Spectroscopic Study of the Effects of Bioprotectant Systems on the Protein Stability

In the present article the effect of kosmotrope compounds, i.e. systems having the capability to stabilize biological macromolecules, is investigated by using complementary techniques. The attention is focused on the kosmotrope character of trehalose, a glucose disaccharide, compared to its homologous maltose and sucrose. Complementary techniques of neutron scattering, such as Inelastic Neutron Scattering (INS) and Quasi Elastic Neutron Scattering (QENS) allow to point out the capability of trehalose to strongly affect both the structural and dynamical properties of water. Finally the stabilization effect of trehalose on a well know protein, lysozyme, is studied as a function of temperature by Small Angle Neutron Scattering (SANS)

Young deceased donor kidneys show a survival benefit over older donor kidneys in transplant recipients aged 20-50 years:a study by the ERA-EDTA Registry

Background: Updated survival outcomes of young recipients receiving young or old deceased donor kidneys are required when considering accepting a deceased donor kidney. Methods: We examined outcomes in 6448 European kidney allografts donated from younger (≥20-<50 years) and older (≥50-<70 years) deceased donors when transplanted into very young (≥20-<35 years) or young (≥35-<50 years) adult recipients. Outcomes of first kidney transplantations during 2000-13 and followed-up to 2015 were determined via competing risk, restricted mean survival and Cox regression methods. Results: The 10-year cumulative incidence of graft failure was lowest in very young {22.0% [95% confidence interval (95% CI) 19.1-24.9]} and young [15.3% (95% CI 13.7-16.9)] recipients of younger donor kidneys and highest in very young [36.7% (95% CI 31.9-41.5)] and young [29.2% (95% CI 25.1-33.2)] recipients of older donor kidneys. At the 10-year follow-up, younger donor kidneys had a 1 year (very young) or 9 months (young) longer mean graft survival time compared with older donor kidneys. Graft failure risk in younger donor kidneys was 45% [very young adjusted hazard ratio (aHR) 0.55 (95% CI 0.44-0.68)] and 40% [young aHR 0.60 (95% CI 0.53-0.67)] lower compared with older donor kidneys. A 1-year increase in donor age resulted in a 2% [very young aHR 1.02 (95% CI 1.00-1.04)] or 1% [young aHR 1.01 (95% CI 1.00-1.01)] increase in the 10-year risk of death. Conclusions: Younger donor kidneys show survival benefits over older donor kidneys in adult recipients ages 20-50 years. Updated survival outcomes from older deceased donors are necessary due to advances in transplantation medicine and the increasing role these donors play in organ transplantation

Temporal trends in the quality of deceased donor kidneys and kidney transplant outcomes in Europe:an analysis by the ERA-EDTA Registry

BACKGROUND: We investigated 10-year trends in deceased donor kidney quality expressed as the kidney donor risk index (KDRI) and subsequent effects on survival outcomes in a European transplant population. METHODS: Time trends in the crude and standardized KDRI between 2005 and 2015 by recipient age, sex, diabetic status and country were examined in 24 177 adult kidney transplant recipients in seven European countries. We determined 5-year patient and graft survival probabilities and the risk of death and graft loss by transplant cohort (Cohort 1: 2005–06, Cohort 2: 2007–08, Cohort 3: 2009–10) and KDRI quintile. RESULTS: The median crude KDRI increased by 1.3% annually, from 1.31 [interquartile range (IQR) 1.08–1.63] in 2005 to 1.47 (IQR 1.16–1.90) in 2015. This increase, i.e. lower kidney quality, was driven predominantly by increases in donor age, hypertension and donation after circulatory death. With time, the gap between the median standardized KDRI in the youngest (18–44 years) and oldest (>65 years) recipients widened. There was no difference in the median standardized KDRI by recipient sex. The median standardized KDRI was highest in Austria, the Netherlands and the Basque Country (Spain). Within each transplant cohort, the 5-year patient and graft survival probability were higher for the lowest KDRIs. There was no difference in the patient and graft survival outcomes across transplant cohorts, however, over time the survival probabilities for the highest KDRIs improved. CONCLUSIONS: The overall quality of deceased donor kidneys transplanted between 2005 and 2015 has decreased and varies between age groups and countries. Overall patient and graft outcomes remain unchanged

Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis

Robust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual-patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for SVT. Medline, Embase, and clincaltrials.gov were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies of a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range, 1-730 days). Overall, incidence rates for recurrent venous thromboembolism (VTE), major bleeding, and mortality were 5.3 per 100 patient-years (p-y; 95% confidence interval [CI], 5.1-5.5), 4.4 per 100 p-y (95% CI, 4.2-4.6), and 13.0 per 100 p-y (95% CI, 12.4-13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.27-0.64), major bleeding (HR, 0.47; 95% CI, 0.30-0.74), and mortality (HR, 0.23; 95% CI, 0.17-0.31). Results were consistent in patients with cirrhosis, solid cancers, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent nonmalignant risk factors. In patients with SVT, the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes. © 2022 by The American Society of Hematology

Characteristics and Outcomes of Patients With Systemic Sclerosis (Scleroderma) Requiring Renal Replacement Therapy in Europe : Results From the ERA-EDTA Registry

Rationale & Objective: Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT. Study Design: Registry study of incidence and prevalence and a matched cohort study of clinical outcomes. Setting & Participants: Patients represented in any of 19 renal registries that provided data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry between 2002 and 2013. Predictor: Scleroderma as the identified cause of ESRD. Outcomes: Incidence and prevalence of ESRD from scleroderma. Recovery from RRT dependence, patient survival after ESRD, and graft survival after kidney transplantation. Analytical Approach: Incidence and prevalence were calculated using population data from the European Union and standardized to population characteristics in 2005. Patient and graft survival were compared with 2 age- and sex-matched control groups without scleroderma: (1) diabetes mellitus as the cause of ESRD and (2) conditions other than diabetes mellitus as the cause of ESRD. Survival analyses were performed using Kaplan-Meier analysis and Cox regression. Results: 342 patients with scleroderma (0.14% of all incident RRT patients) were included. Between 2002 and 2013, the range of adjusted annual incidence and prevalence rates of RRT for ESRD due to scleroderma were 0.11 to 0.26 and 0.73 to 0.95 per million population, respectively. Recovery of independent kidney function was greatest in the scleroderma group (7.6% vs 0.7% in diabetes mellitus and 2.0% in other primary kidney diseases control group patients, both P Limitations: No data for extrarenal manifestations, treatment, or recurrence. Conclusions: Survival of patients with scleroderma who receive dialysis for more than 90 days was worse than for those with other causes of ESRD. Patient survival after transplantation was similar to that observed among patients with ESRD due to other conditions. Patients with scleroderma had a higher rate of recovery from RRT dependence than controls.Peer reviewe