is the best treatment option for patients with end-stage kidney disease (ESKD) with a superiority of graft survival after living kidney donation (LKD) compared to deceased donation. However, a large part of potential donors and recipients are ineligible for LKD. Here, we analyze the leading causes for disqualification of potential living donor-recipient pairs from the LKD program and the health-related consequences for ESKD patients excluded from the LKD program in a German transplant center.MethodsIn this single-center retrospective cohort study we evaluated all candidates (potential donors and recipients) presenting for assessment of LKD from 2012 to 2020 at our transplant center. Thereby we focused on candidates excluded from the LKD program. Main reasons for disqualification were categorized as medical (donor-related), psychosocial, immunological, recipient-related, and unknown.ResultsOverall, 601 donor-recipient pairs were referred to our transplant center for LKD assessment during the observation time. Out of those, 326 (54.2%) discontinued the program with 52 (8.7%) dropouts and 274 (45.6%) donor-recipient pairs being ineligible for LKD. Donor-related medical contraindications were the main reason for disqualification [139 out of 274 (50.7%) potential donors] followed by recipient-related contraindications [60 out of 274 (21.9%) of potential donor-recipient pairs]. Only 77 out of 257 (29.9%) potential recipients excluded from the LKD program received a kidney transplant afterward with a median waiting time of 2 (IQR: 1.0–4.0) years. Overall, 18 (7.0%) ESKD patients initially declined for LKD died in this period.ConclusionA large percentage of donor-recipient pairs are disqualified from the German LKD program, mostly due to medical reasons related to the donor and with partly severe consequences for the potential recipients. For these, alternative solutions that promptly enable kidney transplantation are essential for improving patient quality of life and survival.