Postoperative coagulation profiles of patients undergoing adult-to-adult living donor liver transplantation?A single-center experience

Objective: To characterize the pre- and postoperative coagulation profiles of patients undergoing adult-to-adult living donor liver transplantation (LDLT), using various coagulation tests and rotational thromboelastometry (ROTEM). Methods: This single-center observational study evaluated the various coagulation profiles of 22 patients (13 men and 9 women). Blood samples were obtained immediately after the induction of anesthesia (PRE) and on postoperative days (PODs) 1, 3, 5, and 7 after LDLT surgery. Results: Most procoagulant factors (fibrinogen, platelet, and coagulation factors II, VII, VIII, and IX) improved to levels equal to or greater than the PRE levels on POD 7. The levels of von Willebrand factor significantly increased after surgery, whereas those of disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13 decreased. Although the thrombin-antithrombin III complex increased immediately after surgery, the plasmin-α 2 plasmin inhibitor complex increased only on POD 7. The level of plasminogen activator inhibitor-1 increased on POD 1, returning to PRE levels on POD 3. Almost all ROTEM parameters were decreased or prolonged, compared to the PRE levels, on POD 7. Conclusions: The values of most coagulation tests showed the improvement or acceleration of coagulability on POD 7 than at PRE, with almost all the ROTEM parameters decreased or prolonged. Therefore, it cannot be concluded whether ROTEM reflects the net effect of hemostatic balance after liver transplantation

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

エリサンシボウタイサイボウノデンシケンビキョウテキケンキュウ

京都大学0048新制・論文博士理学博士乙第228号論理博第48号新制||理||33(附属図書館)658UT51-51-L147(主査)教授 市川 衞, 教授 中村 健児, 教授 宮地 傅三郎学位規則第5条第2項該当Kyoto UniversityDA

PURIFICATION OF THE BRAIN HORMONE OF THE SILKWORM BOMBYX MORI

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