Prevention and treatment of hemostatic complications in liver disease

This thesis on the prevention and treatment of hemostatic complications in liver disease starts with a detailed study on the hemostasis in cirrhosis. Our in-depth hemostatic profiling of primary, secondary, and tertiary hemostasis in a group of patients with CPT A/B cirrhosis showed no large differences between etiologies, and was consistent with a general hypercoagulable profile in patients with mild cirrhosis. These results suggest that patients with cirrhosis have an increased risk of thrombosis, irrespective of their etiology.Whether this translates to a similar effect of anticoagulants was tested in vitro in patients with cirrhosis due to ASH or NASH. Low-molecular-weight-heparin, dabigatran and apixaban were tested and showed no differences on a hemostatic level between groups.For the in vivo testing of anticoagulants we studied the effect of a therapeutic dose of edoxaban in patients and controls. Edoxaban strongly effects the hemostatic activity in patients, but not as much as in controls. Whether this difference translates into a higher risk of thrombosis and necessitates dose-adjustments in patients with cirrhosis should be further assessed.In vitro testing of commonly used anticoagulants in patients undergoing hepato-pancreatico-bilairy surgery showed a profoundly altered efficacy as compared to healthy controls, which may have implications for anticoagulant dosing in the early postoperative period. In the correction of perioperative bleeding complications, prothrombin complex concentrate (PCC) appear much more potent than fresh frozen plasma or recombinant factor VIIa, and PCCs may require conservative dosing and caution in use in patients undergoing HPB surgery

Mechanisms of enhanced thrombin generating capacity in patients with cirrhosis.

The liver is the site of synthesis of many proteins involved in hemostasis including pro- and anticoagulant proteins, pro- and antifibrinolytic proteins, and thrombopoietin. Consequently, patients with liver disease acquire complex changes within their hemostatic system[1]. Historically, these changes were thought to result in a bleeding diathesis. Although bleeding complications are common in patients with chronic liver disease, the most common bleeding complication, variceal bleeding, is a consequence of portal hypertension, rather than hemostatic failure

Immune defects in the risk of infection and response to vaccination in monoclonal gammopathy of undetermined significance and multiple myeloma

The plasma cell proliferative disorders monoclonal gammopathy of undetermined significance (MGUS) and malignant multiple myeloma (MM) are characterized by an accumulation of transformed clonal plasma cells in the bone marrow and production of monoclonal immunoglobulin. They typically affect an older population, with median age of diagnosis of approximately 70 years. In both disorders, there is an increased risk of infection due to the immunosuppressive effects of disease and conjointly of therapy in MM, and response to vaccination to counter infection is compromised. The underlying factors in a weakened immune response in MGUS and MM are as yet not fully understood. A confounding factor is the onset of normal aging, which quantitatively and qualitatively hampers humoral immunity to affect response to infection and vaccination. In this review, we examine the status of immune alterations in MGUS and MM and set these against normal aging immune responses. We focus primarily on quantitative and functional aspects of B-cell immunity. Furthermore, we review the current knowledge relating to susceptibility to infectious disease in MGUS and MM, and how efficacy of conventional vaccination is affected by proliferative disease-related and therapy-related factors

New risks and opportunities for food security: scenario analyses for 2015 and 2050

"Given the number of undernourished people in the developing world and the increasingly complex risks to food security, policymakers are faced with an enormous agenda. Freeing people from hunger will require more and better-targeted investments, innovations, and policy actions, driven by a keen understanding of the dynamic risks and forces that shape the factors affecting people's access to food and the links with nutrition. The International Food Policy Research Institute's (IFPRI's) International Model for Policy Analysis of Agricultural Commodities and Trade (IMPACT) provides insight into the management of these risks through appropriate policy actions. By projecting future global food scenarios to 2050, IMPACT explores the potential implications of policy action and inaction in several main risk areas as well as the effects on child malnutrition in the developing world, commodity prices, demand, cereal yields, production, and net trade. In the progressive policy actions scenario, which assumes increased investment in rural development, health, education, and agricultural research and development, developing country governments and the international community are able to dramatically reduce the number of food-insecure people, leading to a worldwide decline in hunger. Under these conditions, Latin America and China are able to virtually eliminate child malnutrition by 2050. Bolstered by the development and dissemination of improved technologies and better infrastructure, crop production and yields increase in developing countries. Notably, the bulk of the growth in production is driven by yield increases rather than by expanding land area. Spurred by growth in the agricultural sector, average incomes in developing countries increase. Rising incomes bolster demand for high-value agricultural products, such as meat, dairy, and fruits and vegetables; global livestock production more than doubles, for example. Average per capita calorie supplies for developing countries exceed 3,400 per day, well in excess of minimum requirements. The policy failure scenario assumes greater political discord and more extensive agricultural protectionism, together with the failure of policies to deal with food emergencies related to conflict. Slow growth and trade restrictions lead to stagnation in average per capita calorie availability, which remains only slightly above minimum requirements until after 2030, when availability increases. In addition, crucial investments in agriculture, rural development, and poverty reduction are forgone or displaced. Because of limited investment in agricultural research and technology, this scenario has a high level of crop area expansion as a result of relatively rapid population growth and slim yield improvements in developing countries. This scenario also results in flat maize prices, declining per capita cereal demand, falling beef prices, and relatively flat meat demand. As a result of the policies in this scenario, the number of malnourished children in developing countries rises between 1997 and 2015, after which there are only modest declines. In the technology and natural resource management failure scenario, yield growth falls even more than under the preceding scenario, forcing farmers to move into marginal producing areas, which causes a more rapid expansion of cereal area into less productive land that does not compensate for the yield shortfalls (and causes environmental degradation). As a result, cereal prices rise substantially through 2030 and then fall off only gradually. Beef and other meat prices, which are affected by the price of feed, follow a similar pattern. Developing-country per capita calorie availability is essentially unchanged over 1997–2050 and remains at a barely adequate average level. Given unequal access to the food that is available, millions of people actually consume less than the minimum. The occurrence of child undernourishment is even higher than under the policy failure scenario in all developing-country regions. Overall, the technology and natural resource management failure scenario results in the worst impact on food security and child malnourishment in the developing world. The progressive policy scenario outlines several of the most crucial positive steps. National governments and the international community must assume a new focus on agricultural growth and rural development, along with increasing their investments in education, social services, and health. Policies to encourage synergistic growth in the nonfarm sectors are also needed to spur broad-based economic growth. Underpinning these strategies and research agendas must be a firm commitment to reducing hunger and improving the welfare of the world's undernourished people." From Authors' Executive SummaryImpact model, Caloric intake, Safety nets,

Hemostatic Complications in Hepatobiliary Surgery

Hepatobiliary surgery is a well-known risk factor for thrombotic complications but is also associated with substantial perioperative blood loss. Given the central role of the liver in hemostasis, hepatobiliary surgery is frequently accompanied by complex changes in the hemostatic system. Increasing knowledge of these changes has resulted in an improved understanding of the etiology of some of the hemostatic complications. In the early postoperative period a prolongation of conventional coagulation test times, such as the prothrombin time, is frequently seen. Together with a decreased platelet count, this suggests a hypocoagulable state. The concomitant decline of anticoagulant factors and development of a von Willebrand factor/ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) imbalance, however, suggest a hypercoagulable state, potentially contributing to the risk of thromboembolism. Postoperative thromboprophylaxis should be initiated early to avoid thrombosis, and intensified prophylaxis might benefit high-risk patients. The risk of hemorrhagic complications during hepatobiliary surgery has diminished over time, mainly due to improved surgical and anesthesiological techniques. However, bleeding can still be profound in individual patients and is difficult to predict using (global) hemostasis tests. A restrictive transfusion and fluid infusion policy to maintain a low central venous pressure is crucial in prevention of perioperative bleeding. However, when active bleeding occurs, proactive prohemostatic management is required

Patient and Provider Perspectives on HIV and HIV-Related Stigma in Dutch Health Care Settings

Ensuring that people living with HIV (PLWH) feel accepted in health care settings is imperative. This mixed methods study explored the perspectives of PLWH and health professionals on their interactions. A total of 262 predominantly gay men of Dutch origin participated in a survey study of possible negative interactions with health professionals, and semi-structured interviews were subsequently conducted with 22 PLWH and 14 health professionals. Again, most PLWH were gay men of Dutch origin. All health professionals were Dutch. PLWH reported negative experiences with health professionals including awkward interactions, irrelevant questions, rude treatment, blame, pity, excessive or differential precautions, care refusal, unnecessary referrals, delayed treatment, poor support, and confidentiality breaches. They also reported positive experiences including equal treatment, being valued as a partner in one's health, social support provision, and confidentiality assurances. Health professionals reported having little experience with PLWH and only basic knowledge of HIV. They contended that PLWH are treated equally and that HIV is no longer stigmatized, but also reported fear of occupational infection, resulting in differential precautions. Additionally, they conveyed labeling PLWH's files to warn others, and curiosity regarding how patients acquired HIV. The findings suggest that there is a gap in perception between PLWH and health professionals regarding the extent to which negative interactions occur, and that these interactions should be improved. Implications for stigma reduction and care optimization are discussed

bMagazine 2020

bMagazine is part annual report and part showcase of people thinking bigger and thinking differently about what's possible in communities across the Bush Foundation's region of Minnesota, North Dakota, South Dakota and the 23 Native nations that share that geography

Is the uncertain self good at detecting lies?: The influence of personal uncertainty on deception detection

Five experiments (total number of judging participants = 1309, four different kinds of stimulus materials with a total of 464 messages, total number of judgements = 19,634) investigated the influence of personal uncertainty on the process of lie detection in social relationships. Building on and extending basic assumptions of uncertainty management models, we reasoned that uncertainty about themselves motivates people to evaluate the quality of their relationships. A crucial aspect of the quality of relationships with other people is the truthfulness with which they communicate verbally with you and anyone else. We proposed that if these assumptions are valid, reminding people of their personal uncertainties should lead them to use valid verbal cues in veracity judgements more. This enhanced usage of valid verbal cues should result in better accuracy in deception detection. An internal meta-analysis of the five experiments reveals only a small, not significant, overall effect of uncertainty salience on detection accuracy with larger effect sizes for experiments conducted in the laboratory than for those conducted online. Hence, if personal uncertainty plays a role in the process of deception detection, it seems to be subject to moderators such as methodological or motivational factors

Peer learning and cultural evolution

In this article, we integrate cultural evolutionary theory with empirical research from developmental psychology, cultural anthropology, and primatology to explore the role of peer learning in the development of complex instrumental skills and behavioral norms. We show that instrumental imitation, contingent teaching, generative collaboration, and selective copying contribute to domain-specific transmission of knowledge between peers. Stages of development and characteristics inherent to the learner and model influence how and when children learn from each other. Peer learning is persistent across societies despite cultural beliefs that favor adult–child transmission in some settings. Comparative research hints at the possibility that children's greater motivation to interact with and learn from each other may set humans apart from other primates. We conclude by outlining avenues for future research, including how individual characteristics and developmental changes in social networks, motivation, and cognition may contribute to cultural evolution.</p

Efficacy of pro- and anticoagulant strategies in plasma of patients undergoing hepatobiliary surgery

BACKGROUND: In vitro efficacy of pro- and antihemostatic drugs is profoundly different in patients with compensated cirrhosis and in those who have cirrhosis and are critically ill. OBJECTIVES: Here we assessed the efficacy of pro- and anticoagulant drugs in plasma of patients undergoing hepato-pancreato-biliary (HPB) surgery, which is associated with unique hemostatic changes. METHODS: We performed in vitro analyses on blood samples of 60 patients undergoing HPB surgery and liver transplantation: 20 orthotopic liver transplantations, 20 partial hepatectomies, and 20 pylorus-preserving pancreaticoduodenectomies. We performed thrombin generation experiments before and after in vitro addition of fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), low molecular weight heparin (LMWH), unfractionated heparin, dabigatran, and rivaroxaban. RESULTS: We showed that patients undergoing HPB surgery are in a hypercoagulable state by thrombin generation testing. FFP and rFVIIa had minimal effects on thrombin generation, whereas PCC had a more pronounced procoagulant effect in patients compared with controls. Dabigatran showed a more pronounced anticoagulant effect in patients compared with controls, whereas rivaroxaban and LMWH had a decreased anticoagulant effect in patients. CONCLUSION: We demonstrate profoundly altered in vitro efficacy of commonly used anticoagulants, in patients undergoing HPB surgery compared with healthy controls, which may have implications for anticoagulant dosing in the early postoperative period. In the correction of perioperative bleeding complications, PCCs appear much more potent than FFP or rFVIIa, and PCCs may require conservative dosing and caution in use in patients undergoing HPB surgery