Introduction: Mechanical ventilation and the effect of respiratory muscle unloading on the diaphragm cause ventilator-induced diaphragmatic dysfunction (VIDD). Atrophy of the diaphragmatic muscle is a major part of VIDD, and has a rapid onset in most animal models. We wanted to assess the clinical evolution and risk factors for VIDD in an adult intensive care unit (ICU) by measuring diaphragm thickness using ultrasound. Method: We performed a single-centre observational cohort study, including 54 mechanically ventilated patients. The right hemidiaphragm was measured daily at the zone of apposition on the midaxillary line. Results: Mean baseline thickness was 1.9 mm (SD ± 0.4 mm), and mean nadir was 1.3 mm (SD ± 0.4 mm), corresponding with a mean change in thickness of 32 % (95 % CI 27–37 %). Length of mechanical ventilation (MV) was associated with the degree of atrophy, whereas other known risk factors for muscle atrophy in an ICU were not. The largest decrease in thickness occurred during the first 72 hours of MV. Conclusions: Diaphragm atrophy occurs quickly in mechanically ventilated patients and can accurately be monitored using ultrasound. Length of MV, as opposed to other variables, is associated with the degree of atrophy. Clinical trial registration: Clinicaltrials.gov NCT02299986. Registered 10/11/2014

Background: Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes. Methods: Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: < 10 kcal/kg, < 0.8 g/kg; moderate: 10–20 kcal/kg, 0.8–1.2 g/kg, high: > 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV). Results: A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (− 2.74 [− 3.28; − 2.21] and − 0.12 [− 0.15; − 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements. Conclusions: Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes. Trial registrationNCT04143503, registered on October 25, 2019. Graphical

BACKGROUND: SARS-CoV-2 infection induces mucin overexpression, further promoting disease. Given that mucins are critical components of innate immunity, unraveling their expression profiles that dictate the course of disease could greatly enhance our understanding and management of COVID-19. METHODS: Using validated RT-PCR assays, we assessed mucin mRNA expression in the blood of patients with symptomatic COVID-19 compared with symptomatic patients without COVID-19 and healthy controls and correlated the data with clinical outcome parameters. Additionally, we analyzed mucin expression in mucus and lung tissue from patients with COVID-19 and investigated the effect of drugs for COVID-19 treatment on SARS-CoV-2–induced mucin expression in pulmonary epithelial cells. RESULTS: We identified a dynamic blood mucin mRNA signature that clearly distinguished patients with symptomatic COVID-19 from patients without COVID-19 based on expression of MUC1 , MUC2 , MUC4 , MUC6 , MUC13 , MUC16 , and MUC20 (AUC _ROC of 91.8%; sensitivity and specificity of 90.6% and 93.3%, respectively) and that discriminated between mild and critical COVID-19 based on the expression of MUC16, MUC20, and MUC21 (AUC _ROC of 89.1%; sensitivity and specificity of 90.0% and 85.7%, respectively). Differences in the transcriptional landscape of mucins in critical cases compared with mild cases identified associations with COVID-19 symptoms, respiratory support, organ failure, secondary infections, and mortality. Furthermore, we identified different mucins in the mucus and lung tissue of critically ill COVID-19 patients and showed the ability of baricitinib, tocilizumab, favipiravir, and remdesivir to suppress expression of SARS-CoV-2–induced mucins. CONCLUSION: This multifaceted blood mucin mRNA signature showed the potential role of mucin profiling in diagnosing, estimating severity, and guiding treatment options in patients with COVID-19. FUNDING: The Antwerp University Research and the Research Foundation Flanders COVID-19 funds.

Background: Anticoagulation is recommended to maintain the patency of the circuit in continuous renal replacement therapy (CRRT). However, anticoagulation-associated complications can occur. We performed a systematic review and meta-analysis to compare the efficacy and safety of citrate anticoagulation to heparin anticoagulation in critically ill patients treated with CRRT. Methods: Randomised controlled trials (RCTs) evaluating the safety and efficacy of citrate anticoagulation and heparin in CRRT were included. Articles not describing the incidence of metabolic and/or electrolyte disturbances induced by the anticoagulation strategy were excluded. The PubMed, Embase, and MEDLINE electronic databases were searched. The last search was performed on 18 February 2022. Results: Twelve articles comprising 1592 patients met the inclusion criteria. There was no significant difference between the groups in the development of metabolic alkalosis (RR = 1.46; (95% CI (0.52–4.11); p = 0.470)) or metabolic acidosis (RR = 1.71, (95% CI (0.99–2.93); p = 0.054)). Patients in the citrate group developed hypocalcaemia more frequently (RR = 3.81; 95% CI (1.67–8.66); p = 0.001). Bleeding complications in patients randomised to the citrate group were significantly lower than those in the heparin group (RR 0.32 (95% CI (0.22–0.47); p < 0.0001)). Citrate showed a significantly longer filter lifespan of 14.52 h (95% CI (7.22–21.83); p < 0.0001), compared to heparin. There was no significant difference between the groups for 28-day mortality (RR = 1.08 (95% CI (0.89–1.31); p = 0.424) or 90-day mortality (RR 0.9 (95% CI (0.8–1.02); p = 0.110). Conclusion: regional citrate anticoagulation is a safe anticoagulant for critically ill patients who require CRRT, as no significant differences were found in metabolic complications between the groups. Additionally, citrate has a lower risk of bleeding and circuit loss than heparin.

Objective and Importance Boerhaave's syndrome is a sudden and rare form of oesophageal rupture and is often complicated by local or systemic infection of the mediastinum or pleural cavity. Several micro-organisms are documented as cause of pleural empyema in patients with Boerhaave's syndrome. Intervention (& Technique) We report on a previously healthy 74-year-old male who was admitted at a regional hospital with severe retrosternal and abdominal pain after an episode of vigorous vomiting the morning after ingestion of large quantity of beer. A CT-scan confirmed the diagnosis of Boerhaave's syndrome, an oesophageal stent was placed and a left-sided pleural empyema necessitated chest tube drainage. Pleural fluid samples were cultured every two days and were positive for Proteus mirabilis on day 2 after admission and for Saccharomyces cerevisiae on day 8 after admission. Intravenous fluconazole 800 mg per day was added to the antibacterial treatment. Pleural fluid culture became negative for P. mirabilis on day 23 and for S. cerevisiae on day 13. Recurrent empyema necessitated intrapleural thrombolysis. The patient could be discharged from the ICU after 43 days, from the normal ward to a rehabilitation centre after an additional 13 days. Conclusion Pleural empyema caused by S. cerevisiae, commonly known as 'Brewers' yeast', has never been described in such patients. Our case illustrates that clinicians should be aware of infection with S. cerevisiae after oesophageal perforation, soon after ingestion of beer. Adequate antimycotic treatment was successful and led to negative culture of pleural fluid after 5 days.