Late dihydroartemisinin-piperaquine treatment failure of P. falciparum malaria attack related to insufficient dosing in an obese patient.

We report the case of an obese patient who experienced late failure on day28 of a well-conducted treatment with artesunate, followed by dihydroartemisinin-piperaquine (DHA-PPQ) for a severe P. falciparum malaria attack. The same P. falciparum strain was evidenced at day0 and day28. Genotypic and phenotypic resistance tests could not explain this treatment failure. The low plasma piperaquine concentration at failure may explain the poor elimination of residual parasites.

Characteristics of deep vein thrombosis in the critically ill COVID-19 patient - an observational cohort study with Doppler ultrasound measurements.

OBJECTIVE: COVID-19 is associated with an increased prevalence of deep venous thrombosis (DVT), mainly in the lower limbs. However, the characteristics and rheological conditions, which contribute to facilitating DVT occurrence have been poorly investigated. We aimed to report DVT characteristics, vein diameters and peak blood flow velocities (PBFV) in the common femoral veins (CFVs) of critically ill COVID-19 patients. PATIENTS AND METHODS: We conducted a prospective single-center cohort study in March-October 2020 including all consecutive mechanically ventilated COVID-19 adults. Doppler ultrasound of the lower limbs was performed systematically during the first week of hospitalization. In DVT-free patients, a second Doppler ultrasound was performed seven days later. Data are expressed as medians (interquartile ranges) or percentages. Comparisons were performed using Mann-Whiney and Wilcoxon signed-rank tests or Fischer's exact tests, as appropriate. RESULTS: Fifty-five patients [age, 63 years (56-74); female/male ratio, 0.62; body-mass index, 29 kg/m2 (26-33); hypertension, 47%; diabetes, 38%; ischemic heart disease, 11%] were included. DVT was diagnosed in 19 patients (35%) including in 5 femoral (9%), 2 popliteal (4%) and 12 below-the-knee sites (22%). CFV diameter was increased to 12.0 mm (11.0-15.0) (normal range, 9.1-12) and PBFV reduced to 11.9 cm/s (8.8-15.8) (normal range, 21.3-49.2) [right-side values]. In four patients who had ultrasound before intubation, CFV diameter increased from 12.5 mm (11.8-13.3) before to 14 mm (13.6-15.3) after intubation (p = 0.008). CONCLUSIONS: DVT in the CFV occurred in 9% of the critically ill COVID-19 patients with an overall 35%-DVT prevalence. Venous return difficulty evidenced by larger than normal CFV diameters and lower than normal PBFVs may have facilitated proximal DVT occurrence.

Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.

OBJECTIVE: Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE). PATIENTS AND METHODS: We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%). We developed a comprehensive analysis of hemostasis. RESULTS: Ninety-two consecutive mechanically ventilated COVID-19 patients (age, 62 years [53-69] (median [25th-75th percentiles]); M/F sex ratio, 2.5; body-mass index, 28 kg/m2 [25-32]; past hypertension (52%) and diabetes mellitus (30%)) admitted to the Intensive Care Unit (ICU) from 03/11/2020 to 5/05/2020, were included. When tested, patients were receiving prophylactic (74%) or therapeutic (26%) anticoagulation. Forty patients (43%) were diagnosed with VTE. Patients displayed inflammatory and prothrombotic profile including markedly elevated plasma fibrinogen (7.7 g/L [6.1-8.6]), D-dimer (3,360 ng/mL [1668-7575]), factor V (166 IU/dL [136-195]) and factor VIII activities (294 IU/dL [223-362]). We evidenced significant discrepant protein C anticoagulant and chromogenic activities, combined with slightly decreased protein S activity. Plasma D-dimer >3,300 ng/mL predicted VTE presence with 78% (95%-confidence interval (95% CI), 62-89) sensitivity, 69% (95% CI, 55-81) specificity, 66% (95% CI, 51-79) positive predictive value and 80% (95% CI, 65-90) negative predictive value [area under the ROC curve, 0.779 (95%CI, 0.681-0.859), p=0.0001]. CONCLUSIONS: Mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway. Plasma D-dimer may be a useful biomarker at the bedside for suspicion of VTE.

Exogenous acquisition of Pseudomonas aeruginosa in intensive care units: a prospective multi-centre study (DYNAPYO study).

BACKGROUND: Pseudomonas aeruginosa remains one of the most common nosocomial pathogens in intensive care units (ICUs). Although exogenous acquisition has been widely documented in outbreaks, its importance is unclear in non-epidemic situations. AIM: To elucidate the role of exogenous origin of P. aeruginosa in ICU patients. METHODS: A chronological analysis of the acquisition of P. aeruginosa was performed using samples collected in 2009 in the DYNAPYO cohort study, during which patients and tap water were screened weekly. Molecular relatedness of P. aeruginosa isolates was investigated by pulsed-field gel electrophoresis. Exogenous acquisition was defined as identification of a P. aeruginosa pulsotype previously isolated from another patient or tap water in the ICU. FINDINGS: The DYNAPYO cohort included 1808 patients (10,402 samples) and 233 water taps (4946 samples). Typing of 1515 isolates from 373 patients and 375 isolates from 81 tap water samples identified 296 pulsotypes. Analysis showed exogenous acquisition in 170 (45.6%) of 373 patients. The pulsotype identified had previously been isolated from another patient and from a tap water sample for 86 and 29 patients, respectively. The results differed according to the ICU. CONCLUSION: Exogenous acquisition of P. aeruginosa could be prevented in half of patients. The overall findings of this survey support the need for studies on routes of transmission and risk assessment approach to better define how to control exogenous acquisition in ICUs.

A 2-year multicenter, observational, prospective, cohort study on extracorporeal CO2 removal in a large metropolis area.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) is a promising technique for the management of acute respiratory failure, but with a limited level of evidence to support its use outside clinical trials and/or data collection initiatives. We report a collaborative initiative in a large metropolis. METHODS: To assess on a structural basis the rate of utilization as well as efficacy and safety parameters of 2 ECCO2R devices in 10 intensive care units (ICU) during a 2-year period. RESULTS: Seventy patients were recruited in 10 voluntary and specifically trained centers. The median utilization rate was 0.19 patient/month/center (min 0.04; max 1.20). ECCO2R was started under invasive mechanical ventilation (IMV) in 59 patients and non-invasive ventilation in 11 patients. The Hemolung Respiratory Assist System (Alung) was used in 53 patients and the iLA Activve iLA kit (Xenios Novalung) in 17 patients. Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median V T was observed in ARDS patients from 5.9 to 4.1 ml/kg (p <0.001). A reduction in PaCO2 values was observed in AE-COPD patients from 67.5 to 51 mmHg (p< 0.001). Median duration of ECCO2R was 5 days (IQR 3-8). Reasons for ECCO2R discontinuation were improvement (n = 33), ECCO2R-related complications (n = 18), limitation of life-sustaining therapies or measures decision (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which being ECCO2R-related. CONCLUSIONS: Based on a registry, we report a low rate of ECCO2R device utilization, mainly in severe COPD and ARDS patients. Physiological efficacy was confirmed in these two populations. We confirmed safety concerns such as hemolysis, bleeding, and thrombosis, with different profiles between the devices. Such results could help to design future studies aiming to enhance safety, to demonstrate a still-lacking strong clinical benefit of ECCO2R, and to guide the choice between different devices. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT02965079 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02965079.

[The American opioid overdose crisis: A threat for France?] / La crise des overdoses américaines : une menace pour la France ?

Since the 2000s, a concerning increase in opioid-analgesic-related overdoses and deaths has been reported in the United States. In contrast with opioid overdoses reported in the 80-90s mostly involving heroin, currently it is the misuse of opioid analgesics that is mainly responsible for opioid overdoses. This crisis is related to factors (not limited to the US) which occurred during the 90s and which have led to a broad prescription of opioids in non-cancer pain. In Europe and France, there is (but to a much lesser extent) an increase in strong opioid consumption and in opioid prescription related morbi-mortality. This situation, which can be described as "worrying" today, requires awareness among the French medical community, both upstream (rational prescription of opioids) and downstream (optimal management of opioid poisoning) from the opioid prescription.

[The serotonin syndrome: An updated literature review]. / Le syndrome sérotoninergique : une revue actualisée de la littérature.

The serotonin syndrome is a potentially deadly complication resulting from drug adverse effect, drug-drug interaction or overdose involving one or more serotonergic molecules, e.g., antidepressants, psychostimulants and sometimes an "ignored" serotonergic compound. The serotonin syndrome typically consists of a clinical triad including cognitive/behavioral, neurovegetative and neuromuscular features. However, this syndrome is characterized by major clinical heterogeneity, making the diagnosis difficult in practice. Moreover, many practitioners are quite unaware of this syndrome. Available scores and classifications can help physicians in their diagnosis approach. Knowing the responsible molecules, their potential interactions and mechanisms of action can help preventing this complication allowing therapeutic education among patients. This updated article reviews the clinical presentation, prevention, management, and pathophysiology of the serotonin syndrome, and addresses the most recent advances in pharmacogenetics regarding this syndrome.