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Funding Acknowledgements Type of funding sources: None. Background Renal dysfunction has been shown as an independent predictor of mortality in patients with heart failure (HF). However, data on the long-term outcomes of cardiac resynchronization therapy (CRT) in patients with chronic kidney disease is scarce due to underrepresentation of such patients in clinical trials on CRT. Aim To determine outcome and mortality predictors in patients with HF and elevated creatinine level treated with cardiac resynchronization therapy. Methods Study population consisted of 1059 consecutive patients with CRT implanted between 2002 and 2019 in a tertiary care university hospital, in a densely inhabited, urban region of Poland (949 subjects [89.6%] with CRT-D; 110 patients with CRT-P [10.4%]; 832 men [78.6%]). Results The median creatinine level before CRT implantation was 96 umol/L (10th and 90th percentile: 67-160). We divided all CRT patients into quartiles per creatinine level: I Conclusions Compared to patients without renal dysfunction prior to CRT implantation, mortality rates of those with creatinine level ≥118 umol/L are significantly higher and reach 70% in 4.5 years of median observation. Almost 9 out of 10 CRT recipients with creatinine level ≥118 umol/L and left ventricular ejection fraction ≤ 20% die within 4.5 years since CRT implantation. Figure 1. Kaplan-Meier curves for survival of patients treated with cardiac resynchronization therapy as a function of creatinine level

Funding Acknowledgements Type of funding sources: None. Background Cardiac resynchronization therapy (CRT) is a proven therapy in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF). However, little is known about the long-term prognosis and the risk of cardiac device-related infective endocarditis (CDRIE) in patients with HF and diabetes mellitus (DM) treated with CRT. Aim To assess the long-term outcomes, mortality predictors, and the risk of CDRIE in patients with HF and DM undergoing CRT. Methods Study population consisted of 1059 consecutive patients with CRT implanted between 2002 and 2019 in a tertiary care university hospital in a densely inhabited, urban region of Poland (949 subjects [89.6%] with CRT-D; 110 patients with CRT-P [10.4%]; 832 men [78.6%]). Population was divided into DM and control group (without DM); n=367 (34.7%) vs. n=692 (65.3%), respectively. Results During the median follow-up of 1661 days (10th and 90th percentile: 323-3995), all-cause mortality in DM group was significantly higher than in control group (61.9% vs. 50.3%, P=0.0003; Figure 1). The risk of CDRIE was 6.5% vs. 4.9% respectively in both groups (P=0.27). On multivariable regression analysis, older age (HR 1.03, 95%CI 1.01-1.05, P Conclusions Compared with patients without diabetes, mortality rates of those with DM treated with CRT implantation are significantly higher and nearly 2/3 of patients die within 4.5 years. Advanced age, ischemic cardiomyopathy, lower left ventricular ejection fraction, higher creatinine level, and diabetes treated with insulin are independent mortality predictors in subjects with HF and DM treated with cardiac resynchronization therapy. Figure 1. Kaplan-Meier curves for survival of patients with and without diabetes mellitus (DM) treated with cardiac resynchronization therapy (log rank P

I extract, and then analyze critically, the epistemological ideas that are implicit in Robin DiAngelo's best-selling book White Fragility and her other writings. On what grounds, according to DiAngelo, can people know what they claim to know? And on what grounds does DiAngelo know what she claims to know?

Background Data on efficacy of cardiac resynchronization therapy (CRT) and prognosis of CRT recipients with extremely enlarged left ventricular prior to device implantation are scarce. Aim To determine outcome and mortality predictors in patients with heart failure (HF) and extremely increased left ventricle end-diastolic diameter (LVEDD) treated with cardiac resynchronization therapy. Methods Study population consisted of 1059 consecutive patients with CRT implanted between 2002 and 2019 in a tertiary care university hospital, in a densely inhabited, urban region of Poland (949 subjects [89.6%] with CRT-D; 110 patients with CRT-P [10.4%]). Results The median LVEDD before CRT implantation was 68 mm (56–80). We divided all CRT patients into quartiles as per LVEDD: I 65 years and with severe MR was 90%. Exclusion of subjects with severe MR and aged >65 from quartile IV resulted in similar mortality rate (53.1%) as for patients in lower quartiles. Conclusions Mortality rates in CRT recipients with extremely enlarged LVEDD is significantly higher compared to those with LVEDD 65 years) should be very carefully assessed and other HF therapies (i.e. left ventricular assist devices) should be considered, as more than 90% of those die within 4 years since CRT implantation. Funding Acknowledgement Type of funding sources: None.

Background Cardiac resynchronization therapy (CRT) has been proven therapy in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). However, little is known about the prognosis, and the risk of cardiac device-related infective endocarditis (CDRIE) in patients with HF after cardiac surgery other than coronary artery bypass grafting (CABG) treated with CRT. Aim To assess the long-term outcome, mortality predictors, and the risk of CDRIE in patients with HF after cardiac surgery other than CABG treated with CRT. Methods The study population consisted of 1059 consecutive patients with CRT implanted between 2002 and 2019 in a tertiary care university hospital in a densely inhabited, urban region of Poland (949 subjects [89.6%] with CRT-D; 110 patients with CRT-P [10.4%]). Results The studied population was divided into two groups according to be or not after cardiac surgery other than CABG (n=74 patients [6.9%] vs. n=985 patients [93.1%]). During the median follow-up of 1661 days (10th and 90th percentile: 323–3995), all-cause mortality in patients after cardiac surgery other than CABG did not differ significantly in comparison to other CRT recipients (50% vs. 54.4%, P=0.46). Also, the risk of CDRIE was not statistically significant differ (2.7% vs. 5.7%, P=0.28). On multivariable regression analysis, only older age (HR 1.04, 95% CI 1.01–1.07, P=0.02) was identified as independent predictor of higher mortality in patients after cardiac surgery treated with CRT. Kaplan-Meier curves of survival of patients after cardiac surgery other than CABG treated with cardiac resynchronization therapy in comparison to other CRT recipients are presented on Picture 1. Conclusions The mortality rate in patients after cardiac surgery other than CABG is similar to other subjects treated with CRT and reaches 50% within 4.5 years. The risk of device-related infective endocarditis is not higher than in other patients treated with CRT. Advanced age is an independent mortality predictor in subjects after cardiac surgery other than CABG undergoing CRT. Funding Acknowledgement Type of funding sources: None.

Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially life-saving treatments for a number of cardiac conditions, but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased healthcare costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, anti-bacterial envelopes, prolonged antibiotics post-implantation, and others. Guidance on whether to use novel device alternatives expected to be less prone to infections and novel oral anticoagulants is also limited, as are definitions on minimum quality requirements for centres and operators and volumes. Moreover, an international consensus document on management of CIED infections is lacking. The recognition of these issues, the dissemination of results from important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections. This article is simultaneously published also in Eur J Cardiothorac Surg. (https://doi.org/10.1093/ejcts/ezz296) and European Heart Journal (https://doi.org/10.1093/eurheartj/ehaa010). Minor differences in style may appear in each publication, but the article is substantially the same in each journal.

Aims The number of patients with heart failure (HF) and implantable cardiac electronic devices has been growing steadily. Remote monitoring care (RC) of cardiac implantable electronic devices can facilitate patient-healthcare clinical interactions and prompt preventive activities to improve HF outcomes. However, studies that have investigated the efficacy of remote monitoring have shown mixed findings, with better results for the system including daily verification of transmission. The purpose of the RESULT study was to analyse the impact of remote monitoring on clinical outcomes in HF patients with implantable cardioverter-defibrillator [ICD/cardiac resynchronization therapy-defibrillator (CRT-D)] in real-life conditions. Methods and results The RESULT is a prospective, single-centre, randomized trial. Patients with HF and de novo ICD or CRT-D implantation were randomized to undergo RC vs. in-office follow-ups (SC, standard care). The primary endpoint was a composite of all-cause death and hospitalization due to cardiovascular reasons within 12 months after randomization. We randomly assigned 600 eligible patients (299 in RC vs. 301 in SC). Baseline clinical and echocardiographic characteristics were well-balanced and similar in both arms. The incidence of the primary endpoint differed significantly between RC and SC and involved 39.5% and 48.5% of patients, respectively, (P = 0.048) within the 12-month follow-up. The rate of all-cause mortality was similar between the studied groups (6% vs. 6%, P = 0.9), whereas hospitalization rate due to cardiovascular reasons was higher in SC (37.1% vs. 45.5%, P = 0.045). Conclusion Remote monitoring of HF patients with implanted ICD or CRT-D significantly reduced the primary endpoint rate, mostly as a result of a lower hospitalization rate in the RC arm (ClinicalTrials.gov Identifier: NCT02409225).

Background Asymptomatic (“silent”) atrial fibrillation is common and associated with poor outcomes. It is important to determine the risk factors that predispose elderly individuals from the general population to atrial fibrillation (AF). However, population-based data for silent AF (SAF) are limited. Design First, to study the risk factors for symptomatic AF and SAF in an elderly (≥65 years) general population. Second, to develop a risk stratification model for predicting SAF. Methods Continuous ECG monitoring was performed for up to 30 days using a vest-based system in a cohort from NOMED-AF, a cross-sectional study based on a nationwide population sample. The independent risk factors for AF and SAF were determined using multiple logistic regression. ROC analysis was applied to validate developed risk stratification score. Results From the total cohort of 3014 subjects, AF was diagnosed in 680 individuals (mean age, 77.5±7.9; 50.1% men) with AF, and of these, 279 (41%) had SAF. Independent associations with an increased risk of AF were age, male gender, coronary heart disease, thyroid diseases, prior ischemic stroke or transient ischemic attack (ICS/TIA), diabetes, heart failure, chronic kidney disease (CKD), obesity (BMI>30) and NT-proBNP >125 ng/ml. Prior revascularization was negatively associated with risk of AF. The main risk factors for SAF were age, male gender, prior ICS/TIA, diabetes, heart failure, CKD and NT-proBNP >125 ng/ml. We developed a simple clinical risk scale (MR-DASH score) which had good prediction in the derivation cohort (AUC 0.726) and the validation cohort (AUC 0.730). Conclusions SAF is associated with various clinical risk factors in a population sample of individuals ≥65 years. Stratifying individuals from the general population according to their risk for SAF may be possible using the MR-DASH score, facilitating targeted screening programs of individuals with high risk of SAF Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Centre for Research and Development

Background Cardiac resynchronization therapy (CRT) is an effective method of treatment in patients with HF, but as complex device with three electrodes, it is prone to electrode dysfunctions and the need to replace them. However little is known about the frequency of need for leads replacement in subjects undergone CRT in a very long-term follow up. Aim To determine the frequency of leads replacement in patients undergoing CRT during long term follow-up. Methods Study population consisted of 1059 consecutive patients with CRT implanted between 2002 and 2019 in tertiary care university hospital, in a densely inhabited, urban region of Poland. The data about lead replacement was collected. Results During the median follow-up of 1661 days (IQR: 815–2792) for non-infectious reasons (dislocation, dysfunction, fracture etc.) a total of 324 leads in 251 patients (23.7%) were replaced. Median time from CRT implantation to the first lead replacement was 359 days (42–1413). The electrode replacement within first year after CRT implantation was performed in 126 subjects (50.2%), in the rest of patients (49.8%) the leads were replaced after one year of device implantation. In patients with above ten years of follow up (n=143; 13.5%) 67 subjects (46.8%) had one or more lead replacement during follow up. Patients with electrode replacement during follow-up were younger (63 vs 66 years, P Conclusions The need for leads replacement due to non-infectious reasons reaches almost 25% of patients with CRT within 4.5 years. Half of the patients have lead replacement within one year after CRT implantation and the other half during long term follow up. The duration of the first procedure (CRT device implantation) is strong predictor of lead replacement during follow up. Funding Acknowledgement Type of funding sources: None.

Background Advanced heart failure with reduced ejection fraction (HFrEF) is associated with poor prognosis. Cardiac resynchronization therapy (CRT) is an effective method of treatment for advanced HFrEF to reduce HF hospitalizations and mortality. Nonetheless, very long-term observation of HF patients undergoing CRT implantation is scarce. Aim To assess very long-term survival (≥10 years) and predictors of shorter survival (death within 10 years from CRT implantation). Methods We screened a large dataset of CRT population from a tertiary care university hospital comprising consecutive HF patients implanted with CRT from 2002 through 2019 to select those who were alive ≥10 years and those who died within 10 years since device implantation. We analyzed various patients' baseline, clinical and procedural characteristics and sought for predictors of mortality within 10 years from CRT implantation. Results Of 1059 CRT patients, 143 (13.5%) were alive ≥10 years since CRT implantation. On multivariable regression analysis the independent predictors for all-cause death up to 10 years from CRT implantation were as follows: age, HR 1.02, 95% CI 1.01–1.31; male sex, 1.27, 95% CI 1.01–1.60; primary prevention of sudden cardiac death (SCD), HR 0.72, 95% CI 0.58–0.89; ischemic cardiomyopathy, HR 1.41, 95% CI 1.76–1.70; NYHA class at implantation, HR 1.38, 95% CI 1.17–1.62; baseline left ventricle ejection fraction (EF), HR 0.97, 95% CI 0.96–0.98; severe mitral regurgitation, HR 1.38; 95% CI 1.08–1.75; baseline NT-proBNP concentration, HR 1.00, 95% CI 1.00–1.00; and creatinine level, HR 1.00, 95% CI 1.00–1.01. Conclusions In a real-life patient population with CRT only 13.5% survived over 10 years since device implantation. Independent predictors for death within 10 years since CRT implantation were older age, male sex, secondary prevention of SCD, ischemic and more advanced heart failure along with renal impairment. Funding Acknowledgement Type of funding sources: None.

Background Triple-Site versus Standard Cardiac Resynchronization Therapy Randomized Trial (TRUST CRT) was initiated in 2009 to verify the hypothesis whether triple-site (single right, double left) cardiac resynchronization therapy (CRT) may be superior to conventional, biventricular resynchronization in patients with advanced heart failure. Objectives To report 6-month outcomes and 10-year survival in TRUST CRT. Methods 100 consecutive patients with moderate to severe heart failure, ejection fraction of 35% or less, electrical and mechanical dyssynchrony, were randomly assigned in a 1:1 fashion to triple-site CRT defibrillator (TRIV) or to conventional CRT-D. The primary objective evaluated response-rate, defined as the 6-month's combined end point of alive status, freedom from hospitalization for heart failure or heart transplantation, relative≥10% increase in ejection fraction, ≥10% in peak oxygen consumption, and ≥10% in 6-minute walking distance. The secondary objective was to assess the occurrence of major adverse cardiovascular events (hospitalization for exacerbated heart failure requiring modification of pharmacotherapy, heart transplant or death) at month 6 and during remote observation. Results At month 6, the response-rate was higher in triple-site than conventional CRT-D group (51.1 vs. 26.5%, P=0.014). There were 2 deaths or heart failure events in the triple-site group (4%) as compared with 8 in the group assigned to conventional CRT-D (16%). A triple-site resynchronization resulted in 12% absolute risk reduction for secondary end point (hazard ratio 0.25; 95 percent confidence interval, 0.05 to 1.17, P=0.056, in comparison with the conventional CRT-D group). After 10 years of observation (median follow up of 7.1 years; range: 1.2–10.4) 57 patients (58.2%) died: 24 (53.3%) in the triple-site group, 31 (60.8%) in the conventional group (P=0.46) and 2 patients with and ICD (failed CRT implantation) [Figure]. Conclusions In patients with advanced heart failure, triple-site resynchronization combined with an ICD did not result in better survival than conventional resynchronization therapy in a median observation of 7.1 years. Figure 1 Funding Acknowledgement Type of funding source: None

Background It is important to determine the risk factors that predispose elderly subjects from the general population for symptomatic atrial fibrillation and atrial flutter (AF/AFl), but population-based data for silent AF (SAF) are limited. Aim To study risk factors for symptomatic AF and SAF in a general population screen for subjects age ≥65 where continuous monitoring was performed up to 30 days with a vest-based monitor. Methods The NOMED-AF study was a cross-sectional study based on a representative population sample (n=3014; mean age 77.5±7.9 years; F=1479). In 680 subjects AF/AFl (including 279 with SAF) was diagnosed. Independent risk factors for AF/AFl and SAF were determine on weighted data using multiple logistic regression. Results The independent risk factors for AF/AFl and SAF are summarised in the Table. There are nine independent risk factors for AF/AFl and eight for SAF. Revascularization and obesity were independently associated with patients with (symptomatic) AF/AFl, and CKD was associated with SAF. Other risk factors are common for AF/AFl and SAF. Conclusions AF/AFl and SAF have slightly different associated clinical risk factors in this representative population sample aged ≥65 years. This may facilitated targeted screening programmes for high risk subgroups, particularly for SAF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The research has received funding from the National Centre for Research and Development under grant agreement (STRATEGMED2/269343/18/NCBR/2016)

Aim To assess the incidence, clinical significance of depression and the impact of a cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) implantation on psychiatric status in patients with heart failure (HF). Methods The prospective, single-center study encompassed 575 consecutive HF patients implanted with a CRT-D or ICD. Finally, the study population consisted of 494 subjects (186 ICD and 308 CRT-D patients), as 81 patients taking antidepressants were excluded from the analysis. All patients underwent psychiatric examination at the time of implantation, and the assessment of psychiatric status was repeated after 3, 6, 12 and 24 months. The study population was divided into 4 groups: Group 1 encompassed 101 (20.4%) patients with persistent depression, Group 2 constituted of 95 (19.2%) patients with depression that developed after ICD/CRT-D implantation, whereas 43 (8.7%) patients with remission of depression comprised Group 3, and Group 4 encompassed 255 (51.6%) patients with never diagnosed depression. Data on long-term follow-up (median 34.1 months) were screened to identify patients who developed a composite endpoint defined as death or hospitalization for decompensated HF. Results The cumulative incidence of depression at the baseline assessment was 39.1%. Depression developed in 95 (27.1%) patients, whereas remission of depression was observed in 43 (29.9%) subjects after ICD/CRT-D implantation. ICD intervention (HR 3.3) and increase in NYHA class by at least one class (HR 2.6) were the independent risk factors for depression development, whereas mitral regurgitation reduction (HR 1.9), as well as improvement in NYHA class by at least one class (HR 2.4) were the independent predictors for depression remission. Patients with persistent depression (Group 1) and those with newly developed depression (Group 2) were at significantly higher risk of a composite endpoint compared to patients in Group 3 and Group 4 (Table 1). Conclusions Depression is a common comorbidity associated with HF, as it affects 4 of 10 HF patients. ICD intervention and HF worsening are the strongest predictors for depression development after ICD/CRT-D implantation. Depression is a strong, independent risk factor of poor outcomes in HF population. Funding Acknowledgement Type of funding source: None

Background Atrial fibrillation (AF) confers a high healthcare burden from stroke, heart failure, dementia and hospitalisation, and one challenge is. Early detection of this arrhythmia in the community, given that it is often asymptomatic. Aim To perform population screening for atrial fibrillation and flutter (AF/AFl) using a mobile long-term continuous ECG telemonitoring vest in a representative Polish and European population aged ≥65 years (age range 65–100 years). Methods The NOMED-AF study is a cross-sectional study based on a representative sample of adults aged ≥65 years (n=3014; mean age 77.5±7.9 years; 49.1% female). All study participants were equipped with a mobile long-term continuous ECG telemonitoring vest. National and European estimations were calculated on weighted data. Results In 680 subjects AF/AFl (including 279 with SAF; 9.3%) was confirmed. In the NOMED-AF population, the prevalence of AF/AFl was 22.6%, estimated to be 19.2% for Poland [1,251,100 (95% CI: 1,158,300–1,344,000) and 480,100 (95% CI: 426,60–533,700) subjects with AF/AFl and SAF, respectively] and 20.4% for Europe [20,300,000 (95% CI 18.8–21.9 M), including 8,000,000 (95% CI: 6.9–9.3 M) subjects with AF/AFl and SAF, respectively]. The prevalence of AF/AFl was 2.56-fold higher in men than in women and the incidence of silent AF (SAF) was 4.73-fold higher in men than in women. Although the risk of either AF/AFl or SAF increased with age, the odds ratio was significantly higher in women of a particular age group than in men of the corresponding age. Based on our survey, the total number of subjects with AF/AFl in Europe is estimated to be roughly 20.3 million (95% CI 18.8–21.9M), including 8.0 million (95% CI: 6.9–9.3M) subjects with silent AF/AFl (Figure). Conclusions Approximately 1 in 5 subjects aged ≥65 years suffers from AF/AFl. The risk for AF/AFl and SAF is higher in men than that in women, but when correlated to a particular age group, the risk increases significantly in women. Continuous ECG telemonitoring allows for more credible AF/AFl and SAF detection. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The research has received funding from the National Centre for Research and Development under grant agreement (STRATEGMED2/269343/18/NCBR/2016

Aims Diabetes mellitus (DM) is one of the most important cardiovascular risk factors. The aim of this study was to evaluate clinical correlates of DM, including management and outcomes, in the EURObservational Research Programme (EORP)-Atrial Fibrillation (AF) General Pilot (EORP-AF) Registry of the European Society of Cardiology. Methods and results We studied consecutive patients (N = 3101) enrolled in 70 centres of nine European countries between February 2012 and March 2013, and compared diabetics with non-diabetics during a 1-year follow-up. In the overall cohort, the prevalence of DM was 20.6%. Diabetics were older (71 +/- 9 vs. 68 +/- 12 years, P < 0.0001) and had more comorbidities, higher CHA(2)DS(2)-VASc score (4.6 +/- 1.6 vs. 2.9 +/- 1.7, P < 0.0001) and higher prevalence of permanent AF (21.5 vs. 16.0%, P = 0.0022). Quality of life amongst DM patients was significantly worse [atrial fibrillation quality of life questionnaire (AF-QoL) score 45.2 +/- 19.2 vs. 49.3 +/- 20.1, P < 0.0001]. Amongst diabetics, the use of electrical cardioversion (16.2 vs. 24.6%, P < 0.0001) and catheter ablation (3.3 vs. 8.6%, P < 0.0001) was lower, whilst oral anticoagulants were more often prescribed (84.3 vs. 78.9%, P = 0.0027). After one year, diabetic patients had significantly higher all-cause (11.9 vs. 4.9%, P < 0.0001), cardiovascular (6.2 vs. 1.9%, P < 0.0001), and non-cardiovascular mortality (2.3 vs. 1.1%, P = 0.0356). Conclusion In AF patients, DM is associated with a higher prevalence of comorbidities and a worse quality of life. After one year, all-cause, cardiovascular, and non-cardiovascular mortality were significantly higher in diabetic subjects.

Background Cancer-associated acute cholangitis (CAAC) are becoming more frequent and their characteristics may be changing with the evolution of cancer management. Our aim was to compare clinical, microbiological and outcome characteristics of CAAC to those of cancer-free acute cholangitis (CFAC). Methods All consecutive cases of acute cholangitis (AC) from November 2015 to March 2017 were collected retrospectively in a single tertiary care hospital in Clichy, France, specialized in gastroenterology. Hospital stays referred as AC by coding were screened. Patients fulfilling the 2018 Tokyo Guidelines diagnostic criteria for definite AC were included. Data were collected using a standardized form. CAAC were defined as AC that occurred in patients who had active cancer or history of cancer in the five previous years. CFAC were defined as AC in patient who no history of cancer, or in remission for more than 5 years. Comparison was made using Fisher or Student’s t-test. P < 0.05 was considered as significant. Results 156 episodes of AC in 130 patients were analyzed. 101 had CAAC and 55 had CFAC. Age and sex did not differ (table 1), but CAAC had a higher Charlson’s comorbidity index (4.4 vs. 1.7, P < 0.0001). Despite similar clinical presentation, CAAC had more pronounced cholestasis (Gamma GT 659 vs. 391UI/L; Alkaline phosphatases 526 vs. 309 UI/L; P < 0.0001 for both) and C-reactive protein level (133 vs. 97mg/L, P = 0.008, Table 2). E. coli was more common in CFAC (72.4% vs. 54% of positive blood cultures, P = 0.004). In bile cultures, Enterococci and multi-drug-resistant Gram negatives tended to be more frequent in CAAC than in CFAC (63 vs. 17%, P = 0.07 and 9.1% vs. 4.1%, P = 0.33, Table 2), respectively. CAAC more frequently required drainage (86.1% of cases vs. 43.6% in CFAC (P < 0.0001), including radiological drainage (42.5% vs. 12.5%; P = 0.008) and with multiple sessions (28.7% vs. 8.3%, P < 0.0001, Table 3). Antibiotherapy duration did not differ between the two groups. Despite similar initial severity, only 51.5% of patients with CAAC were alive, without febrile recurrence or other biliary drainage at day 28, vs. 85.5% of patients with CFAC (P < 0.0001, Table 3). Conclusion Despite comparable initial clinical presentation, management is more complex and outcome less favorable in CAAC vs. CFAC. Disclosures All authors: No reported disclosures.

Summary Previous studies have suggested that the susceptibility of newborns to infections is linked to the immaturity of their immune system, but very few data are available on the early stages of maturation of the immune response. Therefore, we decided to investigate the evolution of the interferon (IFN)-α and interleukin (IL)-10 responses in neonatal mononuclear cells. To this end, mononuclear cells isolated from cord blood and peripheral blood of 2-, 6- and 18-month-old children and adults were stimulated with unmethylated cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) 2216 (IFN-α response) or lipopolysaccharide (LPS) (IL-10 response) for 24 h. The production of IFN-α and IL-10 was then measured in culture supernatants using enzyme-linked immunosorbent assay (ELISA) or a 6-plex cytokine array, respectively. Compared to adults, we found a significant impairment in both the IFN-α and IL-10 responses of neonatal mononuclear cells. Interestingly, both responses had increased significantly after 2 months, but remained lower than the adult responses throughout the first 18 months of life. This study shows that although the immune response of neonates tends to mature fairly quickly, it remains different when compared to the adult immune response throughout the first 18 months of life. This could have important consequences on children's ability to mount an appropriate immune response to various challenges and to establish tolerance and immune homeostasis.

The therapeutic imperative for Alzheimer disease (AD) and Parkinson disease (PD) calls for discovery and validation of biomarkers. Increased cerebrospinal fluid (CSF) τ and decreased amyloid (A) β 42 have been validated as biomarkers of AD. In contrast, there is no validated CSF biomarker for PD. We validated our proteomics-discovered multianalyte profile (MAP) in CSF from 95 control subjects, 48 patients with probable AD, and 40 patients with probable PD. An optimal 8-member MAP agreed with expert diagnosis for 90 control subjects (95%), 36 patients with probable AD (75%), and 38 patients with probable PD (95%). This MAP consisted of the following (in decreasing order of contribution): τ, brain-derived neurotrophic factor, interleukin 8, Aβ 42 , β 2 -microglobulin, vitamin D binding protein, apolipoprotein (apo) AII, and apoE. This first large-scale validation of a proteomicdiscovered MAP suggests a panel of 8 CSF proteins that are highly effective at identifying PD and moderately effective at identifying AD. Alzheimer disease (AD) and Parkinson disease (PD) are major public health problems. Key to the effort to obtain new therapeutics will be novel biomarkers to aid in diagnosis, identify subsets of patients, and objectively monitor progression and response to treatment. Several discovery proteomic studies of human cerebrospinal fluid (CSF) have been reported using relatively small numbers of patients with AD compared with control subjects without dementia. 1-6

BACKGROUND: To date, there is no commercially available vaccine to prevent infectious mononucleosis, a disease frequently induced by Epstein-Barr virus (EBV) infection in adolescents or adults devoid of preexisting immunity to the virus. METHODS: A total of 181 EBV-seronegative, healthy, young adult volunteers were randomized in a double-blind fashion to receive either placebo or a recombinant EBV subunit glycoprotein 350 (gp350)/aluminum hydroxide and 3-O-desacyl-4'-monophosphoryl lipid A (AS04) candidate vaccine in a 3-dose regimen. RESULTS: The vaccine had demonstrable efficacy (mean efficacy rate, 78.0% [95% confidence interval {CI}, 1.0%-96.0%]) in preventing the development of infectious mononucleosis induced by EBV infection, but it had no efficacy in preventing asymptomatic EBV infection. One month after receipt of the final dose of gp350 vaccine, 98.7% of subjects showed seroconversion to anti-gp350 antibodies (95% CI, 85.5%-97.9%), and they remained anti-gp350 antibody positive for >18 months. Furthermore, there were no concerns regarding the safety or reactogenicity of the gp350/AS04 vaccine. CONCLUSION: These data support the clinical feasibility of using an EBV vaccine to prevent infectious mononucleosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00430534.

BACKGROUND: The most frequent site of metastases from prostate cancer is bone. Adjuvant bisphosphonate treatment improves outcomes of patients with bone metastasis-negative breast cancer, but the effects of bisphosphonates on bone metastases in prostate cancer are not known. METHODS: We performed a randomized double-blind placebo-controlled trial to determine whether a first-generation bisphosphonate could improve symptomatic bone metastasis-free survival (time to symptomatic bone metastases or death from prostate cancer) in men with nonmetastatic prostate cancer who were at high risk of developing bone metastases. Between June 1, 1994, and December 31, 1997, 508 men from 26 UK sites and one New Zealand site who were within 3 years of initial prostate cancer diagnosis with no evidence of metastases from current bone scanning were randomly assigned to daily oral sodium clodronate (2080 mg/day, n = 254) or placebo (n = 254) for a maximum of 5 years. Estimates of outcome risks were compared using Kaplan-Meier analyses. RESULTS: The groups allocated to each treatment were well balanced. After a median follow-up of nearly 10 years, no evidence of benefit to the clodronate group was observed in terms of bone metastases-free survival (clodronate versus placebo, 80 events versus 68 events; hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 0.88 to 1.68) or overall survival (clodronate versus placebo, 130 deaths versus 127 deaths; HR = 1.02; 95% CI = 0.80 to 1.30). Adverse events, notably gastrointestinal problems and increased lactate dehydrogenase levels, were more frequent in the clodronate group than in the placebo group; otherwise, clodronate was well tolerated. Modification of trial drug dose was more frequent in the clodronate group than the placebo group (HR = 1.63, 95% CI = 1.21 to 2.19). CONCLUSION: Adjuvant sodium clodronate does not modify the natural history of nonmetastatic prostate cancer.

The characteristics and evolution of hepatitis C virus (HCV) infection were retrospectively investigated in a study of 224 HCV RNA-seropositive white children who were consecutively recruited at 7 European centers in 1980-1998. At presentation, all patients were positive for antibodies to hepatitis C virus, 87% were asymptomatic, and 48% had alanine aminotransferase (ALT) levels that wereor =2 times the upper limit of the range considered to be normal. Of 200 children followed for 1-17.5 years (mean follow-up +/- standard deviation [SD], 6.2+/-4.7 years), only 12 (6%) achieved sustained viremia clearance and normalization of the ALT level. In 92 revised liver biopsy specimen analyses, the mean fibrosis score (+/-SD) was 1.5+/-1.3 for children15 years of age and 2.3+/-1.2 for childrenor =15 years of age (range, 0-6 years; P.01). Pediatric HCV infection is usually mild, but few patients, especially those who are perinatally infected, clear viremia in the medium-term follow-up. Conversely, the higher rates of fibrosis observed in older patients suggest the possibility of an insidious progression of HCV-associated liver disease.