International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n1⁄42,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n1⁄43,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombinedo5108) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist

Improvement of exercise tests and reduction of heart failure biomarkers in short term follow up after comprehensive rehabilitation program of patients with implanted LVAD

Abstract Background There is increasing recognition of the importance of rehabilitating patients after LVAD implantation. The novel method of comprehensive rehabilitation starting directly after LVAD implantation was designed for our LVAD patients population. Aim of the study The study aimed to determine, if novel rehabilitation program improves functional and biochemical parameters in patients after recent LVAD implantation. Study group 37 recent LVAD (22 Heart Mate III, 15 HeartWare) recipients (19–67, mean 58.7 years, 35 men) participated in specially designed rehabilitation program. The program included 4–5 weeks of sationary rehabilitation: supervised endurance training on cycloergometer (5 times per week), resistance training, general fitness exercises with elements of equivalent and coordination exercises (every day). It was followed by individual exercises performed at home. At the beginning and at the end of rehabilitation program the patients performed 6 minute walking test (6MWT), cardiopulmonary exercise test (CPET). Following prognostic biomarkers of heart failure: NT-proBNP, galectin-3 and ST2 were also measured. Results See table 1. Increase of 6MWT distance, higher maximal workload, peak VO2 and upward shift of anaerobic threshold in CPET were observed in all patients. Significant reductions of NTproBNP, ST2 and galectin-3 levels were observed. There were no major adverse events during rehabilitation. Conclusions Comprehensive novel rehabilitation in LVAD recipients is safe and results in significant improvement of functional tests and biomarkers of heart failure. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Center for Research and Development: National grant - STRATEGMED II, </jats:sec

The sarcopenia and physical frailty in older people: multi-component treatment strategies (SPRINTT) project: description and feasibility of a nutrition intervention in community-dwelling older Europeans

Abstract Background The “Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies” (SPRINTT) project sponsored a multi-center randomized controlled trial (RCT) with the objective to determine the effect of physical activity and nutrition intervention for prevention of mobility disability in community-dwelling frail older Europeans. We describe here the design and feasibility of the SPRINTT nutrition intervention, including techniques used by nutrition interventionists to identify those at risk of malnutrition and to carry out the nutrition intervention. Methods SPRINTT RCT recruited older adults (≥ 70 years) from 11 European countries. Eligible participants (n = 1517) had functional limitations measured with Short Physical Performance Battery (SPPB score 3–9) and low muscle mass as determined by DXA scans, but were able to walk 400 m without assistance within 15 min. Participants were followed up for up to 3 years. The nutrition intervention was carried out mainly by individual nutrition counseling. Nutrition goals included achieving a daily protein intake of 1.0–1.2 g/kg body weight, energy intake of 25–30 kcal/kg of body weight/day, and serum vitamin D concentration ≥ 75 mmol/L. Survey on the method strategies and feasibility of the nutrition intervention was sent to all nutrition interventionists of the 16 SPRINTT study sites. Results Nutrition interventionists from all study sites responded to the survey. All responders found that the SPRINTT nutrition intervention was feasible for the target population, and it was well received by the majority. The identification of participants at nutritional risk was accomplished by combining information from interviews, questionnaires, clinical and laboratory data. Although the nutrition intervention was mainly carried out using individual nutritional counselling, other assisting methods were used as appropriate. Conclusion The SPRINTT nutrition intervention was feasible and able to adapt flexibly to varying needs of this heterogeneous population. The procedures adopted to identify older adults at risk of malnutrition and to design the appropriate intervention may serve as a model to deliver nutrition intervention for community-dwelling older people with mobility limitations. </jats:sec

Impact of chronic coronary syndromes on cardiovascular hospitalization and mortality: the ESC-EORP CICD-LT registry

Abstract Aims In Europe, global data on guideline adherence, geographic variations, and determinants of clinical events in patients with chronic coronary syndrome (CCS) remain suboptimal. The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischemic Cardiovascular Disease Long-Term (CICD-LT) registry is a prospective European registry, and was designed to describe the profile, management, and outcomes of patients with CCS across the ESC countries. Methods and results We aimed to investigate clinical events at 1-year follow-up from the ESC EORP CICD-LT registry. One-year outcomes of 6655 patients from the 9174 recruited in this European registry were analysed. Overall, 168 patients (2.5%) died, mostly from cardiovascular (CV) causes (n = 97, 1.5%). Northern Europe had the lowest CV mortality rate, while southern Europe had the highest (0.5 vs. 2.0%, P = 0.04). Women had a higher rate of CV mortality compared with men (2.0 vs. 1.3%, P = 0.02). During follow-up, 1606 patients (27.1%) were hospitalized at least once, predominantly for CV indications (n = 1220, 20.6%). Among the population with measured low-density lipoprotein-cholesterol level at 1 year, 1434 patients (66.5%) were above the recommended target. Age, history of atrial fibrillation, previous stroke, liver disease, chronic obstructive pulmonary disease or asthma, increased serum creatinine, and impaired left ventricular function were associated with an increased risk of CV death or hospitalization. Conclusion In the CICD registry, the majority of patients with CCS have uncontrolled CV-risk factors. The 1-year mortality rate is low, but these patients are frequently hospitalized for CV causes. Early identification of comorbidities may represent an opportunity for enhanced care and better outcomes. </jats:sec

The ESC-EORP Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry

Abstract Aims The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry aims to study the clinical profile, treatment modalities, and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular (CV) risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid- and long-term outcomes and their determinants in this population. Methods and results Nine thousand one hundred and seventy-four patients over 18 years with documented CICD defined by a history acute coronary syndrome with/without ST elevation, previous coronary revascularization, or stable coronary artery disease were enrolled between 1 May 2015 and 31 July 2018. Individual patient data on clinical profile, biology, and treatment modalities were collected across 154 centres from 20 ESC countries. Two years of follow-up is scheduled in order to determine the following clinical outcomes: all-cause and CV death, all-cause and CV hospitalizations, changes in medications, and quality of life using the EuroQol5D-5L score. Conclusion The CICD LT is an international registry of care and outcomes of patients hospitalized with CICD which will provide insights into the contemporary profile and management of patients with this common disease. </jats:sec