Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update

Daptomycin pharmacokinetics may not depend on renal function only and it significantly differs between healthy volunteers and severely ill patients. Herein, we propose a population pharmacokinetics model based on 424 plasma daptomycin concentrations collected from 156 patients affected by severe Gram-positive infections during a routine therapeutic drug monitoring protocol. Model building and validation were performed using NONMEM 7.2 (ICON plc), Xpose4 and Perl-speaks-to-NONMEM. The final pop-PK model was a one-compartment first-order elimination model, with a 2.7% IIV for drug clearance (Cl), influence of creatinine clearance on drug clearance and of sex on distribution volume. After model validation, we simulated 10,000 patients with the Monte-Carlo method to predict the efficacy and tolerability of different daptomycin daily dosages. For the most common 6 mg/kg daily dose, the simulated probability of overcoming the toxic minimum concentration (24.3 mg/L) was 14.8% and the efficacy (expressed as a cumulative fraction of response) against methicillin-resistant S. aureus, S. pneumoniae and E. faecium was 95.77%, 99.99% and 68%, respectively. According to the model-informed precision dosing paradigm, pharmacokinetic models such as ours could help clinicians to perform patient-tailored antimicrobial dosing and maximize the odds of therapy success without neglecting toxicity risk

Severe heart failure and intracardiac thrombosis: going beyond the appearance for diagnosis and treatments

We describe the case of a 45-year-old female affected by asthma and nasal polyposis who presented to the emergency department because of worsening dyspnea and paresthesia of the left lower limb. Comprehensive instrumental examinations revealed the presence of severe left ventricle dysfunction, intra-cardiac thrombus, deep vein thrombosis, pulmonary embolism, lung infiltrates, polyserositis, and neurological involvements. Finally, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, a rare vasculitis of small-medium blood vessels with several organ involvements. Treatment with anticoagulants, corticosteroids, and cyclophosphamide led to a significant clinical improvement. However, a subcutaneous cardiac defibrillator was implanted because of the persistence of severe left ventricular dysfunction and the high cardiovascular risk phenotype. Indeed, several cardiac manifestations may occur in EGPA, particularly in patients with anti-neutrophil cytoplasmic antibody-negative disease. Therefore, clinicians should have high clinical suspicion because cardiac involvement in EGPA results in a poor prognosis if not diagnosed and adequately treated

Superior Vena Cava Defibrillator Coils Make Transvenous Lead Extraction More Challenging and Riskier

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Influences of Human Cognition and Visual Behavior on Password Strength during Picture Password Composition

Visual attention, search, processing and comprehension are important cognitive tasks during a graphical password com-position activity. Aiming to shed light on whether individual differences on visual behavior affect the strength of the created passwords, we conducted an eye-tracking study (N=36) and adopted an accredited cognitive style theory to interpret the results. The analysis revealed that users with different cognitive styles followed different patterns of visual behavior which affected the strength of the created passwords. Motivated, by the results of the first study, we introduced adaptive characteristics to the user authentication mechanism, aiming to assist specific cognitive style user groups to create more secure passwords, and conducted a second study with a new sample (N=40) to test the adaptive characteristics. Results strengthen our assumptions that adaptive mechanisms based on users’ differences in cognitive and visual behavior uncover a new perspective for improving the password’s strength within graphical user authentication realms

Insight into contact force local impedance technology for predicting effective pulmonary vein isolation

BackgroundHighly localized impedance (LI) measurements during atrial fibrillation (AF) ablation have the potential to act as a reliable predictor of the durability of the lesions created.ObjectiveWe aimed to collect data on the procedural parameters affecting LI-guided ablation in a large multicenter registry.MethodsA total of 212 consecutive patients enrolled in the CHARISMA registry and undergoing their first pulmonary vein (PV) isolation for paroxysmal and persistent AF were included.ResultsIn all, 13,891 radiofrequency (RF) applications of ≥3 s duration were assessed. The first-pass PV isolation rate was 93.3%. A total of 80 PV gaps were detected. At successful ablation spots, baseline LI and absolute LI drop were larger than at PV gap spots (161.4 ± 19 Ω vs. 153.0 ± 13 Ω, p < 0.0001 for baseline LI; 22.1 ± 9 Ω vs. 14.4 ± 5 Ω, p < 0.0001 for LI drop). On the basis of Receiver operating characteristic curve analysis, the ideal LI drop, which predicted successful ablation, was >21 Ω at anterior sites and >18 Ω at posterior sites. There was a non-linear association between the magnitude of LI drop and contact-force (CF) (r = 0.14, 95% CI: 0.13–0.16, p < 0.0001) whereas both CF and LI drop were inversely related with delivery time (DT) (−0.22, −0.23 to −0.20, p < 0.0001 for CF; −0.27, −0.29 to −0.26, p < 0.0001 for LI drop).ConclusionAn LI drop >21 Ω at anterior sites and >18 Ω at posterior sites predicts successful ablation. A higher CF was associated with an increased likelihood of ideal LI drop. The combination of good CF and adequate LI drop allows a significant reduction in RF DT.Clinical trial registrationhttp://clinicaltrials.gov/, identifier: NCT03793998

Effective Percutaneous Repositioning of an Active Fixation ICD Lead

We report a case of effective trans catheter repositioning of an ICD lead that was displaced during a trans venous extraction procedure of another malfunctioning ICD lead. This original technique was effective also in screwing-in the active fixation tip of the lead. Skilled operators could take into account this technique to avoid the re-opening of the device pocket, when dealing with specific situations at high risk of infection.</p

To abandon or not to abandon: Late consequences of pacing and ICD lead abandonment

Introduction The increasing number of cardiac implantable electronic device complications represents a current problem. Abandoned leads are difficult to manage, even because indications to transvenous lead extraction (TLE) cannot be generalized. The aim of the study was to assess the late consequences of previous abandoned leads. Methods We did a retrospective analysis of clinical data from 3,810 patients undergoing TLE in two high-volume centers (Poland and Italy) in the years 2006-2017. In order to evaluate the effects of lead abandonment, the patients were divided into a group of 582 (15.3%) subjects with abandoned leads (AL) and a group of 3,228 (84.7%) subjects with functional leads (FL). Results Infective indications to TLE were predominant in the AL group (61.34% vs 43.4%; P &lt; 0.001). AL was associated with a higher number of leads per patient, longer lead dwell times, more frequent venous occlusion, higher probability of intracardiac lead abrasion, and tricuspid regurgitation (P &lt; 0.001 for all factors). The presence of AL was connected with more frequent technical complications of TLE (odds ratio [OR] 1.617; confidence interval [CI] 1.412-1.852; P = 0.000), lower procedural success rate (OR 0.270; CI 0.199-0.363; P = 0.000), and with higher mortality rate during 3.518 years of follow-up [hazard ratio 1.286; 95% CI (1.062-1.558), P = 0.010]. Conclusions Presence of previously abandoned leads was associated with the risk of device infections, technical problems during subsequent lead extraction, dysfunction of tricuspid valve, and worse long-term outcomes

Influence of the type of pathogen on the clinical course of infectious complications related to cardiac implantable electronic devices

The specific role of the various pathogens causing cardiac implantable electronic devices-(CIEDs)-related infections requires further understanding. The data of 1241 patients undergoing transvenous lead extraction because of lead-related infective endocarditis (LRIE-773 patients) and pocket infection (PI-468 patients) in two high-volume centers were analyzed. Clinical course and long-term prognosis according to the pathogen were assessed. Blood and generator pocket cultures were most often positive for methicillin-sensitive Staphylococcus aureus (MSSA: 22.19% and 18.13% respectively), methicillin-sensitive Staphylococcus epidermidis (MSSE: 17.39% and 15.63%) and other staphylococci (11.59% and 6.46%). The worst long-term prognosis both in LRIE and PI subgroup was in patients with infection caused by Gram-positive microorganisms, other than staphylococci. The most common pathogens causing CIED infection are MSSA and MSSE, however, the role of other Gram-positive bacteria and Gram-negative organisms is also important. Comparable, high mortality in patients with LRIE and PI requires further studies