It is now well known that patients with SARS‐CoV‐2 infection admitted in ICU and mechanically ventilated are at risk of developing invasive pulmonary aspergillosis (IPA). Nevertheless, symptomatology of IPA is often atypical in mechanically ventilated patients, and radiological aspects in SARS‐CoV‐2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in airway specimens (detected by culture, galactomannan antigen or specific PCR) remains to be fully understood. To decipher the relevance of the detection of Aspergillus, we performed a comprehensive review of all published cases of respiratory Aspergillus colonisation and IPA in COVID‐19 patients. The comparison of patients receiving or not antifungal treatment allowed us to highlight the most important criteria for the decision to treat. The comparison of surviving and non‐surviving patients made it possible to unveil criteria associated with mortality that should be taken into account in the treatment decision.

Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic (PKpop) model of isavuconazole plasma concentrations in intensive care unit patients with CAPA. Nonlinear mixed-effect modeling Monolix software were used for PK analysis of 65 plasma trough concentrations from 18 patients. PK parameters were best estimated with a one-compartment model. The mean of ISA plasma concentrations was 1.87 [1.29–2.25] mg/L despite prolonged loading dose (72 h for one-third) and a mean maintenance dose of 300 mg per day. Pharmacokinetics (PK) modeling showed that renal replacement therapy (RRT) was significantly associated with under exposure, explaining a part of clearance variability. The Monte Carlo simulations suggested that the recommended dosing regimen did not achieve the trough target of 2 mg/L in a timely manner (72 h). This is the first isavuconazole PKpop model developed for CAPA critical care patients underlying the need of therapeutic drug monitoring, especially for patients under RRT.

Background and aims Sarcopenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in hemodialysis patients. It is generally assumed that sarcopenia is driven by muscle atrophy related to protein energy wasting. However, dynapenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopenia. The aim of this study was to compare the characteristics and prognosis of sarcopenic and dynapenic patients among a prospective cohort of chronic haemodialysis (CHD) patients. Methods Two hundred and thirty two chronic haemodialysis patients were enrolled from January to July 2016 and then followed prospectively until December 2018. At inclusion, weakness and atrophy were respectively evaluated by maximal voluntary force (MVF) and creatinine index (CI). Sarcopenia was defined as the association of weakness and atrophy (MVF and CI below the median) while dynapenia was defined as weakness not related to atrophy (MVF below the median, and CI above the median). Results From a total of 187 prevalent CHD patients (65% of men, age 65,3 (49,7-82,0) years), 44 died during the follow-up period of 23.7 (12,4-34,9) months. Sarcopenia and dynapenia were observed in 33.7% and 16% of patients respectively. Compared to patients with sarcopenia, patients with dynapenia were younger and with a lower Charlson score. By contrast, mortality rate was similar in both groups (38 and 27% respectively). After adjustment for age, sex, LTI, serum albumin, hs-CRP, haemoglobin, nPCR, dialysis vintage and Charlson score, only patients with dynapenia were at increased risk of death (HR = 2.99 CI (1.18-7.61) p = 0.02) . Conclusions Screening for muscle functionality is highly warranted to identify patients with muscle functional impairment without muscle atrophy. By contrast to sarcopenia, dynapenia should appear as a phenotype induced by uremic milieu, characterized by young patients with low Charlson score and poor prognosis outcome independently of serum albumin, hs-CRP, haemoglobin, nPCR and dialysis vintage.

Background: Rapid diagnostic tests (RDTs) detecting the histidine-rich protein 2 (PfHRP2) have a central position for the management of Plasmodium falciparum infections. Yet, variable detection of certain targeted motifs, low parasitaemia, but also deletion of pfhrp2 gene or its homologue pfhrp3, may result in false-negative RDT leading to misdiagnosis and delayed treatment. This study aimed at investigating the prevalence, and understanding the possible causes, of P. falciparum RDT-negative infections at Montpellier Academic Hospital, France. Methods: The prevalence of falsely-negative RDT results reported before and after the introduction of a loop-mediated isothermal amplification (LAMP) assay, as part as the malaria screening strategy in January 2017, was analysed. Negative P. falciparum RDT infections were screened for pfhrp2 or pfhrp3 deletion; and exons 2 were sequenced to show a putative genetic diversity impairing PfHRP2 detection. Results: The overall prevalence of P. falciparum negative RDTs from January 2006 to December 2018 was low (3/446). Whereas no cases were reported from 2006 to 2016 (0/373), period during which the malaria diagnostic screen was based on microscopy and RDT, prevalence increased up to 4.1% (3/73) between 2017 and 2018, when molecular detection was implemented for primary screening. Neither pfhrp2/3 deletion nor major variation in the frequency of repetitive epitopes could explain these false-negative RDT results. Conclusion: This paper demonstrates the presence of pfhrp2 and pfhrp3 genes in three P. falciparum RDT-negative infections and reviews the possible reasons for non-detection of HRP2/3 antigens in a non-endemic setting. It highlights the emergence of falsely negative rapid diagnostic tests in a non-endemic setting and draws attention on the risk of missing malaria cases with low parasitaemia infections using the RDT plus microscopy-based strategy currently recommended by French authorities. The relevance of a novel diagnostic scheme based upon a LAMP assay is discussed.