Aims The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.
The objective of this study was to estimate tacrolimus population parameter values and to evaluate the ability of the maximum a posteriori probability (MAP) Bayesian fitting procedure to predict tacrolimus blood levels, using the traditional strategy of monitoring only trough levels, for dosage individualization in liver transplant patients. Forty patients treated with tacrolimus after liver transplantation were studied during the early posttransplant phase (first 2 weeks). This phase was divided into four time periods (1-4 days, 5-7 days, 8-11 days, 12-14 days). Tacrolimus was administered twice daily. Approximately one determination of a tacrolimus trough level on whole blood was performed each day. The NPEM2 program was used to obtain population pharmacokinetic parameter values. With each individual pharmacokinetic parameter estimated by the MAP Bayesian method for a given period, the authors evaluated the prediction of future levels of tacrolimus for that patient for the next period. This evaluation of Bayesian fitting predictive performance was performed using the USC*PACK clinical software. Mean pharmacokinetic parameter values were in the same general range as previously published values obtained with richer data sets. However, during each period, the percentage of blood levels predicted within 20% did not exceed 40%. The traditional strategy of obtaining only trough whole blood levels does not provide enough dynamic information for the MAP Bayesian fitting procedure (the best method currently available) to be used for adaptive control of drug dosage regimens for oral tacrolimus. The authors suggest modifying the blood concentration monitoring scheme to add at least one other concentration measured during the absorptive or distributive phase to obtain more information about the behavior of the drug. D-Optimal design and similar strategies should be considered.
We evaluated a semiquantitative PCR assay prospectively in 40 liver transplant recipients as an aid in making a prompt diagnosis of cytomegalovirus (CMV) infection. For 2 months after transplantation, clinical specimens from patients were tested weekly by PCR, virus isolation from peripheral blood and urine, and CMV serology. The incidence of active CMV infection was 70%. The levels of CMV DNA determined by hybridization of PCR samples and densitometric scanning of blots were assigned a score of 1 to 4 by comparison with four external standards amplified in parallel and corresponding to a range of 80 to 80,000 genomes. The first detection of CMV in blood by PCR occurred at a mean of 15 days, and high-level PCR scores of 3 or 4 were obtained 21 days after transplantation, whereas viremia occurred 33 days after transplantation. Significantly higher levels of CMV DNA were seen in patients with CMV disease (P < 0.05) than in asymptomatic patients. The prevalence of symptomatic CMV infection was 30%. The positive predictive value of PCR was 48%, while the negative predictive value was 100%. After treatment, the clearance of CMV DNA was always observed and the disappearance of symptoms occurred concomitantly with undetectable PCR signals.
Purpose High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. Methods Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. Results As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive ). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06-2.13], p = 0.0210; 1-yr: HR 1.58[1.21-2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). Conclusion Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients.
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