| 1. |
- Bruhn-Olszewska, Bozena, et al.
(författare)
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Loss of Y in leukocytes as a risk factor for critical COVID-19 in men.
- 2022
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Ingår i: Genome medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription.Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs.Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93-143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e-11).We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.
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| 2. |
- Bülow Anderberg, Sara, et al.
(författare)
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Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients
- 2021
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Ingår i: Cytokine. - : Springer Nature. - 1043-4666 .- 1096-0023. ; 138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The infection caused by SARS CoV-2 has been postulated to induce a cytokine storm syndrome that results in organ failure and even death in a considerable number of patients. However, the inflammatory response in Corona virus disease-19 (Covid-19) and its potential to cause collateral organ damage has not been fully elucidated to date. This study aims to characterize the acute cytokine response in a cohort of critically ill Covid-19 patients.METHOD: 24 adults with PCR-confirmed Covid-19 were included at time of admission to intensive care a median of eleven days after initial symptoms. Eleven adult patients admitted for elective abdominal surgery with preoperative plasma samples served as controls. All patients were included after informed consent was obtained. 27 cytokines were quantified in plasma. The expression of inflammatory mediators was then related to routine inflammatory markers, SAPS3, SOFA score, organ failure and 30-day mortality.RESULTS: A general increase in cytokine expression was observed in all Covid-19 patients. A strong correlation between respiratory failure and IL-1ra, IL-4, IL-6, IL-8 and IP-10 expression was observed. Acute kidney injury development correlated well with increased levels of IL-1ra, IL-6, IL-8, IL-17a, IP-10 and MCP-1. Generally, the cohort demonstrated weaker correlations between cytokine expression and 30-day mortality out of which IL-8 showed the strongest signal in terms of mortality.CONCLUSION: The present study found that respiratory failure, acute kidney injury and 30-day mortality in critically ill Covid-19 patients are associated with moderate increases of a broad range of inflammatory mediators at time of admission.
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| 3. |
- Ekbom, Emil, et al.
(författare)
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Impaired diffusing capacity for carbon monoxide is common in critically ill Covid-19 patients at four months post-discharge
- 2021
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Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 182
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Tidskriftsartikel (refereegranskat)abstract
- There is limited knowledge about the long-term effects on pulmonary function of COVID-19 in patients that required intensive care treatment. Spirometry and diffusing capacity for carbon monoxide (DLCO) were measured in 60 subjects at 3-6 months post discharge. Impaired lung function was found in 52% of the subjects, with reduced DLCO as the main finding. The risk increased with age above 60 years, need for mechanical ventilation and longer ICU stay as well as lower levels of C-reactive protein at admission. This suggests the need of follow-up with pulmonary function testing in intensive-care treated patients.
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| 4. |
- Elfwen, Ludvig, et al.
(författare)
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Post-resuscitation myocardial dysfunction in out-of-hospital cardiac arrest patients randomized to immediate coronary angiography versus standard of care
- 2020
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Ingår i: IJC Heart & Vasculature. - : ELSEVIER IRELAND LTD. - 2352-9067. ; 27
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immediate coronary angiography with subsequent percutaneous coronary intervention (PCI) has the potential to reduce post-resuscitation myocardial dysfunction in out-of-hospital cardiac arrest (OHCA) patients. The aim of this study was to see if immediate coronary angiography, with potential PCI, in patients without ST-elevation on the ECG, influenced post-resuscitation myocardial function and cardiac biomarkers.Methods: A secondary analysis of the Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest (DISCO) trial (ClinicalTrials.gov ID: NCT02309151). Patients with bystander-witnessed OHCA, without ST-elevations on the ECG were randomly assigned to immediate coronary angiography within two hours of cardiac arrest (n = 38) versus standard-of-care with deferred angiography (n = 40). Outcome measures included left ventricle ejection fraction (LVEF) at 24 h, peak Troponin T levels, lactate clearance and NT-proBNP at 72 h.Results: In the immediate-angiography group, median LVEF at 24 h was 47% (Q1-Q3; 30-55) vs. 46% (Q1-Q3; 35-55) in the standard-of-care group. Peak Troponin-T levels during the first 24 h were 362 ng/L (Q1-Q3; 174-2020) in the immediate angiography group and 377 ng/L (Q1-Q3; 205-1078) in the standard-of-care group. NT-proBNP levels at 72 h were 931 ng/L (Q1-Q3; 396-2845) in the immediate-angiography group and 1913 ng/L (Q1-Q3; 489-3140) in the standard-of-care group.Conclusion: In this analysis of OHCA patients without ST-elevation on the ECG randomized to immediate coronary angiography or standard-of-care, no differences in post-resuscitation myocardial dysfunction parameters between the two groups were found. This finding was consistent also in patients randomized to immediate coronary angiography where PCI was performed compared to those where PCI was not performed.
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| 5. |
- Gradin, Anna, et al.
(författare)
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Urinary cytokines correlate with acute kidney injury in critically ill COVID-19 patients
- 2021
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Ingår i: Cytokine. - : Springer Nature. - 1043-4666 .- 1096-0023. ; 146
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients.METHODS: Urine was collected from COVID-19 patients (n = 29) in intensive care and compared to a preoperative group of patients (n = 9) with no critical illness. 92 urinary cytokines were analyzed in multiplex using the Olink Target 96 inflammation panel and compared to clinical characteristics, and urinary markers of kidney injury.RESULTS: There were strong correlations between proinflammatory cytokines and between urinary cytokines and urinary kidney injury markers in 29 COVID-19 patients. Several cytokines were correlated to kidney injury, 31 cytokines to AKI stage and 19 cytokines correlated to maximal creatinine.CONCLUSIONS: Urinary inflammatory cytokines from a wide range of immune cell lineages were significantly upregulated during COVID-19 and the upregulation correlated with acute kidney injury as well as urinary markers of kidney tissue damage.
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| 6. |
- Harhash, Ahmed A., et al.
(författare)
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Incidence of cardiac interventions and associated cardiac arrest outcomes in patients with nonshockable initial rhythms and no ST elevation post resuscitation
- 2021
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Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 167, s. 188-197
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Tidskriftsartikel (refereegranskat)abstract
- Background: Out of Hospital Cardiac arrest (OHCA) survivors with ST elevation (STE) with or without shockable rhythms often benefit from coronary angiography (CAG) and, if indicated, percutaneous coronary intervention (PCI). However, the benefits of CAG and PCI in OHCA survivors with nonshockable rhythms (PEA/asystole) and no STE are debated.Methods: Using the International Cardiac Arrest Registry (INTCAR 2.0), representing 44 centers in the US and Europe, comatose OHCA survivors with known presenting rhythms and post resuscitation ECGs were identified. Survival to hospital discharge, neurological recovery on discharge, and impact of CAG with or without PCI on such outcome were assessed and compared with other groups (shockable rhythms with or without STE).Results: Total of 2113 OHCA survivors were identified and described as; nonshockable/no STE (Nsh-NST) (n = 940, 44.5%), shockable/no STE (Sh-NST) (n = 716, 33.9%), nonshockable/STE (Nsh-ST) (n = 110, 5.2%), and shockable/STE (Sh-ST) (n = 347, 16.4%). Of Nsh-NST, 13.7% (129) were previously healthy before CA and only 17.3% (161) underwent CAG; of those, 30.4% (52) underwent PCI. A total of 18.6% (174) Nsh-NST patients survived to hospital discharge, with 57.5% (100) of such survivors having good neurological recovery (cerebral performance category 1 or 2) on discharge. Coronary angiography was associated with improved odds for survival and neurological recovery among all groups, including those with NSh-NST.Conclusions: Nonshockable initial rhythms with no ST elevation post resuscitation was the most common presentation after OHCA. Although most of these patients did not undergo coronary angiography, among those who did, 1 in 4 patients had a culprit lesion and underwent revascularization. Invasive CAG should be at least considered for all OHCA survivors, including those with nonshockable rhythms and no ST elevation post resuscitation.
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| 7. |
- Harhash, Ahmed A., et al.
(författare)
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Risk Stratification Among Survivors of Cardiac Arrest Considered for Coronary Angiography
- 2021
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 77:4, s. 360-371
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.ObjectivesThis study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.MethodsUsing the INTCAR (International Cardiac Arrest Registry), the impact of each proposed “unfavorable feature” on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.ResultsSeven unfavorable features (of 10 total) were captured in 2,508 patients successfully resuscitated after cardiac arrest (ongoing cardiopulmonary resuscitation and noncardiac etiology were exclusion criteria in our registry). Chronic kidney disease was used in lieu of end-stage renal disease. In total, 39% survived to hospital discharge. The odds ratio (OR) of survival to hospital discharge for each unfavorable feature was as follows: age >85 years OR: 0.30 (95% CI: 0.15 to 0.61), time-to-ROSC >30 min OR: 0.30 (95% CI: 0.23 to 0.39), nonshockable rhythm OR: 0.39 (95% CI: 0.29 to 0.54), no bystander cardiopulmonary resuscitation OR: 0.49 (95% CI: 0.38 to 0.64), lactate >7 mmol/l OR: 0.50 (95% CI: 0.40 to 0.63), unwitnessed arrest OR: 0.58 (95% CI: 0.44 to 0.78), pH <7.2 OR: 0.78 (95% CI: 0.63 to 0.98), and chronic kidney disease OR: 0.96 (95% CI: 0.70 to 1.33). The presence of any 3 or more unfavorable features predicted <40% survival. Presence of the 3 strongest risk factors (age >85 years, time-to-ROSC >30 min, and non-ventricular tachycardia/ventricular fibrillation) together or ≥6 unfavorable features predicted a ≤10% chance of survival to discharge.ConclusionsPatients successfully resuscitated from cardiac arrest with 6 or more unfavorable features have a poor long-term prognosis. Delaying or even forgoing invasive procedures in such patients is reasonable.
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| 8. |
- Johansson, Anna, et al.
(författare)
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Quantitation of seven sedative and analgesic drugs in whole blood from intensive care patients using liquid chromatography mass spectrometry
- 2021
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Ingår i: TOXICOLOGIE ANALYTIQUE ET CLINIQUE. - : Elsevier. - 2352-0078 .- 2352-0086. ; 33:4, s. 327-337
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Tidskriftsartikel (refereegranskat)abstract
- We present the development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantification of clonidine, dexmedetomidine, fentanyl, ketamine, ketobemidone, midazolam and morphine in whole blood. These are drugs predominately used in intensive care units (ICUs) but they are also encountered in forensic investigations. The analytes were recovered from 0.25 g of blood by protein precipitation with a mixture of acetonitrile and ethanol. Separation was performed on a BEH phenyl column. Mobile phases consisted of 0.05% formic acid in 10 mM ammonium formate and 0.05% formic acid in methanol, respectively, and the flow rate was 600 mu L/min. The mass spectrometer was operated in positive electrospray ionization mode with multiple reaction monitoring. Validation included selectivity, qualitative matrix effects, calibration model, limit of detection, lower limit of quantification, within- and between-day accuracy and precision, process efficiency, dilution integrity, carry over and stability. Selectivity was high and no ion suppression or enhancementwas observed in the areas were the analytes eluted. Calibration curves were linear over arange of 0.25-50 ng/g for dexmedetomidine, 0.05-50 ng/g for fentanyl and 5.0-500 ng/g formorphine and quadratic over a range of 0.5-50 ng/g for clonidine, 50-5000 ng/g for ketamine, 5.0-500 ng/g for ketobemidone and midazolam. The method showed acceptable within- and betweenday accuracies and precisions. All analytes were stable in whole blood for three weeksat 4. C. Concentrations in patient samples ranged between 42-760 ng/g for midazolam (n = 15), 0.3-1.5 ng/g for dexmedetomidine (n = 13), 0.6-6.4 ng/g for clonidine (n = 13), 8-62 ng/g for morphine (n = 16), 5-19 ng/g for ketobemidone (n = 5), 0.07-3.1 ng/g for fentanyl (n = 43), and 562000 ng/g for ketamine (n = 10). We conclude that the method was successfully validatedand applied to ante-mortem and post-mortem blood samples from critically ill adult patientsin a general ICU.
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| 9. |
- Lagedal, Rickard, et al.
(författare)
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Coronary angiographic findings after cardiac arrest in relation to ECG and comorbidity
- 2020
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 146, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The relations between specific ECG patterns and coronary angiographic findings in cardiac arrest patients with different comorbidities are not properly assessed. More evidence is needed to identify patients with the highest risk for acute coronary artery disease as a cause of the cardiac arrest. This study aims to describe the coronary artery findings after cardiac arrest in relation to ECG and comorbidity.Method: A retrospective study of out-of-hospital cardiac arrest patients, with coronary angiography performed within 28 days. ECG on admission, comorbidity, PCI attempts and angiographic findings are described. Data were retrieved from national registries in Sweden.Results: Among 1133 patients with available ECG and angiography information the mean age was 64 years. The rate of shockable rhythm was 79 degrees 0. The total incidence of any significant stenosis in cardiac arrest patients without ST-elevation who underwent coronary angiography within 28 days was 71 degrees 0. The incidence of any stenosis in patients with normal ECG was 62.1 degrees 0 and in patients with LBBB, 59.3 degrees 0. In patients with ST-depression or RBBB, PCI attempts were made in 47.1 degrees 0 and 42.4 degrees 0 respectively, compared with 33.3 degrees 0 in patients with normal ECG. Among patients without ST-elevation, those with diabetes mellitus and those with initial shockable rhythm respectively, 84.8 degrees 0 and 71.5 had at least one significant stenosis.Conclusion: Our study suggests, that evaluation of ECG patterns and comorbidities in out-of-hospital cardiac arrest patients without ST-segment elevation may be important to identify those with a high risk of coronary artery lesions that could benefit from early revascularization.
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| 10. |
- Lagedal, Rickard, 1981-
(författare)
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Coronary angiography after out-of-hospital cardiac arrest
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Out-of-hospital cardiac arrest (OHCA) is a common cause of death with a survival rate of 10% in Sweden. The chance of survival depends on rapid recognition, high quality cardiopulmonary resuscitation and post-resuscitation care including searching and treating the cause of the arrest. Ischaemic cardiac disease including acute coronary artery occlusions is the most common cause of OHCA. Acute coronary artery lesions can be diagnosed and treated with coronary angiography and subsequent PCI. This thesis analyses various aspects of coronary angiography after OHCA. Paper I+II describes the rational, protocol and the results from the pilot phase (n=117) of a randomized multicentre clinical trial. We compared a strategy of immediate coronary angiography in patients successfully resuscitated after OHCA with a strategy without immediate coronary angiography. We did not reach the stipulated time of 120 minutes from first medical contact to angiography, but our study strategy was feasible. No major unexpected safety issues were reported. The main phase of the study could therefore be started with only minor changes from the pilot phase protocol. In a registry study of 1133 patients (Paper III) coronary angiographic findings were compared with ECG and comorbidities in unconscious patients after OHCA. In patients without ST-elevation, the rate of PCI attempts was higher in patients with ST-depression (47%) and in patients with ECG classified as “other findings” (45%) compared to patients with normal ECG (33%), OR 1.78 (CI 1.13-2.82) and OR 1.65 (CI 1.04-2.61), respectively. When analysing patients without ST-elevation, no difference in PCI rates were found between the comorbidity groups and neither between patients with shockable compared to non-shockable initial ECG rhythm. Paper IV is a registry study (n=3906) analysing the impact of patient income on the probability to receive early coronary angiography after OHCA. When dividing patients into income quarters and adjusting for confounders, increasing income was associated with higher rates of early coronary angiography. Thirty-six percent of patients in the highest income quarter received early angiography compared to fifteen percent in the lowest income quarter, OR 1.64 (1.27-2.11). Adding potential mediators to explain this finding gradually decreased the difference, and the main explanatory factor for this difference was that higher income is associated with higher rates of shockable ECG rhythm. 30-day survival was also higher in the highest income quarter compared to the lowest income group in the fully adjusted analysis, OR 1.51 (CI 1.22-1.89).
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