Evaluation of preanalytical and postanalytical phases in clinical biochemistry laboratory according to IFCC laboratory errors and patient safety specifications

IntroductionThe aim of the study was to determine the current state of laboratory’s extra-analytical phase performance by calculating preanalytical and postanalytical phase quality indicators (QIs) and sigma values and to compare obtained data according to desired quality specifications and sigma values reported by The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group – Laboratory errors and Patient Safety.Materials and methodsPreanalytical and postanalytical phase data were obtained through laboratory information system. Rejected samples in preanalytical phase were grouped according to reasons for rejection and frequencies were calculated both monthly and for 2019. Sigma values were calculated according to “short term sigma” table.ResultsThe number of rejected samples in laboratory was 643 out of 191,831 in 2019. Total preanalytical phase rejection frequency was 0.22%. According to the reasons for rejection, QIs and sigma values were: “Samples with excessive transportation time”: 0.0036 and 5.47; “Samples collected in wrong container” 0.02 and 5.11. In December, QIs and sigma values were: “Samples with excessive transportation time”: 0.01 and 5.34; “Samples collected in wrong container”: 0.03 and 4.98. The postanalytical QIs and sigma values were: “Reports delivered outside the specified time”: 0.34 and 4.21; “Turn around time of potassium”: 56 minute and 3.84, respectively. There were no errors in “Critical values of inpatients and outpatients notified after a consensually agreed time”.ConclusionsExtra-analytical phase was evaluated by comparing it with the latest quality specifications and sigma values which will contribute to improving the quality of laboratory medicine.     

The response of total testing process in clinical laboratory medicine to COVID-19 pandemic

IntroductionFollowing a pandemic, laboratory medicine is vulnerable to laboratory errors due to the stressful and high workloads. We aimed to examine how laboratory errors may arise from factors, e.g., flexible working order, staff displacement, changes in the number of tests, and samples will reflect on the total test process (TTP) during the pandemic period.Materials and methodsIn 12 months, 6 months before and during the pandemic, laboratory errors were assessed via quality indicators (QIs) related to TTP phases. QIs were grouped as pre-, intra- and postanalytical. The results of QIs were expressed in defect percentages and sigma, evaluated with 3 levels of performance quality: 25^th, 50^th and 75^th percentile values.ResultsWhen the pre- and during pandemic periods were compared, the sigma value of the samples not received was significantly lower in pre-pandemic group than during pandemic group (4.7σ vs. 5.4σ, P = 0.003). The sigma values of samples transported inappropriately and haemolysed samples were significantly higher in pre-pandemic period than during pandemic (5.0σ vs. 4.9σ, 4.3σ vs. 4.1σ; P = 0.046 and P = 0.044, respectively). Sigma value of tests with inappropriate IQC performances was lower during pandemic compared to the pre-pandemic period (3.3σ vs. 3.2σ, P = 0.081). Sigma value of the reports delivered outside the specified time was higher during pandemic than pre-pandemic period (3.0σ vs. 3.1σ, P = 0.030).ConclusionIn all TTP phases, some quality indicators improved while others regressed during the pandemic period. It was observed that preanalytical phase was affected more by the pandemic.     

Nanotechnology for the management of COVID-19 during the pandemic and in the post-pandemic era

Following the global COVID-19 pandemic, nanotechnology has been at the forefront of research efforts and enables the fast development of diagnostic tools, vaccines and antiviral treatment for this novel virus (SARS-CoV-2). In this review, we first summarize nanotechnology with regard to the detection of SARS-CoV-2, including nanoparticle-based techniques such as rapid antigen testing, and nanopore-based sequencing and sensing techniques. Then we investigate nanotechnology as it applies to the development of COVID-19 vaccines and anti-SARS-CoV-2 nanomaterials. We also highlight nanotechnology for the post-pandemic era, by providing tools for the battle with SARS-CoV-2 variants and for enhancing the global distribution of vaccines. Nanotechnology not only contributes to the management of the ongoing COVID-19 pandemic but also provides platforms for the prevention, rapid diagnosis, vaccines and antiviral drugs of possible future virus outbreaks.     

Detection of preanalytical errors in arterial blood gas analysis

IntroductionBlood gas analysis (BGA) is an essential test used for years to provide vital information in critically ill patients. However, the instability of the blood gases is a problem. We aimed to evaluate time and temperature effects on blood gas stability.Materials and methodsArterial blood was collected from 20 patients into syringes. Following BGA for baseline, syringes were divided into groups to stand at 4°C and 22°C for 30, 60, 90, 120 minutes. All were tested for pH, partial pressure of carbon dioxide (pCO₂), partial pressure of oxygen (pO₂), oxygen saturation (sO₂), oxyhemoglobin (O₂Hb), sodium, potassium, glucose, lactate, oxygen tension at 50% hemoglobin saturation (p50), and bicarbonate. A subgroup analysis was performed to detect the effect of air on results during storage. Percentage deviations were calculated and compared against the preset quality specifications for allowable total error.ResultsAt 4°C, pO₂ was the least stable parameter. At 22°C, pO₂ remained stable for 120 min, pH and glucose for 90 min, lactate and pCO₂ for 60 min. Glucose and lactate were stable when chilled. Air bubbles interfered pO₂ regardless of temperatures, whereas pCO₂ increased significantly at 22°C after 30 min, and pH decreased after 90 min. Bicarbonate, sO₂, O₂Hb, sodium, and potassium were the unaffected parameters.ConclusionsCorrect BGA results are essential, and arterial sample is precious. Therefore, if immediate analysis cannot be performed, up to one hour, syringes stored at room temperature will give reliable results when care is taken to minimize air within the blood gas specimen.     

Seroprevalence of SARS-CoV-2 infection among children in Children’s Hospital Zagreb during the initial and second wave of COVID-19 pandemic in Croatia

IntroductionThe study aimed to investigate the prevalence and titres of anti-SARS-CoV-2 antibodies in children treated at the Children’s Hospital Zagreb in the first and the second wave of the COVID-19 pandemic. Statistical significance of difference at two time points was done to determine how restrictive epidemiological measures and exposure of children to COVID-19 infection affect this prevalence in different age groups.Materials and methodsAt the first time point (13th to 29th May 2020), 240 samples and in second time point (24th October to 23rd November 2020), 308 serum samples were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECLIA). Confirmation of results and titre determination was done using virus micro-neutralization test. Subjects were divided according to gender, age and epidemiological history.ResultsSeroprevalence of anti-SARS-CoV-2 antibodies differs significantly in two time points (P = 0.010). In first time point 2.9% of seropositive children were determined and in second time point 8.4%. Statistically significant difference (P = 0.007) of seroprevalence between two time points was found only in a group of children aged 11-19 years. At the first time point, all seropositive children were asymptomatic with titre < 8. At the second time point, 69.2% seropositive children were asymptomatic with titre ≥ 8.ConclusionsThe prevalence of anti-SARS-CoV-2 antibodies was significantly lower at the first time point than at the second time point. Values of virus micro-neutralization test showed that low titre in asymptomatic children was not protective at the first time point but in second time point all seropositive children had protective titre of anti-SARS-CoV-2 antibodies.     

Agile and adaptive governance in crisis response: Lessons from the COVID-19 pandemic

Countries around the world have had to respond to the COVID-19 outbreak with limited information and confronting many uncertainties. Their ability to be agile and adaptive has been stressed, particularly in regard to the timing of policy measures, the level of decision centralization, the autonomy of decisions and the balance between change and stability. In this contribution we use our observations of responses to COVID-19 to reflect on agility and adaptive governance and provide tools to evaluate it after the dust has settled. Whereas agility relates mainly to the speed of response within given structures, adaptivity implies system-level changes throughout government. Existing institutional structures and tools can enable adaptivity and agility, which can be complimentary approaches. However, agility sometimes conflicts with adaptability. Our analysis points to the paradoxical nature of adaptive governance. Indeed, successful adaptive governance calls for both decision speed and sound analysis, for both centralized and decentralized decision-making, for both innovation and bureaucracy, and both science and politics.     

The twin-beginnings of COVID-19 in Asia and Europe—one prevails quickly

In the spread of SARS-CoV-2, there have been multiple waves of replacement between strains, each of which having a distinct set of mutations. The first wave is a group of four mutations (C241T, C3037T, C14408T and A23403G [this being the amino acid change D614G]; all designated 0 to 1 below). This DG (D614G) group, fixed at the start of the pandemic, is the foundation of all subsequent waves of strains. Curiously, the DG group is absent in early Asian samples but present (and likely common) in Europe from the beginning. European data show that the high fitness of DG1111 requires the synergistic effect of all four mutations. However, the European strains would have had no time to evolve the four DG mutations (0 to 1), had they come directly from the early Asian DG0000 strain. Very likely, the European DG1111 strain had acquired the highly adaptive DG mutations in pre-pandemic Europe and had been spreading in parallel with the Asian strains. Two recent reports further support this twin-beginning interpretation. There was a period of two-way spread between Asia and Europe but, by May 2020, the European strains had supplanted the Asian strains globally. This large-scale replacement of one set of mutations for another has since been replayed many times as COVID-19 progresses.     

An Unusual Presentation of Superior Mesenteric Venous Occlusion in Mild COVID-19

SARS-CoV-2, an etiological agent of COVID-19, has been reported to inflict remarkably diverse manifestations in different subjects across the globe. Though patients with COVID-19 predominantly have fever, respiratory and constitutional symptoms, atypical presentations are becoming increasingly evident.COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilization, and diffuse intravascular coagulation in moderate to severe symptomatic cases. In this case report, we are reporting thromboembolic complications of COVID-19 in a mild symptomatic subject incidentally diagnosed with mesenteric venous occlusion with no abdominal symptoms.Early recognition of the abdominal symptoms, diagnosis, initiation of anticoagulants, and timely surgical intervention may improvise the outcome in a patient with COVID-19 infection-induced mesenteric thrombosis. Superior mesenteric artery and venous thrombosis may lead to subsequent ischemia necessitating emergency laparotomy. Thus, the usage of low-dose anticoagulants in all the patients of COVID-19 irrespective of the categorization into mild, moderate, and severe COVID-19 disease should be considered.     

The concurrence of the current postanalytical phase management with the national recommendations: a survey of the Working Group for Postanalytics of the Croatian Society of Medical Biochemistry and Laboratory Medicine

IntroductionThe detection and prevention of errors in the postanalytical phase can be done through the harmonization and standardization of constituent parts of this phase of laboratory work. The aim was to investigate how well the ongoing management of the postanalytical phase corresponds to the document “Post-analytical laboratory work: national recommendations” in Croatian medical biochemistry laboratories (MBLs).Materials and methodsAll 195 MBLs participating in the national external quality assessment scheme, were invited to undertake a part in a survey. Through 23 questions the participants were asked about management of the reference intervals (RI), delta check, reflex/reflective testing, postanalytical quality indicators and other parts of the postanalytical phase recommended in the national recommendations. The results are presented in numbers and percentages.ResultsOut of 195 MBLs, 119 participated in the survey, giving a response rate of 61%. Not all of the respondents provided answers to all the questions. Delta check has not been used in 59% (70/118) of the laboratories. Only 22/113 (20%) laboratories use reflex and/or reflective testing. In 53% of the laboratories, critical results were reported within 30 minutes of the confirmation of the results. In 34% (40/118) of the laboratories, turnaround time and reporting of critical results are two most often monitored postanalytical quality indicators.ConclusionThe results showed the critical results reporting and monitoring of postanalytical quality indicators are in the line with the recommendations. However, the management of RI verification, the use of delta check and reflex/reflective testing still must be harmonized among Croatian MBLs.     

Information resource orchestration during the COVID-19 pandemic: A study of community lockdowns in China

The outbreak of the COVID-19 pandemic has created significant challenges for people worldwide. To combat the virus, one of the most dramatic measures was the lockdown of 4 billion people in what is believed to be the largest quasi-quarantine in human history. As a response to the call to study information behavior during a global health crisis, we adopted a resource orchestration perspective to investigate six Chinese families who survived the lockdown. We explored how elderly, young and middle-aged individuals and children resourced information and how they adapted their information behavior to emerging online technologies. Two information resource orchestration practices (information resourcing activities and information behavior adaptation activities) and three mechanisms (online emergence and convergence in community resilience, the overcoming of information flow impediments, and the application of absorptive capacity) were identified in the study.     

Association of serum ADMA,SDMA and L-NMMA concentrations with disease progression in COVID-19 patients

IntroductionThis study determines and compares the concentrations of arginine and methylated arginine products ((asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), n-monomethyl-1-arginine (L-NMMA) and homoarginine (HA)) for assessment of their association with disease severity in serum samples of COVID-19 patients.Materials and methodsSerum arginine and methylated arginine products of 57 mild-moderate and 29 severe (N = 86) COVID-19 patients and 21 controls were determined by tandem mass spectrometry. Moreover, the concentrations of some of the routine clinical laboratory parameters -neutrophil lymphocyte ratio (NLR), C-reactive protein, ferritin, D-dimer, and fibrinogen measured during COVID-19 follow-up were also taken into consideration and compared with the concentrations of arginine and methylated arginine products.ResultsSerum ADMA, SDMA and L-NMMA were found to be significantly higher in severe COVID-19 patients, than in both mild-moderate patients and the control group (P < 0.001 for each). In addition, multiple logistic regression analysis indicated L-NMMA (cut-off =120 nmol/L OR = 34, 95% confidence interval (CI) = 3.5-302.0, P= 0.002), CRP (cut-off = 32 mg/L, OR = 37, 95% CI = 4.8-287.0, P < 0.001), and NLR (cut-off = 7, OR = 22, 95% CI = 1.4-335.0, P = 0.020) as independent risk factors for identification of severe patients.ConclusionsThe concentration of methylated arginine metabolites are significantly altered in COVID-19 disease. The results of this study indicate a significant correlation between the severity of COVID-19 disease and concentrations of CRP, NLR and L-NMMA.     

The Remarkable Roles of the Receptor for Advanced Glycation End Products (RAGE) and Its Soluble Isoforms in COVID-19: The Importance of RAGE Pathway in the Lung Injuries

The respiratory symptoms of acute respiratory distress syndrome (ARDS) in the coronavirus disease 2019 (COVID-19) patients is associated with accumulation of pre-inflammatory molecules such as advanced glycation end-products (AGES), calprotectin, high mobility group box family-1 (HMGB1), cytokines, angiotensin converting enzyme 2 (ACE2), and other molecules in the alveolar space of lungs and plasma. The receptor for advanced glycation end products (RAGEs), which is mediated by the mitogen-activated protein kinase (MAPK), plays a critical role in the severity of chronic inflammatory diseases such as diabetes mellitus (DM) and ARDS. The RAGE gene is most expressed in the alveolar epithelial cells (AECs) of the pulmonary system. Several clinical trials are now being conducted to determine the possible association between the levels of soluble isoforms of RAGE (sRAGE and esRAGE) and the severity of the disease in patients with ARDS and acute lung injury (ALI). In the current article, we reviewed the most recent studies on the RAGE/ligands axis and sRAGE/esRAGE levels in acute respiratory illness, with a focus on COVID-19–associated ARDS (CARDS) patients. According to the research conducted so far, sRAGE/esRAGE measurements in patients with CARDS can be used as a powerful chemical indicator among other biomarkers for assessment of early pulmonary involvement. Furthermore, inhibiting RAGE/MAPK and Angiotensin II receptor type 1 (ATR1) in CARDS patients can be a powerful strategy for diminishing cytokine storm and severe respiratory symptoms.     

Role of Matrix Degradation,Oxidative Stress,Inflammation & Trace Elements in COVID-19 Patients: A Multivariate Study from India

The interrelationship between matrix degradation, oxidative stress, inflammation and trace elements can be speculated in COVID-19. The objective of the study was to evaluate the oxidative stress, inflammation and matrix degradation markers and trace elements in COVID-19 positive patients. A group of confirmed severe COVID-19 positive patients (n = 30) along with COVID-19 negative patients (n = 30) with similar symptoms were included. Both group of patients were assessed for oxidative stress markers, inflammatory cytokines, matrix metalloproteinase (MMP)s and their inhibitors along with trace elements in blood. All the data were subjected to univariate as well as multivariate analysis including PCA, PLS-DA, OPLS-DA. Diagnostic accuracy was tested by ROC curve analysis. Further relationship with Neutrophil/ lymphocyte (N/L) ratio was established if any. Increased oxidative stress, inflammation and matrix degradation is evidenced by significant rise in oxidative markers, inflammatory cytokines and MMP9/TIMP-1 ratio. Decreased Cu/Zn ratio is also observed in COVID-19 positive patients. Multivariate analysis identified SOD, Cu/Zn ratio, IL-6 and TOS, as effective discriminant among the two groups of patients. Further, accuracy was confirmed by ROC curves. Neutrophil/ lymphocyte (N/L) ratio, shows significant negative association with SOD (r= -0.75, p < 0.005) and Cu/Zn ratio (r = -0.88, p < 0.005). These data suggest the attributes of these biomarkers in disease severity. The potential use of these blood-based laboratory markers in disease prognosis seems promising and warrants further attention. Given by the symptoms and severity of the disease, it will be promising to monitor Cu/Zn ratio along with other prognostic indicators.     

Untangling the contributions of meteorological conditions and human mobility to tropospheric NO2 in Chinese mainland during the COVID-19 pandemic in early 2020

In early 2020, unprecedented lockdowns and travel bans were implemented in Chinese mainland to fight COVID-19, which led to a large reduction in anthropogenic emissions. This provided a unique opportunity to isolate the effects from emission and meteorology on tropospheric nitrogen dioxide (NO₂). Comparing the atmospheric NO₂ in 2020 with that in 2017, we found the changes of emission have led to a 49.3 ± 23.5% reduction, which was ∼12% more than satellite-observed reduction of 37.8 ± 16.3%. The discrepancy was mainly a result of changes of meteorology, which have contributed to an 8.1 ± 14.2% increase of NO₂. We also revealed that the emission-induced reduction of NO₂ has significantly negative correlations to human mobility, particularly that inside the city. The intra-city migration index derived from Baidu Location-Based-Service can explain 40.4% ± 17.7% variance of the emission-induced reduction of NO₂ in 29 megacities, each of which has a population of over 8 million in Chinese mainland.