ObjectivesSeverity of a first pulmonary embolism (PE) is sometimes proposed as a criterion for prolonging anticoagulant treatment. However, little evidence supports this idea. We attempted to ...determine the connection between severity of first PE and the risk of recurrence.ParticipantsPatients admitted with PE between 2012 and 2018 and for whom anticoagulant treatment had been discontinued were followed. PEs were classified according to the severity into the following two groups: those with associated cardiac involvement (increased cardiac biomarker(s) and/or echocardiographic right ventricular dysfunction) and those with no cardiac involvement which were classified as non-severe. Recurrence-free survivals were estimated using the Kaplan-Meier method and compared using the log-rank test.Results417 patients with PEs (186 with cardiac involvement) were followed for at least 1 year after discontinuation of treatment with a mean follow-up of: 3.5±1.9 years. 72 patients (17.3%) experienced venous thromboembolism recurrence: 24 (5.8%), 44 (12 %) and 72 (28.3 %) respectively, at 1, 2 and 5 years. In 63 patients (88%), recurrence was a PE. Mean time to onset of recurrence was 24.9±19.9 months. At 5 years, the recurrence rate is higher when the first PE was associated with cardiac involvement p=0.043. In contrast, in patients with provoked PE, the recurrence rate is higher when the first PE event was associated with cardiac involvement: p=0.032. Multivariate analysis demonstrates that PE severity is an independent factor of recurrence (HR 1.634 (1.015–2.632), p=0.043).ConclusionWe report for the first time a possible link between a higher recurrence rate and the severity of the first PE. This result which must be confirmed in a dedicated prospective trial could become an important criterion for the duration of anticoagulant therapy after a PE.Trial registration numberNCT04980924.
Background
Echocardiography realization can be challenging in the presence of breasts implants (BI). It is less known if electrocardiograms (ECG) may be modified in the presence of BI.
Methods
ECG ...from women with BI (and without any known cardiac structural disease) were sent and analyzed by two experienced electrophysiologists (EP1 and EP2) who were blinded and completely unaware of the context of the patients (Group 1). ECG from a control matched‐group of female women without BI (Group 2) were also blindly sent for analysis.
Results
ECG were collected from 28 women with BI (42 ± 8 years) without any acute medical condition. A proportion of 42% of the ECG were considered abnormal by EP1 and 46% by EP2. The abnormalities were for EP1: negative T waves (5), ST depression in inferolateral leads (2), absence of R wave progression from V1 to V4 (4), left ventricular (LV) hypertrophy (1), long QT(1), early repolarization (1), short PR (1); For EP2: negative T waves (6), ST depression in inferolateral leads (2), absence of R wave progression from V1 to V4 (4), LV hypertrophy(3), long QT (1), early repolarization (1). ECG from group 2 were considered abnormal in only 1 patient (5%) for EP1, and normal in all for EP2 (P = 0.0002 between the groups).
Conclusions
ECG from women with BI were considered abnormal in 42% to 46% of the cases by expert readers. ECG interpretation can thus be misleading in these women.
The deleterious cellular effects of ionizing radiation are well-known, but the mechanisms causing DNA damage are poorly understood. The accepted molecular events involve initial oxidation and ...deprotonation at guanine sites, triggering hydrogen atom abstraction reactions from the sugar moieties, causing DNA strand breaks. Probing the chemistry of the initially formed radical cation has been challenging. Here, we generate, spectroscopically characterize, and examine the reactivity of the Watson-Crick nucleobase pair radical cation in the gas phase. We observe rich chemistry, including proton transfer between the bases and propagation of the radical site in deoxyguanosine from the base to the sugar, thus rupturing the sugar. This first example of a gas-phase model system providing molecular-level details on the chemistry of an ionized DNA base pair paves the way toward a more complete understanding of molecular processes induced by radiation. It also highlights the role of radical propagation in chemistry, biology, and nanotechnology.
Aims
The very early management of pulmonary embolism (PE), a part from antithrombotic treatment, has been little studied. Our aim was to compare the effects of diuretic therapy (DT) versus volume ...expansion (VE) in patients hospitalized for PE with RV dysfunction.
Methods and Results
We conducted a randomized open-label multicentric study including patients with intermediate high-risk PE. Patients were randomized between diuretics or saline infusion. The primary endpoint was time to troponin (Tp) normalization. Secondary endpoints were time to normalization of B-type natriuretic peptide (BNP), changes in echocardiographic RV function parameters and treatment tolerance. Sixty patients presenting intermediate high-risk PE were randomized. Thirty received DT and 30 VE. We noted no changes in Tp kinetics between the two groups. In contrast, faster normalization of BNP was obtained in the DT group: 56 28–120 vs 108 48–144 h:
p
= 0.05, with a shorter time to 50%-decrease from peak value 36 24–48 vs 54 41–67 h,
p
= 0.003 and a higher rate of patients with a lower BNP concentration within the first 12 h (42% vs 12%
p
< 0.001). RV echocardiographic parameters were unchanged between the groups. One dose 40 mg furosemide was well-tolerated and not associated with any serious adverse events.
Conclusion
In the acute management of intermediate high-risk PE, initial therapy including diuretic treatment is well-tolerated and safe. Although changes in Tp kinetics and echocardiographic RV dysfunction parameters did not differ, normalization of BNP is achieved more quickly in the DT group. This finding, which need to be confirmed in trials with clinical end points, may reflects a rapid improvement in RV function using one dose 40 mg furosemide.
Trial Registry
Clinical Trial Registration NCT02531581.
Encephalitis is a worldwide public health issue, with a substantially high burden among children in southeast Asia. We aimed to determine the causes of encephalitis in children admitted to hospitals ...across the Greater Mekong region by implementing a comprehensive state-of-the-art diagnostic procedure harmonised across all centres, and identifying clinical characteristics related to patients' conditions.
In this multicentre, observational, prospective study of childhood encephalitis, four referral hospitals in Cambodia, Vietnam, Laos, and Myanmar recruited children (aged 28 days to 16 years) who presented with altered mental status lasting more than 24 h and two of the following minor criteria: fever (within the 72 h before or after presentation), one or more generalised or partial seizures (excluding febrile seizures), a new-onset focal neurological deficit, cerebrospinal fluid (CSF) white blood cell count of 5 per mL or higher, or brain imaging (CT or MRI) suggestive of lesions of encephalitis. Comprehensive diagnostic procedures were harmonised across all centres, with first-line testing was done on samples taken at inclusion and results delivered within 24 h of inclusion for main treatable causes of disease and second-line testing was done thereafter for mostly non-treatable causes. An independent expert medical panel reviewed the charts and attribution of causes of all the included children. Using multivariate analyses, we assessed risk factors associated with unfavourable outcomes (ie, severe neurological sequelae and death) at discharge using data from baseline and day 2 after inclusion. This study is registered with ClinicalTrials.gov, NCT04089436, and is now complete.
Between July 28, 2014, and Dec 31, 2017, 664 children with encephalitis were enrolled. Median age was 4·3 years (1·8-8·8), 295 (44%) children were female, and 369 (56%) were male. A confirmed or probable cause of encephalitis was identified in 425 (64%) patients: 216 (33%) of 664 cases were due to Japanese encephalitis virus, 27 (4%) were due to dengue virus, 26 (4%) were due to influenza virus, 24 (4%) were due to herpes simplex virus 1, 18 (3%) were due to Mycobacterium tuberculosis, 17 (3%) were due to Streptococcus pneumoniae, 17 (3%) were due to enterovirus A71, 74 (9%) were due to other pathogens, and six (1%) were due to autoimmune encephalitis. Diagnosis was made within 24 h of admission to hospital for 83 (13%) of 664 children. 119 (18%) children had treatable conditions and 276 (42%) had conditions that could have been preventable by vaccination. At time of discharge, 153 (23%) of 664 children had severe neurological sequelae and 83 (13%) had died. In multivariate analyses, risk factors for unfavourable outcome were diagnosis of M tuberculosis infection upon admission (odds ratio 3·23 95% CI 1·04-10·03), coma on day 2 (2·90 1·78-4·72), supplementary oxygen requirement (1·89 1·25-2·86), and more than 1 week duration between symptom onset and admission to hospital (3·03 1·68-5·48). At 1 year after inclusion, of 432 children who were discharged alive from hospital with follow-up data, 24 (5%) had died, 129 (30%) had neurological sequelae, and 279 (65%) had completely recovered.
In southeast Asia, most causes of childhood encephalitis are either preventable or treatable, with Japanese encephalitis virus being the most common cause. We provide crucial information that could guide public health policy to improve diagnostic, vaccination, and early therapeutic guidelines on childhood encephalitis in the Greater Mekong region.
Institut Pasteur, Institut Pasteur International Network, Fondation Merieux, Aviesan Sud, INSERM, Wellcome Trust, Institut de Recherche pour le Développement (IRD), and Fondation Total.
Short‐QT Syndrome. A 28‐year‐old man was admitted after aborted sudden cardiac death while sleeping. QTc was 320 ms, suggesting short‐QT syndrome (SQTS). The patient then presented with electrical ...storm with 8 successive episodes of ventricular fibrillation while on deep sedation and hypothermia. Isoproterenol infusion was introduced, leading to rapid cessation of any arrhythmic event. Isoproterenol can be effective in managing electrical storm in patients with SQTS. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1028‐1030, September 2012)
In patients with complete atrioventricular block (AVB), the prevalence and clinical characteristics of patients with pause-dependent AVB (PD-AVB) is not known. Our objective was to assess the ...prevalence of PD-AVB in a population of patients with complete (or high-grade) AVB.
Twelve-lead electrocardiogram (ECG) and/or telemonitoring from patients admitted (from September 2020 to November 2021) for complete (or high-degree) AVB were prospectively collected at the University Hospital of Nice. The ECG tracings were analyzed by an electrophysiologist to determine the underlying mechanism of PD-AVB.
100 patients were admitted for complete (or high-grade) AVB (men 55%; 82 ± 12 years). Arterial hypertension was present in 68% of the patients. Baseline QRS width was 117 ± 32 ms, and mean left ventricular ejection fraction was 56 ± 7%. Fourteen patients (14%) with PD-AVB were identified, and presented similar clinical characteristics in comparison with patients without PD-AVB, except for syncope (which was present in 86% versus 51% in the non-PD-AVB patients,
= 0.01). PD-AVB sequence was induced by: Premature atrial contraction (8/14), premature ventricular contraction (5/14), His extrasystole (1/14), conduction block in a branch (1/14), and atrial tachycardia termination (1/14). All patients with PD-AVB received a dual-chamber pacemaker during hospitalization.
The prevalence of PD-AVB was 14%, and may be underestimated. PD-AVB episodes were more likely associated with syncope in comparison with patients without PD-AVB.
Oxidative damage to DNA yields guanine radical cations. Their gas-phase IR spectroscopic signature and acidity have been modelled by the radical cation of 9-methylguanine. Comparisons with quantum ...chemistry calculations suggest that radical cation formation produces the ground-state keto tautomer, which has an N-H acidity enhanced by ~470 kJ mol(-1).
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