Publications by authors named "Andreas Barratt-Due"

61 Publications

Remdesivir modifies interferon response in hospitalized COVID-19 patients.

J Infect 2022 Jul 30. Epub 2022 Jul 30.

Institute of Clinical Medicine, University of Oslo, Oslo 0318, Norway; Division of Critical Care and Emergencies, Oslo University Hospital, Oslo, Norway. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2022.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338165PMC
July 2022

High circulating levels of the homeostatic chemokines CCL19 and CCL21 predict mortality and disease severity in Covid-19.

J Infect Dis 2022 Jul 25. Epub 2022 Jul 25.

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Background: Immune dysregulation is a major factor in the development of severe Covid-19. The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in SARS-CoV-2 infection is limited. We thus investigated the levels of these chemokines in Covid-19 patients.

Methods: Serial blood samples were obtained from patients hospitalized with Covid-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and three-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms.

Results: A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the three-month follow-up.

Conclusions: Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in Covid-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in Covid-19.
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http://dx.doi.org/10.1093/infdis/jiac313DOI Listing
July 2022

Anti-PF4/polyanion antibodies in COVID-19 patients are associated with disease severity and pulmonary pathology.

Platelets 2022 May 28;33(4):640-644. Epub 2022 Feb 28.

Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.

Thromboembolic events are frequent and associated with poor outcome in severe COVID-19 disease. Anti-PF4/polyanion antibodies are related to heparin-induced thrombocytopenia (HIT) and thrombus formation, but data on these antibodies in unselected COVID-19 populations are scarce. We assessed the presence of anti-PF4/polyanion antibodies in prospectively collected serum from an unselected cohort of hospitalized COVID-19 patients and evaluated if elevated levels could give prognostic information on ICU admission and respiratory failure (RF), were associated with markers of inflammation, endothelial activation, platelet activation, coagulation and fibrosis and were associated with long-term pulmonary CT changes. Five out of 65 patients had anti-PF4/polyanion reactivity with OD ≥0.200. These patients had more severe disease as reflected by ICU admission without any evidence of HIT. They also had signs of enhanced inflammation and fibrinogenesis as reflected by elevated ferritin and osteopontin, respectively, during the first 10 days of hospitalization. Increased ferritin and osteopontin persisted in these patients at 3 months follow-up, concomitant with pulmonary CT pathology. Our finding shows that the presence of anti-PF4/polyanion antibodies in unselected hospitalized COVID-19 patients was not related to HIT, but was associated with disease severity, inflammation, and pulmonary pathology after 3 months.
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http://dx.doi.org/10.1080/09537104.2022.2042238DOI Listing
May 2022

Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations.

J Intern Med 2022 06 17;291(6):801-812. Epub 2022 Mar 17.

Department of Anesthesia and Intensive Care, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.

Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown.

Methods: Plasma was collected during hospital admission and after 3 months from the NOR-Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DL ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene.

Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DL below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO /fiO (P/F ratio) <26.6 kPa. LBP levels remained elevated during and after hospitalization and were associated with low-grade inflammation and respiratory dysfunction after 3 months.

Conclusion: Respiratory dysfunction after COVID-19 is associated with altered gut microbiota and persistently elevated LBP levels. Our results should be regarded as hypothesis generating, pointing to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.
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http://dx.doi.org/10.1111/joim.13458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115297PMC
June 2022

Complement ratios C3bc/C3 and sC5b-9/C5 do not increase the sensitivity of detecting acute complement activation systemically.

Mol Immunol 2022 01 11;141:273-279. Epub 2021 Dec 11.

Department of Immunology, Oslo University Hospital and University of Oslo, Norway; Division of Emergencies and Critical Care, Oslo University Hospital, Norway. Electronic address:

Background: Complement activation plays an important pathogenic role in numerous diseases. The ratio between an activation product and its parent protein is suggested to be more sensitive to detect complement activation than the activation product itself. In the present study we explored whether the ratio between the activation product and the parent protein for C3 (C3bc/C3) and for C5 (sC5b-9/C5) increased the sensitivity to detect complement activation in acute clinical settings compared to the activation product alone.

Materials And Methods: Samples from patients with acute heart failure following ST-elevated myocardial infarction (STEMI) and from patients with out-of-hospital cardiac arrest (OHCA) were used. C3, C3bc and C5, sC5b-9 were analysed in 629 and 672 patient samples, respectively. Healthy controls (n = 20) served to determine reference cut-off values for activation products and ratios, defined as two SD above the mean.

Results: Increased C3bc/C3- and sC5b-9/C5 ratios were vastly dependent on C3bc and sC5b-9. Thus, 99.5 % and 98.1 % of the increased C3bc/C3- and sC5b-9/C5 ratios were solely dependent on increased C3bc and sC5b-9, respectively. Significantly decreased C3 and C5 caused increased ratios in only 3/600 (0.5 %) and 4/319 (1.3 %) samples, respectively. Strong correlations between C3bc and C3bc/C3-ratio and between sC5b-9 and sC5b-9/C5-ratio were found in the STEMI- (r = 0.926 and r = 0.786, respectively) and the OHCA-population (r = 0.908 and r = 0.843, respectively; p < 0.0001 for all). Importantly, sC5b-9 identified worse outcome groups better than sC5b-9/C5-ratio.

Conclusion: C3bc and sC5b-9 were sensitive markers of complement activation. The ratios of C3bc/C3 and sC5b-9/C5 did not improve detection of complement activation systemically.
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http://dx.doi.org/10.1016/j.molimm.2021.11.016DOI Listing
January 2022

Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9.

Sci Rep 2021 12 1;11(1):23205. Epub 2021 Dec 1.

Department of Pulmonary Medicine, Oslo University Hospital Ullevål, Nydalen, Postboks 4950, 0424, Oslo, Norway.

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DL), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DL was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO/FO ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DL, and persistent CT-findings was observed. Low pO/FO ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.
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http://dx.doi.org/10.1038/s41598-021-02547-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636497PMC
December 2021

Assessing the evidence on remdesivir.

Lancet Infect Dis 2021 12;21(12):1630-1631

Université de Paris, IAME, INSERM, Paris, France.

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http://dx.doi.org/10.1016/S1473-3099(21)00695-2DOI Listing
December 2021

Reduced Cardiac Function by Echocardiography in a Minority of COVID-19 Patients 3 Months after Hospitalization.

J Am Soc Echocardiogr 2022 02 7;35(2):243-244. Epub 2021 Nov 7.

ProCardio Center for Innovation, Department of Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway; Institute for Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address:

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http://dx.doi.org/10.1016/j.echo.2021.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572552PMC
February 2022

Vitamin C, Hydrocortisone, and the Combination Thereof Significantly Inhibited Two of Nine Inflammatory Markers Induced by Escherichia Coli But Not by Staphylococcus Aureus - When Incubated in Human Whole Blood.

Shock 2022 01;57(1):72-80

Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway.

Abstract: Vitamin C combined with hydrocortisone is increasingly being used to treat septic patients, even though this treatment regimen is based on questionable evidence. When used, a marked effect on key players of innate immunity would be expected, as sepsis is featured by a dysregulated immune response.Here, we explored the effect of vitamin C and hydrocortisone alone and combined, in an ex vivo human whole-blood model of Escherichia coli- or Staphylococcus aureus-induced inflammation. Inflammatory markers for activation of complement (terminal C5b-9 complement complex [TCC]), granulocytes (myeloperoxidase), platelets (β-thromboglobulin), cytokines (tumor necrosis factor [TNF], IL-1β, IL6, and IL-8), and leukocytes (CD11b and oxidative burst) were quantified, by enzyme-linked immunosorbent assay, multiplex technology, and flow cytometry.In E. coli- and S. aureus-stimulated whole blood, a broad dose-titration of vitamin C and hydrocortisone alone did not lead to dose-response effects for the central innate immune mediators TCC and IL-6. Hence, the clinically relevant doses were used further. Compared to the untreated control sample, two of the nine biomarkers induced by E. coli were reduced by hydrocortisone and/or vitamin C. TNF was reduced by hydrocortisone alone (19%, P = 0.01) and by the combination (31%, P = 0.01). The oxidative burst of monocytes and granulocytes was reduced for both drugs alone and their combination, (ranging 8-19%, P < 0.05). Using S. aureus, neither of the drugs, alone nor in combination, had any effects on the nine biomarkers.In conclusion, despite the limitation of the ex vivo model, the effect of vitamin C and hydrocortisone on bacteria-induced inflammatory response in human whole blood is limited and following the clinical data.
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http://dx.doi.org/10.1097/SHK.0000000000001834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8663529PMC
January 2022

Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial.

Ann Intern Med 2021 09 13;174(9):1261-1269. Epub 2021 Jul 13.

Institute of Clinical Medicine, Oslo University Hospital, Oslo, Norway (A.R.H., S.D., J.T.A., K.T., A.S., F.M., A.M.D., M.T.).

Background: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known.

Objective: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx.

Design: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616).

Setting: 23 hospitals in Norway.

Patients: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection.

Intervention: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir ( = 42), HCQ ( = 52), or standard of care (SoC) ( = 87).

Measurements: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables.

Results: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance.

Limitation: The trial had no placebo group.

Conclusion: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19.

Primary Funding Source: National Clinical Therapy Research in the Specialist Health Services, Norway.
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http://dx.doi.org/10.7326/M21-0653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279143PMC
September 2021

Bacteremia in critically ill immunocompromised patients with acute hypoxic respiratory failure: A post-hoc analysis of a prospective multicenter multinational cohort.

J Crit Care 2021 08 17;64:114-119. Epub 2021 Apr 17.

Medical Intensive Care Unit, APHP, Hôpital Saint-Louis, Famirea Study Group, ECSTRA team, and Clinical Epidemiology, UMR 1153, Center of Epidemiology and Biostatistics, Sorbonne Paris Cité, CRESS, INSERM, Paris Diderot Sorbonne University, Paris, France.

Purpose: The characteristics and impact of bacteremia have not been widely investigated in immunocompromised patients with acute respiratory failure (ARF).

Methods: We performed a secondary analysis of a prospective cohort of immunocompromised patients with ARF (EFRAIM study). After exclusion of blood cultures positive for coagulase negative Staphylococci, we compared patients with (n = 236) and without (n = 1127) bacteremia.

Results: The incidence of bacteremia was 17%. Bacterial pneumonia and extra-pulmonary ARDS were the main causes of ARF in bacteremic patients. Bacteremia involved gram negative rods (48%), gram positive cocci (40%) or were polymicrobial (10%). Bacteremic patients had more hematological malignancy, higher SOFA scores and increased organ support within 7 days. Bacteremia was associated with higher crude ICU mortality (40% versus 32%, p = 0.02), but neither hospital (49% versus 44%, p = 0.17) nor 90-day mortality (60% versus 56%, p = 0.25) were different from non-bacteremic patients. After propensity score matching based on baseline characteristics, the difference in ICU mortality lost statistical significance (p = 0.06), including in a sensitivity analysis restricted to patients with pneumonia.

Conclusions: We analyzed a large population of immunocompromised patients with ARF and an incidence of bacteremia of 17%. We could not demonstrate an impact of bacteremia on mortality after adjusting for baseline characteristics.
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http://dx.doi.org/10.1016/j.jcrc.2021.03.014DOI Listing
August 2021

Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19.

J Neurol 2021 Oct 20;268(10):3574-3583. Epub 2021 Mar 20.

Department of Neurology, Oslo University Hospital, Oslo, Norway.

Objective: To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients.

Methods: Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects.

Results: In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 × 10) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02).

Conclusion: Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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http://dx.doi.org/10.1007/s00415-021-10517-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980743PMC
October 2021

General anaesthesia related mortality in a limited resource settings region: a retrospective study in two teaching hospitals of Butembo.

BMC Anesthesiol 2021 02 23;21(1):60. Epub 2021 Feb 23.

Department of Anaesthesia and Intensive Care, College of Medicine, University of Malawi, Blantyre, Malawi.

Background: General anaesthesia (GA) in developing countries is still a high-risk practice, especially in Africa, accompanied with high morbidity and mortality. No study has yet been conducted in Butembo in the Democratic Republic of the Congo to determine the mortality related to GA practice. The main objective of this study was to assess mortality related to GA in Butembo.

Methods: This was a retrospective descriptive and analytic study of patients who underwent surgery under GA in the 2 main teaching hospitals of Butembo from January 2011 to December 2015. Data were collected from patients files, anaesthesia registries and were analysed with SPSS 26.

Results: From a total of 921 patients, 539 (58.5%) were male and 382 (41.5%) female patients. A total of 83 (9.0%) patients died representing an overall perioperative mortality rate of 90 per 1000. Out of the 83 deaths, 38 occurred within 24 h representing GA related mortality of 41 per 1000. There was a global drop in mortality from 2011 to 2015. The risk factors of death were: being a neonate or a senior adult, emergency operation, ASA physical status > 2 and a single deranged vital sign preoperatively, presenting any complication during GA, anaesthesia duration > 120 minutes as well as visceral surgeries/laparotomies. Ketamine was the most employed anaesthetic.

Conclusion: GA related mortality is very high in Butembo. Improved GA services and outcomes can be obtained by training more anaesthesia providers, proper patients monitoring, improved infrastructure, better equipment and drugs procurement and considering regional anaesthesia whenever possible.
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http://dx.doi.org/10.1186/s12871-021-01280-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901086PMC
February 2021

The use of eculizumab in Capnocytophaga canimorsus associated thrombotic microangiopathy: a case report.

BMC Infect Dis 2021 Feb 1;21(1):137. Epub 2021 Feb 1.

Department of Transplant Medicine, Oslo University Hospital, Birch-Reichenwaldsgate 34, NO-0483, Oslo, Norway.

Background: The use of complement inhibition is well established for complement mediated thrombotic microangiopathy, but its role in secondary forms of thrombotic microangiopathy is debated. We here present a case of thrombotic microangiopathy triggered by Capnocytophaga canimorsus, illustrating the diagnostic difficulties in discriminating between different thrombotic microangiopathies, and the dilemmas regarding how to treat this disease entity.

Case Presentation: A previously healthy 56-year-old woman presented with fever and confusion. She was diagnosed with sepsis from Capnocytophaga canimorsus and thrombotic microangiopathy. Marked activation of both T-cells, endothelium and complement were documented. She was successfully treated with antimicrobial therapy, the complement inhibitor eculizumab and splenectomy. After several weeks, a heterozygote variant in complement factor B was localized, potentially implying the diagnosis of a complement mediated TMA over an isolated infection related TMA.

Conclusions: We discuss the possible interactions between complement activation and other findings in severe infection and argue that complement inhibition proved beneficial to this patient's rapid recovery.
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http://dx.doi.org/10.1186/s12879-021-05789-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852365PMC
February 2021

Intraperitoneal microdialysis detects intestinal leakage earlier than hemodynamic surveillance and systemic inflammation in a pig model.

Scand J Gastroenterol 2021 Feb 28;56(2):219-227. Epub 2020 Dec 28.

Division of Emergencies and Intensive Care, Oslo, Norway.

Objective: Anastomotic leakage is a common complication following large abdominal surgery, often developing to life-threatening abdominal sepsis due to late diagnosis. Currently, diagnostics rely on systemic hemodynamic and infection monitoring. We hypothesized that intraperitoneal microdialysis allows detection of peritonitis prior to changes in standard clinical parameters in a pig model.

Materials And Methods: We included six pigs; five underwent intraperitoneal fecal contamination, one had sham surgery for a total of 10 h. Microdialysis was established in four intraabdominal quadrants and two hepatic lobes. All pigs were hemodynamically monitored with pulmonary artery and femoral artery catheters. Blood samples were assessed for inflammatory markers, terminal complement complex (TCC), interleukin (IL)-6, IL-10, and plasminogen activator inhibitor-1 (PAI-1).

Results: Microdialysis showed intraperitoneal lactate increase during the first two hours after fecal contamination, which remained elevated throughout the observation time with concurrent decrease of glucose. Arterial lactate remained within reference range (<1,6mM). Systemic inflammatory markers TCC, IL-6, IL-10 and PAI-1 increased significantly after minimum four hours. Mean arterial pressure, stroke volume variation and cardiac output were not compromised the first five hours. Sham surgery did not influence any of the parameters.

Conclusion: Intraperitoneal fecal contamination leads to a rapid and pronounced intraperitoneal increase in lactate, decrease in glucose while pyruvate and glycerol levels remain unchanged. This distinct metabolic pattern of peritoneal inflammation can be easily detected by microdialysis. Observation of this pattern may minimize time to safe diagnosis of intestinal perforations after intraperitoneal fecal contamination.
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http://dx.doi.org/10.1080/00365521.2020.1863459DOI Listing
February 2021

Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

N Engl J Med 2021 02 2;384(6):497-511. Epub 2020 Dec 2.

The affiliations of the members of the writing and steering committees are as follows: the Nuffield Department of Population Health and Medical Research Council Population Health Research Unit, University of Oxford, Oxford (H.P., R.P.), and the University of Bristol, Bristol (E.A., S.B., H.B.C.C.-P., D.H., J.K., C.A.R., J.A.C.S.) - both in the United Kingdom; the World Health Organization, Geneva (A.-M.H.-R., M.-P.P., V.S., P. Lydon, M.C.M.-M., K.S., S.S.), the University of Bern, Bern (S.A., M.B., S. McGinty, S.T.), and Lausanne University Hospital, Lausanne (O.M.) - all in Switzerland; the Centre for the AIDS Programme of Research in South Africa, Durban (Q.A.K.), and the University of the Witwatersrand (J.N.) and the Wits Reproductive Health and HIV Institute (H.R.), Johannesburg - all in South Africa; the Institute of National Epidemiology, National Institutes of Health, University of the Philippines, Manila (M.M.A.); the Agency of Medicine and Medical Devices (C.H.G.) and Hospital Clínico San Carlos, Universidad Complutense de Madrid, Spanish Clinical Research Network, Instituto de Investigación Sanitaria San Carlos (A.P.), Madrid; INSERM, Paris (M.-P.K.), and Hospices Civils de Lyon, Lyon (F.A.) - both in France; the Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran (R.M.); the University of British Columbia, Vancouver (S. Murthy), and the Public Health Agency of Canada, Ottawa (M.I.S.) - both in Canada; the Public Health Foundation of India, New Delhi (K.S.R.), and the Indian Council of Medical Research, National AIDS Research Institute, Pune (S.G.) - both in India; the National Academy of Sciences of Buenos Aires (M.R.P.) and Fundación del Centro de Estudios Infectológicos (G.L.), Buenos Aires; Rafic Hariri University Hospital (P.A.H.) and the Ministry of Public Health (R.H.), Beirut, Lebanon; the Ministry of Health (A.M.A.-B.) and Infectious Diseases Hospital (A. Alhasawi), Kuwait City, Kuwait; Universidad Nacional de Colombia and Clinica Colsanitas (C.A.A.-M.) and the Ministry of Health (M.L.M.R.), Bogota, Colombia; the Ministry for Preventive Health, Riyadh, Saudi Arabia (A. Asiri, A. Alotaibi); Oslo University Hospital (P.A., A.B.-D.) and Research Council of Norway (J.-A.R.), Oslo; Secretaria de Salud de Honduras (N. Cerrato) and the National Autonomous University of Honduras (M.T.M.), Tegucigalpa; Penang Hospital, Penang (T.S.C.), and Hospital Sungai Buloh and Jalan Hospital, Selangor (S.K.) - both in Malaysia; University Hospital Center Mother Theresa (N. Como) and the National Agency for Medicines and Medical Devices (N.S.), Tirana, Albania; the HRB Clinical Research Facility, University College Cork, Cork (J.E.), and the Department of Health and Children, Dublin (P. Lennon, T.M.) - both in Ireland; Universidad Peruana Cayetano Heredia, Lima, Peru (P.J.G., E.G.); Vilnius University Hospital Santaros Klinikos (L.G.) and Vilnius University, Institute of Clinical Medicine (L.J.), Vilnius, Lithuania; Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan (M. Hassan, A.R.); the National Hepatology and Tropical Medicine Research Institute (M. Hassany) and the Ministry of Health and Population (H.Z.), Cairo; the National Institute of Health Research and Development (I.I.) and Rumah Sakit Umum Pusat Persahabatan (M.R.R.), Jakarta, Indonesia; the Italian Medicines Agency, Rome (N.M.), and the University of Verona, Verona (E.T.) - both in Italy; the Ministry of Health (S. Manevska) and the University Clinic of Infectious Diseases and Febrile Conditions (M.S.), Skopje, North Macedonia; the Oswaldo Cruz Foundation, Rio de Janeiro (E.P.N., P.P.S.R.); and the Finnish Institute for Health and Welfare and the University of Finland (M.P.) and Helsinki University Hospital (K.A.O.T.), Helsinki, and South Karelian Central Hospital, Lappeenranta (K.A.O.T.) - all in Finland.

Background: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19).

Methods: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.

Results: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.

Conclusions: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).
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http://dx.doi.org/10.1056/NEJMoa2023184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727327PMC
February 2021

Acute respiratory failure in immunocompromised patients: outcome and clinical features according to neutropenia status.

Ann Intensive Care 2020 Oct 22;10(1):146. Epub 2020 Oct 22.

Medical Intensive Care Unit, APHP, Hôpital Saint‑Louis, Famirea Study Group, ECSTRA Team and Clinical Epidemiology, UMR 1153, Center of Epidemiology and Biostatistics, Sorbonne Paris Cité, CRESS, INSERM, Paris Diderot Sorbonne University, Paris, France.

Background: The impact of neutropenia in critically ill immunocompromised patients admitted in a context of acute respiratory failure (ARF) remains uncertain. The primary objective was to assess the prognostic impact of neutropenia on outcomes of these patients. Secondary objective was to assess etiology of ARF according to neutropenia.

Methods: We performed a post hoc analysis of a prospective multicenter multinational study from 23 ICUs belonging to the Nine-I network. Between November 2015 and July 2016, all adult immunocompromised patients with ARF admitted to the ICU were included in the study. Adjusted analyses included: (1) a hierarchical model with center as random effect; (2) propensity score (PS) matched cohort; and (3) adjusted analysis in the matched cohort.

Results: Overall, 1481 patients were included in this study of which 165 had neutropenia at ICU admission (11%). ARF etiologies distribution was significantly different between neutropenic and non-neutropenic patients, main etiologies being bacterial pneumonia (48% vs 27% in neutropenic and non-neutropenic patients, respectively). Initial oxygenation strategy was standard supplemental oxygen in 755 patients (51%), high-flow nasal oxygen in 165 (11%), non-invasive ventilation in 202 (14%) and invasive mechanical ventilation in 359 (24%). Before adjustment, hospital mortality was significantly higher in neutropenic patients (54% vs 42%; p = 0.006). After adjustment for confounder and center effect, neutropenia was no longer associated with outcome (OR 1.40, 95% CI 0.93-2.11). Similar results were observed after matching (52% vs 46%, respectively; p = 0.35) and after adjustment in the matched cohort (OR 1.04; 95% CI 0.63-1.72).

Conclusion: Neutropenia at ICU admission is not associated with hospital mortality in this cohort of critically ill immunocompromised patients admitted for ARF. In neutropenic patients, main ARF etiologies are bacterial and fungal infections.
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http://dx.doi.org/10.1186/s13613-020-00764-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581668PMC
October 2020

The use of antibiotics in the intensive care unit of a tertiary hospital in Malawi.

BMC Infect Dis 2020 Oct 19;20(1):776. Epub 2020 Oct 19.

Department of Anaesthesia and Intensive Care, Queen Elizabeth Central Hospital, Blantyre, Malawi.

Background: Antibiotic resistance is on the rise. A contributing factor to antibiotic resistance is the misuse of antibiotics in hospitals. The current use of antibiotics in ICUs in Malawi is not well documented and there are no national guidelines for the use of antibiotics in ICUs. The aim of the study was to describe the use of antibiotics in a Malawian ICU.

Methods: A retrospective review of medical records of all admissions to the main ICU in Queen Elizabeth Central Hospital in Blantyre, Malawi, between January 2017 and April 2019. Data were extracted from the ICU patient register on clinical parameters on admission, diagnoses, demographics and antibiotics both prescribed and given for all patients admitted to the ICU. Usage of antibiotics in the ICU and bacterial culture results from samples taken in the ICU and in the peri-ICU period, (from 5 days before ICU admission to 5 days after ICU discharge), were described.

Results: Six hundred-and-forty patients had data available on prescribed and received medications and were included in the analyses. Of these, 577 (90.2%) were prescribed, and 522 (81.6%) received an antibiotic in ICU. The most commonly used antibiotics were ceftriaxone, given to 470 (73.4%) of the patients and metronidazole to 354 (55.3%). Three-hundred-and-thirty-three (52.0%) of the patients received more than one type of antibiotic concurrently - ceftriaxone and metronidazole was the most common combination, given to 317 patients. Forty five patients (7.0%) were given different antibiotics sequentially. One-hundred-and-thirty-seven patients (21.4%) had a blood culture done in the peri-ICU period, of which 70 (11.0% of the patients) were done in the ICU. Twenty-five (18.3%) of the peri-ICU cultures were positive and eleven different types of bacteria were grown in the cultures, of which 17.2% were sensitive to ceftriaxone.

Conclusion: We have found a substantial usage of antibiotics in an ICU in Malawi. Ceftriaxone, the last-line antibiotic in the national treatment guidelines, is commonly used, and bacteria appear to show high levels of resistance to it, although blood culture testing is infrequently used. Structured antibiotic stewardship programs may be useful in all ICUs.
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http://dx.doi.org/10.1186/s12879-020-05505-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574463PMC
October 2020

ICU-acquired pneumonia in immunosuppressed patients with acute hypoxemic respiratory failure: A post-hoc analysis of a prospective international cohort study.

J Crit Care 2021 06 29;63:243-245. Epub 2020 Sep 29.

Medical Intensive Care Unit, APHP, Hôpital Saint-Louis, Famirea Study Group, ECSTRA Team, and Clinical Epidemiology, UMR 1153, Center of Epidemiology, France.

Objective: Intensive Care Units (ICU) acquired Pneumonia (ICU-AP) is one of the most frequent nosocomial infections in critically ill patients. Our aim was to determine the effects of having an ICU-AP in immunosuppressed patients with acute hypoxemic respiratory failure.

Design: Post-hoc analysis of a multinational, prospective cohort study in 16 countries.

Settings: ICU.

Patients: Immunosuppressed patients with acute hypoxemic respiratory failure.

Intervention: None.

Measurements And Main Results: The original cohort had 1611 and in this post-hoc analysis a total of 1512 patients with available data on hospital mortality and occurrence of ICU-AP were included. ICU-AP occurred in 158 patients (10.4%). Hospital mortality was higher in patients with ICU-AP (14.8% vs. 7.1% p < 0.001). After adjustment for confounders and centre effect, use of vasopressors (Odds Ratio (OR) 2.22; 95%CI 1.46-3.39) and invasive mechanical ventilation at day 1 (OR 2.12 vs. high flow oxygen; 95%CI 1.07-4.20) were associated with increased risk of ICU-AP while female gender (OR 0.63; 95%CI 0.43-94) and chronic kidney disease (OR 0.43; 95%CI 0.22-0.88) were associated with decreased risk of ICU-AP. After adjustment for confounders and centre effect, ICU-AP was independently associated with mortality (Hazard Ratio 1.48; 95%CI 14.-1.91; P = 0.003).

Conclusions: The attributable mortality of ICU-AP has been repetitively questioned in immunosuppressed patients with acute respiratory failure. This manuscript found that ICU-AP represents an independent risk factor for hospital mortality.
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http://dx.doi.org/10.1016/j.jcrc.2020.09.027DOI Listing
June 2021

Acute Respiratory Failure Outcomes in Patients with Hematologic Malignancies and Hematopoietic Cell Transplant: A Secondary Analysis of the EFRAIM Study.

Transplant Cell Ther 2021 01 2;27(1):78.e1-78.e6. Epub 2020 Oct 2.

Department of Medicine, Sinai Health System, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.

Patients with allogeneic hematopoietic cell transplantation (HCT) who develop acute respiratory failure (ARF) are perceived to have worse outcomes than autologous HCT recipients and non-transplant patients with hematologic malignancy (HM). Within a large international prospective cohort, we evaluated clinical outcomes in these 3 populations. We conducted a secondary analysis of the EFRAIM study, a multicenter observational study of immunocompromised adults with ARF admitted to 62 intensive care units (ICUs) in 16 countries. We described characteristics and compared outcomes of patients with HM who did not undergo transplantation and patients who underwent autologous or allogeneic HCT using multivariable logistic regression and propensity score-matched analyses. A total of 801 patients were included: 570 who did not undergo transplantation, 86 autologous HCT recipients and 145 allogeneic HCT recipients. Acute myelogenous leukemia (171 of 570; 30%) was the most common HM and most common indication for allogeneic HCT (76 of 145; 52%). Compared with the patients who did not undergo HCT and autologous HCT recipients, allogeneic HCT recipients were younger, had fewer comorbid conditions, and were more likely to undergo diagnostic bronchoscopy in the ICU. Unadjusted ICU and hospital mortality were 35% and 45%, respectively, across the entire cohort. In multivariable regression analysis, autologous HCT (odds ratio [OR], 1.07; 95% confidence interval [CI], .57 to 2.03; P = .82) and allogeneic HCT (OR, .99; 95% CI, .60 to 1.66; P = .98) were not associated with higher hospital mortality compared with the no-HCT cohort, adjusting for demographic, functional, clinical, malignancy, and ARF characteristics. The results were similar when analyzed using propensity score-matching techniques. Our findings indicate that autologous and allogeneic HCT recipients who develop ARF and require ICU admission have similar hospital mortality as patients with HM not treated with HCT.
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http://dx.doi.org/10.1016/j.bbmt.2020.09.035DOI Listing
January 2021

Elevated plasma sTIM-3 levels in patients with severe COVID-19.

J Allergy Clin Immunol 2021 01 21;147(1):92-98. Epub 2020 Sep 21.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Microbiology, Oslo University Hospital, Oslo, Norway.

Background: The pathogenesis of coronavirus disease 2019 (COVID-19) is still incompletely understood, but it seems to involve immune activation and immune dysregulation.

Objective: We examined the parameters of activation of different leukocyte subsets in COVID-19-infected patients in relation to disease severity.

Methods: We analyzed plasma levels of myeloperoxidase (a marker of neutrophil activation), soluble (s) CD25 (sCD25) and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) (markers of T-cell activation and exhaustion), and sCD14 and sCD163 (markers of monocyte/macrophage activation) in 39 COVID-19-infected patients at hospital admission and 2 additional times during the first 10 days in relation to their need for intensive care unit (ICU) treatment.

Results: Our major findings were as follows: (1) severe clinical outcome (ICU treatment) was associated with high plasma levels of sTIM-3 and myeloperoxidase, suggesting activated and potentially exhausted T cells and activated neutrophils, respectively; (2) in contrast, sCD14 and sCD163 showed no association with need for ICU treatment; and (3) levels of sCD25, sTIM-3, and myeloperoxidase were inversely correlated with degree of respiratory failure, as assessed by the ratio of Pao to fraction of inspired oxygen, and were positively correlated with the cardiac marker N-terminal pro-B-type natriuretic peptide.

Conclusion: Our findings suggest that neutrophil activation and, in particular, activated T cells may play an important role in the pathogenesis of COVID-19 infection, suggesting that T-cell-targeted treatment options and downregulation of neutrophil activation could be of importance in this disorder.
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http://dx.doi.org/10.1016/j.jaci.2020.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503135PMC
January 2021

Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients.

Proc Natl Acad Sci U S A 2020 10 17;117(40):25018-25025. Epub 2020 Sep 17.

Department of Internal Medicine, Vestre Viken Hospital Trust, 3004 Drammen, Norway.

Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO/FiO ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure ( = 0.008 and = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin ( = 0.64, < 0.001; = 0.69, < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials.
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http://dx.doi.org/10.1073/pnas.2010540117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547220PMC
October 2020

How does COVID-19 affect the brain?

Tidsskr Nor Laegeforen 2020 06 29;140(10). Epub 2020 May 29.

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http://dx.doi.org/10.4045/tidsskr.20.0444DOI Listing
June 2020

Respiratory Mechanics and Outcomes in Immunocompromised Patients With ARDS: A Secondary Analysis of the EFRAIM Study.

Chest 2020 11 20;158(5):1947-1957. Epub 2020 Jun 20.

Division of Pulmonary and Critical Care, Penn State University College of Medicine, Hershey, PA.

Background: In view of the high mortality rate of immunocompromised patients with ARDS, it is important to identify targets for improvement.

Research Question: This study investigated factors associated with mortality in this specific ARDS population, including factors related to respiratory mechanics (plateau pressure [Pplat,rs], compliance [Crs], and driving pressure [ΔPrs]).

Study Design And Methods: This study consisted of a predefined secondary analysis of the EFRAIM data. Overall, 789 of 1,611 patients met the Berlin criteria for ARDS, and Pplat,rs, ΔPrs, and Crs were available for 494 patients. A hierarchical model was used to assess factors at ARDS onset independently associated with hospital mortality.

Results: Hospital mortality was 56.3%. After adjustment, variables independently associated with hospital mortality included ARDS of undetermined etiology (OR, 1.66; 95% CI, 1.01-2.72), need for vasopressors (OR, 1.91; 95% CI, 1.27-2.88), and need for renal replacement therapy (OR, 2.02; 95% CI, 1.37-2.97). ARDS severity according to the Berlin definition, neutropenia on admission, and the type of underlying disease were not significantly associated with mortality. Before adjustment, higher Pplat,rs, higher ΔPrs, and lower Crs were associated with higher mortality. Addition of each of these individual variables to the final hierarchical model revealed a significant association with mortality: ΔPrs (OR, 1.08; 95% CI, 1.05-1.12), Pplat,rs (OR, 1.07; 95% CI, 1.04-1.11), and Crs (OR, 0.97; 95% CI, 0.95-0.98). Tidal volume was not associated with mortality.

Interpretation: In immunocompromised patients with ARDS, respiratory mechanics provide additional prognostic information to predictors of hospital mortality. Studies designed to define lung-protective ventilation guided by these physiological variables may be warranted in this specific population.
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http://dx.doi.org/10.1016/j.chest.2020.05.602DOI Listing
November 2020

Etiologies and Outcomes of Acute Respiratory Failure in Solid Organ Transplant Recipients: Insight Into the EFRAIM Multicenter Cohort.

Transplant Proc 2020 Dec 1;52(10):2980-2987. Epub 2020 Jun 1.

Medical Intensive Care Unit, Hôpital Saint-Louis, APHP.Nord-Université de Paris ECSTRA team, and Clinical Epidemiology, UMR 1153, Center of Epidemiology and Biostatistics, Sorbonne Paris Cité, CRESS, INSERM Paris Diderot Sorbonne University, Paris, France.

Background: Respiratory complications of solid organ transplant (SOT) are a diagnostic and therapeutic challenge when requiring intensive care unit (ICU) admission. We aimed at describing this challenge in a prospective cohort of SOT recipients admitted in the ICU.

Methods: In this post hoc analysis of an international cohort of immunocompromised patients admitted in the ICU for an acute respiratory failure, we analyzed all SOT recipients and compared their severity, etiologic diagnosis, prognosis, and outcome according to the performance of an invasive diagnostic strategy (encompassing a fiber-optic bronchoscopy and bronchoalveolar lavage), the type of transplanted organ, and the need of invasive ventilation at day 1.

Results: Among 1611 patients included in the primary study, 142 were SOT recipients (kidney, n = 73; 51.4%; lung, n = 33; 23.2%; liver, n = 29; 20.4%; heart, n = 7; 4.9%). Lung transplant recipients were younger than other SOT recipients, and severity did not differ across type of received organ. An invasive diagnostic strategy was more frequently performed in lung transplant recipients with a trend toward a higher rate of bacterial etiology in lung than kidney transplant recipients. Overall ICU survival of SOT recipients was 75.4%. Invasive diagnostic strategy, type of transplanted organ, and need of invasive mechanical ventilation at day 1 did not affect ICU prognosis.

Conclusions: ICU management of hypoxemic acute respiratory failure in SOT recipients translated into a low ICU mortality rate, whatever the transplanted organ or the acute respiratory failure cause. The post-ICU burden of acute respiratory failure SOT recipients remains to be investigated.
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http://dx.doi.org/10.1016/j.transproceed.2020.02.170DOI Listing
December 2020

Practice of standard monitoring during anaesthesia in hospitals of North Kivu: a survey of health facilities of the health antenna of Butembo.

BMC Health Serv Res 2020 Mar 30;20(1):262. Epub 2020 Mar 30.

Department of Anaesthesia and Intensive care, College of Medicine, University of Malawi, Blantyre, Malawi.

Background: Standard monitoring during anaesthesia is a core element of patient safety and practice of safe anesthesia has reduced morbidity and mortality worldwide. The main objective of this study was to assess the practice of standard monitoring during anaesthesia in the hospitals of North Kivu, so as to establish a baseline overview of the situation, and orientate plans towards safe anaesthesia in the region.

Methods: This study was a cross-sectional survey of health facilities of the Health Antenna of Butembo in Democratic Republic of Congo and was conducted from October to December 2018. Questionnaires were brought to anaesthesia providers in the health facilities. The study included 1 answer from the anaesthesia practitioners who accepted to participate. The practices of standard monitoring in the health facilities were compared to WHO-WSFA guidelines. Data was captured and analyzed with Epi Info 7.

Results: Forty out of 90 health facilities (44.4%) of 10 health zones responded on the questionnaire. Twenty-three health facilities (57.5%) were from private sector and 17 (42.5%) from public sector. Sixteen health facilities (40.0%) were from the Butembo health zone. The median number of anaesthesia providers was 2 per health facility. Of all the anaesthesia providers, none were physicians, 47.5% were nurses practicing anaesthesia without any training in anaesthesia and 47.5% were nurse anaesthetists. All the health facilities were providing general anaesthesia whereas spinal anaesthesia was provided in 22 out of 40 centers (55%). Seventy percent (28/40) of the facilities were below standard according to WHO-WSFA guidelines. Only 40% (16/40) were using a pulse oximeter and 10% (4/40) declared that ECG was occasionally used.

Conclusion: The practice of standard monitoring is poor in health facilities of the Health Antenna of Butembo. Efforts should be made to improve monitoring which is a key element of safe anaesthesia.
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http://dx.doi.org/10.1186/s12913-020-05076-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106833PMC
March 2020

Correction to: Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura.

Intensive Care Med 2020 Mar;46(3):570-571

Division of Pulmonary and Critical Care, Penn State University College of Medicine, Hershey, PA, USA.

The original version of this article unfortunately contained a mistake. The penultimate row of Table 4 shows INR > 1.5 which is incorrect. The correct figure is INR < 1.5. The authors apologize for the mistake. The correct table is given below.
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http://dx.doi.org/10.1007/s00134-019-05904-7DOI Listing
March 2020
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