Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation

Introduction

Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR.

Methods

We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro).

Results

E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001).

Conclusions

This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.     

Proposal for a multiphase fall model based on real-world fall recordings with body-fixed sensors

Falls are by far the leading cause of fractures and accidents in the home environment. The current Cochrane reviews and other systematic reviews report on more than 200 intervention studies about fall prevention. A recent meta-analysis has summarized the most important risk factors of accidental falls. However, falls and fall-related injuries remain a major challenge. One novel approach to recognize, analyze, and work better toward preventing falls could be the differentiation of the fall event into separate phases. This might aid in reconsidering ways to design preventive efforts and diagnostic approaches. From a conceptual point of view, falls can be separated into a pre-fall phase, a falling phase, an impact phase, a resting phase, and a recovery phase. Patient and external observers are often unable to give detailed comments concerning these phases. With new technological developments, it is now at least partly possible to examine the phases of falls separately and to generate new hypotheses. The article describes the practicality and the limitations of this approach using body-fixed sensor technology. The features of the different phases are outlined with selected real-world fall signals.     

Physical activity behavior after total hip arthroplasty (THA): a prediction based on patient characteristics

OBJECTIVE: To determine to what extent aspects of patient characteristics (age, gender, family status, education and comorbidity) are predictive for the level of physical activity of persons with a total hip arthroplasty (THA). METHODS: A cross-sectional study including 372 patients. Demographics, comorbidity and physical activity behavior were assessed by means of a questionnaire and from medical records. Linear regression analysis was used to determine to what extent patient characteristics are predictive of level of physical activity. Binary logistic regression modeling was used to determine the extent to which patient characteristics are predictive in meeting international guidelines on health-enhancing physical activity. RESULTS: Age, education and family status significantly predict level of physical activity (R(2)=0.19). Only gender significantly predicts meeting international guidelines on health-enhancing physical activity (OR=2.06, 95% CI 1.20-3.54). CONCLUSION: Patients at risk can be identified by means of patient characteristics. Increasing age, lower education and living alone are associated with a physically inactive lifestyle. PRACTICE IMPLICATIONS: Health care workers involved in the treatment of THA patients should lay an emphasis on the beneficial aspects of physical activity.     

Groningen orthopaedic exit strategy: Validation of a support program after total hip or knee arthroplasty

OBJECTIVE: Validation of the program theory of the Groningen orthopaedic exit strategy (GOES), a theory-driven program aiming to improve the rehabilitation of total hip and knee arthroplasty patients after shortened hospital stay. First part of the program theory is the action theory, hypothesising that the GOES treatment positively influences the mediating variables (self-efficacy, social support, pain-coping). The second part, the conceptual theory, hypothesis a positive relationship between these variables and the outcome variables (ADL functioning, physical activity behaviour, quality of life). METHODS: Patients were randomly assigned to the GOES or control groups. Questionnaires were used to assess mediating and outcome variables in 103 patients (50 GOES, 53 controls) pre-operatively, and 6 and 26 weeks post-operatively. RESULTS: No difference was seen between the two groups in terms of changes between pre-operative and post-operative mediating variables (action theory). Moderate-to-large correlations explaining reasonable amount of variance (22%, 25%, 56%) were found between the mediating and outcome variables (conceptual theory). CONCLUSION: The conceptual theory is supported; however, as the treatment did not influence the mediating variables (action theory), it has no added value in its current form. PRACTICE IMPLICATIONS: The treatment needs to be adjusted; it is discussed that individualised treatment could be more effective.     

An update on the use of anticoagulant therapy in ST-segment elevation myocardial infarction

Introduction: Together with antiplatelet therapy, anticoagulants are vital to improve outcomes in patients presenting with ST-segment elevation myocardial infarction.

Challenges lie in finding the optimal balance between the risk of bleeding and preventing thrombotic complications such as reinfarction or stent thrombosis. During the last decade, bivalirudin was introduced as a valid alternative to heparin for patients undergoing primary percutaneous coronary intervention. Several trials have been conducted to identify the agent with the best antithrombotic results at the lowest bleeding complication rate. In a rapidly evolving field with changes in vascular access, available P2Y₁₂ inhibitors, and indications for glycoprotein IIb/IIIa inhibitor administration, conflicting evidence became available.

Areas covered: This paper mainly focuses on the evidence above and gives brief discussion to the recent literature on anticoagulation in fibrinolytic therapy and advances in antiplatelet therapy.

Expert opinion: To date, no robust evidence is available challenging unfractionated heparin as the primary choice for anticoagulation in patients presenting with ST-segment elevation myocardial infarction. Further research should include efforts to refine anticoagulation strategies on an individual patient level. For patients undergoing primary percutaneous coronary intervention, bivalirudin could be used as an alternative to unfractionated heparin, while enoxaparin or fondaparinux is an alternative agent for patients treated with fibrinolytic therapy.     

Recovery of gait after short-stay total hip arthroplasty

OBJECTIVE: To describe recovery of gait after total hip arthroplasty (THA) based on the assessment of spatiotemporal gait parameters determined with an ambulatory system. DESIGN: A 6-month inception cohort study. SETTING: Inpatient and outpatient setting in an academic hospital. PARTICIPANTS: Sixty-three patients participating in a short-stay program for THA. INTERVENTION: Primary unilateral THA. MAIN OUTCOME MEASURES: Walking speed, step length, step duration, and variability coefficient assessed at different walking speeds while performing an additional cognitive task and an endurance test. All measures were obtained preoperatively and 6 weeks and 6 months postoperatively. RESULTS: Patients improved significantly over time; however, extent and speed of recovery of gait parameters differed for each test part. The relation between walking speed and step length showed systematic improvement when analyzed over a range of speeds. At 6 months, the variability coefficient of the additional task test part was comparable with the preferred walking variability coefficient. The endurance test results could be predicted from the results of preferred walking. CONCLUSIONS: Assessment of recovery of gait function requires more than only assessment of "normal" walking. Particularly, an analysis of walking at different speeds and walking while performing an additional cognitive task demonstrate different aspects of gait recovery after THA.