Establishment and validation of reference interval of D-dimer in plasma of healthy pregnant women in Xi ′an / 中华检验医学杂志

Objective:To provide normal reference thresholds for clinical dynamic monitoring of the risk of microthrombus during pregnancy, we aimed to establish reference intervals of D-dimer in healthy pregnant women during different periods of gestation in Xi′an.Method:From December 2020 to March 2022, a total of 1502 healthy pregnant women and healthy non-pregnant women (healthy non-pregnant control group) who received routine prenatal examination in Northwest Women and Children′s Hospital were recruited in the study by questionnaire, including 1236 healthy pregnant women and 266 healthy non-pregnant control group. Plasma D-dimer concentration was detected by STA-R Evolution automatic blood coagulation analyzer and the concentration levels of D-dimer in different pregnancies and age groups were calculated using Graph Prism 9.0 software. In addition, 20 samples were collected in each pregnancy to verify the established reference interval.Results:There was no significant difference in plasma D-dimer levels between<30 years old and ≥30 years old at different gestational weeks. Plasma D-dimer level in healthy pregnant women group was significantly higher than that in healthy non-pregnant women group of the same age (P<0.05). With the increase of gestational week, plasma D-dimer level in pregnant women increased significantly, and plasma D-dimer level at different gestational weeks ≤13 weeks, 13+ 1-20 weeks, 20+ 1-27 weeks, 27+ 1-35 weeks, ≥35 +1 week were 0.33 (0.26, 0.47) μg/ml, 0.41 (0.30, 0.51) μg/ml, 0.71 (0.48, 0.94) μg/ml, 0.91 (0.70, 1.27) μg/ml, 1.30 (0.96, 1.72) μg/mlrespectively. Unilateral reference interval acuities were≤0.89 μg/ml, ≤1.53 μg/ml, ≤2.44 μg/ml, ≤2.74 μg/ml, ≤3.82 μg/ml respectively. The reference range established in this study was verified by 20 independent samples from each of the 5 gestational age groups, and the results were acceptable. Conclusion:This study preliminarily established the reference interval of plasma D-dimer in healthy pregnant women at different gestational weeks in Xi ′an area, which is helpful for the auxiliary diagnosis of thrombotic diseases during pregnancy.

A case report of dermatitis herpetiformis with positive gluten-sensitive intestinal disease autoantibodies / 中华检验医学杂志

A middle-aged male patient initially appeared scattered erythema with pruritus all over the body without obvious cause. According to the skin manifestations of the patient, combined with pathological diagnosis, direct immunofluorescence examination, and different serum autoantibody spectrum, the diagnosis and differential diagnosis of the patient was made by clinicians. The diagnosis of dermatitis herpetiformis was confirmed by the use of autoantibodies in the absence of any apparent history of pasta discomfort. With targeted treatment, the patient′s symptoms and laboratory indicators improved significantly.

Value of reflex testing in clinical practice of laboratory medicine / 中华检验医学杂志

Reflex tests are ordered when a particular test result indicates that additional testing should be performed according to the guidelines or the feedback process formulated by clinical consultation. The application scope of the reflex tests involves various subspecialties of laboratory medicine. The clinical application needs the support of qualified laboratory doctors, comprehensive information and financial system, clinical guidelines, and so on. Active application of reflex tests can promote the standardization of evidence-based medicine in clinical practice, save medical resources, and shorten the diagnosis and treatment time of patients.

Epidemiological and Clinical Characteristics of COVID-19 Patients with Cancers: A Systematic Review and Meta-Analysis of Global Data

SummaryBackground Data on the prevalence of cancer in coronavirus disease 2019 (COVID-19)-infected patients and the severe illness incidence and mortality of COVID-19 patients with cancers remains unclear. MethodsWe systematically searched PubMed, Embase, Cochrane Library, and Web of Science, from database inception to July 15, 2020, for studies of patients with COVID-19 infection that had available comorbidity information on cancer. The primary endpoint was the pooled prevalence of cancer in COVID-19 patients and the secondary endpoint was the outcomes of COVID-19-infected cancer patients with incidence of severe illness and death rate. We calculated the pooled prevalence and corresponding 95% confidence intervals (95% CIs) using a random-effects model, and performed meta-regression analyses to explore heterogeneity. Subgroup analyses were conducted based on continent, country, age, sample size and study design. FindingsA total of 107 eligible global studies were included in the systematic review. 90 studies with 94,845 COVID-19 patients in which 4,106 patients with cancer morbidity were included in the meta-analysis for prevalence of cancer morbidity among COVID-19 patients. 21 studies with 70,969 COVID-19 patients in which 3,351 patients with cancer morbidity who had severe illness or death during the studies. The overall prevalence of cancer among the COVID-19 patients was 0.07 (95% CI 0.05{bsim}0.09). The cancer prevalence in COVID-19 patients of Europe (0.22, 95% CI 0.17{bsim}0.28) was higher than that in Asia Pacific (0.04, 95% CI 0.03{bsim}0.06) and North America (0.05, 95% CI 0.04{bsim}0.06). The prevalence of COVID-19-infected cancer patients over 60 years old was 0.10 (95% CI 0.07{bsim}0.14), higher than that of patients equal and less than 60 years old (0.05, 95% CI 0.03{bsim}0.06). The pooled prevalence of severe illness among COVID-19 patients with cancers was 0.35 (95% CI 0.27{bsim}0.43) and the pooled death rate of COVID-19 patients with cancers was 0.18 (95% CI 0.14{bsim}0.18). The pooled incidence of severe illness of COVID-19 patients with cancers from Asia Pacific, Europe, and North America were 0.38(0.24, 0.52), 0.36(0.17, 0.55), and 0.26(0.20, 0.31), respectively; and the pooled death rate from Asia Pacific, Europe, and North America were 0.17(0.10, 0.24), 0.26(0.13, 0.39), and 0.19(0.13, 0.25), respectively. InterpretationTo our knowledge, this study is the most comprehensive and up-to-date metaanalysis assessing the prevalence of cancer among COVID-19 patients, severe illness incidence and mortality rate. The prevalence of cancer varied significantly in geographical continents and age. The COVID-19 patients with cancer were at-risk for severe illness and a high death rate. The European COVID-19 patients had the highest cancer prevalence among the three continents examined and were also the most likely to progress to severe illness and death. Although the Asia Pacific COVID-19 patients had the lowest cancer prevalence, their severe illness rate was similar to that of Europeans. Research in context Evidence before this studyCoronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a newly discovered coronavirus, which leads to respiratory illness and can be transmitted from person to person. As the infection has become widespread, concern for the influence of COVID-19 on patients with cancer has grown. Previous studies suggest that patients with a history of active malignancy might be at increased risk for COVID-19, developing COVID-19-related complications and having a poorer prognosis. Until now, however, few studies explored the following two questions: 1) what is the estimated prevalence of cancer patients with COVID-19 infection; and 2) do COVID-19-infected cancer-patients have distinct clinical courses and worse outcomes compared with COVID-19-infected patients without cancers. The latter is based on the former to further explore the characteristics of clinical outcomes of such patients. The clarification of these two questions will greatly help to understand the relationship between COVID-19 and cancer in terms of clinical epidemiology, and thus facilitate the formulation of targeted and relevant public health policies. Added value of this studyTo our knowledge, this systematic review and meta-analysis of 107 studies is the most comprehensive and up-to-date assessing the prevalence of cancer among COVID-19 patients, the incidence of severe illness and mortality rate of COVID-19 patients with cancers. We provided a relatively accurate overall cancer prevalence among the all COVID-19 patients (7%), stratified by geographical continent, country, age, study sample size, and study design type. We also presented the pooled severe illness and mortality rates stratified by continent. European COVID-19-infected cancer patients seemed the most likely to both develop cancer and progress to severe illness and death. Implications of all the available evidenceOur findings have reinforced important considerations of clinical care and emphasized the urgent unmet needs for COVID-19 patients with cancers using the pooled prevalence, incidence of severe illness, and death rates as evidence. Also, after comparing the cancer prevalence, incidence of severe illness, and death rate of COVID-19 patients from different continents, European population may require stronger control measures than the Asia Pacific and North American populations. In the future, as more data will be available, it will be interesting to further investigate the differences of sociodemographic and climcopathological features between COVID-19-infected patients with cancer and without cancer.

The change pattern and significance of IgM and IgG in the progress of COVID-19 disease

BackgroundTo investigate the significance of IgM and IgG in the progress of COVID-19. MethodA multicenter cross-sectional study conducted in suspected and confirmed patients from four hospitals of China and a cohort study to identify the change pattern and significance in the process of COVID-19 disease. ResultsA total of 571 patients were enrolled in the cross-sectional study, including 235 confirmed SARS-CoV-2 infection with 91.9% patients IgG positive and 92.3% IgM positive. 30 patients diagnosed with SARS-CoV-2 infection were enrolled in the cohort study for flowing-up in 20 days. The peak of IgM and IgG reached in 10th and 20 th day separately after symptom onset. The relationship between clinical classification and serological antibodies were analysed. The positive rate of COVID-19 IgG and IgM increased along with the clinical classification and the delay of treatment time. ConclusionWe demonstrated the kinetics of IgM and IgG SARS-CoV-2 antibody in COVID-19 patients, which may contribute to explain the results of IgM and IgG SARS-CoV-2 antibody test and predict the prognosis of COVID-19.

Multi-center Performance Evaluations of Tacrolimus and Cyclosporine Electrochemiluminescence Immunoassays in the Asia-Pacific Region

BACKGROUND: The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are vital for solid organ transplant patients to prevent rejection. However, toxicity is a concern, and absorption is highly variable across patients; therefore, ISD levels need to be precisely monitored. In the Asia-Pacific (APAC) region, tacrolimus and cyclosporine concentrations are typically measured using immunoassays. The objective of this study was to assess the analytical performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence immunoassays (ECLIAs). METHODS: This evaluation was performed in seven centers across China, South Korea, and Malaysia. Imprecision (repeatability and reproducibility), assay accuracy, and lot-to-lot reagent variability were tested. The Elecsys ECLIAs were compared with commercially available immunoassays (Architect, Dimension, and Viva-E systems) using whole blood samples from patients with various transplant types (kidney, liver, heart, and bone marrow). RESULTS: Coefficients of variation for repeatability and reproducibility were ≤5.4% and ≤12.4%, respectively, for the tacrolimus ECLIA, and ≤5.1% and ≤7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even closer agreements with the Architect, Dimension, and Viva-E systems (slope values of 1.04, 1.04, and 1.09, respectively). No major differences were observed among the different transplant types. CONCLUSIONS: The tacrolimus and cyclosporine ECLIAs demonstrated excellent precision and close agreement with other immunoassays tested. These results show that both assays are suitable for ISD monitoring in an APAC population across a range of different transplant types.

The application of modified capillary immunotyping technique for cryoglobulin identification / 中华检验医学杂志

Objective To establish and evaluate the application of modified capillary immunotyping for cryoglobulin qualification .Methods Referred to literature and benchwork experience , a modified capillary immunotyping technique was set up for cryoglobulin identification . Seventy-eight cryoglobulin positive specimens were collected by a standard method in Peking Union Medical College Hospital from November 2016 to July 2017.Thirty-nine samples were identified the type of the cryoglobulin simultaneously by modified capillary immunotyping ( CI ) and immunofixation electrophoresis ( IFE ) .Results Using the modified capillary immunotyping method , the types of cryoglobulin in seventy-eight specimens were identified.The number of cases decreased in the order of Ⅲ, Ⅱ and Ⅰ type of cryoglobulin .The clinical characteristics coincidence with previous reports .The modified CI method had a dramatic advantage in the speed, clarity, and accuracy of results compared with IFE .The ratio of reportable cases between these two methods was 1:0.87.Conclusion The modified capillary immunotyping was an accurate and easy method for cryoglobulin qualification , and feasible for clinical application .

Survey of vitamin D status in apparently healthy younger and elder adults / 中华检验医学杂志

Objective To analyze the vitamin D status among apparently healthy younger and elder adults in Beijing based on liquid chromatography tandem mass spectrometry.Methods This is an observational study.Participants included 287 apparently healthy young adults(143 males and 144 females) with an average of (32.2 ± 6.9) years old (19-44 years).At the same time 198 middle-and elder-aged adults were recruited [90 males,108 females,(55.6 ± 7.6) years],and fasting blood samples were collected and serum were isolated.They measured 25-hydroxyvitamin D (25OHD:25OHD2 and 25OHD3)using liquid chromatography tandem mass spectrometry method.Vitamin D with deficiency,insufficiency,sufficiency and intoxication was categorized as 25OHD ＜ 20 ng/ml,20-30 ng/ml,30-150 ng/ml,and ≥ 150 ng/ml,respectively.ALT,Ca,P,Cr,Glu,TG,TC and iPTH wereanalyzed using automatic analyzers.Statistical analysis was performed using SPSS17.0.Results The median 25OHD level in the total studied younger adults was 16.0 [2.5％-97.5％:(6.1-29.0) ng/ml] which didn't show significant difference with that of middle-and elder-aged adults.Younger males had significant higher level of 25OHD than females [17.9 (8.3-32.3) ng/ml vs.14.4 (5.4-26.4) ng/ml,Z =-4.238,P ＜ 0.01].Of the total younger subjects,the rate of vitamin D with deficiency (＜ 20 ng/ml),insufficiency (20-30 ng/ml)and sufficiency (≥30 ng/ml) was 72.8％,25.1％,2.1％,respectively,while that of middle-and elderaged adults was 76.3％,21.2％,2.5％ respectively,and that of younger males was 65.0％,30.8％,4.2％,respectively while that of younger females was 80.6％,19.4％,0％,respectively.Younger females had significantly higher rate of 25OHD deficiency (x2 =31.766,P ＜ 0.01).With adjusting sex,age and BMI,serum iPTH (r =-0.264,P ＜ 0.01) was significantly negatively correlated with 25OHD while Cr (r =0.221,P ＜ 0.01) showed significantly positively correlation with 25OHD.Conclusion Vitamin D deficiency is prevalent in both younger and elder adults in Beijing,especially in younger females.

Comparison of five automated 25OHD immunoassays and liquid chromatography tandem mass spectrometry method / 中华检验医学杂志

Objective To compare the concordance of five automated 25OHD immunoassays with liquid chromatography tandem mass spectrometry method ( LC-MS/MS) .Methods During May to July in 2014, 245 clinical serum samples that requested 25OHD tests were selected, with a total 25OHD range of 2.8 ng/ml-64.0 ng/ml, in which 154 samples did not contain 25OHD2 and 91 samples contains both 25OHD2 and 25OHD3 .To used a LC-MS/MS method that built in our laboratory to measure 25OHD, five commercial automated chemiluminescent immunoassays from Abbott Diagnostics ( A ) , DiaSorin LIASON (B), IDS-iSYS(C), Roche Diagnostics(D), and Siemens ADVIA Centaur(E).Taking the reference method LC-MS/MS as a standard , to compared the concordance and performance of the five automated 25OHD immunoassays.And used the commonly accepted cutoffs for 25OHDdeficiency (<20 ng/ml), and insufficiency ( 20 -30 ng/ml ) , and sufficiency (≥30 ng/ml ) to compare the uniformity of different methods .Statistical analysiswere performed by MedCalc software , Passing & Bablok regression , Bland &Altaman plots and Box and whisker plots were performed to compare the differences of the methods .Results The medium ( range:2.5% -97.5%) 25OHD of the 245 serum samples of the six methods was 23.5 (5.8-44.2) ng/ml(LC-MS/MS),20.6 (7.1-43.5)ng/ml(A),19.0 (5.4-38.0) ng/mL (B),23.0 (10.0-38.1) ng/ml(C),20.1 (5.1 -46.0) ng/ml (D),31.3 (12.3 -71.1) ng/ml (E), respectively .Passing and Bablok regression showed that method B had the best correlation coefficient with LC-MS/MS (r=0.894), while methods A, C and D had relatively small bias compared withLC-MS/MS and method E had the large bias .If the serum samples did not contain 25OHD2 , all the five automated immunoassays correlated well with LC-MS/MS with a correlation coefficient higher than 0.84, and B has the best correlation with LC-MS/MS ( r=0.930 ) .While all the correlation coefficient between immunoassays and LC-MS/MS decreasedwhen analyzing the samplescontaining 25OHD2.Using the clinical cutoffs, A, B, C, D and E had a concordance of 68.6%, 64.9%, 67.8%, 70.6% and 51.8% compared with LC-MS/MS, respectively .Conclusions There are significant differences between different detection systems of 25OHD.All the immunoassays results were affected by the existence of 25OHD2 .The concordance of serum 25OHD resultswas poor between different methods , and it may be necessary to built exclusive cutoffs for different methods.

Validation study of chronic kidney disease epidemiology collaboration predictive equations based on serum creatinine and cystatin C in Chinese chronic kidney disease patients / 中华检验医学杂志

Objective To validate the four chronic kidney disease epidemiology collaboration (CKD-EPI) predictive equations based on serum creatinine (SCr) and cystatin C (Cys C) in Chinese CKD patients,and try to develop the GFR predictive equations for Chinese CKD patients.Methods254 CKD patients were randomly selected from four Grade ⅢA hospitals in different regions in China from September 2007 to December 2010.Clearance of dual plasma sampling 99mTc-DTPA was used to measure glomerular filtration rate (rGFR) in 254 CKD patients.The serum concentration of Cr and Cys C were measured.CKD-EPI SCr equation,Cys C equation,Cys C equation adjusted for age,sex and race,SCr/Cys C combinated equation adjusted for age,sex and race were used to estimate GRF ( labeled as eGFR1,eGFR2,eGFR3 and eGFR4,respectively).The correlation,bias and precision of eGFRs were compared with rGFR by Wilcoxon signed rank test,intraclass correlation coefficient (ICC) and Spearman correlation analysis.The deviation degree between rGFR and different eGFRs was compared via Bland-Altman graph.The accuracy within 15％,25％,30％ ( P15,P25,P30) and the staging correctness of eGFR against CKD at different stages was calculated.ResultsThe rGFR in 254 CKD participants was [ 48.07 (26.19 -92.97 )] ml · min -1·(1.73 m2) -1.The Spearman correlatiou coefficients (CC) of eGFR and rGFR varied within the range of 0.873 - 0.896 ( P =0.000 ).The intra-class CC ( ICC ) varied within the range of 0.920 - 0.942.The correlation of eGFR4 was the best.The absolute deviations of 4 eGFRs and deviation precision were eGFR4 ＜eGFR3 ＜ eGFR2 ＜ eGFR1.The 95％ confidence intervals for the regression line of 4 eGFRs shown by Bland-Altman graphs were 92.5,87.3,83.0 and 76.1 ml · min-1 · ( 1.73 m2 ) -1,respectively,with the best result of eGFR4.For P30,the correctness of 4 eGFRs were eGFR4 ＞ eGFR3 ＞ eGFR2 ＞ eGFR1,but no significant difference was found by Chi square test (x2 =6.448,P =0.092).The overall correctness rate in 4 eGFRs against CKD stages were 48.4％ -57.5％,with the highest consistency of eGFR4,but their staging correctnessratewerenotideal(Kappa values were 0.405,0.348,0.366 and 0.463,respectively).Conclusions Compared with CKD-EPI SCr equation,no advantage was found in CKD-EPI Cys C equation.The Cys C equation adjusted by age and sex shows a little advantages over CKD-EPI Cys C equation in bias,precision,correlation and accuracy.The CKD-EPI SCr/Cys C combinated equation adjusted by age,sex and race has advantage over other three equations not only in bias,precision,correlation and accuracy,but also in staging correctness.However,the validation of this equation is still not fairly ideal for Chinese CKD patients.Based on these findings,it is essential for the Chinese CKD patients to develop SCr/Cys C combined predictive equation which adjusted by age,sex or other factors.(Chin J Lab Med,2012,35:798-804)