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Clinica chimica acta
Elsevier
Clinica chimica acta

Elsevier

0009-8981

Clinica chimica acta/Journal Clinica chimica actaSCIISTPIC
正式出版
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    An online alpha-thalassemia carrier discrimination model based on random forest and red blood cell parameters for low HbA2 cases

    Feng P.Li Y.Liao Z.Yao Z....
    5页
    查看更多>>摘要:? 2021 Elsevier B.V.Background: Since screening of α-thalassemia carriers by low HbA2 has a low positive predictive value (PPV), the PPV was as low as 40.97% in our laboratory, other more effective screening methods need to be devised. This study aimed at developing a machine learning model by using red blood cell parameters to identify α-thalassemia carriers from low HbA2 patients. Methods: Laboratory data of 1213 patients with low HbA2 used for modeling was randomly divided into the training set (849 of 1213, 70%) and the internal validation set (364 of 1213, 30%). In addition, an external data set (n = 399) was used for model validation. Fourteen machine learning methods were applied to construct a discriminant model. Performance was evaluated with accuracy, sensitivity, specificity, etc. and compared with 7 previously published discriminant function formulae. Results: The optimal model was based on random forest with 5 clinical features. The PPV of the model was more than twice the PPV of HbA2, and the model had a high negative predictive value (NPV) at the same time. Compared with seven formulae in screening of α-thalassemia carriers, the model had a better accuracy (0.915), specificity (0.967), NPV (0.901), PPV (0.942) and area under the receiver operating characteristic curve (AUC, 0.948) in the independent test set. Conclusion: Use of a random forest-based model enables rapid discrimination of α-thalassemia carriers from low HbA2 cases.

    Dramatically prolonged coagulation screening tests in a patient with positive lupus anticoagulant and monoclonal immunoglobulin M without bleeding manifestations

    Marijancevic D.Kozmar A.Anic B.Coen Herak D....
    6页
    查看更多>>摘要:? 2021 Elsevier B.V.Background: Concomitant presence of lupus anticoagulant (LA) and monoclonal immunoglobulin in the same patient is uncommon and the influence of this finding on coagulation results is still unknown. Case report: We present a patient with a diagnosis of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) with permanently positive LA who presented with accidental finding of newly discovered monoclonal IgM in a high concentration and dramatically prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), without bleeding manifestations. Conclusion: Concomitant presence of extremely prolonged PT and aPTT with unusual coagulation reaction kinetics, consistent LA ratio over the follow-up period and normalization of coagulation screening results with decreasing monoclonal IgM concentration elicited suspicion that PT and aPTT prolongation could be attributed to M?protein with antiphospholipid specificity. Low LA-sensitive aPTT reagent Actin FS demonstrated exceptional sensitivity, whereas human placental thromboplastin in contrast to recombinant reagents showed significantly lower sensitivity to monoclonal IgM with antiphospholipid specificity. Changes in the activity of SLE observed during the follow-up period were inversely related to monoclonal IgM concentration, while the presence of secondary APS was consistent. Described analytical interference on PT and aPTT without bleeding manifestation should point towards suspicion of previously unidentified monoclonal IgM with antiphospholipid sensitivity.

    Serum iron concentrations in non-iron induced acute liver injury

    Mudan A.Lebin J.A.Wu A.H.B.Livshits Z....
    3页
    查看更多>>摘要:? 2021 Elsevier B.V.Acute liver injury (ALI) is seen in conjunction with elevated iron concentrations in the setting of acute iron toxicity. However, occult or delayed presentations of iron toxicity can be difficult to identify clinically and there is limited data describing iron concentrations in ALI without a confirmed history of iron overdose. This was a single center observational before-and-after study of adult patients who developed acute liver injury during hospitalization. Patients with a serum ALT > 500 U/L were identified by a daily hospital laboratory report and met inclusion if the ALT< 80 U/L at the time of admission, no history of overdose (iron, acetaminophen, or other ingestion), and no underlying liver disease. Serum AST, iron, and ferritin concentrations were obtained from blood samples at the time of admission and at peak serum ALT. Ten patients met inclusion criteria. The median age was 69 years old and 60% were male. There was a significant difference in serum AST (p = 0.005), serum ALT (p = 0.005), and ferritin (p = 0.005) before and after development of ALI. Serum iron concentrations were not clinically or significantly different (median: 23 mcg/dL vs 27 mcg/dL, p = 0.8). In this cohort of patients with non-iron induced acute liver injury, serum iron concentrations did not significantly change with the observed rise in aminotransferases. These data help to further characterize patterns of serum iron concentrations in patients with ALI.

    Assessment of tryptophan and kynurenine as prognostic markers in patients with SARS-CoV-2

    Michaelis S.Zelzer S.Schnedl W.J.Baranyi A....
    5页
    查看更多>>摘要:? 2021 Elsevier B.V.Background: Immune dysregulation and inflammation in patients with SARS-CoV-2 is associated with a poor clinical outcome. We investigated the value of the inflammatory markers tryptophan and kynurenine in predicting the survival outcome of patients with SARS-CoV-2. Methods: The study included 252 inpatients with a SARS-CoV-2 infection hospitalized between August 2020 and April 2021. Two groups were generated based on disease survival (survival group: n = 199; deceased group: n = 53). Plasma concentrations of tryptophan, kynurenine and interleukin-6 (IL-6) were measured on admission. In a subset of patients (n = 105; 81 survivors and 24 deceased) concentrations of tryptophan and kynurenine were checked 7 days after admission. The kynurenine/tryptophan ratio (TRP/KYN ratio) was calculated. Results: On admission, the deceased group showed significantly higher concentrations of kynurenine and a significantly higher KYN/TRP ratio compared to the survival group (p-values < 0.001). Kynurenine and the KYN/TRP ratio significantly correlated with IL-6 (ρ = 0.441 and 0.448, p-values < 0.001). In the survival group, kynurenine and the KYN/TRPratio were significantly lower after seven days (p-values < 0.001). In the deceased group, no significant differences were found between the measurements. Conclusion: Kynurenine and the KYN/TRP ratio are potentially useful parameters in predicting the survival outcome in SARS-CoV-2 positive patients.

    Performance verification of five commercial RT-qPCR diagnostic kits for SARS-CoV-2

    Yang M.Cao S.Liu Y.Zhang Z....
    8页
    查看更多>>摘要:? 2021Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused a global pandemic beginning in 2020, can be detected by reverse-transcription polymerase chain reaction (RT-PCR). However, owing to the urgent need for a large number of detection kits, the time spent researching and developing these kits has been shortened during the pandemic, and the kits that are being used commercially have not undergone full and independent evaluation. To ensure the accuracy of SARS-CoV-2 test results, performance verification of commercial Real-Time quantitative PCR (RT-qPCR) kits is required. Methods: The performance of five commercial RT-qPCR diagnostic kits for SARS-CoV-2 used in China was evaluated using a coronavirus disease 2019 (COVID-19) RNA liquid performance verification reference product-manufactured by Guangzhou Bondson (BDS) Biotechnology Co., Ltd.,Guangzhou, China-that uses droplet digital RT-PCR technology combined with fluorescence quantitative PCR. The five kits of Novel Coronavirus 2019-nCoV nucleic acid detection kit (RT-qPCR method) evaluated were Da An (Da An Gene Co., Ltd. of Sun Yat-sen University), Liferiver (Shanghai ZJ Bio-Tech Co., Ltd.), Kinghawk (Beijing Kinghawk Pharmaceutical Co., Ltd.), eDiagnosis (Wuhan Easy Diagnosis Biomedicine Co., Ltd.), and Maccura (Maccura Biotechnology Co., Ltd.). Performance verification criteria included the coincidence rate, limit of detection (LoD), cross-reactivity, precision, and anti-interference. Finally, through the BDS performance verification reference product kit, clinical samples are used to verify its clinical diagnostic efficacy. Results: The coincidence rate was 100% for all kits except for Kinghawk, which was 95%. The LoD for Da An, eDiagnosis and Maccura was 250copies/mL, and it was 1000 copies/ml for Liferiver. Kinghawk was not able to detect its advertised LoD of 500 copies/ml. The cross-reactivity test results were all negative. Moreover, all kits had a coefficient of variation less than 5%; however, Liferiver showed the best precision. Da An, Liferiver, and eDiagnosis showed higher sensitivity to the nucleocapsid (N) gene than they did to the open reading frame (ORF) 1ab genes. Anti-interference results for all five kits were positive. The results of clinical diagnostic efficacy were that the specificity of the four kits was 1.000 (0.877–1.000), the sensitivity of Da An was 1.000 (0.850–1.000), Liferiver was 0.964 (0.798–0.998), Maccura was 0.893 (0.706–0.972), and eDiagnosis was 0.857 (0.664–0.953). Conclusions: All commercial RT-qPCR diagnostic kits for SARS-CoV-2 passed the BDS performance verification, except for Kinghawk (batch No:20200608113) which failed to detect the LoD of 500 copies/mL. Da An and Liferiver have excellent clinical diagnostic specificity and sensitivity. This study can provide guidance for the selection or optimization of RT-qPCR diagnostic test kits for SARS-CoV-2.

    Prognostic value of circulating calprotectin levels on the clinical course of COVID-19 differs between serum, heparin, EDTA and citrate sample types

    Nevejan L.Strypens T.Van Nieuwenhove M.Boel A....
    8页
    查看更多>>摘要:? 2021 Elsevier B.V.Introduction: During the recent SARS-CoV-2 pandemic, circulating calprotectin (cCLP) gained interest as biomarker to predict the severity of COVID-19. We aimed to investigate the prognostic value of cCLP measured in serum, heparin, EDTA and citrate plasma. Materials and methods: COVID-19 patients were prospectively included, in parallel with two SARS-CoV-2 negative control populations. The prognostic value of cCLP was compared with IL-6, CRP, LDH, procalcitonin, and the 4C-mortality score by AUROC analysis. Results: For the 136 COVID-19 patients, cCLP levels were higher compared to the respective control populations, with significantly higher cCLP levels in serum and heparin than in EDTA or citrate. Higher cCLP levels were obtained for COVID-19 patients with i) severe/critical illness (n = 70), ii) ICU admission (n = 66) and iii) need for mechanical ventilation/ECMO (n = 25), but iv) not in patients who deceased within 30 days (n = 41). The highest discriminatory power (AUC [95% CI]) for each defined outcome was i) CRP (0.835 [0.755–0.914]); ii) EDTA cCLP (0.780 [0.688–0.873]); iii) EDTA cCLP (0.842 [0.758–0.925]) and iv) the 4C-mortality score (0.713 [0.608–0.818]). Conclusion: Measuring cCLP in COVID-19 patients helps the clinician to predict the clinical course of COVID-19. The discriminatory power of EDTA and citrate plasma cCLP levels often outperforms heparin plasma cCLP levels.

    Reference intervals for plasma vitamin B12 and plasma/serum methylmalonic acid in Danish children, adults and elderly

    Abildgaard A.Knudsen C.S.Hoejskov C.S.Greibe E....
    7页
    查看更多>>摘要:? 2021 The Author(s)Background: Plasma/serum vitamin B12 (B12) is often used to screen for B12 deficiency complemented with analysis of methylmalonic acid (MMA) in case of low B12. The concentration of both analytes likely depends on age, and we, therefore, aimed at establishing 95% age-adjusted reference intervals (RIs) for plasma B12 and serum/plasma MMA in the Danish population. Methods: We collected and analysed blood samples from healthy children, adults, and elderly individuals and extracted routine clinical B12 and MMA results to establish RIs. We also evaluated the association between matching B12 and MMA results. Results: We suggest the following RIs for plasma B12 and plasma/serum MMA, respectively. 0–<1 year: 180–1400 pmol/L, 0.10–1.25 μmol/L; 1–<11 years: 260–1200 pmol/L, 0.10–0.30 μmol/L; 12–<18 years: 200–800 pmol/L, 0.10–0.35 μmol/L; 18–<65 years: 200–600 pmol/L, 0.10–0.40 μmol/L; 65 + years: 200–600 pmol/L, 0.12–0.46 μmol/L. Finally, the proportion of patients with elevated MMA differed between age groups independently of B12 and was highest in children. Conclusion: We propose new age-adjusted RIs for B12 and MMA and suggest that age-dependent cut-off values should be implemented if plasma B12 is used to screen for B12 deficiency.

    Composition and inhibitory properties of endogenous urinary GAGS are different in subjects from two race groups with different occurrence rates of kidney stones: Pilot studies provide unique evidence in support of an inhibitory role for this group of compounds

    Jappie D.Rodgers A.Ravenscroft N.Webber D....
    7页
    查看更多>>摘要:? 2021 Elsevier B.V.Background: Calcium oxalate (CaOx) kidney stone disease is common in South African whites (W) but is rare in the black population (B). The possible role of endogenous urinary glycosaminoglycans (GAGs) has not been previously investigated in this context. Aim: To determine concentration, composition, structure and CaOx crystal-inhibiting properties of this group of compounds in ultrafiltered urine of healthy subjects from both groups. Materials and methods: GAGS were isolated from 24 h urine samples and were quantified and characterized by sequential precipitation, Bradford protein assay, high performance liquid chromatography, and anion exchange high performance chromatography. CaOx crystal inhibition was determined in ultrafiltered urinary fractions to which purified GAGS (PG) from each group (PGB and PGW) had been added. Nucleation, growth and aggregation were measured by Coulter particle counting, spectrophotometric assay and [14C]-oxalate deposition. Results: Higher concentrations of chondroitin sulfate (CS) were found in PGB than in PGW. PGB inhibited crystallization to a greater extent than PGW. Conclusions: We attribute the stronger inhibitory effect of PGB to its higher content of CS and suggest that the superior inhibition of CaOx crystallization by PGB relative to PGW might be a contributory factor in accounting for the lower stone occurrence rate in B.