The diagnostic performance of a prospective, systematic screening strategy for COVID-19 associated pulmonary aspergillosis (CAPA) during the COVID-19 pandemic was investigated. Patients with COVID... Show moreThe diagnostic performance of a prospective, systematic screening strategy for COVID-19 associated pulmonary aspergillosis (CAPA) during the COVID-19 pandemic was investigated. Patients with COVID-19 admitted to the ICU were screened for CAPA twice weekly by collection of tracheal aspirate (TA) for Aspergillus culture and PCR. Subsequently, bronchoalveolar lavage (BAL) sampling was performed in patients with positive screening results and clinical suspicion of infection. Patient data were collected from April 2020–February 2022. Patients were classified according to 2020 ECMM/ISHAM consensus criteria. In total, 126/370 (34%) patients were positive in screening and CAPA frequency was 52/370 (14%) (including 13 patients negative in screening). CAPA was confirmed in 32/43 (74%) screening positive patients who underwent BAL sampling. ICU mortality was 62% in patients with positive screening and confirmed CAPA, and 31% in CAPA cases who were screening negative. The sensitivity, specificity, positive and negative predictive value (PPV & NPV) of screening for CAPA were 0.71, 0.73, 0.27, and 0.95, respectively. The PPV was higher if screening was culture positive compared to PCR positive only, 0.42 and 0.12 respectively. CAPA was confirmed in 74% of screening positive patients, and culture of TA had a better diagnostic performance than PCR. Positive screening along with clinical manifestations appeared to be a good indication for BAL sampling since diagnosis of CAPA was confirmed in most of these patients. Prospective, systematic screening allowed to quickly gain insight into the epidemiology of fungal superinfections during the pandemic and could be applicable for future pandemics. Show less
Swets, M.C.; Termorshuizen, F.; Keizer, N.F. de; Paassen, J. van; Palmen, M.; Visser, L.G.; ... ; Groeneveld, G.H. 2023
BackgroundAn asymptomatic respiratory viral infection during cardiac surgery could lead to pulmonary complications and increased mortality. For elective surgery, testing for respiratory viral... Show moreBackgroundAn asymptomatic respiratory viral infection during cardiac surgery could lead to pulmonary complications and increased mortality. For elective surgery, testing for respiratory viral infection before surgery or vaccination could reduce the number of these pulmonary complications. The aim of this study was to investigate the association between influenzalike illness (ILI) seasons and prolonged mechanical ventilation and inhospital mortality in a Dutch cohort of adult elective cardiac surgery patients.MethodsCardiac surgery patients who were admitted to the intensive care unit between January 1, 2014, and February 1, 2020, were included. The primary endpoint was the duration of invasive mechanical ventilation in the ILI season compared with baseline season. Secondary endpoints were the median Pao2 to fraction of inspired oxygen ratio on days 1, 3, and 7 and postoperative inhospital mortality.ResultsA total of 42,277 patients underwent cardiac surgery, 12,994 (30.7%) in the ILI season, 15,843 (37.5%) in the intermediate season, and 13,440 (31.8%) in the baseline season. No hazard rates indicative of a longer duration of invasive mechanical ventilation during the ILI season were found. No differences were found for the median Pao2 to fraction of inspired oxygen ratio between seasons. However, inhospital mortality was higher in the ILI season compared with baseline season (odds ratio 1.67; 95% CI, 1.14-2.46).ConclusionsPatients undergoing cardiac surgery during the ILI season were at increased risk of inhospital mortality compared with patients in the baseline season. No evidence was found that this difference is caused by direct postoperative pulmonary complications. Show less
Swets, M.C.; Termorshuizen, F.; Keizer, N.F. de; Paassen, J. van; Palmen, M.; Visser, L.G.; ... ; Groeneveld, G.H. 2023
BackgroundAn asymptomatic respiratory viral infection during cardiac surgery could lead to pulmonary complications and increased mortality. For elective surgery, testing for respiratory viral... Show moreBackgroundAn asymptomatic respiratory viral infection during cardiac surgery could lead to pulmonary complications and increased mortality. For elective surgery, testing for respiratory viral infection before surgery or vaccination could reduce the number of these pulmonary complications. The aim of this study was to investigate the association between influenzalike illness (ILI) seasons and prolonged mechanical ventilation and inhospital mortality in a Dutch cohort of adult elective cardiac surgery patients.MethodsCardiac surgery patients who were admitted to the intensive care unit between January 1, 2014, and February 1, 2020, were included. The primary endpoint was the duration of invasive mechanical ventilation in the ILI season compared with baseline season. Secondary endpoints were the median Pao2 to fraction of inspired oxygen ratio on days 1, 3, and 7 and postoperative inhospital mortality.ResultsA total of 42,277 patients underwent cardiac surgery, 12,994 (30.7%) in the ILI season, 15,843 (37.5%) in the intermediate season, and 13,440 (31.8%) in the baseline season. No hazard rates indicative of a longer duration of invasive mechanical ventilation during the ILI season were found. No differences were found for the median Pao2 to fraction of inspired oxygen ratio between seasons. However, inhospital mortality was higher in the ILI season compared with baseline season (odds ratio 1.67; 95% CI, 1.14-2.46).ConclusionsPatients undergoing cardiac surgery during the ILI season were at increased risk of inhospital mortality compared with patients in the baseline season. No evidence was found that this difference is caused by direct postoperative pulmonary complications. Show less
Paassen, J. van; Graaf-Dijkstra, A. de; Brunsveld-Reinders, A.H.; Jonge, E. de; Klautz, R.J.M.; Tsonaka, R.; ... ; Arbous, M.S. 2023
OBJECTIONS: Development of acute lung injury after cardiac surgery is associated with an unfavourable outcome. Acute respiratory distress syndrome in general is, besides cytokine and interleukin... Show moreOBJECTIONS: Development of acute lung injury after cardiac surgery is associated with an unfavourable outcome. Acute respiratory distress syndrome in general is, besides cytokine and interleukin activation, associated with activation of platelets, monocytes and neutrophils. In relation to pulmonary outcome after cardiac surgery, leucocyte and platelet activation is described in animal studies only. Therefore, we explored the perioperative time course of platelet and leucocyte activation in cardiac surgery and related these findings to acute lung injury assessed via PaO2/FiO(2) (P/F) ratio measurements. METHODS: A prospective cohort study was performed, including 80 cardiac surgery patients. At five time points, blood samples were directly assessed by flow cytometry. For time course analyses in low (< 200) versus high (>200) P/F ratio groups, repeated measurement techniques with linear mixed models were used. RESULTS: Already before the start of the operation, platelet activatability (P = 0.003 for thrombin receptor-activator peptide and P = 0.017 for adenosine diphosphate) was higher, and the expression of neutrophil activation markers was lower (CD18/CD11; P = 0.001, CD62L; P = 0.013) in the low P/F group. After correction for these baseline differences, the peri- and postoperative thrombin receptor-activator peptide-induced thrombocyte activatability was decreased in the low P/F ratio group (P = 0.008), and a changed pattern of neutrophil activation markers was observed. CONCLUSIONS: Prior to surgery, an upregulated inflammatory state with higher platelet activatability and indications for higher neutrophil turnover were demonstrated in cardiac surgery patients who developed lung injury. It is difficult to distinguish whether these factors are mediators or are also aetiologically related to the development of lung injury after cardiac surgery. Further research is warranted. Show less
Grootveld, R. van; Beek, M.T. van der; Janssen, N.A.F.; Erguen, M.; Dijk, K. van; Bethlehem, C.; ... ; CAPA20 Study Grp 2023
Purpose: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential... Show morePurpose: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment.Materials and methods: A retrospective, observational, multicentre study was performed from September 2020-April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria.Results: CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy.Conclusions: CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation. Show less
Peppel, R.J. van de; Grootveld, R. van; Hendriks, B.J.C.; Paassen, J. van; Bernards, S.; Jolink, H.; ... ; Boer, M.G.J. de 2021
World-wide, emerging triazole resistance increasingly complicates treatment of invasive aspergillosis (IA). In settings with substantial (>10%) prevalence of triazole resistance, empiric... Show moreWorld-wide, emerging triazole resistance increasingly complicates treatment of invasive aspergillosis (IA). In settings with substantial (>10%) prevalence of triazole resistance, empiric combination therapy with both a triazole and liposomal amphotericin B (LAmB) can be considered because of the low yields of susceptibility testing. To avoid toxicity while optimizing outcome, a strategy with monotherapy would be preferable. A newly designed treatment algorithm based on literature and expert consensus provided guidance for empiric monotherapy with either voriconazole or LAmB. Over a four and a half year period, all adult patients in our hospital treated for IA were included and patient data were collected. An independent committee reviewed the attributability of death to IA for each patient. Primary outcomes were 30- and 100-day crude mortality and attributable mortality. In total, 110 patients were treated according to the treatment algorithm. Fifty-six patients (51%) were initially treated with voriconazole and 54 patients (49%) with LAmB. Combined attributable and contributable mortality was 13% within 30 days and 20% within 100 days. Treatment switch to LAmB was made in 24/56 (43%) of patients who were initially treated with voriconazole. Combined contributable and attributable 100-day mortality in this subgroup was 21% and was not increased when compared with patients initially treated with LAmB (P = 0.38). By applying a comprehensive clinical decision algorithm, an antifungal-sparing regime was successfully introduced. Further research is warranted to explore antifungal treatment strategies that account for triazole-resistance. Lay summary Due to resistance of Aspergillus against triazoles, combination therapy with liposomal amphotericin B (LAmB) is applied more often as primary therapy against invasive aspergillosis. This study presents the results of a decision tool which differentiated between triazole or LAmB monotherapy. Show less
Peppel, R.J. van de; Grootveld, R. van; Hendriks, B.J.C.; Paassen, J. van; Bernards, S.; Jolink, H.; ... ; Boer, M.G.J. de 2021
AbstractWorld-wide, emerging triazole resistance increasingly complicates treatment of invasive aspergillosis (IA). In settings with substantial (>10%) prevalence of triazole resistance, empiric... Show moreAbstractWorld-wide, emerging triazole resistance increasingly complicates treatment of invasive aspergillosis (IA). In settings with substantial (>10%) prevalence of triazole resistance, empiric combination therapy with both a triazole and liposomal amphotericin B (LAmB) can be considered because of the low yields of susceptibility testing. To avoid toxicity while optimizing outcome, a strategy with monotherapy would be preferable. A newly designed treatment algorithm based on literature and expert consensus provided guidance for empiric monotherapy with either voriconazole or LAmB. Over a four and a half year period, all adult patients in our hospital treated for IA were included and patient data were collected. An independent committee reviewed the attributability of death to IA for each patient. Primary outcomes were 30- and 100-day crude mortality and attributable mortality. In total, 110 patients were treated according to the treatment algorithm. Fifty-six patients (51%) were initially treated with voriconazole and 54 patients (49%) with LAmB. Combined attributable and contributable mortality was 13% within 30 days and 20% within 100 days. Treatment switch to LAmB was made in 24/56 (43%) of patients who were initially treated with voriconazole. Combined contributable and attributable 100-day mortality in this subgroup was 21% and was not increased when compared with patients initially treated with LAmB (P = 0.38). By applying a comprehensive clinical decision algorithm, an antifungal-sparing regime was successfully introduced. Further research is warranted to explore antifungal treatment strategies that account for triazole-resistance. Show less
Moes, D.J.A.R.; Westerloo, D.J. van; Arend, S.M.; Swen, J.J.; Vries, A. de; Guchelaar, H.J.; ... ; Paassen, J. van 2021
Background and Objective In the randomized controlled trial REMAP-CAP, it was shown that next to dexamethasone, the interleukin (IL)-6 receptor antagonist tocilizumab improves outcome, including... Show moreBackground and Objective In the randomized controlled trial REMAP-CAP, it was shown that next to dexamethasone, the interleukin (IL)-6 receptor antagonist tocilizumab improves outcome, including survival in intensive care unit (ICU)-admitted coronavirus disease 2019 (COVID)-19 patients. Therefore tocilizumab has been added to many COVID-19 treatment guidelines. Because obesity is a risk factor for the development of severe COVID-19, concerns have been raised about overtreatment, as well as undertreatment, through weight-based dosing of tocilizumab. The currently applied dose of 8 mg/kg is based on the use of this drug for other indications, however it has not formally been investigated for COVID-19. In this study, the pharmacokinetics and pharmacodynamics of tocilizumab were investigated in ICU-admitted COVID-19 patients. Methods This was an open-label, single-centre, observational population pharmacokinetic and descriptive pharmacodynamic evaluation study. Enrolled patients, with polymerase chain reaction-confirmed COVID-19 were admitted to the ICU for mechanical ventilation or high flow nasal canula oxygen support. All patients were 18 years of age or older and received intravenous tocilizumab 8 mg/kg (maximum 800 mg) within 24 h after admission to the ICU and received dexamethasone 6 mg daily as concomitant therapy. For evaluation of the pharmacokinetics and pharmacodynamics of tocilizumab, all time points from day 0 to 20 days after dose administration were eligible for collection. A nonlinear mixed-effects model was developed to characterize the population pharmacokinetic parameters of tocilizumab in ICU-admitted COVID-19 patients. Covariate analysis was performed to identify potential covariates for dose individualization. For the development of alternative dosing schedules, Monte Carlo simulations using the final model were performed. Results Overall, 29 patients were enrolled between 15 December 2020 and 15 March 2021. A total of 139 tocilizumab plasma samples were obtained covering the pharmacokinetic curve of day 0 to day 20 after tocilizumab initiation. A population pharmacokinetic model with parallel linear and nonlinear clearance (CL) was developed and validated. Average CL was estimated to be 0.725 L/day, average volume of distribution (V-d) was 4.34 L, maximum elimination rate (V-max) was 4.19 mu g/day, and concentration at which the elimination pathway is half saturated (K-m) was 0.22 mu g/mL. Interindividual variability was identified for CL (18.9%) and V-d (21%). Average area under the concentration versus time curve from time zero to infinity of the first dose (AUC(inf 1st DOSE)) was 938 [+/- 190] mu g/mL*days. All patients had tocilizumab exposure above 1 mu g/mL for at least 15 days. Bodyweight-based dosing increases variability in exposure compared with fixed dosing. Conclusions This study provides evidence to support a fixed dose of tocilizumab 600 mg in COVID-19 patients. Fixed dosing is a safe, logistically attractive, and drug expenses saving alternative compared with the current 8 mg/kg recommendation. Show less
Grootveld, R. van; Paassen, J. van; Boer, M.G.J. de; Claas, E.C.J.; Kuijper, E.J.; Beek, M.T. van der; LUMC-COVID-19 Research Grp 2021
Background A high prevalence of COVID-19 associated pulmonary aspergillosis (CAPA) has been reported, though histopathological evidence is frequently lacking. To assess the clinical significance of... Show moreBackground A high prevalence of COVID-19 associated pulmonary aspergillosis (CAPA) has been reported, though histopathological evidence is frequently lacking. To assess the clinical significance of Aspergillus species in respiratory samples of mechanically ventilated COVID-19 patients, we implemented routine screening for Aspergillus in tracheal aspirate (TA).Patients/methods From all adult COVID-19 patients admitted to the intensive care unit (ICU), TA samples were collected twice a week for Aspergillus screening by PCR and or culture. Bronchoalveolar lavage (BAL) sampling was performed in patients with a positive screening result if possible. Clinical information was obtained from the electronic patient record and patients were categorised according to the recently published consensus case definition for CAPA.Results Our study population consisted of 63 predominantly (73%) male patients, with a median age of 62 years and total median ICU stay of 18 days. Aspergillus species were present in TA screening samples from 15 patients (24%), and probable CAPA was diagnosed in 11 (17%) patients. Triazole resistance was detected in one patient (14%). Concordance between TA and BAL was 86%, and all TA culture positives were confirmed in BAL. We were able to withhold treatment in three of fifteen patients with positive screening (20%) but negative BAL results.Conclusions Positive culture, molecular detection and or antigen detection of Aspergillus species do not equal infection. Until we understand the clinical relevance of Aspergillus species detected in respiratory samples of COVID-19 patients, minimal-invasive screening by TA is a feasible method to monitor patients. Positive screening results should be an indication to perform a BAL to rule out upper airway colonisation. Show less
Bruggemann, R.J.; Moes, D.J.A.R.; Rhee, K.P. van; Veer, N. van 't; Koch, B.C.P.; Rossum, M. van; ... ; Heine, R. ter 2021
BackgroundIn the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a... Show moreBackgroundIn the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed.ObjectivesThe aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19.MethodsA systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase and Web of Science from December 1, 2019, until October 1, 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, need for other oxygen therapy, length of hospital stay and secondary infections.ResultsForty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57-0.87). Furthermore, viral clearance time ranged from 10 to 29 days in the corticosteroid group and from 8 to 24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend toward more infections and antibiotic use was present.ConclusionsOur findings from both observational studies and RCTs confirm a beneficial effect of corticosteroids on short-term mortality and a reduction in need for mechanical ventilation. And although data in the studies were too sparse to draw any firm conclusions, there might be a signal of delayed viral clearance and an increase in secondary infections. Show less
Klok, F.A.; Kruip, M.J.H.A.; Meer, N.J.M. van der; Arbous, M.S.; Gommers, D.; Kant, K.M.; ... ; Endeman, H. 2020
Introduction: We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch... Show moreIntroduction: We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses.Methods: We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.Results: We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).Conclusion: In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia. Show less
Klok, F.A.; Kruip, M.J.H.A.; Meer, N.J.M. van der; Arbous, M.S.; Gommers, D.A.M.P.J.; Kant, K.M.; ... ; Endeman, H. 2020
Introduction: COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the... Show moreIntroduction: COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available.Methods: We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.Results: We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.Conclusion: The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. Show less
Polak, S.B.; Gool, I.C. van; Cohen, D.; Thusen, J.H. von der; Paassen, J. van 2020
Since the outbreak of the COVID-19 pandemic, much has been learned regarding its clinical course, prognostic inflammatory markers, disease complications, and mechanical ventilation strategy.... Show moreSince the outbreak of the COVID-19 pandemic, much has been learned regarding its clinical course, prognostic inflammatory markers, disease complications, and mechanical ventilation strategy. Clinically, three stages have been identified based on viral infection, pulmonary involvement with inflammation, and fibrosis. Moreover, low and high elastance phenotypes can be distinguished in mechanically ventilated patients, based on lung mechanics, ventilation-to-perfusion ratio, and CT scans; these two phenotypes have presumed differences in their underlying pathophysiology. Although essential for therapeutic guidance, the pathophysiology of COVID-19 is poorly understood. Here, we systematically reviewed published case reports and case series in order to increase our understanding of COVID-19 pathophysiology by constructing a timeline and correlating histopathological findings with clinical stages of COVID-19. Using PRISMA-IPD guidelines, 42 articles reporting 198 individual cases were included in our analysis. In lung samples (n = 131 cases), we identified three main histological patterns: epithelial (n = 110, 85%), with reactive epithelial changes and DAD; vascular (n = 76, 59%) with microvascular damage, (micro)thrombi, and acute fibrinous and organizing pneumonia; and fibrotic (n = 28, 22%) with interstitial fibrosis. The epithelial and vascular patterns can present in all stages of symptomatic COVID-19, whereas the fibrotic pattern presents starting at similar to 3 weeks. Moreover, patients can present with more than one pattern, either simultaneously or consecutively. These findings are consistent with knowledge regarding clinical patterns of viral infection, development of hyperinflammation and hypercoagulability, and fibrosis. Close collaboration among medical staff is necessary in order to translate this knowledge and classification of pathophysiological mechanisms into clinical stages of disease in individual patients. Moreover, further research, including histopathological studies, is warranted in order to develop reliable, clinically relevant biomarkers by correlating these pathological findings with laboratory results and radiological findings, thus, increasing our understanding of COVID-19 and facilitating the move to precision medicine for treating patients. Show less
Ng, K.T.; Paassen, J. van; Langan, C.; Sarode, D.P.; Arbous, M.S.; Alston, R.P.; Dekkers, O. 2020
Corticosteroids are often administered prophylactically to attenuate the inflammatory response associated with cardiac surgery using cardiopulmonary bypass (CPB). However, the efficacy and safety... Show moreCorticosteroids are often administered prophylactically to attenuate the inflammatory response associated with cardiac surgery using cardiopulmonary bypass (CPB). However, the efficacy and safety profile of corticosteroids remain uncertain. The primary aim of this systematic review and meta-analysis was to investigate the effect of corticosteroids on mortality in adult cardiac surgery using CPB. Secondary aims were to examine the effect of corticosteroids on myocardial adverse events, pulmonary adverse events, atrial fibrillation, surgical site infection, gastrointestinal bleeding and duration of stay in the intensive care unit and hospital. Randomized controlled trials (RCTs) were systematically searched in electronic databases (MEDLINE, EMBASE, CINAHL, CENTRAL and Web of Science) from their inception until March 2019. Observational studies, case reports, case series and literature reviews were excluded. Sixty-two studies (n = 16 457 patients) were included in this meta-analysis. There was no significant difference in mortality between the corticosteroid and placebo groups [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81-1.14; P = 0.65, participants = 14 693, studies = 24, evidence of certainty: moderate]. Compared to those receiving a placebo, patients who were given corticosteroids had a significantly higher incidence of myocardial adverse events (OR 1.17, 95% CI 1.03-1.33; P = 0.01, participants = 14 512, studies = 23) and a lower incidence of pulmonary adverse events (OR 0.86, 95% CI 0.75-0.98; P = 0.02, participants = 13 426, studies = 17). The incidences of atrial fibrillation (OR 0.87, 95% CI 0.81-0.94; P < 0.001, participants = 14 148, studies = 24) and surgical site infection (OR 0.81, 95% CI 0.73-0.90; P < 0.001, participants = 13 946; studies = 22) were all lower in patients who were given corticosteroids. In the present meta-analysis of 62 RCTs (16 457 patients), including the 2 major RCTs (SIRS and DECS trials: 12 001 patients), we found that prophylactic corticosteroids in cardiac surgery did not reduce mortality. The clinical significance of an increase in myocardial adverse events remains unclear as the definition of a relevant myocardial end point following cardiac surgery varied greatly between RCTs. Show less