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Background: Gastrointestinal dysfunction is a common complication of medical nutrition therapy in critically ill patients. Whether prone positioning leads to a deterioration in gastrointestinal function has not been fully clarified. Thus, we aimed to analyze the influence of prone positioning on the tolerance of medical nutrition therapy., Methods: We conducted a retrospective analysis of 102 SARS-CoV-2 infected patients with venovenous extracorporeal membrane oxygenation support (VV ECMO). Gastric residual volume (GRV) was used to assess the tolerance of enteral nutrition., Results: Nutritional data were collected for 2344 days. Undernutrition was observed in 40.8%, with a significantly higher incidence on days in prone position (48.4% versus 38.6%, p < 0.001). On days in supine position, significantly more calories were administered enterally than on days in prone position ( p < 0.001). The mean GRV/24 h was 111.1 mL on days in supine position and 187.3 mL on days in prone position ( p < 0.001). Prone positioning was associated with higher rates of GRV of ≥500 mL/24 h independent of age, disease severity at ECMO start, ECMO runtime and ICU length of stay (adjusted hazard ratio: 4.06; 95%CI: 3.0-5.5; p < 0.001)., Conclusions: Prone position was associated with lower tolerance of enteral nutrition, as indicated by an increased GRV. As a result, reduced enteral nutritional support was administered.

Background: Prolonged critical illness is often accompanied by an impairment of adrenal function, which has been frequently related to conditions complicating patient management. The presumed connection between hypoxia and the pathogenesis of this critical- illness- related corticosteroid insufficiency (CIRCI) might play an important role in patients with severe acute respiratory distress syndrome (ARDS). Since extracorporeal membrane oxygenation (ECMO) is frequently used in ARDS, but data on CIRCI during this condition are scarce, this study reports the behaviour of adrenal function parameters during oxygenation support with veno-venous (vv)ECMO in coronavirus disease 2019 (COVID-19) ARDS., Methods: A total of 11 patients undergoing vvECMO due to COVID-19 ARDS at the Medical University of Vienna, who received no concurrent corticosteroid therapy, were retrospectively included in this study. We analysed the concentrations of cortisol, aldosterone, and angiotensin (Ang) metabolites (Ang I-IV, Ang 1-7, and Ang 1-5) in serum via liquid chromatography/tandem mass spectrometry before, after 1 day, 1 week, and 2 weeks during vvECMO support and conducted correlation analyses between cortisol and parameters of disease severity., Results: Cortisol concentrations appeared to be lowest after initiation of ECMO and progressively increased throughout the study period. Higher concentrations were related to disease severity and correlated markedly with interleukin-6, procalcitonin, pH, base excess, and albumin during the first day of ECMO. Fair correlations during the first day could be observed with calcium, duration of critical illness, and ECMO gas flow. Angiotensin metabolite concentrations were available in a subset of patients and indicated a more homogenous aldosterone response to plasma renin activity after 1 week of ECMO support., Conclusion: Oxygenation support through vvECMO may lead to a partial recovery of adrenal function over time. In homogenous patient collectives, this novel approach might help to further determine the importance of adrenal stress response in ECMO and the influence of oxygenation support on CIRCI., Competing Interests: This study was mainly funded by a grant from the Medical Scientific Fund of the Mayor of the City of Vienna (Project number: 19040) attributed to MH, as well as in parts by a grant from the Medical Scientific Fund of the Mayor of the City of Vienna (Project number: COVID032) attributed to PW. KK reports travel expenses from Biotest GmbH and grants from Apeptico GmbH, Biotest GmbH, Bayer AG and Alterras GmbH. The authors MP and OD were employed by Attoquant Diagnostics, Vienna, Austria. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baumgartner, Wolf, Hermann, König, Maleczek, Laxar, Poglitsch, Domenig, Krenn, Schiefer, Kautzky-Willer, Krebs and Hermann.)

Background: Patients receiving extracorporeal membrane oxygenation (ECMO) support are at high risk for malnutrition. There are currently no general nutrition guidelines for coronavirus disease 2019 (COVID-19) patients during ECMO therapy., Methods: We conducted a retrospective analysis of COVID-19 patients requiring venovenous ECMO support at a large tertiary hospital center. Nutrition goals were calculated using 25 kcal/kg body weight (BW)/day. Associations between nutrition support and outcome were evaluated using Kaplan-Meier and multivariable Cox regression analyses., Results: Overall, 102 patients accounted for a total of 2344 nutrition support days during ECMO therapy. On 40.6% of these days, nutrition goals were met. Undernutrition was found in 40.8%. Mean daily calorie delivery was 73.7% of calculated requirements, mean daily protein delivery was 0.7 g/kg BW/d. Mean energy intake of ≥70% of calculated targets was associated with significantly lower ICU mortality independently of age, disease severity at ECMO start and body mass index (adjusted hazard ratio: 0.372, p = 0.007)., Conclusions: Patients with a mean energy delivery of ≥70% of calculated targets during ECMO therapy had a better ICU survival compared to patients with unmet energy goals. These results indicate that adequate nutritional support needs to be a major priority in the treatment of COVID-19 patients requiring ECMO support.

Background: Vaccination has proven to be effective in preventing SARS-CoV-2 transmission and severe disease courses. However, immunocompromised patients have not been included in clinical trials and real-world clinical data point to an attenuated immune response to SARS-CoV-2 vaccines among patients with multiple sclerosis (MS) receiving immunomodulatory therapies., Methods: We performed a retrospective study including 59 ocrelizumab (OCR)-treated patients with MS who received SARS-CoV-2 vaccination. Anti-SARS-CoV-2-antibody titres, routine blood parameters and peripheral immune cell profiles were measured prior to the first (baseline) and at a median of 4 weeks after the second vaccine dose (follow-up). Moreover, the SARS-CoV-2-specific T cell response and peripheral B cell subsets were analysed at follow-up. Finally, vaccination-related adverse events were assessed., Results: After vaccination, we found anti-SARS-CoV-2(S) antibodies in 27.1% and a SARS-CoV-2-specific T cell response in 92.7% of MS cases. T cell-mediated interferon (IFN)-γ release was more pronounced in patients without anti-SARS-CoV-2(S) antibodies. Antibody titres positively correlated with peripheral B cell counts, time since last infusion and total IgM levels. They negatively correlated with the number of previous infusion cycles. Peripheral plasma cells were increased in antibody-positive patients. A positive correlation between T cell response and peripheral lymphocyte counts was observed. Moreover, IFN-γ release was negatively correlated with the time since the last infusion., Conclusion: In OCR-treated patients with MS, the humoral immune response to SARS-CoV-2 vaccination is attenuated while the T cell response is preserved. However, it is still unclear whether T or B cell-mediated immunity is required for effective clinical protection. Nonetheless, given the long-lasting clinical effects of OCR, monitoring of peripheral B cell counts could facilitate individualised treatment regimens and might be used to identify the optimal time to vaccinate., Competing Interests: Competing interests: MK received travel grants from Merck Serono and Biogen. LR received travel reimbursements from Merck Serono and Sanofi Genzyme. MP's research is funded by the German Multiple Sclerosis Society North Rhine-Westphalia (DMSG), Novartis and the programme "Innovative Medizinische Forschung" (IMF) of the Medical Faculty of the University of Muenster. MB served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis. H-PH has received fees for consulting, speaking and serving on steering committees from Bayer Healthcare, Biogen, GeNeuro, MedImmune, Merck, Novartis, Opexa, Receptos Celgene, Roche, Sanofi Genzyme, CSL Behring, Octapharma and Teva, with approval from the Rector of Heinrich-Heine-University. OA received personal fees from Alexion, Bayer Healthcare, Biogen, Celgene, Merck Serono, MedImmune, Novartis, Roche, Teva and Zambon, and he received research support from the German Science Foundation (DFG) and the German Ministry of Education, Science, Research and Technology (BMBF), outside of the submitted work. PA received compensation for serving on Scientific Advisory Boards and/or speaker honoraria and/or travel support from Novartis, Teva, Biogen, Bristol Meyers Squibb, Celgene, Janssen Cilag, Merz Pharmaceuticals, Ipsen, Allergan, Bayer Healthcare, Esai, UCB and Glaxo Smith Kline, Roche; he received research support from Novartis, Biogen, Celgene, Teva, Merz Pharmaceuticals, Ipsen and Roche. NM has received honoraria for lecturing and travel expenses for attending meetings from Biogen Idec, GlaxoSmith Kline, Teva, Novartis Pharma, Bayer Healthcare, Genzyme, Alexion Pharamceuticals, Fresenius Medical Care, Diamed and BIAL, and has received financial research support from Euroimmun, Fresenius Medical Care, Diamed, Alexion Pharmaceuticals and Novartis Pharma. TR reports grants from German Ministry of Education, Science, Research and Technology, during the conduct of the study; grants and personal fees from Sanofi-Genzyme; personal fees from Biogen; personal fees and non-financial support from Merck Serono; personal fees from Roche; and personal fees from Teva, outside the submitted work. SGM received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Else Kröner Fresenius Foundation, German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology, and by Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche and Teva. DK received travel grants from GeNeuro and Merck, refund of congress participation fees from GeNeuro, Merck and Servier, consulting fees from Grifols, payment for lectures from Grifols, support for research projects from Teva and was funded by the Deutsche Forschungsgemeinschaft (DFG)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Prostaglandin E 1 (alprostadil; PGE 1 ), in addition to low-dose unfractionated heparin, increases the biocompatibility of extracorporeal systems and enhances the efficacy of artificial organs without increasing bleeding risk. Objectives: We investigated the safety and efficacy of PGE 1 in adults receiving venovenous extracorporeal membrane oxygenation (ECMO). Methods: This study was a randomized, double-blind, placebo-controlled phase II pilot trial at two medical intensive care units at the Medical University of Vienna, Austria. Adults with venovenous ECMO were randomly assigned to receive an intravenous infusion of 5 ng/kg/min PGE 1 or placebo (0.9% saline) in addition to standard anticoagulation with unfractionated heparin. Measurements and Main Results: The primary outcome was the rate of transfused packed red blood cells per ECMO day. Secondary outcomes were the incidence of and time to clinically overt bleeding and thromboembolic events. A post hoc subgroup analysis included only patients with coronavirus disease (COVID-19). Between September 2016 and April 2021, of 133 screened patients, 50 patients were randomized, of whom 48 received the assigned study medication (24 per group). The transfusion rate was similar between groups (0.41 vs. 0.39; P  = 0.733). PGE 1 was associated with fewer thromboembolic events (7 vs. 16; P  = 0.020) and longer thromboembolism-free time (hazard ratio [HR], 0.302; P  = 0.01), fewer clinically overt bleeding events (2 vs. 11; P  = 0.017), and longer bleeding-free time (HR, 0.213; P  = 0.047). In patients with COVID-19 ( n  = 25), the HRs for clinically overt bleeding and thromboembolism were 0.276 (95% confidence interval, 0.035-2.186) and 0.521 (95% confidence interval, 0.149-1.825), respectively. Conclusions: Add-on treatment with PGE 1 was safe but did not meet the primary endpoint of reducing the rate of red blood cell transfusions in patients receiving venovenous ECMO. Larger studies need to evaluate the safety and efficacy of additional PGE 1 in ECMO. Clinical trial registered with EudraCT (2015-005014-30) and www.clinicaltrials.gov (NCT02895373).

Objectives: Pulmonary thrombus formation is a hallmark of coronavirus disease 2019 (COVID-19). A dysregulated immune response culminating in thromboinflammation has been described, but the pathomechanisms remain unclear., Methods: We studied 41 adult COVID-19 patients with positive results on reverse-transcriptase polymerase-chain-reaction assays and 37 sex- and age-matched healthy controls. Number and surface characteristics of extracellular vesicles (EVs) and citrullinated histone H3 levels were determined in plasma upon inclusion by flow cytometry and immunoassay., Results: In total, 20 patients had severe and 21 nonsevere disease. The number of EV (median [25th, 75th percentile]) was significantly higher in patients compared with controls (658.8 [353.2, 876.6] vs. 435.5 [332.5, 585.3], geometric mean ratio [95% confidence intervals]: 2.6 [1.9, 3.6]; p  < 0.001). Patients exhibited significantly higher numbers of EVs derived from platelets, endothelial cells, leukocytes, or neutrophils than controls. EVs from alveolar-macrophages and alveolar-epithelial cells were detectable in plasma and were significantly higher in patients. Intercellular adhesion molecule-1-positive EV levels were higher in patients, while no difference between tissue factor-positive and angiotensin-converting enzyme-positive EV was seen between both groups. Levels of EV did not differ between patients with severe and nonsevere COVID-19. Citrullinated histone H3 levels (ng/mL, median [25th, 75th percentile]) were higher in patients than in controls (1.42 [0.6, 3.4] vs. 0.31 [0.1, 0.6], geometric mean ratio: 4.44 [2.6, 7.7]; p  < 0.001), and were significantly lower in patients with nonsevere disease compared with those with severe disease., Conclusion: EV and citrullinated histone H3 are associated with COVID-19 and could provide information regarding pathophysiology of the disease., Competing Interests: None declared., (Thieme. All rights reserved.)

Although extracorporeal membrane ventilation offers the possibility for low-frequency ventilation, protocols commonly used in patients with acute respiratory distress syndrome (ARDS) and treated with extracorporeal membrane oxygenation (ECMO) vary largely. Whether strict adherence to low-frequency ventilation offers benefit on important outcome measures is poorly understood. Background/Objectives: This pilot clinical study investigated the efficacy of low-frequency ventilation on ventilator-free days (VFDs) in patients suffering from ARDS who were treated with ECMO therapy. Methods: In this single-center randomized controlled trial, 44 (70% male) successive ARDS patients treated with ECMO (aged 56 ± 12 years, SAPS III 64 (SD ± 14)) were randomly assigned 1:1 to the control group (conventional ventilation) or the treatment group (low-frequency ventilation during first 72 h on ECMO: respiratory rate 4–5/min; PEEP 14–16 cm H2O; plateau pressure 23–25 cm H2O, tidal volume: <4 mL/kg). The primary endpoint was VFDs at day 28 after starting ECMO treatment. The major secondary endpoint was ICU mortality, 28-day mortality and 90-day mortality. Results: Twenty-three (52%) patients were successfully weaned from ECMO and were discharged from the intensive care unit (ICU). Twelve patients in the treatment group and five patients in the control group showed more than one VFD at day 28 of ECMO treatment. VFDs were 3.0 (SD ± 5.5) days in the control group and 5.4 (SD ± 6) days in the treatment group (p = 0.117). Until day 28 of ECMO initiation, patients in the treatment group could be successfully weaned off of the ventilator more often (OR of 0.164 of 0 VFDs at day 28 after ECMO start; 95% CI 0.036–0.758; p = 0.021). ICU mortality did not differ significantly (36% in treatment group and 59% in control group; p = 0.227). Conclusions: Low-frequency ventilation is comparable to conventional protective ventilation in patients with ARDS who have been treated with ECMO. However, low-frequency ventilation may support weaning from invasive mechanical ventilation in patients suffering from ARDS and treated with ECMO therapy. [ABSTRACT FROM AUTHOR]

Drawing on the nationally representative Census Bureau Household Pulse Survey (N = 443,375), this study examined how pre-pandemic and pandemic-induced vulnerabilities shaped racial inequalities in housing insecurity from August to December 2020. Theorizing the pandemic as a “systemic shock,” this article helps explain how racial inequalities are reproduced both as legacies of long-standing disparities and through widespread, societal moments of disruption. Our results indicated that Black, Hispanic, and Asian households were all significantly more likely to fall behind on housing payments than white households. We found that preexisting racial inequities, including in educational attainment, household income, and homeownership rates, largely explained racial disparities in housing insecurity during COVID-19. However, the pandemic also induced new pathways to racial inequalities. Black and Hispanic households were more likely to lose income and when they lost income, they faced a greater likelihood of experiencing housing insecurity. We conclude by highlighting the importance of theorizing disruptive systemic shocks to understand racial inequalities and discuss findings of both disparities faced by Black and Hispanic households, as well as underrecognized housing insecurity among Asian Americans. [ABSTRACT FROM AUTHOR]

Summary: The pandemic from the SARS-CoV‑2 virus is currently challenging healthcare systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe working environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develop respiratory or circulatory failure that is refractory to conventional treatment, it is of utmost importance to clearly define criteria for the use of ECMO in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients. [ABSTRACT FROM AUTHOR]