COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators ...as predictors for severe courses of COVID-19.
This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies.
Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73).
This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigate the feasibility of molecular-level sample classification of sepsis using microarray gene expression data merged by in silico meta-analysis. Publicly available data series were ...extracted from NCBI Gene Expression Omnibus and EMBL-EBI ArrayExpress to create a comprehensive meta-analysis microarray expression set (meta-expression set). Measurements had to be obtained via microarray-technique from whole blood samples of adult or pediatric patients with sepsis diagnosed based on international consensus definition immediately after admission to the intensive care unit. We aggregate trauma patients, systemic inflammatory response syndrome (SIRS) patients, and healthy controls in a non-septic entity. Differential expression (DE) analysis is compared with machine-learning-based solutions like decision tree (DT), random forest (RF), support vector machine (SVM), and deep-learning neural networks (DNNs). We evaluated classifier training and discrimination performance in 100 independent iterations. To test diagnostic resilience, we gradually degraded expression data in multiple levels. Clustering of expression values based on DE genes results in partial identification of sepsis samples. In contrast, RF, SVM, and DNN provide excellent diagnostic performance measured in terms of accuracy and area under the curve (>0.96 and >0.99, respectively). We prove DNNs as the most resilient methodology, virtually unaffected by targeted removal of DE genes. By surpassing most other published solutions, the presented approach substantially augments current diagnostic capability in intensive care medicine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bloodstream infections remain one of the major challenges in intensive care units, leading to sepsis or even septic shock in many cases. Due to the lack of timely diagnostic approaches with ...sufficient sensitivity, mortality rates of sepsis are still unacceptably high. However a prompt diagnosis of the causative microorganism is critical to significantly improve outcome of bloodstream infections. Although various targeted molecular tests for blood samples are available, time-consuming blood culture-based approaches still represent the standard of care for the identification of bacteria.
Here we describe the establishment of a complete diagnostic workflow for the identification of infectious microorganisms from seven septic patients based on unbiased sequence analyses of free circulating DNA from plasma by next-generation sequencing.
We found significant levels of DNA fragments derived from pathogenic bacteria in samples from septic patients. Quantitative evaluation of normalized read counts and introduction of a sepsis indicating quantifier (SIQ) score allowed for an unambiguous identification of Gram-positive as well as Gram-negative bacteria that exactly matched with blood cultures from corresponding patient samples. In addition, we also identified species from samples where blood cultures were negative. Reads of non-human origin also comprised fragments derived from antimicrobial resistance genes, showing that, in principle, prediction of specific types of resistance might be possible.
The complete workflow from sample preparation to species identification report could be accomplished in roughly 30 h, thus making this approach a promising diagnostic platform for critically ill patients suffering from bloodstream infections.
Here we report on five COVID-19 patients with a median age of 67 years who were admitted to the medical intensive care unit of Heidelberg University Hospital due to respiratory failure. ...all ...patients had multi-organ failure with acute respiratory distress syndrome (ARDS, 4 severe, 1 moderate) and acute kidney injury of at least KDIGO stage 2. During the PE, striking reduction of inflammatory markers C-reactive protein (− 47%, P = 0.0078) and interleukin 6 (− 74%, P = 0.0078), as well as significant reduction of ferritin (− 49%, P = 0.0078), LDH (− 41%, P = 0.0078), and D-dimer (− 47%, P = 0.016) were observed (Fig. 1a–e).
Purpose
Tracheostomy is one of the most frequently performed procedures in intensive care medicine. The two main approaches are open surgical tracheostomy (ST) and percutaneous dilatational ...tracheostomy (PDT). This systematic review summarizes and analyzes the existing evidence regarding perioperative and postoperative parameters of safety.
Methods
A systematic literature search was conducted in the Cochrane Library, EMBASE, LILACS, and MEDLINE to identify all randomized controlled trials (RCTs) comparing complications of ST and PDT and to define the strategy with the lower risk of potentially life-threatening events. Risk of bias was assessed using the criteria outlined in the Cochrane Handbook.
Results
Twenty-four citations comprising 1795 procedures (PDT:
n
= 926; ST:
n
= 869) were found suitable for systematic review. No significant difference in the risk of a potentially life-threatening event (risk difference (RD) 0.01, 95% CI − 0.03 to 0.05,
P
= 0.62,
I
2
= 47%) was found between PDT and ST. There was no difference in mortality (RD − 0.00, 95% CI − 0.01 to 0.01,
P
= 0.88,
I
2
= 0%). An increased rate of technical difficulties was shown for PDT (RD 0.04, 95% CI 0.01, 0.08,
P
= 0.01,
I
2
= 60%). Stomal infection occurred more often with ST (RD − 0.05, 95% CI − 0.08 to − 0.02,
P
= 0.003,
I
2
= 60%). Both techniques can be safely performed on the ICU. Meta-analysis of the duration of procedure was not possible owing to high heterogeneity (
I
2
= 99%).
Conclusion
ST and PDT are safe techniques with low incidence of complications. Both techniques can be performed successfully in an ICU setting. ST can be performed on every patient whereas PDT is restricted by several contraindications like abnormal anatomy, previous surgery, coagulopathies, or difficult airway of the patient.
Systematic review registration
PROSPERO CRD42015021967
Background
COVID-19 pneumonia and subsequent respiratory failure is causing an immense strain on intensive care units globally. Early prediction of severe disease enables clinicians to avoid acute ...respiratory distress syndrome (ARDS) development and improve management of critically ill patients. The soluble receptor of advanced glycation endproducts (sRAGE) is a biomarker shown to predict ARDS. Although sRAGE level varies depending on the type of disease, there is limited information available on changes in sRAGE levels in COVID-19. Therefore, sRAGE was measured in COVID-19 patients to determine sRAGE level variation in COVID-19 severity and to examine its ability to predict the need for mechanical ventilation (MV) and mortality in COVID-19.
Methods
In this single-centre observational cohort study in Germany, serum sRAGE during acute COVID-19, 20 weeks after the start of COVID-19 symptoms, as well as in control groups of non-COVID-19 pneumonia patients and healthy controls were measured using ELISA. The primary endpoint was severe disease (high-flow nasal oxygen therapy (HFNO)/MV and need of organ support). The secondary endpoints were respiratory failure with need of MV and 30-day mortality. The area under the curve (AUC), cut-off based on Youden’s index and odds ratio with 95% CI for sRAGE were calculated with regard to prediction of MV need and mortality.
Results
Serum sRAGE in 164 COVID-19 patients, 101 matched COVID-19 convalescent patients, 23 non-COVID-19 pneumonia patients and 15 healthy volunteers were measured. sRAGE level increased with COVID-19 severity, need for oxygen therapy, HFNO/MV, ARDS severity, need of dialysis and catecholamine support, 30-day mortality, sequential organ failure assessment (SOFA) and quick SOFA (qSOFA) score. sRAGE was found to be a good predictor of MV need in COVID-19 inpatients and mortality with an AUC of 0.871 (0.770–0.973) and 0.903 (0.817–0.990), respectively. When adjusted for male gender, age, comorbidity and SOFA score ≥ 3, sRAGE was independently associated with risk of need for HFNO/MV. When adjusted for SOFA score ≥ 3, sRAGE was independently associated with risk of need for MV.
Conclusions
Serum sRAGE concentrations are elevated in COVID-19 patients as disease severity increases. sRAGE should be considered as a biomarker for predicting the need for MV and mortality in COVID-19.
To test the feasibility of a randomized controlled study design comparing epidural analgesia (EDA) with continuous wound infiltration (CWI) in respect to postoperative complications and mobility to ...design a future multicentre randomized controlled trial.
CWI has been developed to address drawbacks of EDA. Previous studies have established the equivalent analgesic potential of CWI compared to EDA. This is a single centre, non-blinded pilot randomized controlled trial at a tertiary surgical centre. Patients undergoing elective non-colorectal surgery via a midline laparotomy were randomized to EDA or CWI. Endpoints included recruitment, feasibility of assessing postoperative mobility with a pedometer and morbidity. No primary endpoint was defined and all analyses were explorative.
CWI with local anaesthetics (experimental group) vs. thoracic EDA (control).
Of 846 patients screened within 14 months, 71 were randomized and 62 (31 per group) included in the intention-to-treat analysis. Mobility was assessed in 44 of 62 patients and revealed no differences within the first 3 postoperative days. Overall morbidity did not differ between the two groups (measured via the comprehensive complication index). Median pain scores at rest were comparable between the two groups, while EDA was superior in pain treatment during movement on the first, but not on the second and third postoperative day. Duration of preoperative induction of anaesthesia was shorter with CWI than with EDA. Of 17 serious adverse events, 3 were potentially related to EDA, while none was related to CWI.
This trial confirmed the feasibility of a randomized trial design to compare CWI and EDA regarding morbidity. Improvements in the education and training of team members are necessary to improve recruitment.
DRKS00008023.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•The presented method is a rapid and simple option for routine TDM of piperacillin, meropenem, ceftazidime and flucloxacillin in human plasma without extensive sample preparation and using common ...equipment, which is of advantage regarding time and consumables.•Long-term storage of beta-lactam plasma samples at −80°C is possible for 9–13 months, depending on the analyte, thus calibrators and quality control samples can be prepared in advance and stored deep frozen. These findings are of great interest for implementing analytical assays of beta-lactams in laboratory routine, facilitating daily measurements.•Unprocessed whole blood tubes (S-Monovette Lithium-Heparin Gel, Sarstedt) directly after sampling are recommended to be kept refrigerated until analysis, as at room temperature, the compounds meropenem and piperacillin showed considerable degradation after 4h and 6h.
Therapeutic drug monitoring (TDM) is a useful tool to optimize antibiotic therapy. Increasing interest in alternative dosing strategies of beta-lactam antibiotics, e.g. continuous or prolonged infusion, require a feasible analytical method for quantification of these antimicrobial agents. However, pre-analytical issues including sample handling and stability are to be considered to provide valuable analytical results.
For the simultaneous determination of piperacillin, meropenem, ceftazidime and flucloxacillin, a high performance liquid chromatography (HPLC) method including protein precipitation was established utilizing ertapenem as internal standard. Long-term stability of stock solutions and plasma samples were monitored. Furthermore, whole blood stability of the analytes in heparinized blood tubes was investigated comparing storage under ambient conditions and 2–8°C.
A calibration range of 5–200μg/ml (piperacillin, ceftazidime, flucloxacillin) and 2–200μg/ml (meropenem) was linear with r2>0.999, precision and inaccuracy were <9% and <11%, respectively. The successfully validated HPLC assay was applied to clinical samples and stability investigations. At −80°C, plasma samples were stable for 9 months (piperacillin, meropenem) or 13 months (ceftazidime, flucloxacillin). Concentrations of the four beta-lactam antibiotics in whole blood tubes were found to remain within specifications for 8h when stored at 2–8°C but not at room temperature.
The presented method is a rapid and simple option for routine TDM of piperacillin, meropenem, ceftazidime and flucloxacillin. Whereas long-term storage of beta-lactam samples at −80°C is possible for at least 9 months, whole blood tubes are recommended to be kept refrigerated until analysis.
OBJECTIVES:Culture-based diagnostics represent the standard of care in septic patients, but are highly insensitive and in many cases unspecific. We recently demonstrated the general feasibility of ...next-generation sequencing-based diagnostics using free circulating nucleic acids (cell-free DNA) in plasma samples of septic patients. Within the presented investigation, higher performance of next-generation sequencing-based diagnostics was validated by comparison to matched blood cultures.
DESIGN:A secondary analysis of a prospective, observational, single-center study.
SETTING:Surgical ICU of a university hospital and research laboratory.
PATIENTS:Fifty patients with septic shock, 20 uninfected patients with elective surgery as control cohort.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:From 256 plasma samples of 48 septic patients at up to seven consecutive time points within the 28-day observation period, cell-free DNA was isolated and analyzed by next-generation sequencing and relevance scoring. In parallel, results from culture-based diagnostics (e.g., blood culture) were obtained. Plausibility of blood culture and next-generation sequencing results as well as adequacy of antibiotic therapy was evaluated by an independent expert panel. In contrast to blood culture with a positivity rate of 33% at sepsis onset, the positivity rate for next-generation sequencing-based pathogen identification was 72%. Over the whole study period, blood culture positivity was 11%, and next-generation sequencing positivity was 71%. Ninety-six percent of positive next-generation sequencing results for acute sepsis time points were plausible and would have led to a change to a more adequate therapy in 53% of cases as assessed by the expert evaluation.
CONCLUSIONS:Our results show that next-generation sequencing-based analyses of bloodstream infections provide a valuable diagnostic platform for the identification of clinically relevant pathogens with higher sensitivity and specificity than blood culture, indicating that patients might benefit from a more appropriate therapy based on next-generation sequencing-based diagnosis.
Serum amylase activity greater than the institutional upper limit of normal (hyperamylasemia) on postoperative day 0-2 has been suggested as a criterion to define postoperative acute pancreatitis ...after pancreatoduodenectomy, but robust evidence supporting this definition is lacking.
To assess the clinical impact of hyperamylasemia after pancreatoduodenectomy and to define postoperative acute pancreatitis.
Data of 1,235 consecutive patients who had undergone pancreatoduodenectomy between January 2010 and December 2014 were extracted from a prospective database and analyzed. Postoperative acute pancreatitis was defined based on the computed tomography severity index. Logistic regression modeling was used to calculate the postoperative acute pancreatitis rate of the entire study population.
Hyperamylasemia on postoperative day 1 was found in 52% of patients after pancreatoduodenectomy. Patients with hyperamylasemia on postoperative day 1 had statistically significantly greater morbidity and mortality than patients with a normal serum amylase activity on postoperative day 1 with the rates of postoperative pancreatic fistula of 14.5% vs 2.1%, and 90-day mortality of 6.6% vs 2.2%, respectively. Of the 364 patients who underwent postoperative computed tomography, 103 (28%) had radiologic signs of acute pancreatitis, thus defining them as having postoperative acute pancreatitis by our definition. Logistic regression modeling showed a 14.7% rate of postoperative acute pancreatitis for the entire patient cohort and 29.2% for patients with hyperamylasemia on postoperative day 1. Outcomes of patients with postoperative acute pancreatitis defined based on the computed tomography severity index showed a rate of postoperative pancreatic fistula of 32.4% and a 90-day mortality rate of 11.8%, which were worse than those of patients with hyperamylasemia on postoperative day 1 alone.
Hyperamylasemia on postoperative day 1 is a frequent finding after pancreatoduodenectomy, but hyperamylasemia on postoperative day 1 alone is not synonymous with postoperative acute pancreatitis because only 29.2% of such patients have acute pancreatitis based on computed tomography findings. Postoperative acute pancreatitis is a dangerous complication after pancreatoduodenectomy, but its prevalence, according to the gold standard of CT, is not as high as reported previously. Our data suggest that hyperamylasemia on postoperative day 1 and postoperative acute pancreatitis are 2 different entities.
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