Patient blood management in elective orthopaedic surgery

Chapter 2 describes the results of a RCT on the effect of a restrictive trigger on RBC sparing. In three hospitals, a restrictive transfusion policy was compared with standard care transfusion policy. A randomised comparison of transfusion triggers in elective orthopaedic surgery using leucocyte-depleted red blood cells was performed. The clinical consequences of this restrictive transfusion policy on post-operative complications and well-being are discussed in Chapter 3. Quality of Life and fatigue scores in relation to postoperative haemoglobin levels were analysed in Chapter 4. In Chapter 5 we investigated the efficacy and feasibility of two types of postoperative drainage and re-infusion systems and compared these to a control group. To evaluate the immuno-modulatory effects of salvaged blood in the post-operative patient, we analysed the effect of autologous salvaged blood re-infusion on the patients__ cytokine gene expression profiles compared to the effect of surgery itself (Chapter 6). Chapter 7 reports the combined strategies of Epo and autologous salvaged blood on RBC use compared to a control group under a restrictive transfusion policy (TOMaat study). In Chapter 8, future trends and ongoing studies are discussed in order to aim for an optimal and Tailor Made Patient Blood Management Program for elective orthopaedic surgery patients. In the final chapter, Chapter 9, an implementation protocol is described to investigate the barriers and facilitators for implementation of the TOMaat study results in daily practice.UBL - phd migration 201

Hip and knee replacement patients prefer pen-and-paper questionnaires : implications for future patient-reported outcome measure studies

Analysis and Stochastic

Patient acceptable symptom states after total hip or knee replacement at mid-term follow-up. Thresholds of the Oxford hip and knee scores

Analysis and Stochastic

Association of Timing of Plasma Transfusion With Adverse Maternal Outcomes in Women With Persistent Postpartum Hemorrhage

IMPORTANCE Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the association of early plasma transfusion with maternal outcomes. OBJECTIVE To compare the incidence of adverse maternal outcomes among women who received plasma during the first 60 minutes of persistent PPH vs women who did not receive plasma for similarly severe persistent PPH. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study used a consecutive sample of women with persistent PPH, defined as PPH refractory to first-line measures to control bleeding, between January 1, 2011, and January 1, 2013. Time-dependent propensity score matching was used to select women who received plasma during the first 60 minutes of persistent PPH and match each of them with a woman who had shown the same severity and received the same treatment of PPH but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests. Statistical analysis was performed from June 2018 to June 2019. EXPOSURES Transfusion of plasma during the first 60 minutes of persistent PPH vs no or later plasma transfusion. MAIN OUTCOMES AND MEASURES Incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization. RESULTS This study included 1216 women (mean [SD] age, 31.6 [5.0] years) with persistent PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. Seven women (0.6%) died because of PPH, 62 women (5.1%) had a hysterectomy, and 159 women (13.1%) had arterial embolizations. Among women who received plasma during the first 60 minutes of persistent PPH, 114 women could be matched with a comparable woman who had not received plasma at the moment of matching. The incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio, 1.09; 95% CI, 0.57-2.09). Results of sensitivity analyses were comparable to the primary results. CONCLUSIONS AND RELEVANCE In this cohort study, initiation of plasma transfusion during the first 60 minutes of persistent PPH was not associated with adverse maternal outcomes compared with no or later plasma transfusion, independent of severity of PPH

Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI

Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading. This risk may be influenced by systemic factors accompanying BMI. Fluctuations in concentrations of metabolites may mark or even contribute to development of OA. This study explores the association of metabolites with radiographic knee/hip OA prevalence and progression. A 1H-NMR-metabolomics assay was performed on plasma samples of 1564 cases for prevalent OA and 2,125 controls collected from the Rotterdam Study, CHECK, GARP/NORREF and LUMC-arthroplasty cohorts. OA prevalence and 5 to 10 year progression was assessed by means of Kellgren-Lawrence (KL) score and the OARSI-atlas. End-stage knee/hip OA (TJA) was defined as indication for arthroplasty surgery. Controls did not have OA at baseline or follow-up. Principal component analysis of 227 metabolites demonstrated 23 factors, of which 19 remained interpretable after quality-control. Associations of factor scores with OA definitions were investigated with logistic regression. Fatty acids chain length (FALen), which was included in two factors which associated with TJA, was individually associated with both overall OA as well as TJA. Increased Fatty Acid chain Length is associated with OA

Stability of domain structures in multi-domain proteins

Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR

The European Hematology Association Roadmap for European Hematology Research. A Consensus Document

Abstract The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Received December 15, 2015. Accepted January 27, 2016. Copyright © 2016, Ferrata Storti Foundatio

The European Hematology Association Roadmap for European Hematology Research: a consensus document

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and