Abstract Clinical isolates of Pseudomonas aeruginosa exhibiting high-level resistance to carbapenems were recovered from a French patient with cystic fibrosis (CF) who had not received carbapenem ...therapy. This study was conducted to investigate the molecular mechanism conferring the carbapenem-resistant phenotype in clinical isolates of P. aeruginosa recovered from the same CF patient chronically colonised since 2005. Investigation of imipenem resistance of P. aeruginosa strain_02 isolated in May 2011 showed no carbapenemase activity. However, amplification and sequencing of the oprD porin gene revealed disruption of this gene by an insertion sequence (IS) element of 1337 bp that contained a novel transposase of 1227 bp (IS Pa46 ) bordered by two terminal imperfect inverted repeats of 28 bp, which was associated with carbapenem resistance. Retrospective analysis of five additional strains of P. aeruginosa isolated before May 2011 from the same patient revealed that all isolates were likely to be the same clone by multilocus sequence typing analysis (ST540/551), but one of the five isolates was imipenem-susceptible. Although it was possible to demonstrate the presence of IS Pa46 in all strains by PCR, this IS was transposed in the oprD gene only for imipenem-resistant isolates. Therefore, this study reports a novel IS element (IS Pa46 ) in P. aeruginosa clinical isolates of a CF patient in Marseille, France, that was associated with carbapenem resistance and was selected in the absence of carbapenem treatment.
Purpose
Cardiac resynchronization therapy (CRT) devices have multiple programmable pacing parameters. The purpose of this study was to determine the best pacing mode, i.e., associated with the ...greatest acute hemodynamic response, in each patient.
Methods
Patients in sinus rhythm and intact atrioventricular conduction were included within 3 months of implantation of devices featuring SyncAV and multipoint pacing (MPP) algorithms. The effect of nominal biventricular pacing using the latest activated electrode (BiV-Late), optimized atrioventricular delay (AVD), nominal and optimized SyncAV, and anatomical MPP was determined by non-invasive measurement of systolic blood pressure (SBP). CRT response was defined as SBP increase > 10% relative to baseline.
Results
Thirty patients with left bundle branch block (LBBB) were included. BiV-Late increased SBP compared to intrinsic rhythm (128 ± 21 mmHg vs. 121 ± 22 mmHg,
p
= 0.0002). The best pacing mode further increased SBP to 140 ± 19 mmHg (
p
< 0.0001 vs. BiV-Late). The proportion of CRT responders increased from 40% with BiV-Late to 80% with the best pacing mode (
p
= 0.0005). Compared to BiV-Late, optimized AVD and optimized SyncAV increased SBP (to 134 ± 21 mmHg,
p
= 0.004, and 133 ± 20 mmHg,
p
= 0.0003, respectively), but nominal SyncAV and MPP did not. The best pacing mode was variable between patients and was different from nominal BiV-Late in 28 (93%) patients. Optimized AVD was the most frequent best mode, in 14 (47%) patients.
Conclusion
In patients with LBBB, the best pacing mode was patient-specific and doubled the magnitude of acute hemodynamic response and the proportion of acute CRT responders compared to nominal BiV-Late pacing.
Trial registration
ClinicalTrials.gov
: NCT03779802
BACKGROUND:Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the ...implantable cardioverter defibrillator (ICD) in this patient population remain scarce.
METHODS:A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee.
RESULTS:A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5–11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P=0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 95% CI, 1.19–10.11), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 95% CI, 2.96–40.95).
CONCLUSIONS:Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification.
REGISTRATION:URLhttps://www.clinicaltrials.gov; Unique identifierNCT03837574.
Abstract
Aims
We aimed to provide contemporary real-world data on wearable cardioverter-defibrillator (WCD) use, not only in terms of effectiveness and safety but also compliance and acceptability.
...Methods and results
Across 88 French centres, the WEARIT-France study enrolled retrospectively patients who used the WCD between May 2014 and December 2016, and prospectively all patients equipped for WCD therapy between January 2017 and March 2018. All patients received systematic education session through a standardized programme across France at the time of initiation of WCD therapy and were systematically enrolled in the LifeVest Network remote services. Overall, 1157 patients were included (mean age 60 ± 12 years, 16% women; 46% prospectively): 82.1% with ischaemic cardiomyopathy, 10.3% after implantable cardioverter-defibrillator explant, and 7.6% before heart transplantation. Median WCD usage period was 62 (37–97) days. Median daily wear time of WCD was 23.4 (22.2–23.8) h. In multivariate analysis, younger age was associated with lower compliance adjusted odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95–0.99, P < 0.01. A total of 18 participants (1.6%) received at least one appropriate shock, giving an incidence of appropriate therapy of 7.2 per 100 patient-years. Patient-response button allowed the shock to be aborted in 35.7% of well-tolerated sustained ventricular arrhythmias and in 95.4% of inappropriate ventricular arrhythmia detection, finally resulting in an inappropriate therapy in eight patients (0.7%).
Conclusion
Our real-life findings reinforce previous studies on the efficacy and safety of the WCD in the setting of transient high-risk group in selected patients. Moreover, they emphasize the fact that when prescribed appropriately, in concert with adequate patient education and dedicated follow-up using specific remote monitoring system, compliance with WCD is high and the device well-tolerated by the patient.
Graphical Abstract
The objective of this study was to perform an inventory of the extended-spectrum-β-lactamase (ESBL)-producing
isolates responsible for infections in French hospitals and to assess the mechanisms ...associated with ESBL diffusion. A total of 200 nonredundant ESBL-producing
strains isolated from clinical samples were collected during a multicenter study performed in 18 representative French hospitals. Antibiotic resistance genes were identified by PCR and sequencing experiments. The clonal relatedness between isolates was investigated by the use of the DiversiLab system. ESBL-encoding plasmids were compared by PCR-based replicon typing and plasmid multilocus sequence typing. CTX-M-15, CTX-M-1, CTX-M-14, and SHV-12 were the most prevalent ESBLs (8% to 46.5%). The three CTX-M-type EBSLs were significantly observed in
(37.1%, 24.2%, and 21.8%, respectively), and CTX-M-15 was the predominant ESBL in
(81.1%). SHV-12 was associated with ESBL-encoding
strains (37.9%).
,
'
, and
genes were the main plasmid-mediated resistance genes, with prevalences ranging between 19.5% and 45% according to the ESBL results. Molecular typing did not identify wide clonal diffusion. Plasmid analysis suggested the diffusion of low numbers of ESBL-encoding plasmids, especially in
and
However, the ESBL-encoding genes were observed in different plasmid replicons according to the bacterial species. The prevalences of ESBL subtypes differ according to the
species. Plasmid spread is a key determinant of this epidemiology, and the link observed between the ESBL-encoding plasmids and the bacterial host explains the differences observed in the
species.
Resistant acute myeloid leukemia (AML) exhibits mitochondrial energy metabolism changes compared to newly diagnosed AML. This phenotype is often observed by evaluating the mitochondrial oxygen ...consumption of blasts, but most of the oximetry protocols were established from leukemia cell lines without validation on primary leukemia cells. Moreover, the cultures and storage conditions of blasts freshly extracted from patient blood or bone marrow cause stress, which must be evaluated before determining oxidative phosphorylation (OXPHOS). Herein, we evaluated different conditions to measure the oxygen consumption of blasts using extracellular flow analyzers. We first determined the minimum number of blasts required to measure OXPHOS. Next, we compared the OXPHOS of blasts cultured for 3 h and 18 h after collection and found that to maintain metabolic organization for 18 h, cytokine supplementation is necessary. Cytokines are also needed when measuring OXPHOS in cryopreserved, thawed and recultured blasts. Next, the concentrations of respiratory chain inhibitors and uncoupler FCCP were established. We found that the FCCP concentration required to reach the maximal respiration of blasts varied depending on the patient sample analyzed. These protocols provided can be used in future clinical studies to evaluate OXPHOS as a biomarker and assess the efficacy of treatments targeting mitochondria.
Aims/hypothesis
Type 2 diabetes is associated with a high risk of sudden cardiac death (SCD), but the risk of dying from another cause (non-SCD) is proportionally even higher. The aim of the study ...was to identify easily available ECG-derived features associated with SCD, while considering the competing risk of dying from non-SCD causes.
Methods
In the SURDIAGENE (Survie, Diabete de type 2 et Genetique) French prospective cohort of individuals with type 2 diabetes, 15 baseline ECG parameters were interpreted among 1362 participants (mean age 65 years; HbA
1c
62±17 mmol/mol 7.8±1.5%; 58% male). Competing risk models assessed the prognostic value of clinical and ECG parameters for SCD after adjusting for age, sex, history of myocardial infarction, N-terminal pro b-type natriuretic peptide (NT-proBNP), HbA
1c
and eGFR. The prospective Mini-Finland cohort study was used to externally validate our findings.
Results
During median follow-up of 7.4 years, 494 deaths occurred including 94 SCDs. After adjustment, frontal QRS-T angle ≥90° (sub-distribution HR sHR 1.68 95% CI 1.04, 2.69,
p
=0.032) and NT-proBNP level (sHR 1.26 95% CI 1.06, 1.50 per 1 log,
p
=0.009) were significantly associated with a higher risk of SCD. Nevertheless, frontal QRS-T angle was the only marker not to be associated with causes of death other than SCD (sHR 1.08 95% CI 0.84, 1.39,
p
=0.553 ). These findings were replicated in the Mini-Finland study subset of participants with diabetes (sHR 2.22 95% CI 1.05, 4.71,
p
=0.04 for SCD and no association for other causes of death).
Conclusions/interpretation
QRS-T angle was specifically associated with SCD risk and not with other causes of death, opening an avenue for refining SCD risk stratification in individuals with type 2 diabetes.
Graphical Abstract
PDF
