Explore the vast range of titles available.

The FA-PNEU is an automated multiplex PCR test allowing direct detection of 15 bacteria with a semi-quantitative value, 3 atypical bacteria, 9 viruses, and 7 antimicrobial resistance genes within 1 h and 15 min [2]. [...]bacterial documentation is essential to assess co-infection in COVID-19 critically ill. Evaluation of the BioFire FilmArray Pneumonia panel for detection of viral and bacterial pathogens in lower respiratory tract specimens in the setting of a tertiary care academic center.

Low molecular weight heparins (LMWH) are recommended for thromboprophylaxis in ICU patients but often fail to reach adequate peak anti-Xa activity. To compare the pharmacokinetic profiles of intravenous (IV) versus subcutaneous (SC) route of administration of LMWH. This was a prospective, monocentric, randomized trial. Patients were randomized to the IV route of administration with a 4-h infusion of nadroparin 3800 IU or to the SC route of administration. Randomization was stratified according to the need for vasopressor or not. Anti-Xa activity was measured at baseline, and at 1, 2, 4, 6, 8, 12 and 24 h after the administration was started. Sixty patients were included, of whom 30 were randomized to the IV group and 30 to the SC route. Pharmacokinetic profiles were significantly different. Mean peak anti-Xa activity was 0.38 IU/ml in the IV group vs 0.20 IU/ml in the SC group (p < 0.001). Trough values and AUC (0-24 h) were similar in both groups. Pharmacokinetic profiles were similar whether patients received vasopressors or not. The IV route of administration with a 4-h infusion lead to a significantly higher peak anti-Xa activity without affecting trough value or the AUC (0-24 h). Whether the IV administration of LMWH might improve the efficacy of thromboprophylaxis requires further research. Registration: ClinicalTrials.gov, NCT04982055, retrospectively registered 08 July 2021, https://clinicaltrials.gov/ct2/show/NCT04982055?cond=NCT04982055&draw=2&rank=1 •The 4-h IV administration of nadroparin lead to a higher peak anti-Xa activity than the SC administration.•Peak anti-Xa activity is not correlated with vasopressor use.•Body mass index is associated with lower peak anti-Xa activities.

Background The severity of coronavirus disease 2019 (COVID-19) is highly variable between individuals, ranging from asymptomatic infection to critical disease with acute respiratory distress syndrome requiring mechanical ventilation. Such variability stresses the need for novel biomarkers associated with disease outcome. As SARS-CoV-2 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid, we hypothesized that low serum levels of uric acid (hypouricemia) may be associated with severity and outcome of COVID-19. Methods In a retrospective study using two independent cohorts, we investigated and validated the prevalence, kinetics and clinical correlates of hypouricemia among patients hospitalized with COVID-19 to a large academic hospital in Brussels, Belgium. Survival analyses using Cox regression and a competing risk approach assessed the time to mechanical ventilation and/or death. Confocal microscopy assessed the expression of urate transporter URAT1 in kidney proximal tubule cells from patients who died from COVID-19. Results The discovery and validation cohorts included 192 and 325 patients hospitalized with COVID-19, respectively. Out of the 517 patients, 274 (53%) had severe and 92 (18%) critical COVID-19. In both cohorts, the prevalence of hypouricemia increased from 6% upon admission to 20% within the first days of hospitalization for COVID-19, contrasting with a very rare occurrence (< 1%) before hospitalization for COVID-19. During a median (interquartile range) follow-up of 148 days (50–168), 61 (12%) patients required mechanical ventilation and 93 (18%) died. In both cohorts considered separately and in pooled analyses, low serum levels of uric acid were strongly associated with disease severity (linear trend, P  < 0.001) and with progression to death and respiratory failure requiring mechanical ventilation in Cox (adjusted hazard ratio 5.3, 95% confidence interval 3.6–7.8, P  < 0.001) or competing risks (adjusted hazard ratio 20.8, 95% confidence interval 10.4–41.4, P  < 0.001) models. At the structural level, kidneys from patients with COVID-19 showed a major reduction in urate transporter URAT1 expression in the brush border of proximal tubules. Conclusions Among patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation.

Correspondence to Jean-Baptiste Mesland, jean-baptiste.mesland@uclouvain.be and Dr Diego Castanares-Zapatero, diego.castanares@uclouvain.be Description A 17-year-old woman was admitted to the emergency department with a 3-day history of dyspnoea (New York Heart Association Class II) and typical pleuritic pain following a 1-week history of cough and fever. The next day, another echocardiography was carried out, showing more extensive pericardial effusion with tamponade effect. [...]a mass compressing the left atrium was detected (figure 1B). The said opacity had already been observed on a previous image when the patient was 3 years old, in the course of treatment for pneumonia. [...]the diagnosis was confirmed via a CT scan determining a large mediastinal cystic mass measuring 75×53×63 mm and causing compression of the left atrium (figure 2A).

A 68-year-old man with a medical history of hypertension was admitted to the emergency department for diffuse abdominal pain preceded by bloody diarrhea. Upon admission, neurological examination was normal, but he suddenly developed a left-sided hemiparesis. After a normal brain computed tomography, intravenous thrombolysis was administered for a suspicion of ischemic stroke. In the first laboratory investigations, hemoglobin was 16.9 g/dL, platelets 121 × 10 9 /L (150–450), and serum creatinine 1.17 mg/dL. By the second hospital day, the platelet level dropped to 79 × 10 9 /L, with haptoglobin at 0.12 g/L, 3% schistocytes, and normal ADAMTS13 activity (57%). Serum creatinine increased to 1.84 mg/dL with oliguria. The suspicion of thrombotic microangiopathy was supported by the identification of Shiga toxin genes stx1 and stx2 on a rectal swab and the isolation of an eaeA-negative Shiga toxin-producing E. coli O113:H4. The patient presented a generalized tonic-clonic seizure, and orotracheal intubation was required for decreased consciousness. Plasma exchange therapy was started, and eculizumab was given 6 days after symptoms onset. Brain magnetic resonance imaging (MRI) on day 13 showed symmetric hyperintensities within basal ganglia that disappeared on a second MRI on day 37. At 2-month follow-up, the patient had made a complete neurological and renal recovery and eculizumab therapy was stopped.

Chronic obstructive pulmonary disease (COPD), a devastating and irreversible lung disease, causes structural and functional defects in the bronchial epithelium, the (ir)reversibility of which remains unexplored in vitro. This study aimed to investigate the persistence of COPD-related epithelial defects in long-term airway epithelial cultures derived from non-smokers, smokers, and COPD patients. Barrier function, polarity, cell commitment, epithelial-to-mesenchymal transition, and inflammation were evaluated and compared with native epithelium characteristics. The role of inflammation was explored using cytokines. We show that barrier dysfunction, compromised polarity, and lineage abnormalities observed in smokers and COPD persisted for up to 10 wk. Goblet cell hyperplasia was associated with recent cigarette smoke exposure. Conversely, increased IL-8/CXCL-8 release and abnormal epithelial-to-mesenchymal transition diminished over time. These ex vivo observations matched surgical samples' abnormalities. Cytokine treatment induced COPD-like changes in control cultures and reactivated epithelial-to-mesenchymal transition in COPD cells. In conclusion, these findings suggest that the airway epithelium of smokers and COPD patients retains a multidimensional memory of its original state and previous cigarette smoke-induced injuries, maintaining these abnormalities for extended periods.

PurposeIlofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety.MethodsIn this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition.ResultsSix hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0–24] and 14 [0–24], number of days alive and discharged from the ICU through day 28 were 15 [0–22] and 10 [0–22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group.ConclusionAmong critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified.

Background To investigate the possible influence of prolonged ketamine (K) or esketamine (ESK) infusion on the profile of liver cholestatic biomarkers in patients with COVID-19 infection. Methods A retrospective analysis was performed on 135 patients with COVID-19 related ARDS who received prolonged K or ESK infusion. They were compared to 15 COVID-19 ICU patients who did not receive K/ESK while being mechanically ventilated and 108 COVID-19 patients who did not receive mechanical ventilation nor K/ESK. The profile of the liver function tests was analysed in the groups. Results Peak values of ALP, GGT and bilirubin were higher in the K/ESK group, but not for AST and ALT. Peak values of ALP were significantly higher among patients who underwent mechanical ventilation and who received K/ESK, compared with mechanically ventilated patients who did not receive K/ESK. There was a correlation between these peak values and the cumulative dose and duration of K/ESK therapy. Conclusions Based on the observations of biliary anomalies in chronic ketamine abusers, prolonged exposure to ketamine sedation during mechanical ventilation may also be involved, in addition to viral infection causing secondary sclerosing cholangitis. The safety of prolonged ketamine sedation on the biliary tract requires further investigations.

Introduction: Cytomegalovirus (CMV) DNAemia has been described in critically ill patients, including patients with severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection. Our objective is to evaluate the prevalence and clinical impact of CMV DNAemia among patients undergoing invasive mechanical ventilation (IMV) for severe SARS-CoV-2 infection and to explore the association between CMV DNAemia levels and clinical outcomes. Methods: In this retrospective monocentric study, we included patients admitted in a tertiary ICU for severe COVID-19 and who required IMV. We aimed to compare clinical and demographic variables between patients with and without CMV DNAemia. Univariate and Cox regression analyses were performed to identify factors associated with CMV DNAemia. Results: During the study period, CMV blood DNAemia occurred in 30/135 patients (22%). Patients with CMV blood DNAemia had longer ICU and hospital length of stay, as well as longer duration of IMV, and were more likely to have received dexamethasone. However, there was no significant difference in ICU mortality between patients with and without CMV DNAemia (64.8% vs. 56.7%, p = 0.42). The Cox regression analysis showed that dexamethasone was the only factor independently associated with CMV blood DNAemia (HR 4.23 [1.006–17.792], p = 0.049). Conclusions: In patients with severe SARS-CoV-2 pneumonia requiring IMV, CMV DNAemia is common and associated with prolonged ventilation and increased LOS but not with increased mortality.

PurposeHospital-acquired bacterial pneumonia (HABP) is a critical concern in hospitals with ventilator-associated bacterial pneumonia (VABP) remaining the most common infection in the ICU, often due to Staphylococcus aureus, an increasingly difficult to treat pathogen. Anti-infective monoclonal antibodies (mAb) may provide new, promising treatment options. This randomized, double-blinded, placebo-controlled study aimed at assessing the safety and pharmacokinetics of AR-301, an S. aureus alpha toxin-neutralizing mAb, and exploring its clinical and microbiologic outcomes when used adjunctively with standard-of-care antibiotics.MethodsEligibility in this trial required microbiologically confirmed severe S. aureus pneumonia, including HABP, VABP or CABP, treated in the ICU and an APACHE II score ≤ 30. Standard-of-care antibiotics selected by the investigators were administered to all patients in the study following clinical and microbiologic confirmation of S. aureus pneumonia. Adjunctive treatment of AR-301 was to start < 36 h after onset of severe pneumonia. AR-301 was administered to four sequentially ascending dose cohorts. The placebo cohort received antibiotics and a placebo buffer. Clinical outcomes were adjudicated by a blinded committee. S. aureus eradication was declared based on a negative follow-up culture and presumed to be negative when no culture was obtained in the presence of clinical improvement.ResultsThirteen ICUs enrolled 48 patients, with pneumonia attributable to MRSA in six subjects. The study drug displayed a favorable safety profile: Of 343 AEs reported, 8 (2.3%) were deemed related, none serious. In a post hoc subgroup analysis of VABP patients receiving AR-301, ventilation duration was shorter for AR-301-treated patients compared with the placebo group. Overall, there was a trend toward a better and faster microbiologic eradication at day 28. The PK profile of AR-301 is consistent with that of a human IgG1 mAb, with a plasma half-life of about 25 days.ConclusionsAdjunctive treatment of severe S. aureus HABP with anti-staphylococcal mAbs appears feasible and suggests some clinical benefits, but larger randomized studies are needed to better define its safety and efficacy.