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Graft-versus-host disease (GVHD) is the leading cause of mortality after hematopoietic stem cell transplantation and primarily affects barrier organs such as the skin. One-third of cases are refractory to steroid treatment resulting in poor outcomes and the need for novel therapies. Longitudinal analysis of T-cell transcriptomes in patients before the appearance of GVHD symptoms revealed the upregulation of anti-apoptotic regulator B-cell lymphoma 2 (BCL2) at GVHD initiation. To determine the potential of BCL2 inhibition in active GVHD, we analyzed tissues of 88 patients with acute or chronic GVHD. BCL2 RNA was elevated in multiple organs affected by GVHD and expression correlated with transplant-related mortality and steroid-refractory GVHD. BCL2-expressing lymphocytes were present in skin lesions and peripheral blood of patients with acute and chronic GVHD. Inhibition of BCL2 increased the CD4 to CD8 ratio in allogeneic T cells in vitro and induced apoptosis of T cells from patients with steroid-pretreated chronic GVHD ex vivo. In addition, the higher ratio of regulatory to nonregulatory T cells upon blockage of BCL2 could add to the anti-inflammatory effect of BCL2 blockage. Collectively, our results highlight BCL2 as an important factor for GVHD development and introduce BCL2 inhibition as previously unreported and urgently needed targeted therapy in the treatment of steroid-refractory GVHD., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The study was performed to analyze the results of open-heart surgery and bleeding complications after administration of novel oral anticoagulants (NOAC)., Methods: We investigated 81 consecutive patients (median age 74 years, interquartile range [IQR]: 68 to 78) who underwent open-heart operations at our institution between July 2014 and June 2016. All patients presented for surgery while on NOAC therapy: 37 received rivaroxaban (45.7%), 35 apixaban (43.2%), and 9 dabigatran (11.1%). The calculated risk using the European System for Cardiac Operative Risk Evaluation II was 3.5% (IQR: 2.0% to 8.1%)., Results: Surgery was performed at a median 4 days (IQR: 3 to 6) after NOAC withdrawal. Reduced renal function was predictive for length of intensive care unit stay and administration of red blood cells (p < 0.0001 and p = 0.0291, respectively). The NOAC withdrawal interval significantly influenced postoperative drainage volume (p = 0.0056). Five patients needed rethoracotomy because of relevant bleeding (6.2%), 4 after apixaban (11.4%) and 1 after rivaroxaban therapy (2.7%). Apixaban showed a borderline influence on prolonged intensive care unit stay (p = 0.0736). Prolonged cardiopulmonary bypass time was predictive for thrombocyte administration (p = 0.0249). Intensive care unit stay was 2 days after NOAC withdrawal of 10 days, compared with 4.2 days without termination. Thirty-day mortality was 3.7%., Conclusions: A lengthy NOAC withdrawal period, particularly for patients with reduced renal function, is essential for safe open-heart surgery. We conclude that despite official recommendations, patients should whenever possible not be considered for elective cardiac surgery within 10 days of terminating NOAC treatment., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This article provides a descriptive review of four goal-free evaluations (GFE). GFE is an evaluation model where the evaluator conducts the evaluation without knowledge of or reference to the evaluand's stated goals. The four non-randomly sampled evaluation approaches represent articulated evaluation models in which the evaluators ignore the goals of the intervention or project. Data collection consisted of document analyses supplemented by semi-structured interviews with the models' creators. The findings from these case studies include descriptions of the evaluation models, the models' relationship to GFE, and eight commonalities shared among the four models. The conclusion of this study is that these GFEs are similar to other GFEs described in the literature in that they examine outcomes as reported by the intervention's consumers, focus on collecting qualitative data, and use their evaluations to supplement a larger goal-based evaluation strategy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This article provides a descriptive review of four goal-free program evaluations (GFE). GFE is an evaluation model where the independent evaluator is intentionally screened from the program's stated goals and objectives in hopes of reducing potential goal-related tunnel vision. The findings from these GFE case studies are focused in three areas: (1) elements of the programs that were evaluated and their existing evaluation contexts (e.g., pre-evaluation conditions, size of evaluation budget), (2) design of the GFEs (e.g., screening method, data collection methods), and (3) expertise of the goal-free evaluators (e.g., training, degrees attained). The findings indicate that, when employed, GFE is used as a qualitative data collection method; and the GFEs conducted have been relatively small in size and scope. The conclusions are that a more explicit operationalization of GFE is needed for increased use, and that systematic and empirical study comparing GFE with other evaluation models is warranted., (Copyright © 2014 Elsevier Ltd. All rights reserved.)