New susceptibility locus for coronary artery disease on chromosome 3q22.3

We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in approximately 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11).

IDEAL study: A real‐world assessment of pattern of use and clinical outcomes with recombinant coagulation factor IX albumin fusion protein (rIX‐FP) in patients with haemophilia B in Italy

Introduction: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit.Aims: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy.Methods: Patients with moderate/severe haemophilia B on prophylaxis with rIX-FP for >= 6 months, were enrolled in this observational study from October 2017 to February 2019 and followed-up for 2 years. Descriptive analysis included p…

Choice and Outcomes of Rate Control versus Rhythm Control in Elderly Patients with Atrial Fibrillation: A Report from the REPOSI Study

Background: Among rate-control or rhythm-control strategies, there is conflicting evidence as to which is the best management approach for non-valvular atrial fibrillation (AF) in elderly patients. Design: We performed an ancillary analysis from the ‘Registro Politerapie SIMI’ study, enrolling elderly inpatients from internal medicine and geriatric wards. Methods: We considered patients enrolled from 2008 to 2014 with an AF diagnosis at admission, treated with a rate-control-only or rhythm-control-only strategy. Results: Among 1114 patients, 241 (21.6%) were managed with observation only and 122 (11%) were managed with both the rate- and rhythm-control approaches. Of the remaining 751 patie…

Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis

Abstract The efficacy and safety of caplacizumab in individuals with acquired thrombotic thrombocytopenic purpura (aTTP) have been established in the phase 2 TITAN and phase 3 HERCULES trials. Integrated analysis of data from both trials was conducted to increase statistical power for assessing treatment differences in efficacy and safety outcomes. Caplacizumab was associated with a significant reduction in the number of deaths (0 vs 4; P < .05) and a significantly lower incidence of refractory TTP (0 vs 8; P < .05) vs placebo during the treatment period. Consistent with the individual trials, treatment with caplacizumab resulted in a faster time to platelet count response (ha…

Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Baseline Disease Severity

Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy that involves abnormal processing of von-Willebrand factor (vWF) and results in multiple organ dysfunction. Although aTTP remains a very unpredictable disease, risk factors for death include older age, lactate dehydrogenase (LDH) levels >10x the upper limit of normal (ULN), and cerebral involvement (i.e., the French severity score) (Benhamou et al. Haematologica 2012;97:1181-1186). In addition, raised cardiac troponin-I (cTnI) levels of >2.5 µg/L have also been linked with a higher risk of mortality or refractoriness (Benhamou et al. J Thromb Haemost 2015;1…

What changed in the Italian internal medicine and geriatric wards during the lockdown

A total of 48 internal medicine or geriatric wards among the 93 adhering to the register REPOSI answered an online questionnaire aimed to investigate the characteristics and activities of converted and non-converted wards in the crucial period of the first wave of the epidemic, 22 February-4 May 2020

Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study.

BACKGROUND Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy. Caplacizumab, an anti-von Willebrand Factor Nanobody® , is effective for treating aTTP episodes and is well tolerated. OBJECTIVES AND METHODS In the phase 3 HERCULES trial (NCT02553317), patients with aTTP received double-blind caplacizumab or placebo during daily therapeutic plasma exchange (TPE) and for ≥30 days thereafter. Patients who experienced an exacerbation while on blinded study drug treatment switched to receive open-label caplacizumab plus re-initiation of daily TPE. Exacerbations were defined as recurrence of disease occurring within 30 days after ce…

The EHA research roadmap

International audience; In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research(1) aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1-2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published…

Narratives of Patients with Fatal Outcomes During the Phase 2 TITAN and Phase 3 HERCULES Studies

Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening thrombotic microangiopathy, with an untreated mortality rate of >90%. Prompt treatment with therapeutic plasma exchange (TPE) and immunosuppression improves outcomes in patients with aTTP, but 10-20% of patients still die acutely from this disease. The aim of this analysis was to describe in more detail the characteristics and disease courses of the patients who died during the caplacizumab clinical development program. Methods: Patient narratives on all deaths occurring during the phase 2 TITAN and phase 3 HERCULES studies were extracted. Results: In the overall study periods, a total of 6 pat…

INTEGRATED EFFICACY RESULTS FROM THE PHASE 2 AND PHASE 3 STUDIES WITH CAPLACIZUMAB IN PATIENTS WITH ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA

Objective: An integrated analysis based on the Phase 2 TITAN (NCT01151423) and Phase 3 HERCULES (NCT02553317) studies with caplacizumab (CPLZ) in acquired thrombotic thrombocytopenic purpura (aTTP) was performed to assess treatment differences on efficacy and safety outcomes that may have been undetected in the individual trials. Methodology: In both trials, patients with an acute episode of aTTP were randomized to receive CPLZ or placebo (PBO) in addition to therapeutic plasma exchange (TPE) and immunosuppression. All randomized patients from both studies were included in the integrated efficacy analyses (CPLZ: n=108; PBO: n=112), and those who received at least 1 dose of the study drug we…

Redefining outcomes in immune TTP: an international working group consensus report

Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal thrombotic microangiopathy caused by autoantibody-mediated severe deficiency of ADAMTS13. Standardized definitions of response, exacerbation, remission, and relapse were initially proposed in 2003 and modified by the International Working Group for TTP in 2017. These definitions, which have been widely used in clinical practice and research, are based primarily on the platelet count and are benchmarked against the timing of discontinuation of therapeutic plasma exchange (TPE). They do not incorporate ADAMTS13 activity or the temporizing effects on the platelet count of caplacizumab, a novel anti–von W…

Patterns of infections in older patients acutely admitted to medical wards: data from the REPOSI register

In older adults infections are among the leading causes of emergency department visits, hospitalization, morbidity and mortality [1–3]. Infections also occur as adverse events during hospitalization, as highlighted by the large use of antibiotics in this setting, resulting in an increase of hospitalization length and mortality rate [4–6]. There is a paucity of studies, especially in European countries, that did offer a general pattern on all the types of infections occurring in acutely hospitalized older patients, being the literature mainly focused on single type of infections (i.e. pneumonia and urinary tract infections). To fill this gap of knowledge, we chose to observe and describe the…

Hospital Care of Older Patients With COPD: Adherence to International Guidelines for Use of Inhaled Bronchodilators and Corticosteroids

Abstract Objectives We aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes. Design Data were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged ≥65 years. Setting and Participants Older hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD. Measures We evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodi…

Acquired inhibitors of clotting factors: AICE recommendations for diagnosis and management

Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation

Aims: Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older. Methods: Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients …

Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Initial Immunosuppression Regimen

Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is an acute, life-threatening thrombotic microangiopathy that requires urgent and specialized treatment. Prior to the introduction of caplacizumab, the treatment for aTTP was based on daily therapeutic plasma exchange (TPE; to replenish functional ADAMTS13 enzyme) plus immunosuppression (mainly corticosteroids and rituximab; to suppress anti-ADAMTS13 autoantibody production). TPE combined with immunosuppressive therapy improved outcomes in patients; however, episodes of aTTP are still associated with an acute mortality of up to 20% as these therapies do not have an immediate effect on the pathologic microvascular thrombosis. Th…

Long-Term Safety and Efficacy of Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura (aTTP): The Post-HERCULES Study

Abstract Background: The post-HERCULES trial (NCT02878603) evaluated long-term safety and efficacy of caplacizumab in patients with acquired thrombotic thrombocytopenic purpura (aTTP; also known as immune-mediated TTP), and efficacy of repeated use of caplacizumab for aTTP recurrence. Methods: Patients who completed the HERCULES trial were invited to participate in the post-HERCULES study and attend twice-yearly visits for 3 years. In case of aTTP recurrence, patients could receive open-label (OL) caplacizumab with therapeutic plasma exchange (TPE) and immunosuppression (IST). Safety was assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences.…

Sex-Differences in the Pattern of Comorbidities, Functional Independence, and Mortality in Elderly Inpatients: Evidence from the RePoSI Register

Background: The RePoSi study has provided data on comorbidities, polypharmacy, and sex dimorphism in hospitalised elderly patients. Methods: We retrospectively analysed data collected from the 2010, 2012, 2014, and 2016 data sets of the RePoSi register. The aim of this study was to explore the sex-differences and to validate the multivariate model in the entire dataset with an expanded follow-up at 1 year. Results: Among 4714 patients, 51% were women and 49% were men. The disease distribution showed that diabetes, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy were more frequent in men but that hypertension, anaemia, osteoarthritis, de…

Safety of Caplacizumab in Patients Without Documented Severe ADAMTS13 Deficiency During the HERCULES Study

Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy caused by a deficiency in the activity of ADAMTS13 leading to the formation of ultra-large multimers of von Willebrand factor (vWF) and abnormal platelet adhesion in the microvasculature. aTTP requires prompt diagnosis and rapid initiation of treatment to limit the risk of negative or fatal outcomes. The clinical diagnosis of aTTP is based on thrombocytopenia and microangiopathic hemolytic anemia and is confirmed by ADAMTS13 <10%. However, the latter confirmation is not always rapidly available, and treatment is typically initiated based on the clinical diagno…

Pattern of comorbidities and 1-year mortality in elderly patients with COPD hospitalized in internal medicine wards: data from the RePoSI Registry

Currently, chronic obstructive pulmonary disease (COPD) represents the fourth cause of death worldwide with significant economic burden. Comorbidities increase in number and severity with age and are identified as important determinants that influence the prognosis. In this observational study, we retrospectively analyzed data collected from the RePoSI register. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients with the clinical diagnosis of COPD. Socio-demographic, clinical characteristics and laboratory findings were considered. The association between variables and in-hospital, 3-month and 1-year follow-up were analyzed. Among 4696 in-patient…

Adherence to antithrombotic therapy guidelines improves mortality among elderly patients with atrial fibrillation: insights from the REPOSI study

Background: Atrial fibrillation (AF) is associated with a substantial risk of thromboembolism and mortality, significantly reduced by oral anticoagulation. Adherence to guidelines may lower the risks for both all cause and cardiovascular (CV) deaths. Methods: Our objective was to evaluate if antithrombotic prophylaxis according to the 2012 European Society of Cardiology (ESC) guidelines is associated to a lower rate of adverse outcomes. Data were obtained from REPOSI; a prospective observational study enrolling inpatients aged ≥65 years. Patients enrolled in 2012 and 2014 discharged with an AF diagnosis were analysed. Results: Among 2535 patients, 558 (22.0 %) were discharged with a diagnos…

Polypharmacy in older people: lessons from 10 years of experience with the REPOSI register

As a consequence of population aging, we have witnessed in internal medicine hospital wards a progressive shift from a population of in-patients relatively young and mainly affected by a single ailment to one of ever older and more and more complex patients with multiple chronic diseases, followed as out-patients by many different specialists with poor integration and inevitably treated with multiple medications. Polypharmacy (defined as the chronic intake of five or more drugs) is associated with increased risks of drug-drug interactions and related adverse effects, prescription and intake errors, poor compliance, re-hospitalization and mortality. With this background, the Italian Society …

Use of high flow nasal cannula in patients with acute respiratory failure in general wards under intensivists supervision: a single center observational study

Abstract Background Few data exist on high flow nasal cannula (HFNC) use in patients with acute respiratory failure (ARF) admitted to general wards. Rationale and objectives To retrospectively evaluate feasibility and safety of HFNC in general wards under the intensivist-supervision and after specific training. Methods Patients with ARF (dyspnea, respiratory rate-RR > 25/min, 150 < PaO2/FiO2 < 300 mmHg during oxygen therapy) admitted to nine wards of an academic hospital were included. Gas-exchange, RR, and comfort were assessed before HFNC and after 2 and 24 h of application. Results 150 patients (81 male, age 74 [60–80] years, SOFA 4 [2–4]), 123 with de-novo ARF underwent HFNC wi…

Prevalence of use and appropriateness of antidepressants prescription in acutely hospitalized elderly patients.

Depression is often under-recognized in older patients, even if antidepressants (AD) are commonly prescribed, with a prevalence of use that increase with ageing [ 1 ]. Nevertheless, even if a diagnosis of depression is established, inappropriate treatment can occur [ 2 ]. Beers criteria are the most widely screening tools used to detect inappropriate prescription of drugs in people aged 65 years or more [ 3 ]. Since 2010, attempts to adapt the Beers' criteria have been made in Europe [ 4 , 5 ]. Tricyclic drugs are the ADs to be always avoided in the elderly, owing to their anticholinergic side effects, such as cognitive impairment, delirium, urinary retention and falls [ 3 ]. Selective sero…

Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura

Recently, we showed that ADAMTS13 circulates in an open conformation during the acute phase of immune-mediated thrombotic thrombocytopenic purpura (iTTP). Although the cause of this conformational change remains elusive, ADAMTS13 is primarily closed in iTTP patients in remission with ADAMTS13 activity >50% and undetectable anti-ADAMTS13 autoantibodies, as well as after rituximab treatment, suggesting a role for anti-ADAMTS13 autoantibodies. Therefore, immunoglobulin G from 18 acute iTTP patients was purified and added to closed ADAMTS13 in healthy donor plasma. This resulted in open ADAMTS13 in 14 of 18 (78%) samples, proving that anti-ADAMTS13 autoantibodies can induce an open ADAMTS13 con…

Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation

Aims Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older. Methods Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in…

Heart failure and chronic kidney disease in a registry of internal medicine wards

Background: The aim of the present study was to evaluate the association between heart failure (HF) and chronic kidney disease (CKD) in tertiary care centers using the clinical records of patients enrolled in internal medicine departments.Patients and methods: We used the clinical records of 1380 elderly patients to identify patients with a history of HF and CKD using admission ICD codes and glomerular filtration rate (GFR) formulas. Magnitude and strength of such associations were investigated by univariable and multivariable analysis.Results: Of the 1380 patients enrolled, 27.9% had HF (age 80 ± 7, BMI 27 ± 6 kg/m2) and 17.4% CKD (age 81 ± 7, BMI 26.8 ± 6 kg/m2). Both groups were signific…