Showing papers by "German Red Cross published in 2019"

Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference

Abstract: Importance Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs. Objective To develop a set of evidence-based recommendations for patient blood management (PBM) and for research. Evidence Review The scientific committee developed 17 Population/Intervention/Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018. Findings From 17 607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23 143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration Conclusions and Relevance The 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.

Interaction of tumor-associated macrophages and cancer chemotherapy.

Abstract: It has been recently recognized that the tumor microenvironment (TME) is an essential factor that defines the efficiency of chemotherapy. The local TME, consisting of immune cells with diverse phenotypes and functions, can strongly modulate the response to chemotherapy. Tumor-associated macrophages (TAMs) that display pronounced heterogeneity and phenotypic plasticity are the major innate immune component in the microenvironment of solid tumors. In our review, we elucidate the complex role of TAMs in the progression of different types of solid tumors, summarize the current knowledge about the effects of different anticancer chemotherapeutic agents on monocytes/macrophages, and describe the mechanisms of chemotherapy resistance mediated by TAMs.

Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation

Abstract: PurposeClonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT).MethodsWe collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS).ResultsA total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001)....

CAR-Engineered NK Cells for the Treatment of Glioblastoma: Turning Innate Effectors Into Precision Tools for Cancer Immunotherapy

Abstract: Glioblastoma (GB) is the most common and aggressive primary brain tumor in adults and currently incurable. Despite multimodal treatment regimens, median survival in unselected patient cohorts is <1 year, and recurrence remains almost inevitable. Escape from immune surveillance is thought to contribute to the development and progression of GB. While GB tumors are frequently infiltrated by natural killer (NK) cells, these are actively suppressed by the GB cells and the GB tumor microenvironment. Nevertheless, ex vivo activation with cytokines can restore cytolytic activity of NK cells against GB, indicating that NK cells have potential for adoptive immunotherapy of GB if potent cytotoxicity can be maintained in vivo. NK cells contribute to cancer immune surveillance not only by their direct natural cytotoxicity which is triggered rapidly upon stimulation through germline-encoded cell surface receptors, but also by modulating T-cell mediated antitumor immune responses through maintaining the quality of dendritic cells and enhancing the presentation of tumor antigens. Furthermore, similar to T cells, specific recognition and elimination of cancer cells by NK cells can be markedly enhanced through expression of chimeric antigen receptors (CARs), which provides an opportunity to generate NK-cell therapeutics of defined specificity for cancer immunotherapy. Here, we discuss effects of the GB tumor microenvironment on NK-cell functionality, summarize early treatment attempts with ex vivo activated NK cells, and describe relevant CAR target antigens validated with CAR-T cells. We then outline preclinical approaches that employ CAR-NK cells for GB immunotherapy, and give an overview on the ongoing clinical development of ErbB2 (HER2)-specific CAR-NK cells currently applied in a phase I clinical trial in glioblastoma patients.

Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases

Abstract: Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a critical regulator of cell death and inflammation, but its relevance for human disease pathogenesis remains elusive. Studies of monogenic disorders might provide critical insights into disease mechanisms and therapeutic targeting of RIPK1 for common diseases. Here, we report on eight patients from six unrelated pedigrees with biallelic loss-of-function mutations in RIPK1 presenting with primary immunodeficiency and/or intestinal inflammation. Mutations in RIPK1 were associated with reduced NF-κB activity, defective differentiation of T and B cells, increased inflammasome activity, and impaired response to TNFR1-mediated cell death in intestinal epithelial cells. The characterization of RIPK1-deficient patients highlights the essential role of RIPK1 in controlling human immune and intestinal homeostasis, and might have critical implications for therapies targeting RIPK1.

Symptomatology and symptomatic treatment in multiple sclerosis: Results from a nationwide MS registry.

Abstract: Background:Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease. Over time, symptoms accumulate leading to increased disability of patients.Objective:The objective of this a...

A combined immunodeficiency with severe infections, inflammation, and allergy caused by ARPC1B deficiency.

Abstract: We report the natural history, clinical manifestations, genetics, and immunohematological findings in 14 patients from 11 families with ARPC1B deficiency, delineating the spectrum of the disease that appears progressive and challenging to manage clinically.

International Society of Blood Transfusion Working Party on Red Cell Immunogenetics and Blood Group Terminology: Report of the Dubai, Copenhagen and Toronto meetings

Abstract: Background and objectives: The International Society of Blood Transfusion (ISBT) Working Party for Red Cell Immunogenetics and Blood Group Terminology meets in association with the ISBT congress and has met three times since the last report: at the international meetings held in Dubai, United Arab Emirates, September 2016 and Toronto, Canada, June 2018; and at a regional congress in Copenhagen, Denmark, June 2017 for an interim session. Methods: As in previous meetings, matters pertaining to blood group antigen nomenclature and classification were discussed. New blood group antigens were approved and named according to the serologic and molecular evidence presented. Results and conclusions: Fifteen new blood group antigens were added to eight blood group systems. One antigen was made obsolete based on additional data. Consequently, the current total of blood group antigens recognized by the ISBT is 360, of which 322 are clustered within 36 blood groups systems. The remaining 38 antigens are currently unassigned to a known system. Clinically significant blood group antigens continue to be discovered, through serology/sequencing and/or recombinant or genomic technologies.

Clinical Use of Mesenchymal Stromal Cells in the Treatment of Acute Graft-versus-Host Disease.

Abstract: Acute graft-versus-host disease (aGvHD) continues to impact morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). First-line therapy for aGvHD still remains the use of high-dose corticosteroids. Unfortunately, 40–60% of patients with aGvHD exhibit steroid resistance, which is associated with a very poor prognosis. As no effective second-line therapy existed, in recent decades various treatment options were considered for the treatment of therapy-refractory GvHD. Based on their in vitro immunomodulatory properties, the use of mesenchymal stromal cells (MSCs) in the treatment of aGvHD has been introduced. However, most of the clinical data are generated from uncontrolled trials and case series, showing clinical responses to MSCs. Clinical results are more consistent in children despite the use of MSC preparations of various provenance and manufacturing protocols. While these data support the therapeutic principle, the great variability of outcomes strongly suggests that not all MSC preparations are equal and that the specific manufacturing protocols influence therapeutic success in vivo.

The German National Registry of Primary Immunodeficiencies (2012-2017).

Abstract: Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.

Low level of exosomal long non-coding RNA HOTTIP is a prognostic biomarker in colorectal cancer.

Abstract: Molecular risk stratification of colorectal cancer can improve patient outcome. A panel of lncRNAs (H19, HOTTIP, HULC and MALAT1) derived from serum exosomes of patients with non-metastatic...

Quantitation of progenitor cell populations and growth factors after bone marrow aspirate concentration.

Abstract: The number of Mesenchymal Stem/Stromal Cells (MSCs) in the human bone marrow (BM) is small compared to other cell types. BM aspirate concentration (BMAC) may be used to increase numbers of MSCs, but the composition of MSC subpopulations and growth factors after processing are unknown. The purpose of this study was to assess the enrichment of stem/progenitor cells and growth factors in BM aspirate by two different commercial concentration devices versus standard BM aspiration. 120 mL of BM was aspirated from the iliac crest of 10 male donors. Each sample was processed simultaneously by either Emcyte GenesisCS® (Emcyte) or Harvest SmartPReP2 BMAC (Harvest) devices and compared to untreated BM aspirate. Samples were analyzed with multicolor flow cytometry for cellular viability and expression of stem/progenitor cells markers. Stem/progenitor cell content was verified by quantification of colony forming unit-fibroblasts (CFU-F). Platelet, red blood cell and total nucleated cell (TNC) content were determined using an automated hematology analyzer. Growth factors contents were analyzed with protein quantification assays. Statistical analyses were performed by ANOVA analysis of variance followed by Tukey’s multiple comparison test or Wilcoxon matched-pairs signed rank test with p < 0.05 for significance. Cell viability after processing was approximately 90% in all groups. Compared to control, both devices significantly enriched TNCs and platelets, as well as the CD45−CD73+ and CD45−CD73+CD90+ cell populations. Further, Harvest significantly concentrated CD45−CD10+, CD45−CD29+, CD45−CD90+, CD45−CD105+, CD45−CD119+ cells, and CD45dimCD90+CD271+ MSCs, whereas Emcyte significantly enriched CD45dimCD44+CD271+ MSCs. BM concentration also increased the numbers of CFU-F, platelet-derived growth factor, vascular endothelial growth factor, macrophage colony-stimulating factor, interleukin-1b, VCAM-1 and total protein. Neither system concentrated red blood cells, hematopoietic stem cells or bone morphogenetic proteins. This data could contribute to the development of BMAC quality control assays as both BMAC systems concentrated platelets, growth factors and non-hematopoietic stem cell subpopulations with distinct phenotypes without loss of cell viability when compared to unprocessed BM.

Self versus Nonself Discrimination by the Soluble Complement Regulators Factor H and FHL-1.

Abstract: The plasma proteins Factor H (FH) and its alternate splice variant FH-like protein 1 (FHL-1) are the major regulators of the complement alternative pathway. The indiscriminate nature of alternative pathway activation necessitates the regulators to be host selective, but the underlying principles of selectivity remained largely elusive. By analyzing human FH and FHL-1 for protection of different host and foreign cells (rabbit and yeast), we uncovered a 2-fold discriminatory mechanism of FH in favor of self: relative to FHL-1, FH exhibits a regulatory benefit on self but importantly, also, a regulatory penalty on nonself surfaces, yielding a selectivity factor of ∼2.4 for sialylated host surfaces. We further show that FHL-1 possesses higher regulatory activity than known but is relatively unselective. The reason for this unexpected high activity of FHL-1 is the observation that the complement regulatory site in FH exceeds the established first four domains. Affinity for C3b, cofactor and decay-accelerating activities, and serum assays demonstrate that the regulatory site extends domains 1-4 and includes domains 5-7. But unlike FH, FHL-1 exhibits a fast plasma clearance in mice, occurs sparsely in human plasma (at one fortieth of the FH concentration), and resists deregulation by FH-related proteins. These physiological differences and its late phylogenetic occurrence argue that FHL-1 is crucial for local rather than systemic compartments. In conclusion, we demonstrate a 2-fold discriminatory power of FH to promote selectivity for self over foreign and show that FHL-1 is more active than known but specialized for regulation on local tissues.

Gelatin-Methacryloyl (GelMA) Formulated with Human Platelet Lysate Supports Mesenchymal Stem Cell Proliferation and Differentiation and Enhances the Hydrogel's Mechanical Properties.

Abstract: Three-dimensional (3D) cell culture is a major focus of current research, since cultivation under physiological conditions provides more reliable information about in vivo cell behavior. 3D cell cultures are used in basic research to better understand intercellular and cell-matrix interactions. Moreover, 3D cell culture plays an increasingly important role in the in vitro testing of bioactive substances and tissue engineering. Gelatin-methacryloyl (GelMA) hydrogels of different degrees of functionalization (DoFs) are a versatile tool for 3D cell culture and related applications such as bioprinting. Human platelet lysate (hPL) has already demonstrated positive effects on 2D cell cultures of different cell types and has proven a valuable alternative to fetal calf serum (FCS). Traditionally, all hydrogels are formulated using buffers. In this study, we supplemented GelMA hydrogels of different DoF with hPL during adipose tissue-derived mesenchymal stem cell (AD-MSCs) encapsulation. We studied the effect of hPL supplementation on the spreading, proliferation, and osteogenic differentiation of AD-MSCs. In addition, the influence of hPL on hydrogel properties was also investigated. We demonstrate that the addition of hPL enhanced AD-MSC spreading, proliferation, and osteogenic differentiation in a concentration-dependent manner. Moreover, the addition of hPL also increased GelMA viscosity and stiffness.

Children and Adults with Refractory Acute Graft-versus-Host Disease Respond to Treatment with the Mesenchymal Stromal Cell Preparation "MSC-FFM"-Outcome Report of 92 Patients

Abstract: (1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.

Household-level effects of providing forecast-based cash in anticipation of extreme weather events: Quasi-experimental evidence from humanitarian interventions in the 2017 floods in Bangladesh

Abstract: In 2017, Bangladesh experienced the worst floods in recent decades. Based on a forecast and pre-defined trigger level, a Red Cross Red Crescent project distributed an unconditional cash grant of BDT 5000 (USD 60 equivalent) to 1039 poor households in highly vulnerable, flood-prone communities in the Brahmaputra river basin before an early flood peak. Systems that can deliver forecast-based cash grants are a potential adaptation strategy to deal with changes in extreme events linked to climate change. This paper presents the results of a mixed-methods, quasi-experimental study, based on a post-disaster household survey. The research assesses the effectiveness of the forecast-based cash distribution in helping beneficiaries to take preparatory early actions and reduce the negative impacts of the flood on their health, well-being, assets and livelihoods. The assessment shows that the cash grants contributed to improving households' access to food, a reduction in high-interest debt accrual of vulnerable households, and reduced psychosocial stress during and after the flood period, compared to a control group of similarly vulnerable and flood-affected communities that did not receive the forecast-based cash assistance. The intervention may also have prevented households from being forced to make destitution sales of valuable assets, as indicated by qualitative data collected in July, but we do not see these benefits sustained after a second flood peak in August 2017. There is a need for further research to assess the longer-term effects of forecast-based cash on the socio-economic development and well-being of the most vulnerable.

Molecular signature of human bone marrow-derived mesenchymal stromal cell subsets.

Abstract: In the current study we compared the molecular signature of expanded mesenchymal stromal cells (MSCs) derived from selected CD271+ bone marrow mononuclear cells (CD271-MSCs) and MSCs derived from non-selected bone marrow mononuclear cells by plastic adherence (PA-MSCs). Transcriptome analysis demonstrated for the first time the upregulation of 115 and downregulation of 131 genes in CD271-MSCs. Functional enrichment analysis showed that the upregulated genes in CD271-MSCs are significantly enriched for extracellular matrix (tenascin XB, elastin, ABI family, member 3 (NESH) binding protein, carboxypeptidase Z, laminin alpha 2 and nephroblastoma overexpressed) and cell adhesion (CXCR7, GPNMB, MYBPH, SVEP1, ARHGAP6, TSPEAR, PIK3CG, ABL2 and NCAM1). CD271-MSCs expressed higher gene transcript levels that are involved in early osteogenesis/chondrogenesis/adipogenesis (ZNF145, FKBP5). In addition, increased transcript levels for early and late osteogenesis (DPT, OMD, ID4, CRYAB, SORT1), adipogenesis (CTNNB1, ZEB, LPL, FABP4, PDK4, ACDC), and chondrogenesis (CCN3/NOV, CCN4/WISP1, CCN5/WISP2 and ADAMTS-5) were detected. Interestingly, CD271-MSCs expressed increased levels of hematopoiesis associated genes (CXCL12, FLT3L, IL-3, TPO, KITL). Down-regulated genes in CD271-MSCs were associated with WNT and TGF-beta signaling, and cytokine/chemokine signaling pathways. In addition to their capacity to support hematopoiesis, these results suggest that CD271-MSCs may contain more osteo/chondro progenitors and/or feature a greater differentiation potential.

Oncogenic Deregulation of Cell Adhesion Molecules in Leukemia

Abstract: Numerous cell–cell and cell–matrix interactions within the bone marrow microenvironment enable the controlled lifelong self-renewal and progeny of hematopoietic stem and progenitor cells (HSPCs). On the cellular level, this highly mutual interaction is granted by cell adhesion molecules (CAMs) integrating differentiation, proliferation, and pro-survival signals from the surrounding microenvironment to the inner cell. However, cell–cell and cell–matrix interactions are also critically involved during malignant transformation of hematopoietic stem/progenitor cells. It has become increasingly apparent that leukemia-associated gene products, such as activated tyrosine kinases and fusion proteins resulting from chromosomal translocations, directly regulate the activation status of adhesion molecules, thereby directing the leukemic phenotype. These observations imply that interference with adhesion molecule function represents a promising treatment strategy to target pre-leukemic and leukemic lesions within the bone marrow niche. Focusing on myeloid leukemia, we provide a current overview of the mechanisms by which leukemogenic gene products hijack control of cellular adhesion to subsequently disturb normal hematopoiesis and promote leukemia development.

Human Leucocyte Antigen Sensitisation and Its Impact on Transfusion Practice.

Abstract: Human leucocyte antigen (HLA) sensitisation, including the formation of antibodies against HLA, can cause serious effects in patients receiving blood. Under certain circumstances, donor HLA antibodies in the blood product can trigger the patient's granulocytes to release mediators that cause transfusion-associated lung injury (TRALI), a serious complication of transfusion. The HLA systems of both donor and patient are involved in transfusion-associated graft-versus-host disease, which is a rare disease with a high mortality. Patient HLA antibodies can destroy incompatible platelets and may cause refractoriness to platelet transfusion. Identification of a patient's HLA antibody specificities is necessary for issuing compatible platelets to overcome refractoriness. Many techniques for the detection and identification of HLA antibodies have been developed, including complement-dependent cytotoxicity assay, bead-based assays, the platelet adhesion immunofluorescence test, and the monoclonal antibody-specific immobilisation of platelet antigens assay. Different strategies for the selection of HLA-compatible platelets are applied. These strategies depend on the breadth of antibody reactivity and range from avoiding single HLA antigens in the platelet concentrates issued to apheresis of platelets from HLA-identical donors. The mechanisms of HLA sensitisation and the efforts made to provide compatible blood products to sensitised patients are reviewed in this article from the perspective of clinical transfusion medicine.

Secondary Traumatization, Psychological Stress, and Resilience in Psychosocial Emergency Care Personnel.

Abstract: Volunteers active in psychosocial emergency care offer psychological first aid to survivors of accidents and trauma, their relatives, eye witnesses, bystanders, and other first responders. So far, there are no studies that investigate the secondary and primary traumatization of this group of first responders. We included N = 75 volunteers, who filled out questionnaires to assess their secondary (QST/FST) and primary traumatization (PDS), and levels of comorbid psychological stress (PHQ-9, GAD-7, SF-12). We investigated factors of resilience by measuring attachment behavior (ECR-RD, RQ-2), level of personality functioning (OPD-SFK), sense of coherence (SOC-29), social support (F-SozU), and mindfulness (MAAS). The volunteers' levels of secondary and primary traumatization were below cut-off scores. Their levels of comorbid psychological stress were comparable to representative norm samples. Additionally, the volunteers presented high levels of resilience. Gender (β = 0.26; p < 0.05), case discussions (β = -0.37; p < 0.05), and social support (β = 0.45; p < 0.01) were revealed to be predictors of secondary traumatization, while mindfulness turned out to be a predictor of primary traumatization (β = -0.34; p = 0.008). However, we cannot rule out that the low prevalence of traumatization and comorbid psychological stress in our study sample might not be explained by a positive response bias.